Mind-body medicine and cancer.

Mind-body medicine, grounded in a respectful, therapeutic partnership, should be a central element in the care of every person diagnosed with cancer. This article reviews some of the physiologic foundations of mind-body medicine, the introduction of mind-body approaches to cancer care in the 1970s, the specific mind-body approaches that have been used, and the evidence that supports their use. The importance of group support for enhancing the effectiveness of these approaches is discussed. Guidelines are offered for integrating mind-body approaches and perspectives in the care of people who have cancer.

Stressor-specific alterations in corticosterone and immune responses in mice.

Different stressors likely elicit different physiological and behavioral responses. Previously reported differences in the effects of stressors on immune function may reflect qualitatively different physiological responses to stressors; alternatively, both large and subtle differences in testing protocols and methods among laboratories may make direct comparisons among studies difficult. Here we examine the effects of chronic stressors on plasma corticosterone concentrations, leukocyte redistribution, and skin delayed-type hypersensitivity (DTH), and the effects of acute stressors on plasma corticosterone and leukocyte redistribution. The effects of several commonly used laboratory stressors including restraint, forced swim, isolation, and low ambient temperatures (4 degrees C) were examined. Exposure to each stressor elevated corticosterone concentrations, with restraint (a putative psychological stressor) evoking a significantly higher glucocorticoid response than other stressors. Chronic restraint and forced swim enhanced the DTH response compared to the handled, low temperature, or isolation conditions. Restraint, low temperature, and isolation significantly increased trafficking of lymphocytes and monocytes compared to forced swim or handling. Generally, acute restraint, low temperature, isolation, and handling increased trafficking of lymphocytes and monocytes. Considered together, our results suggest that the different stressors commonly used in psychoneuroimmunology research may not activate the physiological stress response to the same extent. The variation observed in the measured immune responses may reflect differential glucocorticoid activation, differential metabolic adjustments, or both processes in response to specific stressors.

Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia.

Footshock stress induces both endocannabinoid mobilization and antinociception. The present studies investigated behavioral plasticity in cannabinoid antinociceptive mechanisms following repeated activation using the tail-flick test. A secondary objective was to ascertain whether blockade of stress antinociception by the CB(1) antagonist rimonabant could be attributed to changes in locomotor activity. The cannabinoid agonist WIN55,212-2 induced hypoactivity in the open field relative to vehicle-treated controls. By contrast, rimonabant, administered at a dose that virtually eliminated endocannabinoid-mediated stress antinociception, failed to alter locomotor behavior (i.e. time resting, ambulatory counts, distance traveled) in rats subjected to the same stressor. Rats exposed acutely to footshock were hypersensitive to the antinociceptive effects of WIN55,212-2 and Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The converse was also true; acute Delta(9)-THC and WIN55,212-2 administration potentiated stress antinociception, suggesting a bidirectional sensitization between endocannabinoid-mediated stress antinociception and exogenous cannabinoid antinociception. Stress antinociception was also attenuated following chronic relative to acute treatment with WIN55,212-2 or Delta(9)-THC. Repeated exposure to footshock (3 min/day for 15 days), however, failed to attenuate antinociception induced by either footshock stress or WIN55,212-2. Our results demonstrate that endocannabinoid-mediated stress antinociception cannot be attributed to motor suppression. Our results further identify a functional plasticity of the cannabinoid system in response to repeated activation. The existence of cross-sensitization between endocannabinoid-mediated stress antinociception and exogenous cannabinoid antinociception suggests that these phenomena are mediated by a common mechanism. The observation of stress-induced hypersensitivity to effects of exogenous cannabinoids may have clinical implications for understanding marijuana abuse liability in humans.

Lipopolysaccharide does not affect acoustic startle reflex in mice.

Bacterial endotoxin (lipopolysaccharide; LPS) evokes in rodents an adaptive sickness behavior. It also produces changes in stress hormones secretion and activity of brain serotonergic and noradrenergic systems that have been implicated in stress responses, fear, and anxiety. Acoustic startle reflex (ASR) is regarded as a protective behavioral response that is enhanced in threatening situations or following an aversive event, and it can be modulated by physiological and emotional state of an animal. Effects of intraperitoneal injections of LPS on ASR, prepulse inhibition (PPI), locomotor activity in open field, and blood plasma corticosterone concentration were studied in lines of mice that display high (HA line) or low (LA line) swim stress-induced analgesia and also differ in emotional behaviors, including the magnitude of ASR. In both lines LPS produced robust sickness behavior, as evidenced by a decrease in locomotion and body weight, and an increase in corticosterone concentration. However, in neither line LPS injections affected responses to acoustic stimuli as assessed by the ASR and PPI magnitudes. The findings suggest that in sickness behavior induced by LPS the protective responses to salient environmental stimuli are not impaired. The significance of this finding for the concept of sickness behavior is discussed.

Intracerebroventricularly administered neurotrophins attenuate blood cerebrospinal fluid barrier breakdown and brain pathology following whole-body hyperthermia: an experimental study in the rat using biochemical and morphological approaches.

Previous studies from our laboratory show that apart from blood-brain barrier (BBB) disruption, the blood-cerebrospinal fluid (CSF) barrier (BCSFB) for proteins is also broken down following whole-body hyperthermia (WBH) in a rat model. Breakdown of the BCSFB alters brain homeostasis and adversely affects the structure and function of the central nervous system (CNS). Since neurotrophins and growth factors (e.g., brain-derived growth factor [BDNF], glial cell line-derived neurotrophic factor [GDNF], and insulin-like growth factor 1 [IGF-1]) are known neuroprotective agents in traumatic and ischemic brain injuries, a possibility exists that these neurotrophins will also attenuate neuronal and choroidal injury in WBH. Subjection of adult rats to 4 h of WBH at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited a profound increase in BCSFB permeability to Evans blue and radioiodine. Degeneration of choroidal epithelial cells and underlying ependyma, dilatation of the lateral ventricular space, and degenerative changes in the adjacent neuropil were frequent. The hippocampus, caudate nucleus, thalamus, and hypothalamus showed profound BBB disruption and brain edema formation. Intracerebroventricular (i.c.v.) administration of BDNF, GDNF, and IGF-1 into the right lateral cerebral ventricle (1, 2, or 5 microg in 30 microL, 24 h before WBH) significantly reduced the BCSFB and BBB breakdown, brain edema formation, and cellular/tissue injuries. These beneficial effects were most pronounced in GDNF- or IGF-1-pretreated animals. These novel observations suggest that neurotrophins administered into ventricular CSF can attenuate BCSFB and BBB damage following WBH and thereby confer neuroprotection. Stabilization of BCSFB function is thus one of the crucial factors in achieving neuroprotection in WBH.

Protective effect of Triphala on cold stress-induced behavioral and biochemical abnormalities in rats.

Stress is one of the basic factors in the etiology of number of diseases. Cold-stress occurs when the surrounding temperature drops below 18 degrees C, the body may not be able to warm itself, and hence serious cold-related illnesses, permanent tissue damage and death may results. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) against the cold stress-induced alterations in the behavioral and biochemical abnormalities in four different groups (saline control, Triphala, cold-stress and Triphala with cold-stress) of Wistar strain albino rats. In this study cold-stress (8 degrees C for 16 h/d/15 days) was applied and the oxidative stress was assessed by measuring the extent of lipid peroxidation (LPO) and the changes in corticosterone levels. Upon exposure to the cold-stress, a significant (P<0.05) increase in immobilization with decrease in rearing, grooming, and ambulation behavior was seen in open field. Following cold-exposure, significant increase in the LPO and corticosterone levels was observed. Oral administration of Triphala (1 g/kg/animal body weight) for 48 days significantly prevented these cold stress-induced behavioral and biochemical abnormalities in albino rats. The results of this study suggest that Triphala supplementation can be regarded as a protective drug against stress.

Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension.

The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain). A characteristic feature of the ISIAH strain is an increase in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the normotensive Wistar albino Glaxo (WAG) rats, and no differences were found in plasma corticosterone. However, the 0.5-h restraint stress produced higher activation of the adrenal cortex in the ISIAH rats. Gluco- and mineralocorticoid responses to the blood volume reduction stresses and ACTH and corticosterone responses to social stress were stronger in the ISIAH than in the control WAG rats. An increase in epinephrine content in adrenals in the basal state and enhanced response of the sympathetic adrenal medullary system to handling stress were observed in the ISIAH rats. Restraint stress produced significantly higher expression of genes encoding corticotropin-releasing hormone-mRNA in hypothalamus and proopiomelanocortin-mRNA in pituitary in the ISIAH than in the WAG rats. Restraint stress produced a decrease in glucocorticoid receptor (GR) gene expression (GR-mRNA) in hippocampus in the ISIAH, but not in the WAG rats. A persistent increase in tyrosine hydroxylase-mRNA in adrenals of the ISIAH rats was found. It is concluded that the ISIAH rat strain is an appropriate model of stress-sensitive hypertension with the predominant involvement of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems in its pathogenesis.

No evidence for enhanced noise induced hearing loss after prenatal stress or dexamethasone.

It was recently implied that prenatal stress and fetal exposure to glucocorticoids may interfere with hearing ability and noise induced hearing loss in adulthood. In the present study pregnant Wistar rats were stressed during gestation by Chronic Mild Stress (CMS, a variable schedule of different stressors) or by dexamethasone (a synthetic glucocorticoid, i.e. a pharmacological stressor). At birth, but not at weaning, the dexamethasone offspring exhibited significantly decreased body weight compared to both control offspring and progeny from dams exposed to CMS during pregnancy. As adults, male offspring were exposed to 105 dB sound pressure level (SPL) wide band noise either continuously for eight hours or for two hours per day on three consecutive days. Oto-acoustic emissions and auditory brainstem responses were recorded before and after exposure to noise. Neither prenatal chronic stress nor prenatal dexamethasone exposure was associated with significantly enhanced noise induced hearing loss compared to controls, and these results were consistent in both subsets of animals. Our data do not support previous reports that prenatal exposure to mild stress nor to dexamethasone is detrimental to the hearing organ per se. However, hearing may be modulated by prenatal stressors under certain circumstances, of which the timing and degree are probably the most important.

The effects of an intensive lifestyle modification program on sleep and stress disorders.

BACKGROUND: To determine if a lifestyle change program can modify behavior to reduce sleep and stress disorders. METHODS: Analyses are based on 2,624 individuals aged 30 to 80 years from the Rockford, Illinois metropolitan area who completed a lifestyle evaluation at baseline and again after four weeks, following participation in a 40-hour educational course given over a four-week period. Participants receive instruction on the importance of making better lifestyle choices related to making long-term improvements in nutrition and physical activity and they learn ways to improve sleep and reduce stress in their lives. RESULTS: Significant percent decreases were observed in the number experiencing selected sleep or stress disorders from baseline to four weeks later for "sleeps restlessly" (-59%), "suffers from insomnia" (-64%), "feels under pressure" (-37%), "easily emotionally upset" (-52%), and "feels fearful or depressed" (-61%). Experiencing a selected sleep or stress disorder after four weeks among those who had the disorder at baseline was significantly more likely in those not physically active and/or not having lowered their BMI after four weeks. Changes in alcohol consumption and smoking did not significantly contribute to changes in the disorders. Those who failed to lower their coffee/tea use after four weeks were significantly more likely to have a sleep disorder and be easily emotionally upset. CONCLUSIONS: Changes in lifestyle behaviors after attending an educational program significantly reduced sleep and stress disorders in as little as four weeks, primarily explained by decreasing BMI and/or increasing exercise.

GABAergic circuits and the stress hyporesponsive period in the rat: ontogeny of glutamic acid decarboxylase (GAD) 67 mRNA expression in limbic-hypothalamic stress pathways.

Development of the hypothalamo-pituitary-adrenocortical (HPA) axis is marked by a diminution in stress responsiveness early in the postnatal period (days 4-14 in the rat). This 'stress hyporesponsive period' (SHRP) is thought to be at least in part centrally mediated. To investigate central mechanisms underlying the SHRP, this study assessed expression of glutamic acid decarboxylase (GAD) 67 in key stress-regulatory regions in the forebrain following acute stress with or without prior maternal deprivation. This isoform of GAD is known to be induced by stress in the adult and is believed to be a major contributor to production of the inhibitory neurotransmitter GABA under stimulated conditions. Expression of GAD67 mRNA was increased in the hippocampus, central amygdala and dorsomedial hypothalamus in pups tested early in the SHRP (day 6) or after its conclusion (day 18). In contrast, restraint caused a down-regulation of GAD67 mRNA in these structures when tested later in the SHRP (day 12). GAD67 mRNA expression was not affected by prior maternal deprivation in these regions. Reduced GABA production in the hippocampus (interneurons) is consistent with enhanced HPA axis inhibition, whereas reduced amygdalar expression predicts impaired stress excitation. Expression of GAD67 mRNA in the bed nucleus of the stria terminalis (BST) was minimally affected by acute restraint or maternal deprivation during the SHRP. However, older animals showed down-regulation of basal expression following maternal deprivation and substantial GAD67 mRNA up-regulation in both deprived and non-deprived groups following acute restraint. In contrast, non-responsiveness of the BST during the SHRP suggests either that BST GABA circuits are not actively engaged by stressors during this period or that circuits regulating BST GAD67 production are not yet in place. Overall, the data implicate forebrain GABA circuits in inhibition of HPA axis activity during the SHRP.

Ultrastructure of neurons in the hypothalamic suprachiasmatic nucleus of rats with different stress reactivity.

The rats were divided into groups demonstrating extremely high and low stress reactivity depending on the results of testing for the nociceptive threshold and thermolability in response to bacterial lipopolysaccharide administration. Specific structural features of the nucleus and mitochondria were revealed in neurons of the hypothalamic suprachiasmatic nucleus in rats with constitutionally high reactivity, which reflects high functional activity and stress-induced lability of these structures. Ultramicroscopic study revealed phenotypic differences in one of the key hypothalamic nucleus, which enables potent and rapid neurogenic response of the stress system in animals with high stress reactivity.

St john's wort (Hypericum perforatum) counteracts deleterious effects of the chronic restraint stress on recall in rats.

This study aimed at verifying a hypothesis that St. John's wort (Hypericum perforatum) alleviates stress-induced memory impairments. Administration of Hypericum perforatum (350 mg kg(-1) daily for 21 days) significantly enhanced recall of passive avoidance behavior (PAB), but had no effect on the acquisition of conditioned avoidance responses (CARs). Rats stressed chronically (2 h daily for 21 days) displayed diminished recall of the PAB and this effect was abolished by St John's wort. Chronic administration of the "equivalent" to the stress dose of exogenous corticosterone (5 mg kg(-1) daily for 21 days) also impaired recall of PAB, and this effect was also reversed by Hypericum perforatum. None of our treatments produced significant motor coordination impairments as tested in a 'chimney' test. It appears that H. perforatum prevents stress-induced deterioration of memory in rats.

Effects of heat stress on Young's modulus of outer hair cells in mice.

Intense sound exposure causes permanent hearing loss due to hair cell and cochlear damage. Prior conditioning with sublethal stressors, such as nontraumatic sound, heat stress and restraint protects the ear from acoustic injury. However, the mechanisms underlying conditioning-related cochlear protection remain unknown. In this paper, Young's modulus and the amount of filamentous actin (F-actin) of outer hair cells (OHCs) with/without heat stress were investigated by atomic force microscopy and confocal laser scanning microscopy, respectively. Conditioning with heat stress resulted in a statistically significant increase in Young's modulus of OHCs at 3-6 h after application, and such modulus then began to decrease by 12 h and returned to pre-conditioning level at 48 h after heat stress. The amount of F-actin began to increase by 3 h after heat stress and peaked at 12 h. It then began to decrease by 24 h and returned to the pre-conditioning level by 48-96 h after heat stress. These time courses are consistent with a previous report in which heat stress was shown to suppress permanent threshold shift (PTS). In addition, distortion product otoacoustic emissions (DPOAEs) were confirmed to be enhanced by heat stress. These results suggest that conditioning with heat stress structurally modifies OHCs so that they become stiffer due to an increase in the amount of F-actin. As a consequence, OHCs possibly experience less strain when they are exposed to loud noise, resulting in protection of mammalian hearing from traumatic noise exposure.

[Relaxation induced by photic stimulation in tinnitus patients]. / Entspannung für Tinnitusbetroffene durch Photostimulation.

The therapeutic effect of applying photic stimulation was evaluated in a sample of 17 patients with chronic tinnitus. The employed optical stimulation technique triggers the activity of brain waves and induces deep relaxation characterized by increased EEG activity in the theta and delta spectrum. The expected therapeutic effect beyond relaxation was a decrease in subjective tinnitus distress and further improvements in well-being. All patients received ten applications of photic stimulation, each lasting 30 min. Every application markedly increased the peripheral blood circulation, thus indicating a relaxation effect. The emotional and cognitive impairments as well as the subjective tinnitus distress significantly decreased during treatment while sleep disturbances showed a tendency towards improvement. Overall, tinnitus distress markedly decreased and general well-being improved. The photic stimulation technique is proposed as a relief for tinnitus patients who do not respond to conventional relaxation techniques.

Stress-induced hyperthermia in the rat: comparison of classical and novel recording methods.

Stress causes a rise in body temperature in laboratory animals (stress-induced hyperthermia). However, the direct effect of common stressors in animal research, i.e. transportation between holding and test rooms or isolation of animals, on body temperature has not been investigated to its full extent. To address this question, it is important to have a reliable and simple monitoring technique, which does not induce stress itself. In the present study, we investigated stress-related changes in body temperature of F344/Hw rats after (1) moving the cage within the holding room, (2) moving the cage from the holding room to another test room and (3) social deprivation (isolation). A combination of two different body temperature recording methods was used to clarify their accuracy and stress-inductive character: rectal temperature recording and peritoneal implanted temperature sensors (Thermochron iButtons).The results demonstrate that (1) different stressors induce a significant rise in body temperature, (2) which is detectable for more than 60 min and (3) it is of importance to standardize temperature recording methods in order to avoid confounding effects of the recording method itself. Furthermore, Thermochron iButtons are more accurate and reliable for body temperature studies than rectal recordings.

Role of TNF-alpha in prenatal alterations in dams of mice under thermal stress.

The possible involvement of cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) that are suspected of causing pregnancy loss and miscarriage has been investigated in dams of mice subjected to hyperthermia. Thermal stress was induced by exposing mice dams at 40+/-2 degrees C for 4 h every day during the different phases of the gestation period whereas the normothermic animals were housed at 22+/-2 degrees C. The effect of maternal thermal stress was measured in pregnant mice at different phases of the gestation period namely, blastogenesis-implantation phase (days 0-5 postconceptionem [p.c.]), organogenesis or embryogenesis phase (days 6-15 p.c.) and fetogenesis phase (days 16-20 p.c.). Uterine examination of dams subjected to hyperthermia on days 6-15 p.c. showed maximum reduction in live fetus number, gestational index and maximum pre and postimplantation loss in comparison with dams housed in normothermic environment and dams exposed to thermal stress between days 0-5 and 16-20 p.c. Maximum resorption rate and number of non-viable fetuses were observed in dams exposed to hyperthermia during days 6-15 p.c. Elevated levels of TNF-alpha and IL-1 beta were observed in the amniotic fluid of dams subjected to hyperthermia during days 6-15 p.c. but IFN-gamma levels remained unaltered. Single intraperitoneal (i.p.) administration of recombinant mouse TNF-alpha at a dose of 1 and 0.5 ng/mice in dams on day 6 in normothermic condition resulted in a reduced number of live fetuses. Administration of anti-TNF-alpha antibody i.p. at a dose of 10 microg/dam on day 6 p.c. and subjected to thermal stress between days 6-15 p.c. increased marginally the number of fetuses but failed to attain statistical significance in comparison with days 6-15 p.c. thermally stressed dams without antibody treatment. It is concluded that the induction of TNF-alpha, in the amniotic fluid is associated with thermal stress during pregnancy and may be linked to the reproductive performances of dams. This study will help in understanding the mechanism of thermal injury in pregnant subjects.

Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress.

Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress.

Effects of fluoxetine on cellular immune response in stressed mice.

We studied the effects of fluoxetine, a non-tricyclic antidepressant drug that selectively inhibits re-uptake of serotonin by presinaptic neurons in the brain, on cellular immune responses in mice exposed to a chronic auditory stressor. The natural killer (NK) cell activity was reduced after 4, 8, 12, 16 and 20 days of stress exposure with a partial recovery on days 16 and 20. Daily treatment with fluoxetine partially reversed these adverse effects of stress in a dose-dependent manner. Significant differences appeared when fluoxetine was administered at 2 mg/kg and maximum effect was reached at doses of 5 mg/kg. The capacity of T cells to generate cytotoxic T-lymphocytes (CTL) in mixed lymphocyte cultures and in vivo was reduced after 4 days of stress application and this effect was partially reduced when mice were injected with 5 mg/kg of fluoxetine. Nevertheless, in our experiments, fluoxetine did not significantly affect the cellular immunity in unstressed mice. In conclusion, fluoxetine seems to partially recover the adverse effects of chronic stress on cellular immune response.

Noise-stress-induced brain neurotransmitter changes and the effect of Ocimum sanctum (Linn) treatment in albino rats.

In this modern world, stress and pollution are unavoidable phenomena affecting the body system at various levels. A large number of people are exposed to potentially hazardous noise levels in daily modern life, such as noise from work environments, urban traffic, and household appliances. A variety of studies have suggested an association between noise exposure and the occurrence of disorders involving extra-auditory organs such as disorders of the nervous, endocrine, and cardiovascular systems. In this study, Wistar strain albino rats were subjected to 100 dB broadband white noise, 4 h daily for 15 days. The high-pressure liquid chromatographic estimation of norepinephrine, epinephrine, dopamine, and serotonin in discrete regions of the rat brain indicates that noise stress can alter the brain biogenic amines after 15 days of stress exposure. Ocimum sanctum (OS), a medicinal herb that is widely claimed to posses antistressor activity and used extensively in the Indian system of medicine for a variety of disorders, was chosen for this study. Administration of the 70% ethanolic extract of OS had a normalizing action on discrete regions of brain and controlled the alteration in neurotransmitter levels due to noise stress, emphasizing the antistressor potential of this plant.

Stress-inducing effect of hypoxia of different origin and its correction with Inula Helenium L. tincture.

In order to evaluate the severity of stress, the effects of single and repeated exposure to hypoxia of different origin (hemic, tissue, and circulatory) on the classical parameters of the Selye triad, cytological characteristics of lymphoid organs, and karyometric parameters (nucleus diameters) were studied in all adrenal zones, and analysis of correlations was carried out. The corrective effect of Inula helenium L. tincture manifested in prolongation of the life-span and normalization of somatic and morphological parameters.