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5 March 1981
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USSR Re ort
p
BIOMEDICAL AND BE~IAVIORAL SCIENCES
CFOUO 6/81)
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NU'I'E FROi~I 'IT-IL' DIRECTOR, FBIS:
~ Forty years ago, tlie U.S. Government inaugurated a new
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~ JPRS L/9591
5 March 19 81
~ USSR REPORT
LIFE $CIENCES
- BIOMEDICAL AND BEHAVIORAL SCIENCES
(FOUO 6/si)
i
; CONTENTS
ADVANCED BIOTECHNOLOGY ,
-i Modern Trends in the Use of Biological Active Substances as Plant
Protection Agents 1
i Prospects for Tndustrial Production of Insect Pheromones 7
i
' Prospects for Using Polymer Materials To Prolong the Effect of
Attractants 10 ~
i
~ Investigation of Insect Sex Pheromones at the All-Union Scientific-
' Research Institute of Biological Methods for Protection df Plants
- (VNIIBMZR)..~ 14
Some Data on the Volatility and Stability of Attractants 19
ADVANCED MEDICAL TECHNOLOGY
i Immobilized Biopreparatians in Medicine 21
i
Antioxidant-Assisted Cell Recovery From Radiation Zn~ur.y, and the
~ Reliability of Biological Systems 25
,
i Proton Magnetic Relaxation in the Study of Burn Pathology Development... 30
Structural-Functional Aspects of Neurophysiology 34
- Cardiogenic Reflexes and Their Role in the Regulation of Blood
Circulation 40 -
ENVIRONMENTAL HAZARDS
Information Macromolecules in Radiation Disturbances of Cells........... 45
' Abstracts From the Collection 'Simulation of the Behavior and Toxic
- Effects of Radionuclides' 51 -
- a- [III - USSR - 21a S&T FOUO]
- ..nn nn.+r~r . r t rnr+ n~?rr ar . ~
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Human Modeling: Distribution of Neutron Radiation 59
PHYSIOLOGY
The Question Concerning the Electrostatic Field of Human Beings......... 62
Correlation Indicators of Brain Electroencephalograms During
Emotional Stress 69
Study of Differential Sensitivity to Changes in Duration of Tonal
Sounds 74
Effect of Different Work-Rest Schedules Following 64-72 Hours of
Wakefulness 84
i
~
I
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ADVANCED BIOTECEINOLOGY
UL1C 632.9.3.2.2. .
MODERN TRENDS IN THE USE OF BIOLOGICAL ACTNE SUBSTANCES AS
PLANT PROTECTION AGENTS
; Moscow BIOLOGICHESKI AKTNNYYE VESHCHESTVA V ZASHCHITE RASTENIY
I in Russian 1979 pp 3-9
-i
j [Article by Ye. M. Shumakov, doctor of biological sciences, pcofessor, All-Union _
I Seientific-Research Institute for Protection of Plants]
[Text] In the past three to five years (1974-1978), new plant protection agents
have enjoyed prae�ical application both in the USSR and abroad, chief among
these being insect pheromones and hormonal compounds.
This has been the result of intensive scientific research efforts carried out by
entomologists in cooperation with animal physiologists and chemists studying the
structure of natural compounds.
In April, 1976, at the Scientific and Technical Council of the USSR Ministry of -
Agriculture (MSKh SSSR), the question of the state of the art and the outlook
of pheromone use to control crop pests was discussed. One of the decisions of
this council emphasized the need for wide-scale comparative testing of domestic
e.nd imported pherornones.
The results of these tests for 1976 were summarized at a special session at the
VDNKh in February, 1977.
~ The Institute of Zoology and Parasitology of the Lithuanian Academy of Sciences
' held two all-union symposia on insect chemoreceptors in Vilnius and published the
; proceedings of these symposia ("Khemoretseptsiya nasekomykh", Vilnius, I, 1971;
j II, 1975; III, 1978~. A third symposium is now in the planning stage.
,
Of late, not a single meeting has been held in our country on the subject of
endocrinology. In this respect, we have had valuable contacts and cooperative
ventures with scientists at the Czechoslovak Academy of Sciences, where
wide-scale investigation of endocrinological problems in insects in both their
- biologi~al and chemical aspects is being carried out. ~
At special symposia of the 15th International Entomological Congress (Washing-
ton, 1976), attention was sharply focused on the study of biologically active
1
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substances which ensure the development of insects and chemical com-
munications among individual organisms. Most scientists tend to accept a
division of biologically active substances into two categories: hormones and
semiotic chemicals. The latter imply chemical messengers which govern
chemical interaction among organisms and in some way affect their social and
sexual behAVior.
In line with this categorization, two basic trends have develcped in the ~tudy of
means to employ biologically active substances in plant protection.
One trend involves the study of new methods to control pests based on the use
of substances which inhibit or suppress growth, development and reproduction of
insects. Among these are the juvenoids, hormonal compounds which inhibit
molti;,g and incorporation of chitin in the insect cuticle, such as the new drug
Dimilin~ [difluronl; substances which inhibit diapause, chemosterilants, etc.
- Another trend in the use of biological active substances as plant protection
agents is based on the use of drugs which affect the social and sexual behavior
of insects and in some way affects the ecology. ~
This category primarily includes various types of pheromones, e.g. sexual, trail, ~
territorial and alarm pheromones, plus a wide variety of substances which
facilitate chemical commui~.~aation among various species in the biocenosis
(called allelochemical compounds in the foreign literature). ,
These include the allomones (scents or toxins which are aversive to foes) and
- kairomones (chemical agents used by entomophags to locate insect hosts and
victims. In a broad sense, they are substances necessary not only to the .
- organism which secretes them, but also to the organism which senses them and -
reacts to them.,
An acquaintance with research trends on biological active substances in the US -
gives an impression that this line of research is considered to be the main -
prospect for discovering new plant protection agents.
The British-American publishing company, Plenum: Publishing, has published the '
Journal of Chemical Ecology quarterly since 1975. This journal reports on
modern achievements in the study of the chemical structure of natural -
compounds and the need for close contact and coordination between chemists
and biologists as being a major prerequisite for advancing the knowledge of
interaction among organisms in nature. In 1976, the journal published 42
articles, most of which dealt with insect and mammalian pheromones. Of the
hormone compounds, the most attention was given to juvenile hormone analogs
(juvenoids). ~
The natural juvenile hormone of insect;; was identified in 1965-1973 by American
scientists. These studies proved the existence of at least three forms of j~~venile
hormone within an insect class: JuH-1, JuH-2 and JuH-3. Their chemical nature
is very similar to the sesquiterpenes and they are derivatives of farnesylic acid.
On-going efforts in the US and other countries to discover, identify and study
2 -
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the biological properties of various forms of JuH and their analogs may provide
a b&se for reverse synthesis of biologically active compo~~nds which have a
_ selective effect on specific insect groups.
Czech investigators have been carrying on a continual quest for new ways and
means of employing synthetic hormonal analogs. Res~arch is continuing in the
- study of the systemic nature of action of juvenogens. A distinetive feature of
these compounds is their ability to change into substances having juve-
nile-hormonal activity in response to some biological or internal factor, but
remain dormant prior to that point.
- In a~ldition, work has recently begun on the study of precocenes (antijuvenile
hormone).
Juvenoids have already been widely tested in pest control. In 1976, treatment
; of the mulberry tree against the first generation of the fall webworm in the
~ Novoanensk region of the Moldavian SSR completely prevented a scourge by this
i species.
i
~ Considerable interest is afforded by another group of hormone-like compounds:
j chitinization inhibitors, which have been undergoing tests here and abroad for
j three years. 'I'hese compounds are for the most part enteric in action and may ~
be successfully employed against a wide range of leaf-eating pests. Preliminary
tests have demonstrated the high eificacy of the most active of th~se
~ompounds: Dimilin~ (difluorn] (active principle is difluorobenzoyl urea) against
such destructive pests as the turnip moth, cutworm, beet w~ebworm, fall
- webworm and others. Dimilin~ and allied compounds are not only non-toxic to
humans and warm-blooded animals (LDgp ranges from 10,000 to 19,000 mg/kg), -
but they are also of low toxicity to most entomophags. The exceptionally high
~ biological activity of Dimilin~ accounts for the small quantity of Dimilin~
required for treatment. For example, a mere 0.03 kg per hectare is virtually
~ 1G0 percent effective against the fall webworm. .
The bibliography on insect pheromones is extensive. In 1976, M. Jacobson's
~ thorough compendium "Sex pheromones of insects" was published in Russian and
the review "Pheromones and hormonal compnunds in the US" (Moscow, 1976) by
Ye. M. Shumakov, V. N. Burov and A. I. Smetnik added new data to Jacobson's
book.
In recent studies, lists have been published of all identified sex pheromones
j according to the latest data in 1976. The American chemical manufacturer
~ Zoecon produced a rather wide variety of pheromones in 1977 for various inse~t
pestso Pheromone-baited insect traps have appeared on the market for 25
species of Lepidoptera and sexual attractants for four species of Drosophila.
Among the pheromones for Lepidoptera, interest has been stimulated by traps
for the ~codling moth, oriental fruit moth, gypsy moth, grape-berry moth and
European corn borer, which are dangerous pests in th~ USSR as well.
Many sexual pheromones of destructive moths have been synthesized and studied
- in the USSR; the results of this eesearch have been discussed in several of the
reports appearing in this collection.
3
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Pheromones of the true bugs have not been thorougt~ly investigated; in fact, to
_ date no single compound has been identified which could be considered a
pheromone of any species of Hemiptera. Meanwhile, in true bugs one would
expect a wide diversity of pheromones, including sexual, trail and territorial
marks. The significance of this problem is def.ined in particular by the fact
_ that amon~ Hemiptera, there are very many serious pests, such as the
destructive shield bug (Eurygaster). Studies by entomologists of the All-tlnion
InstiYute for Protection of Plants (VIZR) and the Institute of Entomology of the
Czechoslovak Academy of Sciences, in particular, have demonstrated that
compounds of the vanillin type play some role in sexual communication in the
shield bugs and are attractants to females.
In 1975, collaboration was begun between the sterilization laboratory of VIZR
and the Laboratory of Natural Compound Chemistry of Leningrad University, _
with the aim of identifying the pherflmones of the shield bug. In view of the
~ low vol~tility of vanillin, it would be anticipated that the sexual pheromones of
the shield bug also sPrve as markers and their individual components can be
identified. _
;
In addition to sexual phero;nones of destructive insects, research on bee I
- pheromones i~ worthy of note; among these, the decenoic acids have been ,
studied in the greatest detail. Some of them have been synthesized by the
Shchelkov branch of the All-Union Scientific-Resea:ch Institute of Chemical s
Used for Plant Protection (VNIIKhSZR) and have been tested by several scientific
institutions.
In the bee family, (E)-9-Oxo-2-decenoic acid (KDA)y or ~Queen Substances, was
identified as an inhibitor of reproductive activity in worker bees. The
domestically produced KDA synthesized by coworkers at the Shchelkov branch of
VNIIKhSZR (Kyskin, Pyatnova, et al., 1971) was investigated at the insect
sterilization and attractant laboratory of VIZR on bees and destructive insects.
Synthetic KDA appears to funetion biologically by retarding ovarian development
in the worker bee in queenless colonies and affects their laying of queen bee
eggs. A substr~te treated with 1 percent KDA in a form resembling a queen bee
caused bees in a queenless ec:ony to form a retinue around it similar to the
retinue formed around a live queen bee.
Laying workers have been successfully controlled with KDA. The return of
worker bees with active ovaries to their normally inactive state with KDA is of
tremendous practical significance in apiculture to control laying worker
development; and offers the prospect that KDR can be used to suppress
reproduction of destructive insects. Furthermore, KDA applied to the body of
u queen bee is successful even when it is transplanted into a laying bee co?ony.
- Colonies in which laying bees have developed will generally not accept the queen
~ bee and will inevitably kill her.
4
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In 1977, the role of KDA in improving flight pollination activity of queenless bee
layers was de?nonstrated in hothouses in the Leningrad oblast; this offers promise
for using KDA in hothouses to intensify the pollinating activity of bees.
Experiments are also in progress on the use of KDA as a chemosterilant for
destructive insects.
More than 100 compoundG have been tested at the laboratory of insect
sterilization and attractants af VIZR with the goal of finding effective
chemosterilants for insects of various orders. Compounds with high sterilizing
activity have been found among the derivatives of ethylenimine, embikhin -
[mechlorethamine HCl], ethylenamines of phosphoric and thiophosphoric acids,
derivatives of phosphonitrylchloride, allylamines of phosphoric acids, hormonal
compounds, and so forth. As a result, sterilizing doses have been established and
methods have been developed for chemical sterilization of 13 species of
destructive insects. As illustrated by the codling moth and the true bug (the
shield bug), the mechanism of action of ethylenimine derivatives on oogenesis
~ has been studied; one of its manifestations is suppression of nucleic acid
synthesis. The effect of "inherited sterility" which occurs in response to
! substerilizing doses of ethylenimine derivatives has been studied in the codling
moth, turnip moth and graphosoma bug.
Research into kairomones carried out by American scientists, mainly at
; Pennsylvania University, made it possible to isolate and synthesize two
kairomonic communication systems:
for the corn earworm (Heliothis zea) and its parasite Trichogramma evanescens
and the predator Chrysopa carnea; -
for the potato moth (Phthorimea opercullela) and its parasite Orgilus lepidus
Muesb. (of the Braconidae).
As has been discovered, in the first case, the squamulae of the corn earworm
contain kairomones which attract Trichogramma and Chrysopa. A hexane
extract of earworm squamulae was used to identify the kairomones. Kairomones
from the earworm squamulae were found to be C21-C25 hydrocarbons. The
I especially saturated hydrocarbon C23 was found to be extremely stimulating to
~ the quest reaction of Trichogram ma.
~ The kairomone system in the potato moth is a mixture of normal aliphatic acids. _
I One of them, heptanoic acid, greatly intensifies the quest reaction of the
' parasite.
- Chrysopa is highly attr~eted to the honeydew secreted by aphids and other
suctorial insects, and the substances it contains stimulate egg lay:ng of
Chrysopa. Some amino acids were narrowly defined as attractants in this
context.
- In 1975, research by entomologists at Pennsylvania University first demonstrated
that substances which are kairomonic are widely represented among the forage
plants of these pests: in maize and potato tubers; in other words, insect
kairomones are of vegetable origin, as has been proven for insect hormones.
~
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These groups of compounds far from exhaust all the biologically active
substances of value in plant protection. The expansion of research into the
diverse groups is a major subject for further investigation.
COPYRIGHT: Izdatel'stvo "Kolos", 1979
[8144/1434-8617]
8617
CSO; 8144/1434
~
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PDC 632.9.3.2.1.3
PROSPEC'r'S FOR INDUSTRIAL PRODUCTION OF INSECT PHEROMONES
Moscow BIOLOGICHESKI AKTNNYYE VESHCHESTVA V ZASHCHITE RASTENIY
in Russian 1979 pp 9-13
[Article by Yu. B. Pyatnova, candidate of chemical soiences]
[Text) The existence of chemical communciation in the insect world has by now -
j been thoroughly demonstrated. Knowledge of the chemical structure of natural
; regulators allows man to control insect behavior. Insect sexual pheromones have
j been wi~ely used for this purpose.
i
In the US, attractants are produced and widely used for the codling moth _
~ (Codlemone~), oriental fruit moth (Orfomone~), plum moth (Funemone~), leaf-
I roller moth, cotton leaf miner, and gypsy moth.
I
j Practical interest in pheromones makes it necessary to develop preparatory
; methods of synthesis. We have developed means of pheromone synthesis for the
i plum, oriental fruit, acodling and gypsy moths.
i
When these subsances are being synthestzed, we consider the need to obtain
~ substances which are maximally pure, free of impurities, including geometric
; isomers; we therefore select methods having high stereospecificity. _
I
~ The plum moth attractant is Z-8-dodecenyl aceta~e. The acetate containing 97
! to 98.5 percent of the Z isomer and 1.5 to 3 percent of the E isomer has the
; highest biological activity. After investigating several methods of synthesizing
Z-8-dodecenyl acetate for pilot production, we recommended a method based on
_ alkylation of 1-sodium pentene of chloroheptanoic acid. The resulting 8- _
dodecenic acid is recovered with lithium aluminum hydride in the appropriate
alcohol, hydrated into Z-8-dodecenol and acetylated. The ~xperimental installa-
tion was planned and assembled according to this arrangement. In the course of
three years we have produced rather large test batches which have been used to
study preparatory forms and for developing application methods.
The attractant of the oriental fruit moth is a mixture which includes one part
Z-8-dodecenyl acetate containing 7-8 percent of the E isomer and 92 to 93
percent of the Z isomer; ten parts of dodecylic alcohol. Therefore, by solving _
the problem of producing Z-8-dodecenyl acetate, we also obtain the attractant
, ~
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of tt~e orientrzl fruit moth. The required proportion of Z:E isomec~s is Achieved
by mixing Z-B-dode~enyl acetate and E-8-dodecenyl acet~te obtained by
- recovery af the alkene precursor by sodium in liquid ~zmmoni~.
Z-8-dodecenyl acetate is also an inhibitor of perception by the codling moth oF
its own sexual pheromone. At VIZR, it~ possible use to control sexual mating
in the codling moth is being investigated.
The natural attractant of male codling moths is E, E-8, 10-dodecadienol. The
- preser~ce of other geometric isomers in the synthetic pheromone is undesirable,
since this reduces its biological activity and sometimes totally ini~i5its it.
Our goal was to synthesize E, E-8, 10-dodecadienol with high biological activity.
Sevei at methods of synthesis of E, E-8, 10-dodecadienol have been developed.
The most suitable for preparatory purposes is the method which uses the Whiting
reaction to create a system of conjugated double bonds.
- Phosphonic acid obtained from 8-bromoctanoic acid and triphenylphosphine, with
treatment by sodium methylsulphinylmethylide in DMSO (dimethylsulfoxide)
yields the phosphoylide, whose interaction with croton aldehyde produces the
8,10-dodeeadienic acid. ~
(
Dodecadienic acid ~btained in the Whiting reaction under these conditions is a i
- mixture of two isomers: primarily Z-8, E-10 isomer and partly the E, E-8, 10-
isomer. This acid is recovered by lithium aluminum hydride in alcohol. In order
to increase the content of the E,E-isomer, the alcohol is isomerized in UV light
in the presence of catalytic quantities of iodine. Pure E, E-8, 10-dodecadienol
is obtained by low-temperature crystallization from pentane.
The described method of synthesis, however, contains technological difficulties
which prevent it from being put into production. We therefore continued our
quest for practical methods of synthesis of E, E-8, 10-dodecadienol.
In field tests conducted by T. P. Bogdanova at VIZR, the dodecadienol which we
synthesized actively attracted male codling moths into the traps and was just as
effective as Codlemone~, the compound produced by Zoecon. Application forms
are currently being developed which are suitable for supervision and regulation
of the codling moth population.
We have also synthesized the attractant of the gypsy moth, Z-7,8-epoxy--
2-methyloctadecane (Disparlur~) by two methods. Starting with 2-methylhexane,
by hydrobromation against the Morkovnikov rule, we obtain 2-methyl-hexyl-
bromide. From decylbromide with sodium acetylenide we obtain dodecene-1, ~
whose lithium product is alkylated with 2-methylhexylbromide. The alkene is
stereodirectionally hydrated to the cis-alkene and is epoxidated. High purity
(99.7 percent) Disparlur~ is ob.tsined. It is extremely high in biological activity:
at a dose of 0.05 microgram it is active for the entire flight period of the gypsy '
moth, i.e. for 45-50 days.
8 .
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_ Disparlur~ has also been synthesized aecording to the Whiting reaction. From
isoamylmagnesium bromide and allylbromide, the isooctene is obtained which
upon hydrobromation yields the isooctylbromide. The phosphonic salt obtained
from the isooctylbromide and triphenylphosphine with sodium methylsulphinyl-
methylide leads to the corresponding ilide which, with undecanol, yields 2-
methyl-Z-7-8-octadecene. Disparlur~ is obtained after epoxidation.
After comparing the biologica~ activity if Disparlur~ obtained by these methods
and the economic indicators we shall select a method for industrial production
of the attractant.
For se~�eral years, N. G. Shaposhnikova at VIZR has been studying the biological
effect of (E)-9-Oxo-2-decenoic acid, one of the components of Queen Substance
of Apis mellifera. She demonstrated the possibility of using this acid in
apiculture ta prevent swarming, for prevention and correction of the laying
' worker activity in bee colonies and to facilitate transplantation of queens. (E)-9-
Oxo-2-decenoic acid inhibits reproductive activity in other insects: in the fly
Drosophila phalerata, in the shield bug, and in the rapeseed sawfly. This opens
~ up the possibilitq for using oxydecenoic acid to control destructive species as a
; natural chemosterilant.
i
In view of the applied value ~f (E)-9-Oxo-2-decenoic acid, we developed two
I methods to synthesize this compound based on ?-chloroenanthic acid. Bromation
~ and deh~ drobromation changes the initial acid to (E)-7-chloro-2-heptenic acid
and this is converted into (E)-7-iodo-2-heptenic acid. Condensation of the latter
I with sodium acetic ester accompanied by alkaline hydrolysis yields (E)-9-Oxo-2-
decenoic acid. Another version includes reaction of 7-exhloroheptanoic acid
_ with met~iyl l;thium, conversion of the resultant 1-chlororoctane-7-one to the
oxyketone; oxidation of the latter to 7-ketooctanol and its condensation with
~ malonic acid.
Both versions of synthesis are simple and may be reproduced on an industrial
i scale. After specific recommendations for practical application, a pilot plant
i can be established for production of (E)-9roxo-2-deeenoic acid.
~ Therefore, we have developed preparatory methods of synthesis of several
~ attractants of the most prevalent and dangerous pests of agricultural crops. This
; will make it soon possible to introduce safe, effective methods of supervision
and control of the development of these species in plant protection.
I COPYRIGHT: Izdatel'stvo "Kolos", 1979
~8144 /1434-8G17 ]
8617
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UDC 632.9.3.2.1
PROSPECTS FOR USING POLYMER MATERIALS TO PROLONG THE EFFECT
OF ATTRACTANTS
~ Moscow BIOI~OGICH~SKI AKTIVNYYE VESHCHESTVA V ZASHCHITE RASTENIY in Russian
1979 pp 13-18
[Article by A. I. Terekhova and L. I. Verzunova, candidates of chemical sciencesJ
[Text] The creation of compounds having reliable control of diffusion of the
~ active principle is one of the chief problems in the use of synthetic pheromones.
- Among the various methods for tackling this problem, methods using polymers
have become most prevalent: prolongation of the action of the attractants is
- achieved by diffusion from polymer/attractant composites or through polymer
films. In the first instance, the polymer is a matrix containing an attractant
whose diffusion depends on the physico-chemical properties af the polymer and ~
- attractant. Various thermoreactive polymers, synthetic or natural rubbers can
be used as the matrix material. Polyurethanes, PVC, polyvinylpyrrolidones
(povidones) and polyethylene glycol have been used; fillers (chalk, clay) are often
used to preform the compounds. The attractant can be added to the polymer
by mixing it with the initial components. If vulcanized rubber is used as the
, matrix, favorable conditions for diffusion of the attractant into the polymer are
created when there is swelling in the attractant or in its solution. The swelli~g
method can be used to prepare very large batches in a short time. But this
method is deficient in that during the swelling process certain components may
be removed from the polymer and the specimens lose their strength and
elasticity; nonproductive losses of attractant are also possible. Thus for
industrial use, preference should be given to the method of premixing of
attractant and components of the rubber mixture.
Compounds have lately been prepared in our country for primary biological tests
~ of attractants of the oriental fruit and plum moths consisting of rubber based
on natural rubber employing the method of swelling in their solutions.
- The solvent should have the following properties: rather high degree of swelling,
absence of destructive effect on the polymer, high volatility. The latter
property is necessary so the solvent leaves the specimen in a short enough time
and does not induce an untoward side effect while the compound is working.
Chloroform, hexane and p-xylene have been tested as solvents. The parameters
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of solubility which characterize the intermolecular interaction of polymer and
these solvents are equal ~o, respectively, delta hexane = 7.3 + 7.4; delta
chloroform 9.3; delta p-xylene 8.8; delta natural rubber 8.1. Degrees of
- impregnation of rubber based on natural rubber in these solvents were
_ determined: alphachloroform = 4.25; alphahexane = 0.89; alphap_xylene = 2.16 (t
- = 22�C). Chloro~orm has a strong destructive effect on rubber and thus the final
products used were hexane and p-xylene. In view of the difference in physico-
chemical properties of attractants of the oriental fruit and plum moths, it was
necessary to determine the variation in degree of impregnation (alpha) of the
polymer in solvents as a funetion of their concentration. The results proved that
alpha linearly varies from 2.75 ( C= 5 percent) to 1.7? (C = 100 pereent) for
attractants of the plum moth and for the attractant of the oriental fruit moth
from 2.6 (C = 5 percent) to 0.4 (C = 90 percent). Because diff~sion of
cis-8-dodecenyl acetate and dodecylic alcohol into the impregnating polymer
- may be different, solutions were analyzed before and after impregnation by the
, gas chPOmatographic methud. Tests showed that the proportion of components
had not changea.
I~ The maximum degree of impregnation was attained after several hours, and it
was determined by the weight of the specimens before (mp) and after
j impregnation (mmax~~
~
i
mmax ' m0
mp .
I
An important part of the development of pheromone compounds is the analysis
of the working characteristics of the compound: consumption of attractants,
duration of effect, resistance to various environmental factors during testing.
The rate of release of attractants from the compound was determined by weight
loss of the s~ecimen subject to conditions close to natural ones (ternperature and
air velocity).
The kinetics of specimen weight change produced by impregnation in solutions
I having a different concentration of plum moth attractant (solvent p-xylene)
shows a sudden drop in weight in the first few hours due to release of the
solvent; with a reduction in the percentage content of the solvent, the curve
; becomes flatter. As these data suggest, the solvent is released almost
completely in the first three to four hours; then the slope of the rectilinear
~ segment of the curve may be considered a constant which quantitatively
describes the consumption of attractant. Curves of the kinetics of release of
oriental fruit moth attractant from a rubber-based compound are the same. In
view of the dual componential nature of the oriental fruit moth attractant, it
is also necessary to refine the composition of the attractant released from the
compound. According to modern concepts, the molecules diffused in the polymer
experience double resistance: "Iateral" and "frontal:" Lateral resistance is
proportional to the number of atoms in the diffusing molecule, while frontal
resistance is proportional to the cross section. Dodecylic alo~hol and cis-8-
dodecinyl acetate have negligibly different characteristics in this case and no
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substantial change in the composition of the gaseous phase was anticipated. Gas -
chromatography corroborated this assumption.
Data on the kinetics of release of attractant from the composite make it .
possible to determine its overall reserve in terms of the difference in weight of
the specimen in the linear segment of the curve and a control specimen
- impregnated in pure solvent (Delta m). A comparison of the relationships of
doses (Delta m) of pheromone in specimens as a funetion of solution
concentration in which they were produced shows that for the plum moth
- attractant, the dose increases linearly, while for the oriental fruit moth this
relationship. has a limit. This would suggest that to prepar~ the plum moth
attractant composite by the impregnation method, the entire range of con-
centrations is suitable; and the criteria for selecting conditions should be the
requirements imposed on attractant consumption, desired period of effect, etc. _
For the oriental fruit moth attractant, an increase in solution concentration -
from ten to ninety percent yields no substantial increase in its dose in specimens
and therefore, an increase in concentration of the active principle in tech- _
nological solutions of more than 10 percent is unprofitable.
~ Analysis of the rate of release of this attractant and the periods of effect of
compounds calculated by the formula t=(Delta m)/v (Delta m= dose in
milligrams, v= consumption of attractant in milligrams/day) showed that an -
increase in the period of effect is observed when switching from 5 percent to
10 percent solutions. With a further increase in concentrations of the solutions,
the rate of diffusion varies in direct proportion to the doses of the active
principle in the composite and the estimated periods of effect remain constant
(about 50 days).
Table. Relationship of the Rate of Release as a Funetion of Dose of Oriental
Fruit Moth Attractant in a Polymer/Attractant Composite
Content o attractant Content o attractant Rate of re- Period of ef ect
in hexane solution, in specimen, lease of at- -
percents milligrams tractant, mg
per day
5 12.5 0.7 16.0
~ 10 40.0 0.8 50.0
20 74.5 1.4 53.0 -
50 100.0 2.1 r ~.0
70 100.0 2.1 50.0
100 90.0 1.8 50.8
Polymer/attractant preparative forms of Disparlur~ prepared by the im- -
pregnation method also demonstrate high biological activity. The concentrations
of attractant in this case were extremely small: 0.5 to 5 micrograms per
specimen. Consumption of Dispar;ur~ from preparative forms was not measured
due to the inadequate sensitivity of the weight method.
In addition to composites in which the polymer is a matrix, composites are also
used in which the dosage of attractant into the environment is carried out by
diffusion through a polymer diaphragm. Polymer ampules and capsules which
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were tested for Attractants of the plum, oriental fruit, codling and gypsy moths
~ are this type of composite.
Ampules were made of polyethylene and polypropylene tubes with a wall
thickness of 0.5 millimeters and capacity of U.04 mi?liliter. The weight method
was used to study the kinetics of release of plum moth attractant from
polypropylene ampules with a capacity of 40 microliters and wall thickness of
_ 0.5 millimeter. For this purpose, specimens of the composite were kept in a
- well-ventilated room and were weighed at specific intervals to within 10-~ gram;
temperature was changed in a rather wide range, from 18 to 35�C. In the course
of six months, consumption of attractants was constant and equalled 0.2 to 0.4
milligrams per day. ~
Results of investigation of the kinetics of release of plum moth attractant show
that in the initial period (several days), much less of the active principle was -
released than in the remaining time. We attribute this phenomenon to the
~ distinetive features of the mechanism of permeability of the polypropylene film.
j As we know, sorption of the substance by the membrane and its impregnation is
~ the first stage in the process of penetration through the polymer membrane. The
microencapsulation form was also tested for these pheromones. Encapsulation of
- the two percent solution of attractant was carried out by the method of complex
I coacervation using gelatin and polyacrylic acid. The capsules with a degree of
dispersion of 1.0 to 1.5 millimeters were applied on paper with the aid of a
special composition containing methyl cellulose and latex.
-i The gelatin envelopes of tl~e capsule have considerably different permeability
I than polypropylene ampule envelopes. This is proven by the fact that thP
solvents (p-xylene, benzene, hexane, etc.) diffuse from polymer ampules at a
- rate of 40 milligrams per day or more, whereas for the microencapsulated form
this rate is 0.2 to 0.4 microgram per day. This is the result of a difference in
the structure of polyrners and the interaction of the polymer and liquid medium.
The microencapsulated form of attractants allows us to widely alter the rate of
diffusion by varying the concentration of the active principle in the en-
capsulation phase and consequently, the concentration of attractants in the air.
This is especially useful for the Disparlur~ attractant of the gypsy moth and
codling moth attractant, because the attraction effect is observed at extremely
I low concentrations. To test capsules containing a 0.2 percent solution of
attractants in p-xylene, they were applied on paper in quantities corresponding
~ to specific doses of the active principle.
I' These results would suggest the promise of preparative forms of pheromones
based on polymer materials.
It should be noted that all the possible kinds of preparative forms of sexual
pheromones of insects have not been covered in this report. Future studies on
synthesis and tests of the spectrum of effect of pheromones will probably widen -
this list in terms of their physio-chemical and biologieal properties.
COPYRIGHT: lzdatel'stvo "Kolos", 1979
_ [8144 /1434-8617 ]
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UDC 652.9.3.2.1.3
INVESTIGATION OF INSECT SEX PHEROMONES AT THE ALL-UNION SCI-
- ENTIFIC-RESEARCH INSTITUTE OF BIOLOGICAL METHODS FOR PROTEC-
TION UF PLANTS (VNIIBMZR)
Moscow BIOLOGICHESKI AKTNNYYE VESHCHESTVA V ZASHCHITE RASTENIY
in Russian 1979 pp 18-23
[Article by B. G. Kovalev, candidate of chemical sciences, VNIIBMZR]
[Text] The need for industrial production of insect sex pheromones is mainly i
dictated by the existence of completed technological developments for their I
application, i.e., the readiness of producers to use sex pheromones in practice. i
With the exception of quarantine pests, whose technolc~gy of employing
pheromones is comparatively simple and requires no long-term research, a great
deal of time is required to develop methods for employing sexual attractants for
the remainder of pests. In the near future, the most likely use of sexual
attractants will be in plant protection as a means of supervision and prediction
_ of the pest population. Because of the simplicity of handling and low cost of
sexual pheromone-baited traps, the existing structure oi the warning service can
be altered. Plant protection agronomists at any sovkhoz or kolkhoz will be able
to easily and reliable determine not only the onset of flight of a pest according
to the traps, but also determine the need for chemical treatments. This last
item is extremely important, because it not only permits improvement of the
economics of protective measures, but also stimulates the local entomological
~ fauna and reduces environmental pollution.
Thus research at VNIIBMZR in sexual pheromones of insects has been carried out
along two fundamental lines: 1) identification of sexual pheromones of insect of
economic importance and 2) development of utilization technology. .
When integrated systems of crop plantation protection are employed, in
addition to the chief pests such as the cadling moth, San Jose scaie and others,
a large group of leaf rollers is important since they destroy from 12 to 20
~percent of the harvest, or as high as 50 to 70 percent in years of mass
= multiplication. For this reason, we began systematic research to find effective
lures for the pests of this group. Studies earried out in 1977 established the
chemical composition of the sex pheromone of the currant leaf-roller Pandemis
ribeana. It was a mixture of cis-trans-isomeric acetates of 11-tetradecenol.
Field tests demonstrated the high attractiveness of the sex lure.
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'Cha sex pheromones of the omnivorous (Archips podana), reticulated (Adoxophyes
reticulana) and rose (Archips rosanus) leaf-rollers are known. Their chemical
composition is shown in Table 1.
Using arrangements earlier developed by us, synthesis of the components of sex
pheromones of these species of leaf-rollers has been effected and they have been
field tested; th~ results are shown in Table 2.
Table 1. Chemical Composition of Sex Pheromones of Three leaf-Roiler Species
Lea -roller species Cotnposition of pheromone proportion of -
- comqonents
omnivorous C15 trans
- C~}(SCH-CH(CH )~~OAc+C~HSCH=
= CH (C71-i,) ,,,OAc
(I : 1) .
cis cis
rose C,IisCH=CA(CHz),oOAc+C,H,CH=
- = CH (CH~) io01 I
(9:1)
reticulated ~ C~HoCfi=~CH(CHz)aOAc+C3H,CH~
=CH (CH~) ~oOAc
(9:1) .
Table 2. Attractiveness of Synthetic Lures far Males of A. podana, A. rosanus,
A. reticulana and P. ribeana
~ Lea -roller species Dose meg Males captured avg. per trap -
~ in 14 davs
! omnivorous 2000 24.5
~ Control 0.0
~ rose 2000 68.0 -
Control =
reticulated 2000 28.2
Control 0.0
currant 2000 22.5
Control 0.0
~
~ Along the same lines of integrated orchard protection, we began a study of the
sex pheromones of two species of the genus Orgyia: Orgyia gonostigma (tussock
~ moth) and orgyia antiqua (vaporer moth). These two species represent a
considerable threat to intensive type orchards and a battle must be fought
- against them some years in Moldavia. We know that the sex pheromone of the
American species Orgyia pseudotsugata is the unsaturated keton cis-6-geney-
cosen-ll-one. Field tests of this substance demonstrated its high attcactiveness
for males of O. antiqua. Males of the species O. gonostigma were not attracted
by this substance. The results of field tests are shown in Table 3.
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'['uble 3. Catch of MAles of O. Antiqua in a Tr~p with Cis-6-Geneycose-llrone
(observations of four tra s over h davs)
dose m eg Males captured average per trap
_ in six davs
~
1000 13.2
100 6.0
10 4.5
Control 0.48
Using the arrangement:
CII,CIi=C11C11=PPh~+OHC(Cl~z)6COOet CH,CIi t CHCH~
= Cl t(C I ~z) cCOOet 1
Cli~(Cl1=Cfi)~(CH,),OH h�- CN~CH=CHCH
CI i (CFI,),OH
the attractant of the codling moth, Codlemone~, was synthesized in 1976. The
activity of the substance is as good as the lures manufactured by Zoecon. -
Testing of specific doses (Table 4) under field conditions showed that there is no
significant difference between a dose of 2000 meg and the compound produced
by Zoecon.
` Table 4. Attractiveness of Various Doses of Codlemone~ for Male Codling Moths
(20 days)
Test version Number o males captured Average
by repetitions Sum
1 2 3 4
Codlemone dose,
m eg: -
100 75 88 64 74 301 75.25
- 1000 197 ?2 90 126 385 96.25
2000 142 138 138 131 549 137.25 ;
Compound of ,
Zoecon 127 130 123 136 516 129.0
HCPpS = 24.0
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The existence of an active compound made it possible in 1976 to begin
development of an application technology. Since 1977, in Moldavia traps
containing Codlemone have been used in a 5,000 hectare area to signal the onset
of fiight of the codling moth, that is, to signal the start of the struggle against
it. In a 500 hectare area, a pilot industrial test is being done on traps with
Codlemone to make the use of traditional toxic chemicals more efficient.
During the 1977 season, VNIIBMZR regularly supplied capsules with Codlemone
to the Armenian NIIZR, Ukrainian Scientific-Research Institute of Horticulture, ~
and the Scientific-Research Zonp.l Institute of Horticulture of the Nonchernozem
belt of the RSFSR.
VNIIBMZR has developed a method to obtain a mixture of isomeric acetates of
7,9-dodecadien-l-ol, wherein 7-trans-9-cis-isomer is a sex attractant to the leaf =
roller moth Lobesia botrana.
~ Synthesis was performed as follows: _
i
~ ~:HsCN ~=Ctl(:Ii=PPhs-}-OliC(CfI~)aCOOet
--CzHsCH ~ CHCH~~
CH(CH~)SCUO~t -
_ ~
C,HSCH=CHCH=CH(CH,)sOH _
- C C~ I
CzHSCH=CHCH=CH~CHz)~O.~C
Field tests of various specimens of sex pheromone made it possible to select the
most promising one which was just as active as Zoecon's (Table 5).
Table 5. Attractiveness for Males of L. botrana of a mixture of cis,trans- -
~ isomeric acetates of 7,9-dodecadien-l-ol
Substance dose, meg Males captured
(avera~e) per tra~
Ferocone USA - 134.6
Ferocone (VNIIBMZR) 2000 116.3
i
! In 1977, the compound was studied in all zones of Moldavia to signal the start
of the struggle against this pest. A pilot test using this method has been running =
on farms in Moldavia since 1978.
In 1977, the compound was widely used at ArmNIIZR where about 800 capsules _
with this pheromone were delivered. -
As a result of systematic research to find sex attractants of cutworms, the most
- dangerous agricultural crop pests, the attractant of the cabbage moth M.
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brassicae was identified t~s cis-ll-hexadecen-l-ol acetate. The substance was
tested under field conditions and was found to be an extremely active attractant
(Table 6).
Table 6. Attractiveness for Males of M. brassicae of Cis-ll-hexadecen-l-ol
acetate (observations of five tra s fo~ 24 days)
Test version dose in meg Males captured avera e qer trap
2000 31.0
one female 10.0
control 0.0
We tested the cis, trans-isomeric acetates of 11-tetradecen-l-ol and their
mix~ures for attractiveness to males of the European corn borer Ostrinia
nubilalis. Mixtures with low content of the trans-isomer were active.
In 1977, in an area of 400 hectar~s, a pilot i~dustrial test was begun of the
method of gypsy moth population prediction with the aid of Disparlur~, the
sexual attractant of this species.
According to the decisions made by the convention on prospects of industrial
production of attractants for fruit moths (1976), VNIIBMZR has conducted
research and found an original trap design for catching fruit moths and leaf
rollers which is just as efficient as the traps made by Zoecon. Effective trap
designs have been tested and selected for capturing male earworms and the
gypsy moth.
COPYRIGHT: Izdatel'stvo "Kolos", 1979
[8144/1434-8617]
8617
CSO: 8144/1434
18
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UDC 632.9.3.2.1.3
SOME DATA ON THE VOLATILITY AND STABILITY OF ATTRACTANTS
Moscow BIOLOGICHESKI AKTNNYYE VESHCHESTVA V ZASHCHITE RASTENIY
in Russian 1979 pp 47-49
(Article by F. P. Vayntraub, candidate of agricultural sciences; L. P. Dron', Ye.
V. Gitsiu, L. S. Keyser and L. L. Chernichuk, All-Union Scientific-Research
; Institute of Biological Methods of Plant Protection]
! [Text] The success of pheromone communication depends on the properties of
~ the pheromones themselves as well as on many environmental factors. The
; volatility of compounds, the effect on this process of temperature, humidity,
~ wind, the nature of the substrate, initial concentration, etc. are very important.
~
~
~ The stability of attracts in the environment also governs their effective use.
In model tests at fixed temperature (25�C) and wind velocity nf 1.5 meters per
second, the effect of the substrate and concentration on the volatility of gypsy
! moth attractant was studied. Some 250, 500 and 1000 micrograms of Disparlur~
~ in one milliliter of hexane were applied to strips of filter paper 5 x 13.5
centimeters in size; 1000 and 2500 micrograms were applied to strips of foil of
I the same dimensions The amount of unevaporated compound was determined by -
~ gas-liquid ChCOmatography (GLC).
~ On various substrates, the loss of Disparlur~ at a given concentration occurs at
~ different rates. It is a geometric process. -
_ I Regardless of the initial concentration, the loss of compound is more rapid in the
i first 6 hours and slows down after 24 hours (regardless of initial concentration).
~
In field tests of these concentrations in traps, the rate of loss correlated well
with laboratory data. ~
The rate of evaporation of the oriental fruit moth attractant (mixture of
cis-8-dodecenyl acetate with 7.5 percent trans-8-dodecenyl acetate and addition
of dodecylic alcohol (a synergist) in a proportion of 1:10, pheromone synergist)
was studied in laboratory and field tests. GLC methods
determine the components in a PVC composite.
19 -
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In the laboratory test (temperature 20-23�C, wind velocity 2.3 meters per
second), relationships which define the rate of evaporation of the attractant in
- time were calculated:
for cis-8-dodecenyl acetate log y= 1.03-0.097 x,
for dodecylic alcohol log y= 2.23-0.17x x,
where y is the rate of evaporation, meg/hour;
x is time in days.
The field test completed in July 1976 showed that over the course of a month
about 80 percent of the initial quantity of cis-8-dodecenyl acetate evaporates.
For the attractant of the codling moth (trans, trans-8, 10-dodecadien-lrol), GLC
me.thods were developed for analysis in rubber-based composites. Evaporation of
the attractant was studied in field tests in May/June, 1977.
The relationships to which the attractant evaporation process is subject when
applied in the trap at various concentrations come t~:
at 1000 meg, y= 176 e'0.305 x~�577 ~ X-423~ '
at 1500 meg, y= 309 e'531 x9�388 ~ X 612~
at 2000 meg, y= 403 e'0.476 x0.423 ~ X-0.577~
where y is the rate of evaporation, meg/day and x is time, in days.
This process, like for Disparlur~, is characterized by high initial rate (150 to 200
meg/day) in the first five days. Then, regardless of the amount of substance
applied, therates equalize (20-30 meg/day).
1t may be assumed that such model tests will permit prediction of periods of
replacement of attractant sources in traps.
- Among the factors affecting the stability of compounds in the environment, we
have specified light (UV and sunlight) and pH of the medium.
Irradiation of Disparlur~ in quartz test tubes with a UV source (80 percent at
wavelength of 365 nm) for 20, 60 and 80 hours led to a loss of up to 80 percent
of the compound (quantum output m-0.5 x 10"4). Research is now being carried
out to study the effect of sunlight on the loss and degradation of Disparlur~.
COPYRIGHT: Izdatel'stvo "Kolos", 1979
~8144/1434-8617]
8617
CSO: 8144/1434
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ADVANCED MIDICAL TECHNOLOGY
IMMOBILIZED BIOPREPARATIONS IN MEDICINE
Moscow IMMOBILIZOBANNYYE BIOPREPARATY V MEDITSINE
in Russian 1980 signed to press 16 Nov 79 pp 2-4, 125-126
I [Annotation, introduction and table of contents from book "Immobilized
, Biopreparations in Medicine", by Konstantin Alekseyevich Makarov and
! Sergey Alekseyevich Kibardin, Izdatel'stvo "Meditsina", 6,000 copies,
! 128 pages]
i
i [Text] Different aspects of the use of enzymes, hormones, -
~ antibi.otics and other drug agents, which are fixed (immobilized)
i in organic and inorganic copolymers (carriers) are examined in
this monograph. The characteristics of such carriers are des-
cribed and the methods to produce the immobilized bioprepara-
tions, their properties and the nature of their application
; in medicine are outlined. The authors discuss the relative
; advantages of immobilized preparations in comparison with anal- _
ogous soluble preparations. Data are presented on the use of
- immobilized preparations for therapeutic purposes: to process
blood, correct enzyme insufficiency in an organism and as anti-
~ cancer preparations. Promising aspects of and results from the
use of immobilized biopreparations in surgical clinics are
examined. The possibility of using them in chemico-pharmaceu-
tical manufacturing is discussed.
, The book is written for workers involved in clinical medicine,
�I instructors, biochemists and workers in chemical-pharmaceutical
manufacturing. 2 figures; 4 tables; bibliography: 169 references.
i Introduction
The term "immobilized preparations" is used to designate all
types of insoluble derived enzymes, hormones, antibiotics and
those compounds which are modified in solution by copolymers.
According to the recommendation~ of the International Commission
on Enzyme Technology for Enzyme Modification by Physical-Chemi-
cal and Chemical Methods, enzymes cais be ~ivided in two large
groups: embedded and coupled. Enzymes included in the structure
21
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of organic and inorganic copolymers belon~ to the embedded
group. Enzymes which are adsorbed by various physical-chemical
_ methods in hard carriers (matrices) belong to the coupled group
as well as those which are coupled with hard carriers in chemi-
cal compounds. All such compounds are called immobilized enzymes.
The more general term--immobilized biopreparations--is used to
designate immobilization of various biologically active compounds _
(enzymes, an; ibiotics, hormones and other drug compounds) .
Immobilized biopreparations can be used for dia~nosis an d treat-
m ent of various diseases, as well as for production of more
modern prost}~eses and apparatus which are used to replace some
of th~ most important human organs. Methods for immobilization
have provided new ways to construct apparatus for an artificial
kidney and liver. Thus, using immobilized urease, successful
tests were conducted on the portable apparatus for an artificial
kidney.
In the opinion of a nu~nber of specialists , the era of enzymes
has replaced the era of antibiotics and hormonal preparations .
Eioti~Tever, widespread use of enzymatic preparations is limited -
by their relative instability during storage, rapid inactiva- ~
tion in the internal environment of the organism, the strong ~
immunologic reaction to them, their high cost and the impossi-
- bility of regeaeration. These inadequacies could be eliminated
- to a significant degree by immobilization of enzymes; that is
coupling them with inorganic and organic polymers.
Immobilized enzymes have been used succssfully to eliminate
various harmful metabolites and for treatment of certain malig-
nant neoplasms such as lymphosarcomas, by using immobilized -
asparaginase. In clinical medicine, different types of bandages
and tampons coated with immobilized enzymes are used. These
_ enzymes are also contained in antibiotics, antiseptics and
other drug preparations.
Immobilized drug agents, combined with various natural and syn-
thetic polymers not only increase the hydrolytic resistance of
these compounds but also increase the effectiveness of these
drugs. The methods for immobilization make possible the pro-
duction of drug preparations with complex effect by the process _
of combined immobilization (co-immobilization) of enzymes, anti-
biotics, hormones and other compounds which have markedly effec-
tive therapeutic properties. Studies conducted at the First
Leningrad Medical Institute showed that the methods of radical
co-polymerization and synthesis of water-soluble medicin al (co)
- polymers--vinylamin, vinylpyrrolidyl, ethenol and acrylic acid
of predetermined composition and structure--can be utilized
effectively in the production of such preparations.
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With the use of immobilized preparation~, more exact and economi-
cal methods have been developed for mass clinical analysis to
determine glucose, lactic acid and insulin leve~~ in the blood,
urea in serum, lactose in urine, penicilli.n in pharmaceutical
preparations. The number of publications, related to the pro-
duction and application of immobilized preparations in medicine
grows every year. This attests to the importance of the problem
of synthesis and use of such preparations in theoretical and
clinical medicine. ~
Contents P~ge
Introduction ..............................................3
Chapter 1. Methods for production of immobilized
medical biopreparations.... . ...........5
Carriers (matrices) for immobilized biologically
active substances ..............................5
Organic carriers ...............................6
; Inorganic carriers .............................8
Methods of immobilization .................................9
Adsorption ........9
; Incorporation in the structure of~a ge1........12
~ Micrbcapsulation ...............................14
Chemical methods of immobilization .......18
Creation of soluble stabilized preparations....18
~ Immobilization in natural (co)polymers.........20
~ Immobilization of drug compounds....... .24
;
~ Immobilization in synthetic (co)polymers.......27
; Macromolecular pharmacotherapy .................28
j Coupled immobilization.......... ..........................37
; Chapter 2. Characteristics of immobilized bioprepara-
' tions......... ...42
I
~ Influence of the nature of~the matrices on the~~properties
~ of immobilized enzymes .........................46
~
Chapter 3. Use of immobilized biopreparations for
~ analytical and preparative purposes in
medicir~e . . . ............50
Use of immobilized biopreparations in~biochemical diag-
nosis and for determination of toxic sub-
stances... ...........50
Use of enzyme electrodes in biomedical research.......,,..56
_ Immunoenzyme methods af analysis.. . ..............59
Use of immobilized compounds in medicine for prepara-
tive purposes . .............65
Affinity chromatography of inedical enzymes.....67
Affinity chromatography of other protein
compounds ......................................69
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Use of immobilized biopreparations in chemical-pharma-
ceutical manufacturing ...........................73
Chapter 4. Use of immobilized biopreparations in
clinical medicine ................................76
Thrombolytic therapy with enzyme preparations ..............76
Use of immobilized biopreparations for correction of
- enzyme insufficiency in an organism and for
activation of~pro-enzymes ...............o........86
Use of immobilized~enzymes as an anti-tumor preparation....89
Use of immobilized preparations in obstetrics and
bYnecology ................91
Use of immobilized preparations in stomatology, otorhino-
laryngology and opthalmology .....................93
_ Use of enzyme preparations in the treatment of respira-
tory diseases . ...........98
Immobilized preparations in treatment of~infectious
diseases ......................................99
Immobilized preparations in nephrology .....................101
Use of immobilized biopreparations in surgery ..............104
Conclusions ................................................112
Bibliography ...............................................115
COPYRIGHT: Izdatel'stvo "Meditsina", Moscow, 1980
[60-9139]
9139
CSO: 1840
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UDC 57:53(2.5);577.3.01;539.1y04;615.1
ANTIOXIDANT-ASSISTED CELL RECOVERY FROM RADIATION INJURY, AND THE RELIABILITY OF
BIOLOGICAL SYSTEMS
Moscow DOKLADY AKADEMII NAUK SSSR in Russian Vol 254,No 3, 1980 pp 760-762
i,
[Article by V. K. Kol'tover, Yu. A. Kutlakhmedov, and Ye. L. Afanas'yeva,
, Chernogolovka Department of ~he USSR Academy of Sciences Institute of Chemical
Physics, Moscow Oblast, and the Ukrainian SSR Academy of Sciences Institute of
Plant Physiology, Kiev]
I
Ii [Text] The viability of cells and multicellular organisms depends on the functional
j reliability of systems protecting subcellular structures and cells from spontaneous
~ and induced injuries, and assisting in their recovery (1). Enzymatic systems
~ assisting in the recovery (repair) of genetic structures play a special role (2).
j One quick � reliability testing method used in engineerin~ involves the testing of
i a system at heightened loads (3). Exposure to ionizing radiation followed by
i analysis of postradiational recovery of cells and tissues, during which the in-
~ tensity of failures rises dramatically and the functional load upon protective and
j recovery systems rises, could be viewed as an analog of this method in biology.
~ Let us assume that cells capable of limitless reproduction--that is,capable of
~ forming macrocolona.es in nutrient agar--are normally functioning cells. The cell
survivability, defined as the ratio of the number of macrocolonies formed by irradi-
ated cells to the number of macrocolonies formed by control cells,could serve as
a statistical measurP of cell rEliability (probability of faultless function).
~ The dependencies of survivability on radiation doses are analogous to the dependen-
I cies of equipment reliability on operating time, since the radiation dose rate
~ corresponds to the intensity of failures arising during irradiation. These primary
failures are a highly simple IPoisson) succession of random events, which simplifies
~ mathematical analysis of the consequences of irradiation. In the rigid conditions
' of postradiational recovery, the positive or negative effects of physiologically
active substances, to include various environmental factors that directly or in.-�
directly alter the reliability of cells and tissues, should manifest themselves
distinctly.
We studied the influence of 2-ethyl-6-methyl-3-oxypyridine chlorhyd.rate (alkyl-
substituted oxypyridine, or AOP) on postradiational recovery of y-irradiated
diploid Megri 139-B Saccluzrorm~ces eZZipsoideus (vini) yeast cells. This anti-
oxidant was found to be an effective radioprotector (4) and geroprotector (5) in
experiments on laboratory animals. The phenomenology of postradiational recovery
of Megri 139-B cells has been studied well, the recovery process is extended in
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= time, and it is easily modified (6, 7); this is why we selected precisely this
_ strain as the system to model. Cells grown on beef-extract agar at 30�C until the
late logarithmic phase were resuspended in sterile tap water at a concentration of
105 cells/ml and irradiated with an 800 Gr dose of 60Co y-quanta at a dose rate ot
0.028 Gr/sec. To determine the recovery genetics, the irradiated cells were incu-
bated at 30�C in the same water. They were periodically seeded on standard nutrient
medium in Petri dishes, and survivability was determined by counting the macro-
colonies (6). The experiments were performed with a fivefold replication. The
results were treated according to a four-factor plan (8) having the radiation dose
(0 or 800 Gr), the moment of addition of AOP to the medium (before or after irradi-
ation), the AOP concentration, and recovery time as the factors. The mobility of
membrane lipids was assessed by the spin probe method (9) using 6-doxylpalmitic
acid as the probe. The probe's EPR spectrum was recorded at 25 � 1�C with a Ye-104
spectrometer.
~oaj .
~o
x
zx
a SO . x
o � ~ I
~ ~
~1~ ~ .~0 ? ~
0
~
JO
- 0 40 BO
( 2 ) Bp~n~? Boctmo,roB.ntau.+ , v
Figure l. Typical Kinetic Curves of Postradiational Recovery of y-Irradiated
Yeast Cells With No AOP in the Recovery Medium (1), With 10-~ M
AOP Introduced Into the Medium Before Irradiation (2), and With
10 3 M AOP Introduced Into the Medium After Irradiation (3)
K.ey :
1. Survivability, ~
- 2. Recovery time, hr
Survivability of cells transferred to agar immediately after irradiation does not
excee~i a few percent (Figure 1). In this case most cells do not have enough time
to repair damaged qenetic structures before the onset of mitosis, resulting in
formation of unviable daughter cells. Incubation in water containing no nutrients,
in which the cells do not divide, affords additional time for repair processes to
occur, and survivability increases correspondingly. In the presence of small AOP
concentrations we observe a rise in the limiting values of survivability (a rise
26
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x .~o ~BX~ao, i/y
tl)
7 ~ % !~F
' ~ .
~i ~
10
S .
\
\
/
3 0 ~ 6
a
! 1
0 ~0'� io 6 ~o-~
, l~o~~, ~t2 )
~ Figure 2. Proportion k of Irreversible Injuries (1,2) and Recovery 3tate
~ R(3,4) of y-Irradiated Yeast Cells Depc?nding on Concentration
~ of AOP Introduced Into the Recovery Medium Before Irradiation
I (2,4) or After Irradiation (1, 3) ; ~k 0.04, ~S 0.008 at P= 0.05
I
j Key;
~ 1. Hr
2 . LAOP J , M
in the plateau of the recovery curve), indicating a lower proportion of irreversible
(irreparable) radiat.ion injuries. Concurrently the rate of recovery declines. The
i kinetics of yeast cell recovery from radiation injury are described by a function
of decreasing effective irradiation dose with time (6,.7):
(t ) D,~ = Do ;k +~i _ k)ex.~~-~t)) .
I
where Do--irradiation dose, R--recovery rate (totial probability of repair of
elementary injury or its transformation into an irreversible form, per unit time),
~ k--proportion of irrewersible injuries. We used a standard curve descri.bing the
I dependence of Megri 139-B cell survivability on dose to compute k and S(7). We
can see from the dependencies of k and R on the AOP concentration, shown in Figure 2,
' that a preparation concentration of 10-~ reduces k by about 25 percent when intro-
~ duced prior to irradiation, and by about 15 percent when added after irradiation.
I S varies symbatically with k. This confirms the hypothesis that irreversible in-
juries are the result of errors made by enzymes responsible for repair (7). k can
be interpreted as an indicator of the functional reliability of these enzymes:
A value of k= 0 corresponds to absolute reliability, while k= 1 corresponds to
absolute functional unreliability of the genetic structure recovery system.
- Reduction of k in the presence of small AOP concentrations means a rise in the
recovery system's reliability. It is possible that AOP (or a product of its
metabolism) modifies primary radiation-caused defects and facilitates their recogni-
tion by repair enzymes. Reduction of ~ apparently promotes a decrease in the
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probability of errors made during recognition and recovery. Pyridoxine analogs,
which include AOP, inhibit RNA-polymerase in other enzymes dependent on pyridoxal-
phosphate (10). Inhibition of such enzymes may cause a delay in cell division,
_ and thus insure additional time for recovery of damaged genetic structures. -
In concentrations exceeding 10'6 M, AOP increases k(Figure 2) and noticeably
inhibits cells reproduction. The orderliness parameter (9) of the 6-doxalpalmitic
acid spin probe in the membranes of intact cells decreases in the presence of
10'3 M AOP from 0.624 � 0.004 to 0.605 � 0.004, indicating growth in the mobility
of the hydrocarbon chains of inembrane lipids. It may be concluded that at least
at large concentrations, AOP has an effect on the structure of cell membranes.
At high irradiation doses the initial segments of the recovery curves can be
approximai:.ely described by the expression:
(2) S(t)-S(0)=nVDo(1 -k)[1 -~XP~-~t))� _
which is easy to obtain from the dependence of Megri 139-B cell survivability on
dose (6, 7) and expression (1) (n--extrapolation number, V--effective target
volume). For the standpoint of reliability theory this means that elementary
acts of recovery performed by repair enzymes make up, at the beginning of the
process, a highly simple succession of random events with intensity The right ~
side of (2) represents the probability that the process would be completed in time '
t, while the factor in front of the bracket represents the effectiveness of the
elementary act of recovery. Deviation of the kinetics from expression (2) at
large t may be associated with disturbance of stable conditions and mutual indepen-
dence of elementary acts of recovery.
We ciote in conclusion that the universality of the postradiational recovery
phenomenon permits use of the suggested approach to test the reliability of
arbitrary biosystems, and to test the radioprotective~geroprotective, and anti-
mutagenic properties of physiologically active compounds.
' The authors are grateful to Academician N. Ni. Emanuel' and Ukrainian SSR Academy
of Sciences Corresponding Member D. M. Grodzinskiy for their constant attention
to the work, and to Prof Yu. K. Kapul'tsevich for his valuable advice in ~he work's
discussion.
BIBLIOGRPHAY
1. Kol'tover, V. K., and Kutlakhmedov, Yu. A., in "Nadezhnost' kletok i tkaney"
(Cell and Tissue Reliability], Kiev, Izd-vo "Naukova dumka", 1980.
2. Zhestyanikov, V. D., "Reparatsiya DNK i yeye bioloqicheskoye znacheniye"
[DNA Repair and Its Biological Significance], Leningrad, Izd-vo "Nauka", 1979.
3. Bazovskiy, I., "Nadezhnost'. Teoriya i praktika" [Reliability. Theory and
Practice], Nk~scow, Izd-vo "Mir", 1965.
28
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4. Burlakova, Ye. B., Gaintseva, V. D., et al., DAN, Vol 155, 1964, p 1398.
5. Emanuel, N. M., and Obukhova, L. K., EXP. GERONTOL., Vol 13, 1978, p 25.
6. Korogodin, V. I., "Problemy postradiatsionnogo v~sstanovleniya" [Problems
of Postradiational Recovery], Moscow, "Atomizdat", 1966.
7. Kapul'tsevich, Yu. G., "Kolichestvennyye zakonoznernosti luchevogo
porazheniya kletok" [Quantitative Laws of Cell Radiation Injury], Moscow,
"Atomizdat", 1978.
8. ,Bondar', A. G., and Satyukha, G. A., "Planirovaniye eksperimenta v khimii i
khimicheskoy tekhnologii" [Experiment Planning in Chemistry and Chemical
Technology], Kiev, Izd-vo "Vishcha shkola", 1976.
~ 9. Kol'tover, V. K., in "Itogi nauki i tekhniki, Biofizika" [Scientific and
' Technical Results, Biophysics], Moscow, Vol 11, 1979.
j 10. Marie, A. L., CANAD. J. BIOCHEM., Vol 54, 1976, p 729.
I
I
i COPYRIGHT: Izdatel'stvo "Nauka", "Doklady akademii nauk SSSR", 1980
' [75-11004 ] -
i 11004
~ CSO: 1840
I
~
I
~ ~
~
~
~
i
i
~I
i
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UDC 577.3
PROTON MAGNETIC RELAXP.TION IN TfiE STUDY OF BURN PATHOLOGY DEVELOPMENT
Moscow DOK~HDY AKADEMII NAUK SSSR in Russian Vol 254,No 3, 1980 pp 763-765
[Article by L. I. Murza, A. I. Sergeyev, V. I. Naydich, L. S., Yevseyenko,
- V. V. Disvetova, and T. V. Bunto, USSR Academy of Sciences Institute of Chemical
Physics, Moscow]
[Text] The times of proton magnetic relaxation in biological cells and tissues are
a basic characteristic of the mobility of water molecules. It was demonstrated
earlier that relaxation.characteristics are associated with the concentration of
water in these biological objects (1, 2). Up to the present, the proton magnetic
relaxation method had i>~en used in experimental and clinical medicine mainly to
_ study tumorous qrowth (2�-4). However, changes in relaxation times may also
characterize other pathological processes associated with accumulation of water in
tissues (edema). This paper is a study of change in the time of proton spin-lattice
relaxation, .T1, in animal tissues during development of experimental burn pathology.
The experiment was conducted on mongrel male rats weighing about 120 gm. The side
of the haunch (4-6 percent of the body surface area) was shaved and then exposed to
95-100�C water for 20 seconds. This produced IIIA-IIIB degree burns, edema, formation
of a scar followed by rejection of some skin, and an inflammatory reaction in muscle
tissue in the muscle area subjected to thermal trauma; no necrosis occurred. During the
experiment the animals were afforded an unrestricted drinking regimen.
The kinetics of change in the time of spin-lattice relaxation in scalded skin and
muscle tissue in the burn area, and in organs not directly subjected to burn trauma--
the liver, kidneys, spleen, brain, and blood--were studied. Tissue samples (100-120
mg) were taken for analysis immediately following asphyxiation, bled on filter
paper, and placed in the working vial of a spectrometer. Measurements were made
at 30 � 1�C for 1 hour following sample preparation. It was established that the
relaxational characteristics of tissues do not change during this ti.me.
The time of proton relaxation was measured with a"Mi.nispek r-20" pulse spectrometer
made by the East German "Bruker" company, having an operating frequency of 20 Nff-Iz.
A two-pulse sequence, 90�-T-90�, was employed for the measurements. Each experi-
mental point on the kinetic curves required tissue samples from five or six animals.
The graphs show the mean values of ii and the standard deviations.
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r,,~ 1) ~2'
Q~ Meimya
QBO
47Z
' 46q
QS6 A,onmpv.~i ~3~---
------------~CD T,,~-----
- Q64 Q71
_ Mamya
4~6 ~'o~ra ( 4 ) QSB _ ~OM/1/pOAI _ _
Q yB 47t
0, 40 A'nnmpose QS6 ~ ~
A'aera
0, JZ 0, 40 ' A'onm~vse
_ ZO 40 60 I
0
aZy { ~5~
~ 0 2 y 6 A 10 /Z ly l6
Bpt.~,v nncar a~wo.u, tym,ru 6)
Figure l. Time of Tissue Spin-Lattice R,elaxation Following Experimental
Burn Injury: Inset shows the initial period of the process
Key:
1. Sec 4. Skin
2. Muscle 5. Min
3. Control 6. Time after burn injury, days
Figure 1 shows the kinetic curves for change in T1 in samples of skin and muscle~
tissue from the burn area. Changes in capillary permeability and diffusion of
blood plasma from vessels into injured tissues caused tissue edema (5, 6)--that is,
an increase in water, which apparently is responsible for the increase in T1. Within
1 hour, the relaxation time of dermal tissue rises by a factor of 1.5, and after
reaching a maximlun, it begins to fall as the injured area dries out and a scar
forms .
Relaxation time increases almost as quickly in scalded muscle tissue. It is commonly
_ known that pathomorphological changes and visible muscle injury are not observed
with III degree burns. Nevertheless the relaxation time ~f muscle tissue remains -
high for a long period of time following burn injury.
Figure 2 shows the nature of change of T1 in liver and kidney tissues--that is, in
tissues not directly exposed to thermal injury. In both cases we observe signifi-
cant growth in relaxation time, which is apparently associated with an increase in
tissue water. Change in T1 in the liver may be a product of higher permeability of
31
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,r,(1) '
~ 2
49Z . A Q0 .
T
QBS
4By
uea - -
A'n.vm~c.i~ ~ 3 ~
Q76
Q~Z~
I
I
- qS6 /lonra (4)
QS2
4~'B - -
A'a~mpowe
4yf
4y0
qa6 nar.,w ( 5 ~
QJ1
Q2e ------,ra,~~,~o.ro------
0 1 4 6 B IO 1Z /4 /6 /0
BotN~ nar.rr o.wa~a, tym~ar ( 6)
Figure 2. Time of Spin-Lattice Relaxation of Tissues Not Subjected to
Direct Burn Injury
Key:
1. Sec. 4. Kidney
~ 2. Blood 5. Liver
3. Control 6. Time after burn injury, days
vessel membranes (5, 7). The function played by kidneys in the water-electrolyte
balance may be another factor influencing change in the relaxation time of ki8ney
tissue, since published data indicate significant changes in this balance in re-
sponse to burn injury (5). Growth in T1 in liver and kidney tissue continues
beyond the lst day, even after the animals recover from shock. The time of higher
T1 values obviously coincides with the period of burn toxemia. This pennits the
hypothesis that the increase in time of spin-lattice relaxation is not associated
with shock, being instead the result of action of burn toxins upon the body (5,8).
It is commonly accepted that burn disease arises over more than 10 percent of
the body surface area with IIIA-IIIB degree burns (8). We discovered change in
relaxation characteristics in response to significantly lesser thermal influence
(a burn area of about 5 percent). This change was observed in organs remote from
the burn area, and obviously it reflects the state of the body as a whole. Thus
we may hypothesize that burn disease can also arise when the injured area is small;
this should be considered when treating burn victims.
Inasmuch as plasma loss and disturbance of tissue metabolism promote blood coagu-
lation (6), we would have expected a decrease in T1 in blood during the initial
phase of burn development. However, changes in blood relaxation time were not
32
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revealed by our experiments in this phase, and as the burn process developed, a
certain increase in the blood T1 was recorded (Figure 2).
Plethora and edema of the brain and brain membranes are invariable signs observed
in victims dying in the burn shock stage (8); thus we were highly interested in
measuring T1 in brain tissues. However, no changes were observed in the brain with
the burn surface area employed here.
The results permit the conclusion that it would be suitable to study the processes
of experi.mental burn pathology with the help of the magnetic relaxation method.
This method reveals subtler changes in tissue subjected to thermal injury than
does conventional morphological analysis. Changes not clinically observable are
revealed at the organismic level. This may make it possible to develop more-
' precise criteria for optim~ut~ treatment of burn disease. Clinical application of
, the method as a means for keeping pathological development and therapeutic effect-
iveness under observation is beginning to show promise in connection with develop-
, ment of ways to measure #:he relaxation characteristics of tissues in v2vo, without
their dissection (9, 10).
i BIBLIOGRAPHY
j 1. Inch, W. R., McCredie, J. A., et al., J. NAT. CANCER INST., Vol 52, 1974, p 353.
2. Murza, L. I., Sergeyev, A. I., et ai., DAN, Vol 237, No 5, 1977, p 1216.
i
I
3. Damadian, R., SCIENCE, Vol 171, 1971, p 1151.
I
~ 4. Emanuel', N. M., Murza, L. ]C., et al., DAN, Vol 225, No 2, 1975, p 460.
5. K,ochetygov, N. I., "Ozhogovaya bolezn [Burn Disease), Leningrad, Izd-vo
~ "Meditsina", 1973.
~ 6. Klyachkin, L. M., Pinchuk, V. M., "Ozhogovaya bolezn [Burn Disease], Leningrad,
I Izd-vo "Meditsina", 1969.
i
7. Dogayeva, K. F., "The Significance of Capillary Permeability in the Pathogenesis
; of Burn Disease (An Experimental Study)," Candidate Dissertation Abstract,
Nbscow, 1964.
I 8. Kamayev, M. F., and Fedorovskiy, A. A., "Ozhogovaya bole2n [Burn Disease],
Kiev, 1973.
9. Lauterbur, P. C., NATURE, Vol 242, 19?3, p 190.
10. Damadian, R., U.S. Patent 3789832, 1972.
COPYRIGHT: Izdatel'stvo "Nauka", "Doklady akademii nauk SSSR", 1980
[75-11004 ]
11004
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STRUCTURAL-FUNCTIONAL ASPECTS OF NEUROPHYSIOLOGY
- Leningrad STRUKTURNO-FUNKTSIONAL'NYYE ASPEKTY NEYROFIZIOLOGII in Russian 1978 signed
to press 22 Mar 78 pp 227-231
[Table of contents from a collection of papers from the Conference of Young Scientists
and Specialists, Scientif ic Council on Complex Problems of the Physiology of Ma.n and
Animals, USSR Academy of Sciences, 500 copies, 231 pages]
I
[Text] Table of Contents ~
Gnetov, A. V. and Fedorov, K. Problems of raising the consciousness of a young ~
scientist and increasing the effectiveness of his work 1
- Avakyan, R. T. Hippocampus-hypothalamus connections in rabbits 5
A1'bertin, S. V. The dynamics of local temperature and electrical activity
in different layers of isolated neocortex during changes in the functional
state of the brain 8
Alekseyev, N. P., Khatazhukhova, E. I. and Darinskaya, V. S. Electrophysio-
logical investigation of single interoceptors 11
Arzhanova, 0. N. Blood catecholamines during physiological stress 13 ~
Arkhipenkova, T. N. Feeding-conditioned reflexes during low frequency stimu- ,
lation of the putamen and caudate nucleus 15
Akhmedzyanov, R. Kh. The role of myenteric plexus neurons in the regulation ,
of motor activity in the small intestine of the cat 17
Bazhenova, S. I. The effect of high frequency stimulation of the caudate
nucleus on realization of the instrumental defense reflex (IDR) in dogs.... 19
_ Baklanova, 0. Ye. The effect of stimulating the amygdaloid complex on elec-
trical activity and rhythm assimilation in the auditory cortex 22
_ Belen'kaya, M. The state of microcirculation under different levels of
arterial pressure (a contact-microscope study on humans) 25
Blank, Yu. A. and Tsikunov, S. G. A study of qualitative characteristics of
interstructural relations by the method of bioregulated micropolarization.. 29
34
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Butkyevich, I. P., Vatayeva, L. A. and Mkhaylenko, V. A. The phenomenon
of output when the lateral field of the puppy hypothalamus is stimu-
- lated 31
Vatayev, S. I. Neural interconnections in submucous plexus ganglia of tlze
small intestine 34
Vatayeva, L. A. Self-stimulation response in the dog at various stages of
ontogenetic development 36
Veyner, T. V. The eff ect of surface anode polarization on the neural
activity of the cat visual cortex under conditions of oxygen
deficiency 39
Vinogradova, Ye. P. The response of cochlear nucleus neurons of the little
brown bat to combina.tion tones 41
Voylokova, N. L. The stitched responses of dogs with damaged neostriatimm
nuclei 44
Voronova, M. L. A mathematical modeling study of the process of training
anthropoids 47
Gerasimenko, Yu. P. The eff ect of stimulus intensity on the electromyo-
graph response of humans in the "loading" and "unloading" reflexes....... 49
Gekhman, B. I. A review of mathematical models for physiological mechanisms `
of the thermoregulation system of a hamoeothermic organism 51
Gnetov, A. V. and Bagayev, V. A. On the possibility of quantitatively esti-
ma.ting the interference of action potentials given a recording of the
electrical activity of an entire nerve trunk 59 _
Golikov, Yu. P. and Shabayev, V. V. The eff ect of emotional state on inter-
hemispherical asymmetry 61
Golovin, V. N. and Stepanov, V. V. Changes of excitability and conductivity _
of the myocardium after hypothermic and electrofibrillar cardioplegia
under conditions of artif icial circulation 64
Goloveshkin, V~ G. A study of a nonlinear model of signal processing in the
peripheral part of the auditory ar~alyzer 68
Goncharenko, 0. I. On characteristics of hand motor responses of right-
handed and latent left-handed people 70
Gorelik, R. E. The transduction of inechanical energy in mechanoreceptors--
Pacinian corpuscles 73
35
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Granstrem, ri. P, and Chikhman, V. N. Computer modeling of the transfer func-
tion of the vocal tract on the basis of electroacoustic analogy..........a ,'6
Donina., Zh. A. The effect of air density on the total gas exchange and
~ oxygen content in muscle tissue 81
Zhuravin, I. A. Modif ication of evoked activity of caudate nucleus neurons
by corticofugal inf luences 84
Zamuruyev, 0. N. The eff ect of ischemia on the metabolism of phospholipids
in var~,;us regions of the rat brain 87
Kazaryan, G. M, Electrophysiological investigation of the interconnections
of the amygdaloid nucleus with striopallidal system structures............ 90
Kibakina, T. V, The functional organization of r eticulospinal and vestibulo-
spinal synaptic processes in lumbar motoneurons of rats 9~
- Kislyakova, L. P. and Kuz'min, D. A. Blood f low and oxygen consumption in
- the mamma.ry gland of the white mouse 94
- Klyuyeva, N. Z. Analysis of the response of the respiration regulatory system
with changes of current resistance in the air passages and the effect of
a hypercapnic stimulus 97
Kozlova, M. V. The intratrunk structure of nerves of the cat celiac plexus
- (according to light and electron microscope data) 99
_ Kolosova, L. I. and Yenin, L. D. Functional characteristics of ltmnbosacral
spinal cord neural structures connected with afferents of organs of the
small pelvis 104
Koptelova, I. A. Evasion of elECtrodermal stimu lation by suppression of the
cutaneogalvanic ref lex 106
Koptyukh, V. V., Get'ma.n, N. I. and Koptyukh, V. V. The effect of intensive
- mental stress on the functional state of the human autonomic nervous
system 107 ,
_ Korzenev, A. V, A comparative analysis of several variants of self-stimu-
lation 112
Kornelishin, N,. F. The eff ect of adrenoblockaders on hypothalamic
mechanisms of cardiovascular regulation 114
Krylov, B. V. and Makovskiy, V. S. Is adaptation in myelinated amphibian
axons the result of activation of a slow potassium channel? 117
Lavrov, V. V. The importance of deafferentation of the upper tubercles of
the quadrigeminal bodies for the analysis of light signals 124
36
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Lacarev, S. G. Electroencephalographic investigation of waking and the o
diurnal form of rest in the grass frog 127
Lychak.ov, D. V. On the problem of the role of bipolar cells supplied by
Landolt's processes 129
_ Malov, A. M. The transport of sodium ions and membrane potentials of the
soma of snail neurons 131
,
~ Mikhayl.ov, A. I. Electrophysiological changes in the sigmoid sinus of the
dog brain in the presence of a pathological inactive motor response...... 133
Mokrushin, A. A. A study of the process of habituation in the visceral
analyzer 135
Monakhova, N. V. Reflexive changes of blood pressure during long perfusion
~ of the small intestine with carbonic acid solutions modeling metabolic
' acidosis 136
; Nikolayenko, N. N. Unilateral electroconvulsant 3eizures as a method of
; studying the functional organization of the human cerebral hemisphere.... 141
~ -
i Pavlinova, L. I. Polyphosphoinosine in the metabolic energetics of the
~ human brain 144
~ Panin, A. I. Models of receptive fields of the visual cortex 146
~ _
Panteleyev, S. S. On the interre~ationship of multineuronal cortical
; activity and the EEG rhythm during activation of the cat brain........... 147
;
; Panyutin, Ye. A. and Snetkov, V. A. An analysis of models of the kinetics of
postsynaptic membrane activation 149
~
_ Petrov, Ye. S., Osipov, Yu. S. and Shabayev, V. V. A study of emotion- -
~ generating properties of limbic brain structures in the dog by the
method of self-stimulation 152
Polyakov, Ye. L. The phenomenon of hypothalamic self-stimulation in the
cat .....................e................................................ 155
Polyanovskiy, A. D. On certain characteristics of thin structures of
- insect photoreceptors 158
Potap'yeva, N. N. A study of the acetylcholine reception of leech neurons... 160
Potekhina, I. L. Bulbar-spinal vasoconstrictor paths 163
Pchelenko, L. D. Regulation of the energetics of muscle contraction by
noradrenalin after adaptation to cold 165
37
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Reyman, S. V. A systems approach to the electrophysiological study of
- neurons in ganglia of the myenteric ple�xus 167
Reyman, S. V. and Gnetov, A. V. Topological characteristics of the
myenteric plexus and the regulation of intestinal tract motor
activity 169
Rodionov, V. D. Modeling of curves of a tone signal amplitude step change
_ by a tone masker......... ~
Rybina, L. Neurophysiological analysis of an unfavorable emotional
state (depression) 172 -
Sanin, G. Yu. The structural-functional organization of submucous plexus
ganglia of the pyloric and ileocecal sphincters 173
- Saul'skaya, N. B. Participation of catecholaminergic brain systems in an ~
increase of avoidance response frequency in rats 176
Semenov, D. G. Morpho-physiological characteristics of cerebral cortex
neurons associated with anemia 180 ~
Talan, M. I. and Polyakova, S. K. The influence of the posterolateral -
hypothalamus on autonomic functions in cats 183
Toporova, S. N. The dependence of tinctorial properties of cerebellar
Purkinje cells on the development and growth of an animal 186
_ Sergeyev, I. V. and Khimonidi, R. K. On the background activi~y of sympa-
thetic-activating neurons 188
Segreyeva, I. G. On the problem of the interrelations between the visual
cortex and the mammillary nuclei of the hypothalamus in cats 191 ~
Slavnova, T. I. The mechanism of the eff~ct of phospholipase on
transmitter release 193
Tyul'kova, Ye. I. The effect of hypobaric hypoxia un the incorporation of -
1-14C-acetate intc hydrophobic and hydrophilic components of brain
phospholipids.......~ 196
- Fedoseyev, Ya. Ye. and Lovchikov, V. A. The dynanics of the change of func-
tional state of certaf.n higher and autonomic nervous system centers with
a change of estrual cycle phase in white rats 199
Chizhenkov, A. M. On organizing the task of experimentally studying the ~
cooperative behavior of monkeys 205
Chistovich, I. A. A model of auditory processing of the signal envelope
in the frequency channel 208
Shabayev, V. V. and Golikov, Yu. P. Interhemispherical asymmetry of excita-
_ tory and inhibitory processes shown by mathematical modeling 210
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Shadrina, N. Kh. On a mathematical model of blood 213
Sharagina, L. M. and Rayze, T. Ye. The presence and intensity of phos-
pholipid metabolism in microsomal and soluble fractions of the rat `
cerebrum under normal and hypoxic conditions 216
Shklyaruk, S. P. Modulation of the functional state of brain regulatory
systems by transcranial micropolarization 219
Shuvayev, V. T. Respor~ses of the superior olivary complex neurons of
insectivorous bats to frequency-modulated signals 221
Yantsev, A. V. Characteristics of afferent activity in small intestine
nerves of the dog in connection with development of the digestive
' process ............................................................e..... 224
II! I332-9342]
,
~ 9342
, CSO: 1840
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UDC 616.127-005.8-06:616-001.36-092.9-001.57
CARDIOGENIC REFLEXES AND THEIR ROLE IN THE REGULATION OF BLOOD CIRCULATION
Kiev KARDIOGENNYYE REFLEKSY I IKH ROL' V REGULYATSII KROVOOBRASHCHENIYA in Russian
- 1979 signed to press 9 Oct 79 pp 2-6, 262-263
[Annotation, introduction and table of contents from book "Cardiogenic Reflexes and
Their Role in the Regulation of Blood Circulation", by A. A. Moyenko, A. A. Bogo-
molets Institute of Physiology, UkSSR Academy of Sciences, Izdatel'stvo "Naukova
dumka", 2100 copies, 264 pp]
[Text] This monograph presents bibliographical data and the results of the authar's
research on the nature of the heart's receptivity and the role of the reflexes of i
the various receptor zones of the heart in the regulation of Ulood circulation under
normal conditions and during ischemia of the myocardium. It is found that cardio-
genic reflexes have great potential significance in the regulation of blood circula- ,
tion and that they play a primary role in the regulation of the activities of the
heart itself. It is established that the receptor zones af the left and right hemis- ;
pheres of the heart are functionally different and that the receptors of the left ~
ventricle are of primary significance in the regulation of vascular tonus of the
= larger circulatory area. It is shown that changes in the contraction activity of
the miocardium and ~~asomotor reactions are ref lex-interrelated. ~
The present state of reflex regulation of blood circulation research is character-
ized by a tendency away from purely analytical studies toward the synthesis of ob- ~
- tained data w3th the goal of developing the basic principles which govern blood cir-
culation. This is related to the accumulation of factual material on the reflex ;
regulation of hemodynamics, the activity of the heart and the vascular tonus, the
develooment of research on the central regulation of blood circulation and the appli- ;
cation of new analytical methods to experimental data. This direction in research
has extraordinary significance in the development of the problem since it generalizes
- the most valuable results obtained by various researchers, indicates the direction
and perspective of further research and at the same time it expresses and emphasizes ~
the incompleteness and lack of factual data as well as of our model of the mechanisms
- of reflex regulation of blood circulation.
In anal.yzing factual ma.terial on the reflexes of the cardiovascular system it is im-
possible not to note that individual reflexogenic zones of the cardio-vascular sys-
tem are not equally well studied. This is especially true of research on the reflex
reactions from.these zones to adequate stimuli.
Almost all of the data on the most important parameters of the function of receptor ;
zones of the circulatory system (the threshold for the appearance of the reflex,
maximum sensitivity, regulatory limits) is obtained on the basis of sinocarotid re-
flexogenic zones. The basic data on this problem is given in the works of Koch (1931),
- 40
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Heymans and Neil (1958), N. N. Gorev (1959), V. M. Khayutina (1964), Korner (1971),
Folkow and Neil (1971), Abboud et al (1976) and others. Corresponding data on the
function of the receptor zone of the arc of the aorta are less numerous, while the
receptor field of the heart in this respect is practically not studied. The signi- -
ficant majority of data on the effect stimuli on the receptor zones have on the con-
tracting function of the myocardium, the cardiac ejection and the regional vascular
resistance is also related to the sinocarotid zone.
The insufficient data on the physiological reality of reflex reactions which are
generated from different receptor zones, on the conditions of their inclusion in
adapting circulatory reactions and on the specifics of their effector structures, ~
on their relative physiological significance as well as on the character and mech-
anism of the interactions of the various afferent apertures is one of the ma.jor ob-
stacles to formulating sound conceptions about the principles of the reflex regula-
tion of blood circulation. Obviously, it is precisely these conditions which nur-ture
the unfailing and recently increased interest of the researchers in the problem of
the receptivity of the heart (Frol'kis, 1952, 1959; Kulayev 1954, 1972; Chernigovskiy
1960; Trubetskoy 19h1; Tkachenko et al, 1964, 1975; Khomazyuk et al, 1965, 1969;
Udel'nov et al, 1966, 1975; Kositskiy et al, 1965, 1975: Khayutin et al, 1970;
Oberg et al, 1968, 1976; Brown et al, 1964, 1971; Malliani et al, 1969, 1977, and
others).
i
The reflexogenic field of the heart occupies a special place in the reflex regula-
tion of circulation, which is deCermined by a series of anatomical and functional
' factors. Especially important is the fact that the heart receptors are located in
~ the central organ of the circulatory system, locked within the heart muscle with a
constantly changing work regime, whose level in turn is regulated by nervous and -
humoral factors. Therefore, afferentation which comes from the reflexogenic field
of the heart can be.realized in the changing function of the heart itself, being
~ within the limits of reflex regulation as a cardiocardial reflex with a closure of
reflex ares at various levels of the central nervous system, and, obviously, in the
~ heart itself (Udel'nov, 1968, 1975; Kositskiy, Chervova 1968).
i
The second, no less important, factor is that the heart is a very large receptor _
~ field, whose zones are distributed among its various parts with individuai function-
~ al characteris*ics. The left and right halves of the heart function with a differ-
i ent degree of diastolic dilatation and resistance load, a different level of ineta-
~ bolic processes. Therefore, it can be supposed that the stimuli conditions of the
; receptors and the functional significance of the reflexes from various parts of the -
~ heart can have real differences.
And f inally, the third characteristic of the reflexogenic field of the heart, which
to a significant degree complicates the task of studying it, consists of the fact
that the heart is a part of a general system of innervations of the organs in the
chest cavity. All extracardiac "heart nzrves" innervate not only the heart but also
its surrounding organs and tissues. In addition, afferent and efferent heart nerves
are intimately intertwined from their emergence from the central nervous system to
the innervating substratum.
These characteristics of the reflexogenic field of the heart in totality result in
extraordinarily great difficulties for experimental study and require the applica-
tion of special methodological tools.
In spite of the fact that the possibility of reflex reactions from the receptor field
of the heart was already described in the work of Bezolid and Hirt (1867) and con- -
clusively proven in the works of Jarisch and Richter (1939a, 1939b), the potential ~
significance of ref lexes from the heart in the regulati.on of circulation has not yet
41
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been determined. Data on the changes of cardiac ejection during reflexes from the
heart and on the change in the contraction function of the miocardium are terribly
insufficie~t or lacking; the information on the regional vascular reactions is
fairly contradictory. -
Studies on comparative characteristics of the hemodynamic and vasomotor reactions
during cardiogenic reflexes and other particular reflexes o� the circulatory system
are almost non-existent.
These conditions determine the first task of our researchers--the study of the ef-
fector structure of the cardiogenic reflexes and the explanation of their potential
significanc.: in the regulation of circulation. Among these are included studies on
the reflex changes in cardiodynamics and in the contracting function of the miocardi-
um; the reflex shif t of the basic hemodynamic parameters (cardiac ejection, systemat-
- ic arterial pressure, general peripheral resistance) and the regional vasomotor. re-
actions in large and small circulatory areas, as well as a comparative evaluation of
the reactions of the cardiovascular system to cardiogenic and sinocarotidic reflexes.
The results of a great majority of morphological and electrophysiological studies i
(Lavrentyev 1927; Hirsch 1947, 1964; Plechkova 1948, 1968; Paintal 1953, 1973, 1977; I
Coleridge et al, 1957, 1973; Khabarova 1961, Seto 1963; Gilev 1963, 1964; Yasinovskaya ;
1964, 1973; Kulayev 1965, 1966; Gilev, Kurilenko.1966; Abraham 1969, Thoren 1972, 1977,
and others) do not leave any doubts that the powerful and varied receptor apparatus of
the heart sharply reacts to cardiodynamic changes which are possible during the most
diverse adapting reactions of the organisms. However, the position that the physio-
logically possible changes in the activity of the heart can lead to the appearance of
expressed cardiogenic vasomotor reflexes is insufficiently proven. The very princi-
ple of including reflexes from the heart in the self-regulatory circulatory system _
remains unexplained; do the cardiogenic reflexes appear in response to changes in the
metabolism of the miocardium or are the changes in cardio-mechanics the prime factors
in their appearance? What precfse changes in the heart regime (an increase in the
hyperemia of the cavities, an increase in the contractibiYity of the miocardium) are
- most important in the appearance of the cardio-cardial and cardio-vascular reflexes.
Our research on the cardiogenic reflexes which appear when physiologically active '
substances act on the receptor zones of the heart and during changes in the work re-
gime of various parts of the heart is motivated by the desire to obtain answers to
these questions.
The author wishes to express his gratiCude to the coworkers of the experimental cardi-
ology section of the A. A. Bogomolets Institute of Physiology of the Academy of Sci-
- ences of the Ukrainian SSR for their cooperation in conducting experimental studies
and expresses his sincere indebtedness to Academician N. N. Gorev of the Academy of
Medical Sciences of the USSR for his constant help.
Table of Contents
Introduction 3
Chapter I: Current Ideas On the Receptivity of the Heart 7 -
42
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Chapter II: Patential Significance of Cardiogenic Reflexes in the
- Regulation of Blood Circulation 23
General characteristics of the cardiogenic reflex 29
Hemodynamic structure of the cardiogenic reflex 34
- The influence of pharmaceutical exclusfon of the nervous regulation of
the heart and vagotomy on the hemodynamic displacement during cardio-
genic ref lex 44
Changes in the contraction function of the miocardium during _
cardiogenic reflex 49 -
Regional vascular structure of the cardiogenic r eflex 52
Studies on the vascular reaction of the small c irculatory area
during stimulation of the receptors in the right half of the heart 64
Chapter III: Cardiogenic Reflexes During the Stimulation of Heart Receptors
by Physiologically Active Substances 74 -
Cardiogenic reflexes during adrenergetic stimulation of the heart's _
activity 76
Cardial and vascular components of the cardiogenic reflex during
adrenergetic stimulation of the heart 78
Relationship between the contraction function of the miocardium and
the tonus of the peripheral vascular elements during adrenergetic
stimulation of the heart's activity 85 _
Reflex reactions from the receptor field of the heart during inCra-
coronary introduction of tyramine 92
Reflex reactions under the effects of ATP and products of its -
metabolism on the receptors of the heart 93
Reflex reactions during the intracoronary introduction of serotonin.
Coronary pressor chemoreflex 98
Reflex reactions under the influence of potass ium chloride, acetylcholine,
aad lactic acid on the heart receptors 109
Chapter IV: Cardiogenic Reflexes Under Changing Work Regimes of the Heart 120
- The receptor field of the heart as a site for the appearance of
- - Bainbridge's phenamenon 125 -
Cardiovascular reflexes during the stimulation of the mechano-
receptors of the right half of the heart 133
- 43
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Cardiovascular reflexes during changes in the work regime of the
left half of the heart 149
Venous return to the heart during cardiogenic reflexes 172
Chapter V: Cardiogenic Reflexes During A Sharp Diszurbance of Coronary
Circulation and Infarct of the Miocardi~ 187
Reflex reactions under lowered blood supply of the hemodynamically
= isolated heart 201
Chapter VI: The Role of Cardiogenic Reflexes in the Reflector Regulation
of Bloc' Circulation 208
Bibliography 230
COPYRIGHT: Izdatel'stvo "Naukova dumka.", 1979
[333-9233] '
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9233 I
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ENVIRONMENTAL HAZARDS
INFORMATIONAL MACROMOLECULES IN RADIATION DISTURBANCES OF
CELLS -
Moscow INFORMATS~ONNYYE MAKROMOLEKULY PRI LUCHEVOM PURAZHENII
KLE TOK in Russian 1980 signed to press 4 Mar 80 pp 2-5, 174-175 -
~Annotation, introduction and table of contents from book "Informational
Macromolecules in Radiation Disturbances of Cells", by V,Ye. Komar and
K.P. Khanson, Atomizdat, 1200 copies, 176 pages] _
[Text] Current data on the structure and functional activity
- of informational macromolecules in response to radiation dis-
turbances of cells are discussed in this book. The results
of multiple studies concerning the effect of ionizing radia-
- tion on the structure and biosynthesis of DNA and transcrip-
tion and translation of genetic information are presented. The
role of disturbances of the informational apparatus in the
- mechanism of reproduction and interphasic death is examined.
Data are presented on the function o� the internuclear genetic
_ apparatus in response to radiation disorders.
This book, discussing some interesting questions on molecular
radiobiology, is relevant to the work of radiobiologists,
physician radiologists as well as specialists in other areas.
46 diagrams; 8 tables; 316 references.
Introduction [by professor Ye. F. Romantsev, corresponding
member of the USSR Academy of Medical SciencesJ
Examination of the molecular bases of the effect or ionizing
radiation on biologic objects is one of the fastest growing
areas in modern radiobiologic research. The rapid accumulation
of new information on this problem has led to the need for
publication of review volumes and monographs related to various
aspects of molecular radio~biology.
In its second edition, this book authored by V. Ye. Komar and
K.P. Khanson presents a compendium of current data on the
- 45
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structure and function of informational macromolecules given
radiation disturbances mainly of cells in higher organisms. The
booic presents to a greate r or lesser extent, all the basic pro-
_ blems of molecular radiobiology. Current data on the nature
and mechanisms of damage to the genome as a result of exposure
to ionizing radiation are p re~nted. Also discussed are the -
molecular mechanisms which protect the cell from damage. Based _
on their own and data foun d in the literature, a detailed
anaiysis of the effect of radiation on the biosynthesis of DNA
and on transcription and t ranslation of genetic information is
pres~nted. -
Chapter 1 is a very concis e and useful discussion of the basic
principles of functian of the system of informational macro-
molecules. Their discussian adds significantly to understanding
this material. The authors present very complete reflections
of the newest achievements in molecular radiobiology which have
served to ciarify the chemical nature of damage to DNA in the
cells, the molecular mechanisms to protect the genome from
damage, the mechanisms to suppress by use of radiation the
biosynthesis of DNA and the significance of this phenomenon in i
the post -radiational state of the cells. Multiple studies by j
a number of laboratories on the process of transcription in =
irradiated cells are discussed,
Data on the effect of ion i zing radiation on the informational
- macromolecule in the mitochondria are reviewed for the first
time. The authors' various theories on the molecular mechanisms
of interphasic death in lymphoid cells are preser?ted in chapter
8. This form of cellular death to a significant degree, deter-
mines the nature of the radiation induced uisease but the -
mechanisms wnich form the basis of interphasic death and the
role of the informational macromolecule in this process is
characteristic for this cellular population.
The authors utilize a broad representation of native and
foreign literature concerned with the effect of radiation on
the system of the informational macromolecule and also their
own experimental data.
The nook is written on a high scientific level, is well illus- -
trated and, without doubt, will be valuable for all scientific
workers concerned with the problems of molecular radiobiology.
Authors' Introduction
After the publication of the first edition of this book (1972)
a large number of new facts on molecular radiobiology have been
accumulated which require interpretation and review. In this
book, we attempted to she d light on current concepts of theeffect
46
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- of ionizing radiation on various components of the system of
informational macromolecules in living cells. With a few ex-
ceptions, the text of this edition has been rewritten.
Questions which we examine have been carefully selected and
- we.have re-examined the scope of individual chapters identi-
- fying those areas in which the most progress has been made.
We excluded the chapter on molecular machanisms of radio-
sensitivity of cells. The interested reader can find a de-
tailed review of this topic in the book entitled: "The Limits
of the Modification Process Produced by Radiation Disturbances"
(Atomizdat, 1978), edited by P.G. Zherebchenko and A.V. Savich.
We expanded significantly sections dealing with questions on
the study of the structural damage to the DNA molecules and
their post-radiational. repair as well as studies on the extra-
nuclear (mitochondrial) genetic system and interphasic cellu-
- lar death.
Considering the recent achievements in molecular biology and
the enormous influence which the field has exerted on radio-
binlogy, we felt it necessary to write a special introductory
chapter concerning current data on the functional principles
of the informational apparatus of cells. Naturally, we tried to
present only the most important �acts. Nevertheless, we assume
that the material presented will encompass the main elements
of current radiobiologic data.
In conclusion, we emphasize that radiobiologic studies now have
special importance because of the constantly expanding sphere
_ of use of ionizing radiation in agriculture, medicine and
science. A wide range of information on the different aspects
- of radiobiology has been accumulated. However, the basic mechan-
_ isms of the biologic effect of radiation remain, to a signifi-
cant degree, undeciphered.
We will consider our task complete if this analysis of the
function of informational macromolecules in irradiated cells
helps progress in this difficult area.
~ Contents Page
Introduction ..............................................3
Authors' Introduction .....................................5
Chapter 1. The basic functional principles of the
informational apparatus of ceils ...............6
1. Structure and replication of DNA ....................6
47
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2. Structural organization of chromatin ..................ll
3. Functional organization of nucieotide
sequences of DNA ......................................13
4. Molecular characteristics of tiie basic
class esof RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16
5. Matrix synthesi~ of RNA ~transcription) ...............18 _
6. Processing of. RNA .................................~...20
7. Synthesis of protein molecules ~translation~......>...22
Chapter 2. Damage to structures of genetic material
as a result of ionizing radiation ................26
1. Moditication and loss of nitrogenous toundations......27
2. Change in the composition of the nucleotide ~
~ sequences of DNA ......................................L9
3. Single and double disruptions in the strands ~
of DNA ................................................35
- 4. Changes in the secondary structures of DNA............36
5. Inter- and intra-molecular crosslinks .................38 i
6. Disturbances of submolecular structures of DNA........38 ,
7. Characteristics of post-radiational changes of
the llNA in bacteria ...................................39
Chapter 3. Molecular mechanisms for repair of structural
damage of DNA induced by exposure to ionizing ;
radiatian ........................................41 '
1. Pre-replicational repair ..............................42
Z. Post-replicational repair .............................56 _
3~ RE~p~.icational repair . . . . . . . . . . . . . . . . . . . . . . . , . . . t 58~ I-
Chaptei� 4. The effect of ionizing radiation on the
biosynthesis of DNA ..............................60
1. Dose-time characteristics of the influence of
radiation on the biosynthesis of DNA ..................60
48
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2. Factors which influence the incorporation of
radioactive precursors in DNA .........................62
3. Mechanisms for inhibition of DNA biosvnthesis -
as a result of exposure to ionizing radiation.........47.
4. Post-radiatiional synthesis of DNA ................73
Chapter 5. The effect of ionizing radiation on the
process of transcription in cells of
higher organ isms .................................76
= 1. The influence of radiation on various components
of kNA-polymerase systems in vitro and in vivo........76
Z. The biosynthesis of different classes of RNA
as a result of radiation ..............................82
3. Qualitative characteristics of RNA synthesized
after irradiation .....................................II7
~ 4. Maturation and transport of informational RNA -
in cells exposured to ionizing radiation ..............92 -
5. Me chanisms of radiational disturbances in the
p rocess of transcription ..............................97
Chapter 6. Radiation disturbances in the process of
translation
1. Influence o.f ionizing radiation on the functional
- p roperties of tRNA ....................................100
2. Influence of ionizing radiation on the activity
of aminoacyl-tRNA-synthetase (ARS) ....................103
3. The effect of ionzing radiation on ribosomes..........109 -
4. The effect of radiation on the protein synthe-
_ sizing system in.vivo .................................lll
Chanter 7. The effect of ionizing radiation on the
system of informational macromolecules in the
mitochondria .....................................122
- 1. Content of DNA in the mitochondria ....................123
2. Biosynthesis of mtDNA .................................125
- 49
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3. Post-radiational repair of DNA in th.e mito-
chondria .............................................130
4. Biosynthesis of RNI~ in the mitochondria ..............131 '
5. Biosynthesis of protein in the mitochondria..........133
Chapter 8. Molecular mechanisms of interphasic death =
of lymphoid cells.......................������...136
l. Molecular characteristics of PDN and the .,,138
possible path-ways of its formation
2. Problems of primary biochemical changes as pre-
cursors of DNP degradation
Conclusions........ . . ..........................146
.
�
Bibliography . . ..148
, .
- Contents..... ...................174
COPYRIGHT: Atomizdat, 1980 -
[19-9139]
9139
CSO: 1840 -
- 50
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- UDC 612,015.3:546.79:577.391:614.876] 519.9 ~
ABSTRACTS FROM THE COLLECTION 'SIMULATION OF THE BEHAVIOR AND TOXIC EFFECTS
OF RADIONUCLIDES'
Sverdlovsk MODELIROVADTIYE POVEDEDTIYA I TOKSICHESKOGO DEYSTVIYA RADIONUKLI-
DOV in Russian ].978 pp 2, 99-104
[Annotation and abstracts from the collection edited by Ye, I. Sukhacheva,
Ural Scientific Center of the USSR Academy of Sciences]
[Text] This collection presents the data on the regularities of toxic ef-
fects of radioactive isotopes on individual systems and on the entire or-
ganism in norma7. and extreme conditions. Mathematical simulation methods
are used to evaluate the toxic effects of radioisotopes, and problems of
thz pharmacodynamics of certain complex-f~rming preparations are examined.
Possibilities of the extrapolation of the obtained data from animals to ma.n
are discussed, A number of articles treat the mechanisms of the distribu- ~
tion of radioactive metals, the effects of biosubstrata on the exchange of
isotopes in the organism, and the physicc~chemical state of radiators in the
blood. The collection is intended for radio biologists, biochemists, toxi-
cologists, biophysicists, pharmacologists, and physiologists.
UDC 615.849.2:546.641:612.35:615.G15.25
- AN ATTEMPT TO ELIMINATE YTTRIUM-91 FROM THE LIVER BY THE EDTA COMPLEXING
SUBSTANCE -
~ � [Abstract of article by A. V. Bazhenov]
[Text] It is shown on the perfusing liver of rats that, after 24 hours of
its treatment with yttrium-91, EDTA [ethylenediaminetetraacetate] does not
_ wash out the radiator. The elimination of the metal occurs through the
bioligands of the blood. Tables 1, bibliography 5 items.
51
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UDC 577.391:546:641+612.354
COMPETITIVE RELATIONS BETWEEN YTTRIUM AND BROMSULPHALEIN FOR ACCUMULATION
TN THE LIVER AFFECTED BY CC14
[Abstract of article by A. V. Bazhenov]
[Text] The author shows in model experiments, i.e., under the effect of
' carbon tetrachloride and with the blocking of the liver by bromsulphalein,
that there exists competition for the absorption of bromsulphalein and
yttrium-91 by the liver; parenchymal cells take a considerable part in this
- process. Bibliography 5 items.
UDC 612.015.3:621.039.85:615.099.08:546.815:519.9
MATHEMATICAL SIMULATIOI~ OF LEAD METABOLISM AFTER ITS SINGLE AND REPEATED
ADMIDTISTRATION TO RATS
[Abstract of article by V. S. Bezel']
[Text] The author examines the metabolism of lead in the organisms of rats.
Individual chambers are isolated in the model: the blood and some internal
organs, muscles and the skin, the liver and kidneys, and the skeleton. The '
- parameters of the model were determined by the experimental data for a
single intravenous administration of lead nitrate-210. '!`wo kinetically dif- -
ferent pools of the metal were isolated in the skeletor muscles, and the
skin of the animals. In the rapid-metabolism fraction of ~ue ~r-'al in the _
skeleton, the maximum amount of_ lead was observed on the second day after
administration. By the 25th-30th day, there forms a weak-metabolism depot,
from which the liberation of inetal into the blood chamber is characterized
by a very low intensity. In the muscles and in the skin, about ten percent ~
of the original content of the metal is fixed in the form of a strongly
bound fraction. The exc:retion of lead with t'ne feces occurs chiefly through
its elimination into the intestines with the bile (up to 80 percent). On~e -
- third or one fourth of the amaunt is eliminated with the urine, chiefly~ due
to the secretion in the tubules of the kidneys. When repeated administra- -
tion of lead was simulated on the model, the levels of the metal content in
the skeleton and the daily elimination with the feces differed somewhat from
the corresponding experimental data. This difference could be caused by the
"weightiness" effect of the metal which was observed in the fluids of the
organism during repeated administrations. Figures 4, bibliography 12
items.
UDC 612.015.3:612.4.44:546.47:615.015.25
THE ROLE OF THE ENDOCRINE SYSTEM OF CALCIUM METABOLISM IN THE ELIMINATION
OF ZINC BY A COMPLEXING SUBSTANCE
[Abstract of article by N. M. Lyubashevskiy, V. S. Bezel', B, V. Popov, and
M. D;. Belova]
52
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[Text~ It is shown that the sodium form of EDTA is more effective in the
elimination of zinc from the organism than the calcium form; the effective-
ness of both forms of EDTA is identical in thyreo-parathyrosialoectomized
animals deprived of the endocrinic regulation of calcium metabolism. The
sodium form of the complex-forming substance has an additional effect of
triggering the endocrinic mPChanism. The latter increases the resorption
of the bone and the removal of additional amounts of the metal contained in
the skeleton into the blood. Tables 3, bibliography 7 items.
- UDC 612.015:3~46.641:621.039.85:591.471.3
_ ANALXSIS OF THE SORPTION AND DESORPTION BY TISSUES OF COMPLEX AND SIMPLE
SALT.S OF YTTRIUM-91 IN EXPERIMENTS ON PERFUSING LIMBS
[Abstract of article by N. M. Lyubashevskiy and S. S. Lekokhmakher]
[Text] The authors conducied experiments on perfusing limbs of rats to
study the delay of radioactive markers during the perfusion of solutions of
= 91y-EIYrA, 91y-NTA, 91y-citrate, and weighable and unweighable concentrations
- of yttrium chloride. The permeability of the capillary wall for the studied
compounds was evaluated by the degree of the accumulation of the radioiso-
- tope. The strength of the fixation by the tissues was determined by the de-
- gree of its washing-off by the blood-substituting fluid (polyglucinum) and
by the EDTA solution. Tables 2, figures 1, bibliography 6 items.
UDC 615.015.13:541.49:615.015.3:546.47:519.9
THE USE OF A MATHEMATICAL MODEL OF ZINC METABOLISM IN STUDYING THE TOXICITY
OF COMPLEX-FORMING SUBSTANCES
[Abstract of article by B. V. Popov and V. S. Bezel']
[Text] A mathematical model of zinc metabolism was used to calculate the
~ dynamics of the content of this element in individual organs and tissues of
albino laboratory rats under the effect of four different modes of introduc-
tion of the complex-forming substance Ca-DTPA [diethylenetriaminopentaacetic
- acid] in doses corresponding to cumulative LD50/30 for each modeo It is
shown that under certain conditions there exists a close correlation between
the toxic effect of the complex-forming substance and the zinc level in the
organs and tis~ues of rats. Figures 3, bibliography 12 items.
UDC 612.015.3:612.352:546.641:547.962.3
, INVESTIGATION OF THE ROLE OF ALBUMIN IN THE DISTRIBUTION OF YTTRIUM-91 IN THE
ORGANISM
[Abstract of article by D. I. Semenov, Ye. I. Sukhacheva, N. M. Lyubashev-
skiy, T. P. Arkhipova, and A. P. I1'inykh]
53
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[Text] The authors studied the effects of serum albumin on the behavior of
radioactive yttrium in the organisms of rats under various weight amounts of
the isotope carrier and a constant dose of protein in the injected solutions
- in intact rats and rats affected by silicosis with disturbances in the pro-
tein metabolism. The yttrium-protein ratios in the solutions were 2�10'6:1;
0.02:1; 0.2:1; 2:1; 20:1. The animals were killed twenty four hours after
- the administration of the solution. For most tissues, the distribution of
- yttrium-91 and labeled protein was identical, which is an indication of the
trans-port role of albumin, In the rats affected by silicosis, the level of
the deposits of labeled protein in the liver decreased sharply, which re-
sulted in a decrease in the deposits of radioactive yttrium in this organ.
It is shown that yttrium cations have a marked effect on the albumin meta-
bolism. Tables 3, figures 3, bibliography 9 items.
UDC 541:546.641/541.8:547.96
INTERACTION OF MICROAMOUI~S OF YTrRIUM WITH SERUM PROTEINS
[Abstract of article by N. V. Mikshevich, D. I. Semenov, Yu. V. Yegorov,
and V. V. Kuptsova]
[Text] Methods of ion exchange, foam chromatography, and gel filtration
- were used to study the state of microamounts of yttrium in solutions of -
_ serum proteins. It was shown in experiments in vitro and in vivo that the
- formation of yttrium complexes with the studied proteins begins at pH 7 3
and in a weak acid medium progresses with the participation of exchange pro-
cesses. In the area of physiological pH, apart from the participation in
the reactions of complex formation, the authors observed the possibility of
the formation of microcomponents as a result of the hydrolysis of complex-
nature colloids. The stability of the complex compounds of ytCrium with
proteins in the area of physiological pH increases in the series: albumin
G alpha-globulin native serum. Figures 3, bibliography 31
items.
- UDC 577.~9:614.876:546.36/42 ~
THE CONTENT OF STRONTIUM-90 AND CESIUM-137 IN AGRICULTURAL PRODUCTS OBTAINED
AT PUBLIC AND INDIVIDUAL FARMS
[Abstract of article by A. M. Skryabin ~nd Z. A. Permikina]
[Text] The authors studied the effects of the methods of conducting agri-
cultural production on the rate of the contamination of milk and potato by '
- long-lived radionuclides, Under the conditions of global radioactive
contamination, the concentration of strontium-90 and cesium-137 in milk and
potatoes produced in the individual sector in rural areas is higher than in _
t}ie public sector. This is connected with the special characteristics of
feeding the lifestock at the two types of farms. On this basis, it is pro-
posed to evaluate differentially the intake of radionuclides and radiation
doses for different groups of rural population. ~
54
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UDC 577.39:614.876:546.42
EXPERIMENTAL STUDIES ON THE DISTRIBUPION OF STROhT IUM-90 OVER THE CROSS
SECTION OF CERTAIN TYPES OF SOILS
- [Abstract of article by Ye. I. Belova and A. Ya. Kogotkov]
[Text] The authors present the results of experimental studies under na-
tural conditions on the distribution of strontium-90 over the cross section of
soils and evaluate the parameters of a migration model on the basis of these
studies. Studies were conducted in the course of twelve years on three types
of soils. In the course of 5-6 years after the introduction of the isotope,
the distribution over the cross section of the soils followed the exponen-
tial law. After 5-6 years, the maximum content of the isotope moved to
deeper strata. The authors obtained the parameters of a semiempirical mo-
del of strontium-90 migration in soils which were used for predicting the
content of this isotope in the root-containing strata of three types of
soils in the interval of 0-60 years for a single introduction of the iso-
tope. Tables 3, figures 1, bibliography 8 items.
UDC 577.39:614.876:546.36/42
ON THE INPERACTION MECHANISM OF RADIOACTIVE ISOTOPES OF STRONTIUM-90 AND
CESIUM-137 WITH THE SOIL
[Abstract of article by R. I. Pogodin and E. A. Polyakova]
[Text] The authors presented the results of studies on the effects of the
time of contact of strontium-90 and cesium-137, the structure of the absorb-
ing complex of the soil, and the content of chemical analogs in the soil on
the migration ability and biological accessibility of the isotopes in the
soil system. Figures 2.
UDC 577.39:614.876:546.36:661.84
DIFFERENTIAL DISLODGEMENT OF CESIUM-137 FROM MINERALS AND SOILS WITH POTAS-
SIUM FERROCYADTIDE SOL
[Abstract of article by G. Ye. Sharonov and R. I. Pogodin]
[Text] The article gives the results of studies on the applicability of
potassium ferrocyanide sol for determining the mobility and content of ex-
change cesium-137 in soils and minerals. Tables 1, figures-1, biblio-
~ graphy 3 items.
55
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UUI: 5//.j:~:bL1.U.iy./6:51`J.`J
SIMULA'rIUN OF '1'HE GA~~IMA-RADIATION FIELD OF A WATER R~SERVOIR UNDER LABORA-
- TORY CONDITIONS
[Abstract of article by V. A. Baturin and I. Ye. Konstantinov]
[Text] The authors studied the dose characteristic of the gamma-field of
an experimental water reservoir. The isotope of cesium-137 which is present
_ in the water and is incorporated in the bottom deposits is responsible for
the values of the dose rates from such a water reservoir. It is practical-
ly impossible to evaluate the share oE the contribution of each of these
sources to the dose rate. The existing calculation methods, for example,
the Monte-Carlo method, are very laborious due to the presence of three com-
ponents of the medium (water, air, soil) and the complexity of the geometry
of the source and require an extremely great amount of the machine time~
By using the method of simulating large sources under laboratory conditions,
the authors obtained values of dose rates which are due to the activity of
the isotope contained in water. The difference of the experimental total
values of the dose rates from the water reservoir and the values obtained
as a result of model studies (from water) makes it possible to evaluate the
share of the contribtition to the dose rate from the isotope incorporated
in the bottom deposits. Figures 1, bibliography 3 items.
UDC 577~39:628.394:546.79
,
ON THE PROBLEM OF THE DISTRIBtTrION OF CERTAIN LONG-LIVED RADIOACTIVE ELE-
MENTS IN A WATER RESERVOIR AND THEIR TRANSITION TO ICE ~
[Abstract of article by V. A. Baturin, I. G. Vodovozova, and L. N. Korchak]
[Text] The authors studied the distribution of a number of radioactive
_ isotopes (strontium-90, cesium-137, cerium-144, ru~henium-106, cobalt-60)
in various components of an experimental water reservoir (silt-water-ice).
In the water-silt system, cesium-137 which is in the cation form has the
highest sorption capacity (Kd-320), and cobalt-60 which is in the snion form
has the lowest sorption capacity (Kd=13). Migration of radionuclides over
the cross section of bottom deposits is described by exponential relations.
The highest freezing effect is observed in cesium-137 (680) and the lowest
in serium-144 (10). Bibliography 9 items.
UDC 577.39:613.648:591.16
EFrECTS OF CHRONIC EXPOSURE OF THE PIRE (Esox lucius L) ON ITS REPRODUCTIVE
FUNCTION
[Abstract of article by G. B. Pitkyanen]
[Text] The author gives the results of studies on the weight increase, fer-
tility, and the quality of the offsprings of the pike which lived for a long
time in an experimental water reservoir polluted by strontium-90 and cesium-
137. The concentration of the pollutants exceeded the global levels by ap-
_ proximately five orders of magn tudes. The annual increase in the weight
of the pike body from the experimental water reservoir was good, but the re-
productive function was lowered, chiefly, due to an increase in deformities
56
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among the offsprings which can be considered to be the result of the irra-
diation of the spawners' sections of the gonads adjacent to the walls of
the intestines. Tables 1, figures 2, bibliography 6 items.
UDC 614.876:53.082.~79
A SCANNING DEVICE FOR THE HUMAI~1-BODY RADIATION SPECTROMETER SICh-9.1
[Abstract of article by B. S. Zaytsev and V. P. Kozheurov] ,
[Text] This article describes a scanning device used in SICh-9.1. It is a
tracking system and consists o~ a control unit and activating motors. The _
relocation law is set by replaceable program. disks which are installed on
the axis of ~he spacing drive controlled by pulses from the "live"-time
timer of the analyzer. Provisions are made for chan.ging the scanning time
and regulating the path length. The error in the adjustment of the pres-
cribed relocation law in the device does not exceed +1%. Figures 2,
bibliography 3 items.
UDC 614.876:53.082.79
CALIBRATION OF THE HUMAN-BODY RADIATION SPECTROMETER SICh-9.1 FOR STRONTIUM-90
[A,bstract of article by V. P. Kozheurov, L. I. Panteleyev, I. M. Rasin, and
I. A. Sarapul'tsev]
- [Text] The most objective information about the content of strontium-90 in
a human organism can be obtained from direct bremsstrahlung measurements on `
SICh units. One of the problems in using this method is the calibration of
the spectrometer. The authors discussed the calibration of the SICh-9.1 by
the bremsstrahlung of strontium-90+yttrium-90 with the aid of a special
anthropomorphic phantom with a natural human skeleton and soft tissues simu-
lated with paraffin. Tables 1, figures 2, bibliography 9 items.
UDC 614.876:53.082.79
AN AUI'OMATIC UNIT FOR INTRAVITAL REGISTRATION OF BETA-ACTIVE RADIOISOTOPES
IN ANIMAL ORGANS AND TISSUES
[Abstract of article by V. A. Baturin and P. M. Ma.lkin]
[Text] The authors describe the circuit of an automatic device consisting
of standard electronic assemblies which is intended for simultaneous regis-
tration of the content of radioactive isotopes beta-emitters in the or-
_ gans and tissues of large experim~ntal animals. This unit makes it possible
to shorten the time and the expendituxe of animals, as well as to increase
_ the accuracy of experiments on the kinetics of the exchange of beta-emitters
in various organs and tissues of large experimental animals. Figures 1,
bibliography 4 items.
57
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UDC 577.391:546.655.3:615.015.25
ACCESSIBILITY OF CERIUM-144 FOR DTPA
[Abstract of article by I. P. Tregubenko, G. A. Men'shikova, and D. I.
Semenov]
[Text] Injection of Ca-DTPA increases shirply the elimination of cerium-144
with the urine and feces on the 3rd, 8t1:, 13th, and 18th day after the in-
corporation of the emitter. The increased elimination lasts for several
days after the first injection; the effect of a repeated injection is con-
siderably less marked. By administering 200 micromoles of DPTA three times
in thP .:ourse of the first two weeks, it is possible to eliminate about 30%
of radiocerium above the 35% naturally eliminated with the urine and feces.
The time changes in the DTPA effectiveness correlates well with the total
cerium-144 content in the organiam by the moment of the injection of the -
complex-forming substance. By repeated DTPA injections, it is possible to
mobilize from the organism over 80% of the cerium-144 deposited in the tis-
sues. Tables 2, figures 2, bibliography 9 items.
COPYRIGHT: UNTs AN SSSR, 1978 ~
[359-10,233] I
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UDC 577.3:539.12.04+539.125.52
HUMAN MODELING: DISTRIBUTION OF NEUTRON RADIATION
Moscow DOZOVAYA NAGRUZKA NA CHELOVEKA V POLYAKH G~-NEYTRONNOGO IZLUCHENIYA in
Russian 1978 signed to press 29 Dec 77 pp 2-4, 165-166
[Annotation, introduction and table of contents from book "Human Dosage Loading in ~
Gammia-Neutron Radiation Fields", by V. L. Gozenbuk, I. B. Keirim-Markus, A. K.
Savinskiy and Ye. N. Ehernov, Atomizdat, 1500 copies, 166 pages]
[Text] The book deals with the tissue distribution of radiation dosage from an ex-
ternal gamma-neutron source in a model of the human body.
- Consideration is given to the formation of a gamma-neutron emission field in nuclear
reactor installations and at critical sites. The results of calculated tissse dos-
_ ages in these fields are presented and analyzed. Special attention is accorded to
calculation of dosage loads at critical organs and tissues. Recommendations are
. given for the use of computers in operative determination of probable sequelae of
acute and chronic gaimna-neutron irradiation.
The book makes it possible to evaluate the sequelae of gamma-neutron irradiation
under various conditions.
The book is intended for workers in the dosimetry of external radiation, research
radiobiologists, radiologists, and dosimetrists, as well as for fellows and students
attending advanced courses with an interest in the theoretical and practical aspects
of dosi.metry.
Introduction
Nuclear energy and ionizing radiation are becoming common facets of modern living.
The energy balance of the various countries of the world shows the increasing im-
portance of atomic energy in providing electric power. The time is fast approach-
ing when thermonuclear power plants will become routine aspects of our technology.
Various categories of nuclear reactors--in research, in transportat~on, in energy--
are sources of gamma-neutron emission which impinges on the attending personnel
during a routine workday.
Considerable attention has been given to safety measures from the very inception of
nuclear energy technology. It is generally recognized that this is one of the saf-
est fields of endeavor. Yet, despite their rarity, radiation-related accidents do
occur in various countries; they affect largely research reactors and the so-called
critical assembly sites. Human irradiation may be significant in such cases and
may have an adverse effect on health. In addition, we cannot neglect the possible
military use of nuclear energy intended to in~ure people with gaumia-neutron radia-
tion from nuclear explosions. -
59
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Gamma-neutron are released by isotope sources and accelerators of charged particl.es.
Finally, the passengers and crews of high-flying future jets wi11 encounter we~k
- gamma-neutron radiation which presently affects only the cosmonauts.
In order to evaluate the levels of radiation to which humans are subjected and the
possible health consequences that this may have, it is necessary to determine the
distribution of the radiation dose on the human body.
The manual "Tissue Doses of Neutrons in the Human Body" [32] contains data on dose
loads imparted to a human phantom by monoenergetic monodirected neutrons. The in-
formation given makes it possible to calcuJ_ate body distribution of a dose load from
- a neutron irradiation of an arbitrary spectral-angular distribution.
However, there are virtually no pure neutron radiation sources. Neutron emissions
are accompanied by gamma rays, a ract which seriously alters the conditions under
which humans are irradiated. Radiation weakens in the body and its interaction with
biological tissue is a very complex factor dependent on the energy and the angular ~
distribution of radiation. Consequently, there was a need for informa.tion on deep I
dosagas of monoenergetic monodirected vhoton emission in the same model of the human
body as used in the neutron manual [32]. Such information, obtained by the authors,
_ is presented in this book.
A step-wise approach was used to determine dose distribution in the body. Initial
consideration is given to the formation of the g3mma-neutron emission field which
acts on humans. Subsequently, computers were employed to calculate the body dose
load. The latter undertaking utilized extensively the data in the manul in ques-
tion [32].
In addition, use was made of anatomic data on the location in the human body of
certain critical organs and, in conjunction with computer techniques, the dose dis-
tribution among these organs was ca lculated. Criteria are presented for the radia-
tion effects on the body which take into consideration doses at critical organs. _
Calculations were taken under the various conditions under which humans are irradi-
ated. This made it possible to evaluate the influence of various factors on dose
loads, such as the spectra and composition of radiation, the selected coeff icient
ot neutron quality, distance fram the source and the dimensions of the room, and the
orientation of the human subject in the radiation field. The results are analyzed.
- The material in the book is largely original. It is intended for those interested
in radiation safety, dosimetry, and biomedical problems related to the use or effects
of gamma-neutron radiation. However, localized irradiation is not discussed.
This is the fourth in a series of books on external radiation dosage being planned _
by collaborators of the Institute of Biophysics of the Ministry of Health USSR. In
addition, Atomizdat has already pub lished the manual alluded to here, i.e., "Tissue
Doses of Neutrons in the Human Body," which was prepared jointly with the workers at
the Physical Energy Institute in Obninsk, and a book by I. A. Bochvar et al. entitled
"Methods of IKS [expansion unknown] Dosimetry." A book by V. I. Popova, "Methods of _
LPE [expansion unknown] Spectrometry of Ionizing Radiation," is due to be published.
60
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- The authors are indebted to I. K. Kalugina, G. V. Noskova, 0. V. Cherkashina, 0. N.
Chernova, and T. K. Shmeleva for their assistance in the preparation of this book,
and Co S. N. Kraytor and I. V. Filyushkin for useful discussions on the formatiott of
emission fields in closed space.
The authors wi11 welcome comments from interested readers.
Contents
Introduction 3
Chapter 1. Dose loads and biological effects of radiation S
1.1 Classification of human irradiation conditions and
dosimetric indexes 5
1.2 Heterogeneity of the human body. Distribution of
critical organs 11
1.3 Dose-effect relationships 15
- Chapter 2. Characteristics of gamma-neutron radiation fields 19
- 2.1 Radiation sources 19
2.2 Formation of radiation fields in chambers and localities 25
2.3 Radiation field under everyday work conditions 31
Chapter 3. Tissue dose of gamma-neutron radiation ia a model of
human body 35
3.1 Tissue dose of monoenergetic focused gamma radiation 35
3.2 Methods of dose calculation (homogeneous model) 41
Set of initial data 47
Preparation of spectral-angular distribution fields
for x?eutrons and gamma rays at the point of human
position 48
Formation of distribution of the components of tissue
dose of neutrons and gamma rays in ter~~.s of cylinder
cross sections 50
Correction of the distribution dose for d~'ffusion of the
- radiation beam 51
Calculation of the activity of sodium in the human body 52
Calculation of the distribution of a dose of mixed
gamma-neutron radiation 53
3.3 Results of calculations for chronic irradiation 54
3.4 Results of calculations for acute irradiation 60
- Chapter 4. Dose loads at critical organs 76
4.1 Methods of calculation 76
4.2 Results of calculations. Dependence on the conditions of
irradi.ation and other initial parameters 87
~ 4.3 Examples of application of the results of calculations 96
Conclusions 101
Bibliography 103
- Appendix 1. Deep dose of focused monoenergetic gamma rays 106
Appendix 2. Description of the computer program and the values
on which it is based 139
COPYRIGHT: Atomizdat, 1978
_ [ 280-12172]
1217 2
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~
PHYSIOLOGY -
THE QIIESTION OONGEBNING TI~ ELECTROSTATIC FIELD OF HUMAN BEINGS ~
- Moscow FIZIOLOGIYA C~LOVEKA in Bnssiaa Vol 6, No 1, Jan-Feb 80 pp 148 152
- [Article by Yu.V. Tornnqev, Novosibirsk Institnte of Physiology~
[Text] The preeence of ineasurable electric fields near living organisms has by
now been reliably establiahed (1-7). These fi~lda originate from diverse eonrces
and they provide information on the fnnctional condition of the organism. '
The fielde of relatively high fr~quency that are asaociated with the actidity of
- the hvman heart muscle have been moet fully investigated. Methods have been de-
= veloped for differentiating fields originating from different sonrces and the in- -
formative significance of these fielda haa been enaluated (3-7~.
So far, however, the problem concerning the aneasnrement of aa organism'e infra- ~
low-fr~quency fields and the mechanisms of the field~a geneais have practically
been bypassed by the reaearchers.
The great interest that has of late been exhibited toward contactless methode of ~
extracting information on the electrophyaiological procesaes in an organism put$ ,
on the agenda the qneation concerning the mechanisms of formation and the inform-
ativ~ significaace of electric fields of the low-freqnency range.
The firat experiments involving the recording of low-frequency electric fields ~
(from 0.1 to 10 c/s) in the air, were carried out by na by means of synchronona ;
accnmulation (1). Analysie of the resnlt~t of these experiments testifiea to the
presence near human beinga and animals of law-frequency electric fields, the
amplituue of which declines as the frequency increases. However, the method used
in the experiment did not allow us to obtain the information in a~fozm accepted in
- electrophyeiology and it did not uneqnivocally ansWer the qaestion concerning the '
mechaniama underlying the field~s formation.
In the atudiee (3,4), man'e electroatatic field in the air is examined and its
direct dependence on tHe organism~a fnnctional state is demonstrated. Ho~rever,
aith the sensory elements uaed by the anthor, it pas not posaible to stndy the
field~s fine strncture; theae experimente did not providn for continuons recording ,
of the field~s potential aver extended time spans. '
It was the aim of the ~reaent stndq farther to innestigate the basic characteris- ~
62 ~
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tics of the electrostatic and infralow-frequency fields formed by a living organism
as Well as the mechanisms of the field's formation.
Msthods -
For measuring the electric field, We proposed the method of recording the carrent
carried bq the condnctor (picknp) moviag in the field investigated (5). As pick-
ups, we nsed metal balls or diaks 10 mm in diameter that were embedded on a non-
conducting bar and that oscillated with a freqneacy of approaimately 1 c/s. The
input stages of the measuring aa~plifier were effectcd on the basis of domeatically '
produced MUS transfators and they maintained a zero drift of 150-200 microvolt for
3 houra. By means of a pen recorder, ae recorded the envelope of the alternating
cnrrent thnt was carried in the picknp dnring its aeovement in the field investi-
gated. -
Measurement of the intenaity or potential of the electric field of man rplative to
the gronnd was carried out in en inanlated cha~aber measuring 2.5 x 2.5 x 2.5 m with
an attenuation factor of 50 c/a over 100. The teat enbject was placed in a hori-
zontal position approximately in the center of the chaaber, in order to reduce any
field recording deviations resnlting from tha study aubject's dissqm~etry relative -
to the chamber's walls (6-9). Aaide from the test snbject aad the field pickups,
the chamber did not contain aisy measnring inatruments or extraneons objects. In -
order to eliminate the undesirable inflneace of a triboelectrical charge on the re-
sults of the experiment, the teat gnbjects were divested--either partially or com-
pletely--of their clothes, which are capable of building np an electrical charge
and austaining it for a~ extended peziod.
The grounding of the test su~ject was carried.out at least S miautes before the be-
binning of the recording; the gronnding electrode was placed at the loWer third of
the test subject~s right ehin. The calibration of the measnriag circnit was done -
- by the method set forth in the eCudiea (6,7) in the field of a parallel-plate ca-
pacitor.
Preaentation and Discnssion of the Stndy Resnlts
The reaults of the experiments conducted demonstrate that in the imm~diate proximi-
ty (5-10 cm) of the human bodq there eaiats a meaenrable electric field that is
made np of several components--a stable component and variable onea. The potential
difference of the electrostatic field relative to the gronnd at a distance of 5 cm
from the surface of the test snbjact~s bodq reaches 1,000 millivolt; in the first
10-20 minutes of the experimea~t, the level of the electric field is rednced, but
subaequently the average magnitude of the signal recorded stabilizes. In this
case, we observed--against the backgroand of a relatively slo~ drift--quasiperiodic
field potential oacillations ranging from 2-5 per minute to 1 per 2 minutes; be-
aidea, the slower conatituents of the signal haa a relatively large amplitude.
' Fignre 1 ehows characteriati.c traces of the eslectric field of ta~o test subjects,
which were recorded 2 and 10 minutes after the beginning of the experiment at a
distance of 5 cm. In both cases, the qaasiperiodic oscillations are clearly traced; _
and as illustrafied in Figure 2, tha electrogrema do not ahory? anq substantial differ-
- ence in regard to the amplitudes and the general tendencq of the signals recorded--
regardlesa of whether or not the test sub,jecta aere grounded. Figure 3 presents
63
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~
' Figure 1. Typical Electrograma of a fluman Field for Different Test Subjacts
(Distance to the Field Picku~~ 5 cm)
~ ) / A 2) L 4
i,
(B)
~
~
~
~
~
~
A
~
6 '
~H
~B) ' -
3) ZM x 3) ~'lMrrx
~ I
Key: I
l. 1: (22 June 1976) Quality traces of electric field changes for two test ~
snbjecte, T. (A) and V. (B)
2. 2: (26 June 1975) Electric field Lraces for two teet subjects., 0.
and T. (B). On the lef t side of the trace-- the proceas of charge dissi-
pation; ou the right side~--the background noiae in the chamber with the
test sub,ject absent immediat~ly after the termination of the experiment.
3. 2 minutes
the electrograms of a hwnan field (A), the changes in the (background) noise level
in the insulated chamber with Che test subject being abaent (B), the fiel~ changes
occurring with placement of the pickup in a standard electroetatic field (C) and
in an infralow-frequency field (D) of a parallel-plate capacitor. Comparing the
tracea, one ascertains that the signals recorded mnat be related to the test anb-
ject's presence in the chamber. '
Figure 4 shows the comparative traces of a hvman f ield and of a field recorded in ~
the proximity of an electrified object. Evidently, the two trac~ea aho~ an identi- `
- cal tendencq. The change in the potential of the field near the electrified ob- _
ject occurs in an exponential fashion in con�ormance with (10) and the potential
recorded tenda toward the backgronnd noise value; there are no oscillations.
Th~ough inclusion of a measuring amplifier 15-20 minntes and more after the be-
ginniag of the experiment, it was posaible to record n~isea (with the test subject
being abaent from the chamber) or eignals reseanbling those present~d in Figure 1,1.
This circumstance allowed the concluaion that the signals recorded--in particular
the first sections of the fieZd trace--are not a result of the transient processes
in the circnits of the capacitor or of thes filters.
- In sll probabilitq, the electric fields recoxded by us can be attributed also to
that class of fields of bio-objects that are egplainpd by the existence of an
~ electrical aurface charge or of a steady dis~riUution of ch�rges on rhe test aub-
ject's body aurface (7). The anrface de~,isity of anch a charge can reachmagnitudes
64
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Figure 2. Electirogrems of a Human Electric Field Obtained on Different Days
C1: 23 June 1975; 2: 20 June 1975)
~ ~
J r i,~ ~i
i~
~
1) ~ ~,,Nv~'
~ f
~
,y�,
r
G
2) luun+ir ~
3) zM,,,,
_
Key:
- Y. Sub~ect not grounded; B: Sub~ect grounded
2. 100 millivolt 3. 2 minutes
Figure 3. Electrogram Models
~A) ~
Ul;~.H/cM L~
Z~+un
C B ~ 6
(C) v
(D) ~
gey:
A. Typical trace of a field near a person
B. Time-ds;~endent zero drift with the test anb~ect abseat from the chamber
C,D. Change in the signal level upon expoenre of the picknp in a standard
alectroetatic field and in an infraloM-frequency field
ranging from 10'S to 10'$ coulomb/cm2 (8) and the formation, buildup and diffusion
of this charge on the body eurface occurs in.the procesa of lively activity on the
part ~f the individual (8). When the individual changes from an active to a�.pae-
aive atate'-which coincides with the beginning of the experiment-~one observes a
procese of dissipation or neutralization of the charge and, as a resuit of this, a
- reduction in the intensitq of the field. In camparing the procesaes of diaeipation
of the charges recorded near the pnrson and near the electrified object (with the
rates of humidity of the surrounding air being equal), one perceinea a difference
betwe~n them. The duration of diasipation from the electrified object depended on
the intensity of the charge and on the properties of the inanlator (10), and in the
course of the experiment we never obaerved anq increase in the field~a potential.
65
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Figure 4. Comparative Electric Field Tracea Recorded Nnar a Person and
Near an Electrified Object (B). Diataace to the Field Picknp: 5 cm
A
_ s (B)
As regarde the measnrement of the electric field near the peraon, the process of
dissipation of the charge conformed onlp at the beginaing of the experiment to
the patterns ehown in study (10). The electric field never reached the zero 1eve1;
we_ observed oacillations of the eignal level and in a avmber of inetances a drift
to the side of augmentation. Nudity of the teat eubject, grouading of the test
sub,ject, a high degree of humidity of the anrrounding air--all of these helped
conaiderably in removing the electrical charge from the bodq surface. However,
there is every reason to assume (2,7) that during the time coincident with the
beginning of the experiment the dynamica of the electric field near the person
are for the moat part determined bq the electrical charge and the formation of
. that charge is closely related to active motion on the part of the person. This
appears to be corroborated by the reaults of ezperimenta involving recording of
the mechanical ma.nifeatations of the activity o� the heart (2,7), the results of
a theoretical investigation of the process of disafpation of the electrical
charge, and the reaults of contact measnrements of the field potential of the hn-
man body that were carried ont by ns in atndq (10).
The fact that after the diaeipation of the electrical charge from the surface of
the gronnded human bodq the electric field does not reach the zero level--as
follows fram studq (10)--may be indicative of aome kind of balance between the
procesaes of charge diesipation and ch~rge snstaitnnent, and the infralow-freqneacy
oacillati~ne of tihe field level upon ramoval of the triboelectrical charge maq be
_ and indtcation of the dynamics of this procese.
The studies (3,8,9) put fon~rard hypotheses concerning the formation of a hnman
electric field of a nontriboelectrical natnre; they shoa this field to be related
to the functional atate of the organiem (3,4); in this case, however, no allow-
ance ia made for the phenomena occurritrg at the interfac~e of the two media (11,12)
(concretely, between the human body and the ~ir) or for the contact phenomena
occurring npon application of the ground electrode during the disaipation of fihe
electrical charge, which phenomena may lead to the emergence of a measnrable
66
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electric field. The resulta of the contact experiments--conducted by us in atudy
(10)--agpear to corrobora.te the hypothesis advanced. At the same time, it is donbt-
ful whether one can assume that in the experimenta (3,4) the triboelectrical charge
. ras totally removed from the body eurface; one cannot rule ont the poasibillty that
the procesa of sustaining that charge is aea~ociated with friction of the body a-~
gainst the air during respiration, dnring the passage of a pnlae wave along the
body. The infralor~r-frequency oscillations of the field potential may be a reault of
changes in the electrical resietance of the bodq's integumznts and veeeels.
Thus, what is required is a more eaact approach to the solutian of the problem coa-
_ cerning the mechanism of the electrostatic �ield formation by the human organism as
' ~ell as greater accuracq in the resaoval of tha triboelectrical charge.
- Conclusions
1. Near the human body, an electroatatic field has been recordedo
2. The preaence of infralow-frequency oacillations of the level of mgn~s electro-
atatic field has been established.
3. In interpreting the reaults of contactless measurements of electrophysiological
_ processes, one mnst take into co nsideration the presence of high-amplitnde os-
cillations of the field potential that in all probability are not directly re-
lated to these processes.
BIBLIOGxAPHY
1. Valeyev, U.S.; Kovalev, D.P.; and Tornuyev, Ya.V. AVTOMETxIYA, No 4,
- Novosibirak, 1959, p 127.
2. Filyakin, B.F.; Tumanovskiy, M.N.; Postnikov, V.S.; and Provotorov, V.M.
BYUL. EKSPERIM. BIOL. I MED., AIo 11, 1970, p 21.
3. Kulin, E.T. DOKL. AN BSSR, Vol 17, No 9, 1973, p 867.
4. Kulin, E.T. DOKL. AN BSSR, Vol 20, No 2, 1976, p 174.
5. Tornuyev, Yu.V.; Sobakinp M.A. In: "SoetoyaY:i}~e i perspektivy razvitiya
meditsinskoq tekhniki" [State and Prospecte of the Development of Medical
Technology], Vol 1, Moacow, 1975, p 150.
6. Valeyev, U.S.; Tornuyev, Yn.V.; and ~talcityaaskiy, D.Yu. BIOFIZIRA, Vol 15,
No 4, 1970, p 652.
7. Valeqev, U.S.; Tornuyev, Yn.V.; 8akityanakiy, D.F.; and Osenniy, A.S.
UKR. FIZIOL. ZH., Vol 1, No 1, 1973, p 99.
8. Tornuyev, Yu.V. "Ekaperimental'noye iasledovaniye elektroetaticheskikh poley,
sozdavayemykh v vozdukhe bioob"yektami"[Experimental Investigation of the
_ Electroetntic Fields Created in the Air by Bioob,jects], Diss., Tomsk, 1971.
67
cnr~ nr. r. ~rr ~ i r tcr. n~~r v
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9. Dokuchayev, V.M. In: "Fizicheakiye, matematicheskiye i biologicheskiye
- problemy deystviya elektromagaitnykh poley i ionizatsii tFOZdnkha" [Phyaical,
Mathematical and Biological Problems Concerning the Effect of Electromagnetic
Fields and of Ionization of the Air], Vol 1, Mo scow, 1975, p 123.
10. Makhnev, V.P.; Tomnyev, Yn.V. FIZIOI.OGIYA CHEI.OVEKA, Vol 5, No 6, 1979,
p 1111.
11. Golikov, G.A. TRUD'Y RAZAIVSK000 KHIMIKO-TEK~IOLOGICHESKOGO INSTITUTA IMENI
KIROVA, No 33, 1964, p 146.
12o Tsarev, B.M. "Kontsktnaqa razaost' potentaialov" [Contact PotenL�ial Differ-
ence], ;:oscow, 1955.
COPYRIGHT: Izdatel~stvo ~'Nauka", "Fiziologiya cheloveka~', 1980
[112-8760]
8760
CSO: 1840 ~
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CORRELATION IrIDICATORS OF BRA.IN ELErTFOENCEPHALOGRAMS DURING ENOTIONAL STP,ESS
Baku KORRELYATSIONNYYE POKAZATELI ELEKTROENTSEFALOGRANiNi.GOLDVNOGO MOZGA PRI EMO-
TSIAL.'NOM STRESSE in Russian 1979 signed to press 18 Jan 80 pp 2-7, 129 ~
[Annotation,. preface, introduction and table of contents from book "Correlation
Indicators of Brain Electroencephalograms During Emo~ional Stress", by A.A.
Mamedov, A.I. Karayeva Institute of Physiology, Azerbaijan SSR Academy of Sciences,
Izdatel'stvo "Elm", 1200 copies, 129 pages ]
(Text~ The book covers one of the urgent problems of modern neurophysiology and
practical medicine, the study of the central mechanism for emotional stresses. Tne
syste;ns approach is used to analyze the results obtained from correlation analysis
_ of EEG-potentials of the brain on automated systems, including computers. The out-
look is shown for the use of these systems.
The book is designed for a broad group of specialists who are working at the junc-
tion of neurophysiology, medicine, mathematics and electronics, and in the field
of biological and medical cybernetics.
It is printed by decree of the editorial-publishing council of the Azerbaijan SSR
Academy of Sciences.
Editors; K. V. Sudakev, G. G. Gasanov, A. I. Shumilina
Contents Page
Preface 3 -
Introduction 6
Section I.
Chapter I.
Urgent Problems of Emotional Stress 8
Nerve Substrate for Emotions 16
Electroencephalographic Indicators oi ~r~otional Reactions 21
Mathematical Correlates 25 -
Chapter II.
Cortical-subcortical Cross-correlation Interrelationships during
Formation of Emotional-stress Conditions 31
Certain Features of the Cortical-subcortical Cross-correlation
Interrelationships 31
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Page
- Correlation Indicators of EEG-Potentials of Different Cerebral
Formations under Conditions of "Signalless Situation~tandonness
Factor" 35
Electrographic C~re~ral Indicators in Animals Who Are Pre-
disposed and Resistant to Emotional Stress 48
- Cross-correlograms of Cerebral Electrical Potentials during
Multiple Time "Stereotype" Effects 51
Chapter III.
Analysis of Spatial-Temporal Organization of EEG-potentials of
' Brain under Conditions of "Signal" Situation 54
- Features o~ Manifestation of AnLicipating and Reinforcing
Excitation 55
Chapter IV. ~
~r Functional Effects on Cerebral Structures 65
Chapter V.
Analysis of Statistical Parameters of Cerebral Electroencephalo- i.
_ grams during Effect of Different Drugs 74 ,
I
Chapter VI. ;
Systems of Emotional Stress Mechanism 87
Section II.
Chapter I.
Theory of Functional Cybernetic Systems of ?,ivir.g Beings 102
Certain Numerical Characteristics of Random EEG-processes 106
- Principl.es of Apparatus Construction of Automated Systems for
Processing Physiological Information on a Computer 108
"Man-Machine" Systems 113
Bibliography 123 '
Pref ace '
~4.
This book is dedicated to the bright memory of my�teacher, Lenin Prize laureate, ,
Academician P. K. Anokhin.
A study of the central mechanisms for stress, which is acquiring an emotional
aspect to an ever greater degree, is among the most urgent problems of modern
neurophysiology and medicine. Rapid scientific and technical progress, having
created complicated conditions of adaptive behavior, requires the processing of
_ an enormous flow of diverse information on hu~ian biological'functions and social -
activiCy.
The WHO experts indicate that emotional stresses caused by an increase in the tempo `
of life, urbanization, information overload and adynamia, in 70% of the cases ,
result in different vascular affections of the brain, heart (hypertonia, myocardial
infarct, insult,atherosclerosis, etc.). They also lead to the development of
neurotic conditions, mental disorders and disorders in normal human adaptation to
social conditions of life. -
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The Soviet neurophysiologists, based on the teaching of I. P. Pavlov on nervosism,
have established tt~a paramount reason for diseases as primary disorders in the
cerebral functions as a result of frequently repeating emotional stresses. Without
belittling at all the most fully developed endocrine-biochemical aspect of stress
of G. S~1'ye, it should be stated that they are most often secondary reactions of
a pathological process that has primarily been formed in th~ central nervous system.
In recent years therefore, questions referring directly to nerve mechanisms have
occupied the central place in the problem of emotional stress. Special scientific
sessions, and all-union and international conferences have covered this aspect of
emotional stress and its role in cardiovascular pathology, and in different cerebral-
visceral disorders.
The monograph of Doctor of biological sciences A. M. Piamedov also treats this
question.
The author is a student and follower of Academician P. K. Anokhin, the founder of
the theory of the functional system. Many years of work in P. K. Anokhin's labora-
tory determined the main feature of this monograph, namely, the broad use of the
theory of the functional system in analyzing mechanisms for cerebral or~anization
of differer�.t stages of emotional stress. E1n engineering education in combination
with the lof.ty erudition of the neurophysiolagist permitted A. M. Mamedov to m~~ke
a special mathematical analysis on computers of. the known phenomenon. This is
- the phenomenon of the appearance of a regular, ordered rhythm of electrical
activity (stress rhythm) of 4-7 oscillations per second that develops in different
cerebral structures under conditions of stress factorso
By analyzing the conditions for formation of emotionally negative stimulations, and
their transition to a static state, the author ~ives very great significance not
only to physical factors, but quite correctly also to purely informational charac-
teristics of the "conflict" situations. Here the long-maintained "signalless"
situation with low probability of "foreseeing" the emotionally unpleasant stimuli
is the most dangerous for the organism. These stimuli result in an irreversible
process, and iri the formation of a new cerebral condition that differs from the
normal and is characterized by disrupted spatial-temporal interrelationships between
the cortex and the subcortical structures.
These finest cross-correlation shifts are based on changes in the polarization of
the analyzed structures due to shifts in the neurochemical mechanisms. Since such
_ a condition of the brain is characterized by a number of somatic-autonomic dis-
orders, it can be catled the "cerebral-visceral syndrome" of emotional stress. It
is one of the initial pathogenetic factors for the formation of pathological shifts
in different functional systems of the body, including the cardiovascular system.
A careful correlation analysis on the computer of the stress rhythm in different
cerebral structures permitted A. M. Mamedov to find the characteristic dynamics for
emotional stress, and the features of the interrelationships between the cortical-
- subcortical formations at different stages of its development. In our opinion, the
most important phenomenon in this respect is the detection of laws governing the
change in phase shifts and functional links between the electrical potentials of the
hypothalamic structures, the cortex of the large hemispheres and the reticular
formation when experimental emotional stress is formed. Of especial interest in
this respect is the establishment of the fact that at the later stages of
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emotional stress, tl~e functional links between the hypothalamic formations and
the cerebral cortex are diminished, and on tre contrary, are intensifie4 with
the ret5_cular formation of the brain. These neurophysiological data shed light on
the problem of the so-called "defense inhibition" that was formulated by Academician _
I. P. Pavlov.
Based on the new, original data that A. M. Mamedov obtained, one can consider that -
a reduction in the functional links between the hypothalamus and the cortex, and a
number of structures in the cerebral limbic formations is the basis for the "defense
inhibition" of cortical components during emotional stresses. Or~ the other hand,
these same mechanisms can be the basis for the development of neurotic conditions
that are often a consequenc~ of strong emotional overstresses.
The book of M. Mamedov is an important stage ir, the study of emotional stress.
It makes a significant contribution to the investigation of the central mechanism
for emotional stress. It goes without saying that it is of considerable importance
for specialists of varying profile who are interested in this problem. ~
Correspo~ding ~fember of the USSR Academy of Medical Sciences, Professor K. V. Sudakov
Introduction ,
4
According to the biological theory of emotions of Academician P. K. Anokhin [5,6], I
emotional excitation has been included during evolution at that point of the central
architecture of the functional system where feedback is used to compare the para- ~
meters for the result of a purposeful behavioral act with the parameters that were
previously prepared in the acceptor of action results. This is based on afferent
synthesis of diverse external and internal factors. An important role among these
factors belongs to the motivational stimulation that dominates at the given momant.
When the parameters~From a completed action coincide, the developing need is
satisfied. This is accompanied by positive emotions. On the contrary, when these
parameters do not coincide, negative emotions develop. When there is a prolonged
discrepancy in conflict situations, they increase and are intensified.
A characteristic feature of negative emotional stimulations is their capacity to
be retained for a long time in the CNS even after the stimuli have stopped. This
is precisely the feature that leads to stabilization of stimulatiuns and is the
most dangerous for the body.
Expanded pathological bonds that are formed on this basis between the environmental
factors and are mediated through the effect of the cortex of the large hemispheres ~
are a mandatory physiological condition for the transition of emotions to the
stationary form, on a high level of excitability of the emotiogenic subcortical
cerebral formations.
The most important questions in emotional stresses are those that are associated
with the spaeial-temporal features of cortical-subcortical interrelationships of '
the brain when emotional stress is formed and their correlation with the autonomic ~
components, the presence and the role of pacemakers for emotionally negative
reactions, as well as the conditions that promote the transition of negative emo- ~
- tional stimuli to the static condition. A study of this basic problem is unthink-
ab.le without the appropriate mathematical analysis and modern electronic equipment, -
incluc~ing computers. ~
,
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Taking into account the random nature of the electrical oscillations in the brain,
and their probability-statistical organization, the use of statistical parameters
of EEG-potentials that develop during negative emtional states as the indicators for
the emotional reaction becomes very effective. The application of statistical
methods, and in particular, of correlation analysis, with all the randomness of
complicated EEG-oscillations, permits isolation of individual, stable parameters thaC
objectively and accurately characterize the specific features of interrelationships
in the studied process.
In reflecting on the means for further development of electroencephalogranhy,
Academician M. H. Livanov [72] was convinced that "it is precisely a study of
the interrelationships of the variously localized processes in time that is _
promising for a clarification of the main laws governing the mechanisms for cere-
bral activity. In fact, localization of even the simplest cortical functions is
not a single point. It is always comnlicated and dynamic, reflecting the inter-
. relationships of numerous cortical and subcortical systems." In this respect it
is precisely correlation analysis that is one of the effective methods for studying
spatial-temporal interrelationships between the cerebral structures. The establish-
_ ment [72,73] of the physiological significance of the cross correlation coefficient
permitted a number of important conclusions on the conditions for transmitting a
stimulus between the cortical analyzer systems. The important role of coherence,
dispersion and phase shifts of EEG-oscillations in this transmission was shown
later, in addition to the functional bond.
A study of the central mechanism for emotional stress from the positions of systems
analysis, and on the basis of mathematical methods characterizes the systems-
cybeLaetic approach to the research object. In this respect, it is shown in the
second section of the book that when physiological information is processed on the
computer, the application of automated systems becomes very important. This -
especially refers to those where the computer is used not only as a"calculator,"
but as the actual controller of the experiment, becoming its organic participant
[72]. This type of system is the prerequisite for the future creation of a unified,
optimally conjugated brain-computer system that promotes the effective solution of
problems of controlling complicated objects.
Thus, the development and final success of modern neurophysiological research are
determined to a considerable measure by the union of traditional physiology with
the ideas and methods of precise sciences. _
COPYRIGHT: Izdatel'stvo "Elm", 1979
[125-9035]
9035
CSO: 1840
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unc: 612.85s
STUDY OF DIFFERENTIAL SENSITIVITY TO CHANGES IN DURATION OF TONAL SOUN,~S
_ Leningrad FIZIOLOGICHESKIY ZHURNAL SSSR IMENI I.M. SECHENOVA in Russian
Vol 61, No 6, 1975 pp 938-944
[Article by V. I. Medvedev, D. Bagrova and A. A. Sagal, Military
Medical Academy imeni S. M. Kirov, Leningrad, submitted 5 May 74]
[TextJ Studies were made of differential sensitivity of
man to duration of tonal stimuli in the range of 50-700 ms. _
The threshold method of constant differences between
stimuli (AX method) and combination of the method of
multiplication of duration by two or three with the AX
method (AB methods) were used. Differential threshold
were obtained as linear functions of standard duration,
the limen being significantly higher with method AB
than with AX. The threshold levels were related to =
multiplication factor, type of psychometric functions
and individual differences between subjects, but they _
- were unrelated to conditioning time.
Differential sensitivity is one of the most important indicators of
activity of the human analyzer system, of quantitative characteristics -
of the latter's capacity to reflect local changes in time and space
features of man's habitat [1]. Numerous works of psychophysicists have
dealt with this capacity, and they constituted the main quantitative -
description of functions of analyzer systems as a whole [4, 6, 13, 16].
Direct quantitative evaluation of the capacity to reflect time-related
characteristics of signals in the form of deter~r.ination of time-related _
sensitivity and capacity to differentiate between duration of stimuli
are of special si~nificance. Expressly this aspect of analyzer func-
tion has been studied much less comprehensively [8, 12, 14, 15]. Data
- have been obtained by qualitatively different methods, without compari- ,
son to data referable to other modalities. The main cause of dis-
crepancy between the obtained data is inadequate testing of optimality -
of psychophysical methods used [8, 14, 15]. Thus, some authors did
not adhere to any standard techniques (for example [8, 10, 15], while
in other works there is no clearcut description at all of the ,
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psychophysical procedures used [3, 7, 8, 14, 152. Control of the method
is particularly important in view af the considerable values of time-
related error, which could be expected when studying time sensitivity
[17, 18].
This circumstance imposes certain requirements on the search for the
optimum psychophysical method that would minimize and stabilize the
time-related error. We have established [2] that the optimum in this
respect is a combination of the supraliminal method of multiplication
with the threshold method of constant differences between stimuli
(abbreviated constant method). This combination decreases by several~
times the time-related error, as compared to other combinations (set
and separation, constant and separation, set ~nd multiplication), even
in the absence of alternation of pair elements: standard comparison
tone within the range of the fixed order of stimuli. This makes it
possible to undertake a systematic study of sense of time in relation
to duration of tonal sounds in the range of 50-700 ms.
Methods
- We used two methods to evaluate differential sensitivity. The first
was the liminal method of constant stimulus differences in its nonsym-
metrical modification [1]. In this modification, there is a dissimilar
number of stimuli xi (2 = 1, 2, n) among the comparison signals,
which are lesser or greater tahn standard signal A, for which the
differential threshold (DT) is calculated. In this study, we used only
one xl signal that was shorter than the standard (Figure 1). Accord-
_ ingly, the experimental results enabled us to plot only one psycho-
metric function, the ascending ogive corresponding to evaluation of
the signal by means of the judgment category of "this signal is longer
than the standard." This method permits rapid gathering of data and
evaluation of differential sensitivity (DS) without appreciable decrease
- in accuracy of evaluation, as compared to the classical symmetrical
method [l, 9]. In the following, we refer to this method as the
direct method of evaluating DS or the AX method [9, 10].
The second was the supraliminal multiplication method combined with the
triple symmetrical method of constant stimulus differences, which was
described in detail previously [2]. Let us recall that, in this method,
for each tone of standard duration A we selected comparison tones x2
distributed in relation to B as mathematical expectation, B being two
or three times greater than standard A: B= kA, k= 2 or 3. In the
following, we refer to th~se as indirect methods AB-2 or AB-3, wir_h k
equaling 2 or 3, respectively. It is logical to refer to AB as indirect
methods, because evaluation of DS is an ancillary procedure, in addition
to their main purpose, that of assessing the capacity to scale sounds.
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~ a ~ b
f00 . ~ ~
~ ~
~ 80 ' . ~ .
F+ ~
3
N
~ 60 . ~ BO I ~~ll i Ill
60 ~ ~ %
" 40 . . ~ i ~ .
u �
~ ~ 40 � i ~ ~
` U ~
e~i Z~ ZO i~ p Pv~
~ 7CA
~ 1f0 130 150 ~ f70 t ~ 160 1B0 200 22 240 260
I~--Il~T -
' Second stimulus, ms ~
Figure 1. Psychometric function with nonsymmetrical method of I
constant stimulus differences (a) and triple category
method of constant stimulus differences (b) ~
I) for z~l II) for r~3 III) for z~2
[Pn, Pv and IN explained in the text]
With methods AX and AB, the tones were presented to subjects in pairs:
first standard A then comparison tone x2 (i = 1, 2, n). With the AB
methods, the tones were evaluated in three judgment categories y~ (~j = 1, ~
2, 3). Thus, with method AB-2, these categories sounded as follows:
yl-- the second signal is less than double the length of the first one;
- y2--"... it is exactly twice as long as the first" and y3--"... it is ,
more than double the first one." Accordingly, with method AB-3 we ;
determined the distribution of comparison signals in relation to the
category of "three times longer signal." For this reason, we obtained ~
three psychometric functions with-the AB methods (Figure lb). -
All of the sounds had a f requency of 1000 Hz and volume of 70 dB above
the audibility threshold. The time thresholds were determined for
standard durations: A= 100, 200, 300, 500 and 700 ms with method AX,
and A= 50, 100, 200, 300 and 500 ms with AB methods. For each standard
A we selected on the linear second scale n= 5-7 gradations for duration -
of comparison tones xZ with scale graduation of 8= 10-30 ms, i.e., so -
that the interval between the shortest and longest comparison tones
would be small as compared to the standard, nd