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The influence of the first and repeated increases of total illumination of the experimental chamber on conditioned activity was studied in chronic experiments on six dogs by the secretory alimentary conditioned reflex method. It was found that such repeated functional loads exert a training effect on the mechanism regulating the general functional state of the brain. In preliminarily trained animals different components of the conditioned reflex are rapidly and synchronously reorganized. In non-trained animals the reorganization of the brain general functional state was prolonged and accompanied by development of a pronounced emotional stress. It has been assumed that training of the functions controlling the general functional state of the brain is based on conditioned mechanisms. An important part is played by the mechanism of conditioned inhibition, which prevents a prolonged retention and reproduction of an excessively intensive level of emotional stress.

I must ask the reader's indulgence for this article's concern with applications of the stress concept, which are distinct from, although related to clinical medicine. It has not been my object to deal with the way physicians have been aided by stress research in the practice of medicine--that information is already widely available. Rather, I have attempted to sketch briefly the history of the stress theory and to demonstrate how this information can help anyone, physician or layman, lead a more complete and satisfying life. The applications of the stress theory have been dealt with at length elsewhere. I believe that we can find within scientifically verified observations the basis of a code of behavior suited to our century. The great laws of nature that regulate the defenses of living beings against stress of any kind are essentially the same at all levels of life, from individual cells to entire complex human organisms and societies. It helps a great deal to understand the fundamental advantages and disadvantages of catatoxic and syntoxic attitudes by studying the biologic basis of self-preservation as reflected in syntoxic and catatoxic chemical mechanisms. When applied to everyday problems, this understanding should lead to choices most likely to provide us the pleasant eustress (from the Greek eu meaning good, as in euphoria) involved in achieving fulfillment and victory, thereby avoiding the self-destructive distress of frustration and failure. So the translation of the laws governing resistance of cells and organs to a code of behavior comes down to three basic precepts: 1. Find your own natural stress level. People differ with regard to the amount and kind of work they consider worth doing to meet the exigencies of daily life and to assure their future security and happiness. In this respect, all of us are influenced by hereditary predispositions and the expectations of our society. Only through planned self-analysis can we establish what we really want; too many people suffer all their lives because they are too conservative to risk a radical change by breaking with hiabits or traditions. 2. Altruistic egoism. The selfish (i.e., self-interested) hoarding of the goodwill, respect, esteem, support, and love of our neighbors is the most efficient way to give vent to our pent-up energy and to create a more enjoyable, beautiful, or useful environment.3. Earn thy neighbor's love. This motto--which is merely a rewording of the command to "love thy neighbor as thyself"--is compatible with man's natural structure, and although it is based on altruistic egoism, it could hardly be attacked as unethical. Who would blame the man who wants to assure his own homeostasis and happiness only by accumulating the treasure of other poeple's benevolence and love? Yet this makes him virtually unassailable, for nobody wants to attack and destroy those upon whom he depends.

The effects of disturbing groups of 24 hr fasted rats on plasma unesterified fatty acid (UFA) and tryptophan concentrations and brain tryptophan concentrations were investigated. Removing rats from cages rapidly increased plasma UFA and corticosterone and decreased plasma and whole blood tryptophan of cage mates. The disturbance also appeared to influence biochemical values of rats in other cages within the same chamber. Effects specific to individual cages were also suggested. In subsequent experiments 24 fasting rats caged together were rapidly transferred to 24 separate cages and killed at intervals. Plasma UFA rose to a maximum by 12 min and then fell toward initial values. Plasma total tryptophan concurrently fell then rose. Its percentage in the free (ultrafilterable) state, and in some experiments the absolute values of free tryptophan rose then fell. When the latter rise was marked then brain tryptophan and the 5-HT metabolite 5-hydroxyindoleacetic acid rose. Tyrosine changes were negligible. Thus altered brain tryptophan level and 5-HT metabolism may be associated with plasma tryptophan changes caused by brief environmental disturbance.

Interhemispheric asymmetry of the "emotional resonance" reaction with a varied degree of emotional action was investigated in rats. Hemisphere inactivation was carried out by means of potassium spreading depression. "Emotional resonance" in rats has been shown to possess hemisphere asymmetry. This asymmetry is dynamic and changes depending upon the conditions under which the reflex is worked out. With equal illumination of both the preferred and the nonpreferred chamber and using "recipients" and "victims" of the same sex, left hemisphere dominance was found in males in carrying out the reaction. With a tenfold difference in chamber illumination and testing animals of the same sex, the right hemisphere dominated in rats working out the reflex quickly, whereas in those working out the reflex more slowly it was the left one. In using "victims" and "recipients" of the opposite sexes and the same darkening of the preferred chamber the right hemisphere dominated in carrying out "emotional resonance." "Emotional resonance" in lactating females to the cry of their pups was also characterized by right hemisphere dominance. Thus, dependence between the force of emotion and the direction of "emotional resonance" lateralization in rats was shown. The interhemispheric asymmetry observed was more expressed in males than in females.

The emotional stress induced in dogs by means of electrodermal stimulation, lowered the blood insulin and increased the corticoids and sugar contents. Bilateral amygdalectomy eliminated the inhibitory effect of the electrodermal stimulation on the insular apparatus and caused a lesser albeit prolonged increase in the blood corticoid content. The blood sugar under these conditions was also somewhat increased. Different effects of separate amygdaloid nuclei on insulin secretion were revealed in acute experiments. The inhibitory effect of amygdaloid nuclei is realised through ventromedial hypothalamic nucleus

A study was made of the physiological effects of smoking, psychological stressors, heat, exercise, and fat ingestion on 12 healthy men. Repeated measurements were made of cardiovascular, neuroendocrine, enzyme, lipid, and other variables in all stressor situations. The main findings were that psychological stressors and exercise were associated with more and larger physiological changes than the other stressors, and widespread response differences in addition to those in lipids were identified between subgroups of seven normolipidaemic men and five hypertriglyceridaemic men.

Several lines of evidence indicate that maternal psychological stress leads to adverse pregnancy outcome in rhesus monkey. Chronic anxiety causes an increased stillbirth rate, fetal growth retardation, and altered placental morphology. On another time scale, lightening of maternal anesthesia during surgery produces an impaired fetal oxygenation while re-institution of anesthesia ameliorates the fetal asphyxia. The present study, for the first time, demonstrates a relationship between specific episodes of meternal psychological stress and exacerbation of fetal asphyxia in utero. Eight term pregnant rhesus monkeys were anesthetized with sodium pentobarbital. Catheters were placed both into the maternal and the fetal femoral arteries for the continuous recording of blood pressure and heart rate and for the intermittent campling of maternal and fetal blood. An open-ended catheter recorded intrauterine pressures. Following a complete repair, the anesthesia of the mothers was allowed to lighten. As the mothers awakened, the fetuses invariably showed the developemnt of fetal asphyxia. A fetal acidosis developed and the fetal oxygenation and repair of acidosis. Studies while the mothers were fully awake showed the repeated and regular development of episodes of heightened fetal asphyxia produced by episodes of stressful stimulation of the mothers. Episodes of maternal psychological stress led to changes in both fetal vital signs and blood chemical findings. These alterations in fetal state regularly followed the onset of the episodes of psychological stress by 50 seconds. These changes also usually remitted 50 seconds following the termination of the periods of stress. These results demonstrated a direct and unequivocal relationship between meternal psychological stress and fetal asphyxia. It is assumed the maternal stress produces impairments in the circulation to the uterus through an increased sympathetic nervous system activity and a shunting of the maternal blood-flow from the abdominal viscera to other organs as occurs in the fight-orflight reaction.

Relative weight of adrenals, thymus, hypophysis and gonads was studied in female mice after 21 days after parturition and in intact males. One group of females was stressed during pregnancy, and another group was intact. All these animals were a progeny of the full diallele cross of 4 inbred mice strains (BALB/c, C3H/He, C57BL/6, AKR/J). On the basis of analysis of general and specific combining ability the conclusion is drawn that the relative weight of the endocrine glands is inherited additively in females of both experimental groups. However, it was found that the size of additive genetic variation for these characters in the population of females, which had been stressed during their pregnancy was larger, than in the control population. A significant role of non-additive genes in the determination of these characters was observed in males. The degree of hypertrophy of adrenals and lysis of thymus in stressed females corresponded to their emotional reactivity. Significant genotypic correlations between the weight of some endocrine glands, on one hand, and the emotional reactivity and the rate of sexual maturation, on the other hand, were found in both experimental groups of females. In the stressed group these correlations were higher.

The paper presents a mathematical method of experimental data processing, using the study of human emotional reaction as an example. The method allows to process data of different signs containing a great uncertainty. Different signs of data observed in the studies of the dependence of degree of human emotional stress on need and uncertainty in goal reaching, emerge in the course of the experiment and classification of the emotional reactions by their intensity. Numerical models for two subjects are created on the base of the minimax Kolmogorov criterion, and the obtained results are discussed.

In order to study the response of plasma prolactin (PRL) to acute psychological stress and to compare it with that of growth hormone (GH), the mirror drawing test (MDT) was performed in 20 normal controls (11 male, 9 female) and 22 neurotic patients (12 male, 10 female). Plasma PRL and GH were measured serially before, during and after the test. In controls, the test caused no significant change in plasma levels of either hormone. In neurotic males, the response of PRL to the test was not consistent, whereas, in neurotic females, plasma PRL level rose significantly following the test. Increase of GH, on the other hand, was apparent in the neurotics of both sexes. The correlation between the responses of the two hormones in the neurotics was low and non-significant. The results indicate that although the psychoendocrine coping mechanism in the neurotics works less effectively for both PRL and GH, the two hormones may have different psychological correlates.

Using a chronic stress model of depression, the biochemical, hormonal, and neurochemical effects of chronic stress were determined in male CD-1 mice. The effects of chronic administration of three tricyclic antidepressants (TCA): chlorimipramine, amitriptyline and desmethylimipramine, as well as fluoxetine, a specific serotonin uptake inhibitor, were also evaluated. Exposure to acute noise/light stress dramatically increased motor activity (behavioral activation) in comparison with basal (unstressed) activity. However, animals with a history of chronic stress exhibited reduced basal activity levels as well as a decreased behavioral activation response to acute stress. There was also exaggerated corticosterone (CS) responding in both of these behavioral test situations attributable to prior chronic stress exposure. Chronic treatment with any of the TCAs significantly restored the behavioral activation response to acute stress and normalized CS responding in chronically stressed animals. Chronic fluoxetine treatment was ineffective. In chronically stressed, but behaviorally untested (quiescent) mice, there were no changes in CS levels, but norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased. However, chronically stressed mice tested for basal motor activity showed large NE decreases, while those receiving acute stress exposure prior to testing showed large NE decreases and further 5-HIAA increases. There were no alterations on neurochemical parameters due to any drug treatment which could be correlated with a possible mechanism for their efficacy, although evidence suggested NE involvement. It was further proposed that the chronic stress paradigm induced conditioned neuroendocrine and neurochemical responses.

Blood was collected from male rats of various ages under control conditions and after introduction of two stress factors. All animals were sacrificed between 15.00 and 16.00 h. Serum prolactin levels in immature male rats were found to be very low between birth and day 15 after birth. Neither exposure to a new environment, for example removal from the animal rooms for the duration of 10 min, nor exposure to concentrated ether vapour resulted in increased serum prolactin levels. Between day 20 and 35 basal serum prolactin levels were increased, they then fell at adult values. During this period of increasing serum prolactin levels pituitary prolactin release became stress-susceptable; i.e. elevated serum prolactin levels were observed after introduction of stress factors as in adult male rats. Serum TSH levels were found to be high between birth and day 10. Low TSH levels measured between day 15 and 40 and adult values were detected after day 40. Neither ether nor removal of the animals from their normal environment changed serum TSH levels at any age tested. The results indicate that the hypothalamo-pituitary in immature rats reacts in a similar way as that in adult animals from day 16-20 onwards. Serum TSH levels in these animals, however, are reduced, indicating that an increase in serum TSH is not necessary for normal processes of maturation.

In 16 young house physicians, each of whom presented a case at grand rounds, the effect on platelet function of the emotional stress involved in presenting the case was determined. Platelet-aggregation curves, using adenosine diphosphate and epinephrine, were determined immediately before, immediately after, and seven days after stress. Platelet aggregation was diminished during the stress period in 15 of the subjects. These findings may possibly be of importance in the relationship between stress and myocardial infarction; they also suggest that the emotional state of the patient must be considered when interpreting platelet-aggregation curves.

Based on experiences gained in psychiatric counselling for patients with problems specific to climacterium virile, the climacterium virile as a time of crisis is compared to the period of puberty. Suggestions are given to provide a crisis management for this particular period of life in order to improve the chances for a satisfactory development during the subsequent years of life.

Rat pups that are separated early from their mothers, at postnatal day 15, become hypothermic when subjected to physical restraint on postnatal day 30. Restraint of separated pups also elicits an unusually high incidence of gastric erosions, as well as insomnia and an increase in quiet wakefulness. If hypothermia during restraint is prevented, neither the erosions nor the behavioral responses occur. Rat pups separated at the customary age (postnatal day 22) do not become hypothermic during restraint, and the restraint of such pups is not associated with either gastric erosion or insomnia.

Investigations into the stress response of patients committed to a special hospital for criminally deviant offences have identified a group of sympathetically hypoactive patients who excrete more noradrenaline and less adrenaline in the urine than either the remaining hospital population or control subjects, during conditions of stresser anticipation. Further investigation of these patients has shown that similar differences in plasma catecholamines exist, and that the group of patients characterised by this imbalance tend to have been committed for the most physically violent crimes.

The paper is concerned with a study of 55 pateints with hypertensive disease and of 14 normals under the conditions of emotional stress. These studies were conducted in order to detect interrelationship between vegetative, EEG and REG indices. In 3 groups of patients distinguished according to symptoms of vegetative changes the indices of the tone in the sympathetical and parasympathetical parts of the nervous system in the working period (i. e. during the period of emotional stress) significantly differed from the indices of the control group. They also correlated with the character of activity and the EEG indices. Unlike normals, patients with hypertension in the working period demonstrate not a dilatation of the frequency spectrum in the EEG, but are somewhat narrower. Correlations between shifts on the EEG and REG were not detected. However, in the group of patients with weakened vegetative reactions in a visual assessment of the REG there was a weakening of the autoregulation of cerebral reactions, which coincided with somewhat less frequent alpha-rhythm in a lower work productivity.

By way of a "psychogenic stimulation" (crowding for 1, 7 and 15 days) neurogenic hypertension was induced in male rats that developed in them within 11--15 days of the tsne of the stress. The biosynthesis of aldosterone, corticosterone, 11-dehydrocorticostrone and desoxycorticosterone by the adrenal glands of the rats in vitro from progesterone-14C appeared to greatly increased on the 1st day of stress. In 7 days of the beginning of stress the production of labelled corticosteroids fell to controlvalues (with the exception of 11-dehydrocorticosterone which production was growing still further). By the 15th day of stress reduction of the biosynthesis of aldosterone, corticosterone and desoxycorticosterone was observed, as well as normalization of the biosynthesis of 11-dehydrocorticosterone.

A total of 105 flight qualified crewmembers, aged 20 to 40, were taken under observation. Coagulographic and thromboelastographic parameters of the venous blood were studied. The most significant changes (an increase in the coagulation time as related to the time of plasma recalcification, a decrease of the plasma tolerance to heparin, R, K, R plus K, a decrease in the coagulation index Si with respect to the thromboelastogram, a significant increase in the fibrinolytic activity and the heparin number) were noted postflight in commanders, pilots and navigators. Less significant variations of the coagulographic parameters were observed in other crewmembers. The above changes (an increase in endogenous heparin, an acceleration of the fibrinolytic activity) can be regarded as the protective-adaptive reaction of the anticoagulatory system aimed at reducing hypercoagulation during the emotional stress-effect of the flight.

Activation of latent associations by word stimuli of different emotional relevance as well as the accompanying electrophysiological tracings reveal statistically significantly characteristics in juvenile essential (arterial) hypertensives as compared to normotensives. This applies to the verbal reactions as well as to the electrophysical concomitants. Under additional cognitive demands both groups achieve better performance. This rise is significantly greater, however for hypertensives than for normotensives. Our special recording system permitted exact phonographic registration of the verbal stimulus and reaction as well as of the PGR.

Emotional stress is conventionally considered to be associated with tachycardia and enhanced sympathetic activity. The electrocardiogram and plasma catecholamine and lipid concentrations were observed in 21 young healthy women undergoing dental procedures. Ten of these received premedication with the beta-blocking agent oxprenolol and 11 with a placebo, administered on a double-blind randomised basis. Mild tachycardia occurred in the placebo group a few minutes before and a few minutes after dentistry, but there was a reduction in heart rate immediately before and during the procedure. The pattern was similar in the group who received oxprenolol, though the heart rates at each stage were lower. Plasma adrenaline concentrations were much higher in the samples taken during the procedure than in those taken shortly before and after it. Plasma noradrenaline and lipid concentrations remained unchanged. A decrease in heart rate in the face of intense emotional arousal and an increased plasma adrenaline concentration suggest that the expectation or experience of pain may be associated with parasympathetic dominance despite greatly enhanced sympathetic activity.

In the past few years, the finding of elevated serum levels of creatine phosphokinase in some acutely psychotic patients has commanded a great deal of interest. Although structural abnormalities in nerve and muscle of some of these patients have been described, the cause remains obscure. Physical stress will raise CPK, but the role of psychological stress has been unclear. CPK levels of medical students were measured before and after an academic examination, but no relationship between examination stress and changes in CPK was found. A significantly higher number of CPK elevations were reported in association with vigorous exercise. These findings are consistent with a hypothesis that psychological stress plays an insignificant role in the CPK elevations seen in some acutely psychotic patients. The importance of physical activity in elevated CPK values was reconfirmed.

Inbred rats from the Maudsley Reactive (MR) strain had lower concentrations of norepinephrine in hypothalamus, heart, and spleen, and lower total catecholamines in adrenal than inbred Maudsley Non-Reactive rats (MNRA line). In contrast, they had a higher concentration of telencephalic NE than MNRA rats. These results confirmed previous findings obtained on rats maintained by non-systematic breeding within the two lines. Comparisons were also made between MR and a second Maudsley Non-Reactive strain (MNR). Rats of the two Non-Reactive lines (MNRA, MNR) have been bred from the same foundation population and selected for the same behavioral characteristics, but have been genetically isolated from each other for many generations. It was found that MR rats showed differences from MNR rats in hypothalamic and peripheral (but not telencephalic) NE concentrations similar to those seen in MR/MNRA comparisons. Since rats of the two Non-Reactive lines differ appreciably from MR rats in open-field defecation (the criterion on which they were selected), their differences from MR rats in a neurochemical system involved in sympathetic function suggests that this system may be functionally related to well established behavioral and physiological differences between the lines.

Male and female engineering students were studies under stress induced by a congnitive-conflict task and in a control condition spent in inactivity. The results showed that (a) in the control condition the sexes did not differ in adrenaline, noradrenaline or cortisol excretion, whereas heart rate was significantly higher in the females; (b) adrenaline excretion and heart rate increased significantly in both sexes during stress; (c) the rise in adrenaline excretion was more pronounced in the males, whereas the rise in heart rate was significantly greater in the females; (d) cortisol excretion increased significantly during stress in the male group only; and (e) self-estimates of effort and performance were consistently higher and increased more over time in the males than in the females, bu these sex differences on the subjective level were not reflected in actual performance. The interaction of biological and social factors in the development of sex differences in stress reactions is discussed.

On the basis of theoretical, clinical and experimental analyses the influence of different stress categories, especially of psycho-emotional and socio-emotional stress, upon cerebro-visceral regulation processes is investigated. Central-nervous information processing in various brain areas (neocortex, limbic system, hypothalamus, formatio reticularis mesencephali etc.) and learning processes are equally affected by stress factors as are haemodynamic and biochemical parameters. Changes of the carbohydrate and lipid metabolism, of plasma renin activity, catechol amine release and the counter-regulatory insulin enhancement are especially pronounced in "stress-sensitive risk persons", e.g. in the hypertensive as a maladaptive dysregulation-as opposed to the adaptive regulation capacity of healthy individuals. The investigated functional patterns of different systems of the organism allow the distinction of hyper- and hyporeactive forms of maladaptation. The pathogenetic efficiency of stress is determined not only by the quantity, quality, duration of exposure and basic processes of the central nervous system, but also by man's personality structure and his sensitivity to stress (genetic predisposition and/or acquired maladaptation). More insight into the neuro-biological processes underlying the motivational and psycho-emotional performance of the brain and its connection withe humoral-hormonal and cardiovascular systems is necessary to treat and to control cerebrovisceral dysregulations such as arterial essential hypertension. It will be a task of psychotherapy to help improve man's adaptive capacity and to desensibilize stress-sensitive risk persons.

Several studies have highlighted the increase in physiological activity which occurs in pilots during flight and especially during takeoffs and landings. For example, it has been clearly demonstrated that pilots' heart rates increase during the landing approach to reach a peak at or just before touchdown. These changes have been attributed to workload and to psychological or emotional stress. This paper examines a number of test pilots' heart rate responses recorded during various flight trials involving different types of aircraft. Examples include ramp takeoffs in a VTOL fighter, automatic landings in fog, supersonic flight through monsoon rain, and a sortie in which the pilot developed acute appendicitis. It is concluded that heart rate responses in experienced pilots are influenced almost entirely by workload-related factors and not by emotional stressors, such as risk and anxiety. Because of the emotional overtones of the word "stress," it is suggested that the term workload should be used when referring to the reason for increased cardiovascular activity of pilots.

Free urine adrenaline, noradrenaline, (additional free plasma catecholamines in the physicians), and blood lactate were determined in 11 ambulance men and 5 physicians to assess stress during medical service. Stress was evaluated employing a stress index, based on difficulties in driving, traffic, severity of injuries or illness. Emergency cases with seriously injured subjects or reanimation were judged to have a 4-fold higher stress index than routine cases where strong physiological or psychological stress was absent. Urine catecholamines and stress indices were estimated in 3-h intervals. The calculations were based on the stress induced catecholamine concentrations minus the basal excretion during the same 3-h interval. Urine adrenaline and noradrenaline in ambulance men and physicians correlated directly with the stress index, as well as the plasma catecholamines of the physicians. Lactate levels showed similar behaviour and a descriptive direct correlation with the plasma catecholamines. Urine adrenaline increased more--dependent on the stress index--than urine noradrenaline. This over-proportional adrenaline response may be an indicator for the additional psychological stress in emergency cases. Therefore physicians showed--based on the same stress index--a tendency to higher urine adrenaline excretion and blood lactate levels than the ambulance men, which might be the consequence of the overall responsibility of the physicians. Because of the observed catecholamine responses during medical service, coronary insufficiency or hypertension might be contra-indications for participation in the medical service; regular clinical investigations including ergometric tests are advisable.