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Adaptation, Physiological↗
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17Beta-oestradiol modulates glucocorticoid, neural and behavioural adaptations to repeated restraint stress in female rats.
Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17beta-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17beta-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17beta-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17beta-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17beta-oestradiol treatment at the higher dose (120 microg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17beta-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17beta-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17beta-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17beta-oestradiol-treated rats. After repeated restraint stress, 17beta-oestradiol-replaced rats spent as much time exploring the open arms of the maze as controls, indicating adaptation. By contrast, nonreplaced rats were still showing a significant reduction in open arm exploration after repeated restraint. The present study presents novel data showing that the HPA axis remains reactive to repeated stress in 17beta-oestradiol-treated ovariectomized rats, but stress-induced anxiety behaviour is reduced.
Adaptation, Physiological↗
Capillary regression in vascular endothelial growth factor-deficient skeletal muscle.
Skeletal muscle angiogenesis is an important physiological adaptation to increased metabolic demand, possibly dependent on vascular endothelial growth factor (VEGF), the increased expression of which is a known early response to exercise. To test the hypothesis that VEGF is essential to muscle capillary maintenance, we evaluated the consequences of targeted skeletal muscle inhibition of VEGF expression in postnatal, cage-confined VEGFloxP(+/+) mice. To delete VEGF, cre recombinase expression was accomplished using direct intramuscular injection of a recombinant adeno-associated cre recombinase expressing viral vector. Four weeks postinfection, VEGF-inactivated regions revealed 64% decreases in capillary density and capillary-to-fiber ratio. Substantial apoptosis was also observed in VEGF-depleted regions. There was no evidence of rescue at 8 wk, with a persistent 67% reduction in capillary-to-fiber ratio and a 69% decrease in capillary density. These data implicate VEGF as an essential survival factor for muscle capillarity and also demonstrate insufficient VEGF-dependent signaling leads to apoptosis in mouse skeletal muscle.
Animals↗
Application of phonocardiography for detecting hypoxia-induced cardiovascular adaptation in the chicken.
Phonocardiography was evaluated as a noninvasive technique for diagnosis of cardiovascular adaptation and disease in broiler chickens. Heart sounds (HSs) were compared in a fast-growing (FG) commercial broiler line that is highly susceptible to chronic right heart failure resulting from pulmonary hypertension syndrome (PHS) and in a non-selected slow-growing (SG) broiler line that is resistant to PHS. HSs were analyzed in broilers reared in hypobaric hypoxia (HYP) and normobaric (CON) conditions. PHS was induced by a combination of embryonic hypoxia and HYP exposure. HSs were recorded with a microphone placed at the thoracic inlet of each chicken. Electrocardiograms were used to mark the sampling interval for the first, second, and total HS. Digitized HS signals were analyzed for peak frequency, mean peak frequency, and band width. Birds were examined for PHS lesions when 6 wk of age, at the end of each experiment. HSs were compared by line and treatment (Experiment 1) or by treatment and week (Experiment 2). In addition, HS frequencies were analyzed within the HYP treatment group for differences between birds with severe or no gross PHS lesions. HS frequencies generally decreased with age and were also lower in the FG than the SG line. Hypobaric exposure decreased all HS frequencies in the SG line and components of the first HSs in the FG line. The SG line did not develop gross lesions of PHS. In the FG line, significant differences in HS frequencies were observed between HYP and CON groups but not between PHS- and PHS+ broilers. Frequency changes described in humans with PHS were not observed. Further development to maximize the resolution of the HS waveforms and improved matching of the sampling interval to the electrical or hemodynamic output of the chicken heart may allow its use as a diagnostic tool for differentiating broilers with normal cardiac function or physiologic adaptation from those with cardiovascular disease.
Acclimatization↗
Prolactin and acid stress in the teleost Oreochromis (formerly Sarotherodon) mossambicus.
Prolactin is probably implicated in the control of physiological adaptation to sublethal acid stress in tilapia. Exposure of fish to water at pH 3 caused death within 72 hr, which was associated with pronounced hemodilution. At pH 4 mortality was low, although a substantial and rapid decrease in plasma osmolality, plasma Na+, and plasma total Ca was observed. These effects were at least partly due to increased permeability of the gills for water and ions. After a few days at pH 4, restoration of plasma osmolality, Na+, and total Ca was noticeable. Control levels were reached after 5 days for Ca, and after 10 days for osmolality, Na+, and branchial osmotic water permeability. Prolactin secretion increased markedly during acid exposure, as was established by morphometrical and biochemical methods. In tilapia, administration of prolactin is known to raise plasma osmolality, Na+, and plasma total Ca. This hormone further has been shown to reduce branchial osmotic water permeability. It is concluded therefore that the restoration of plasma electrolytes and branchial osmotic water permeability during chronic acid stress are causally connected with the observed stimulation of prolactin secretion.
Animals↗
Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR.
The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age compared with normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7-day-old pups at 0800, hypoxia from birth resulted in increased basal (12.2 +/- 1.4 ng/ml; n = 12) and ACTH-stimulated (94.0 +/- 9.4 ng/ml; n = 14) corticosterone levels compared with normoxic controls (basal = 8.3 +/- 0.5 ng/ml; n = 11; stimulated = 51.3 +/- 3.8 ng/ml; n = 8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 +/- 4 vs. 78 +/- 8 pg/ml) or after (481 +/- 73 vs. 498 +/- 52 pg/ml) porcine ACTH injection (20 microg/kg). This effect was similar in the afternoon at 6 days of age and even greater at 5 days of age at 0800. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF)-1alpha mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone but not aldosterone response to ACTH. This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.
Adrenal Glands↗
Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2.
The actions of corticotropin-releasing hormone (Crh), a mediator of endocrine and behavioural responses to stress, and the related hormone urocortin (Ucn) are coordinated by two receptors, Crhr1 (encoded by Crhr) and Crhr2. These receptors may exhibit distinct functions due to unique tissue distribution and pharmacology. Crhr-null mice have defined central functions for Crhr1 in anxiety and neuroendocrine stress responses. Here we generate Crhr2-/- mice and show that Crhr2 supplies regulatory features to the hypothalamic-pituitary-adrenal axis (HPA) stress response. Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive. Crhr2 also appears to modify the recovery phase of the HPA response, as corticosterone levels remain elevated 90 minutes after stress in Crhr2-/- mice. In addition, stress-coping behaviours associated with dearousal are reduced in Crhr2-/- mice. We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn. Feeding is initially suppressed in Crhr2-/- mice following Ucn, but Crhr2-/- mice recover more rapidly and completely than do wild-type mice. In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects. Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis. Our results identify specific responses in the brain and periphery that involve Crhr2.
Adaptation, Physiological↗
Prenatal stress elicits regionally selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress.
Exposure to stress during pregnancy influences the trajectory of brain development resulting in permanent alterations that may contribute to increased susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript, we examined the effects of prenatal stress on the expression of basic fibroblast growth factor (FGF-2), an important molecular regulator of development and plasticity, in adult male rats under basal conditions as well as in response to acute or chronic stress. Baseline FGF-2 mRNA levels were differentially influenced by gestational stress in a variety of brain regions, with significant decreases in prefrontal cortex and increases in entorhinal cortex and striatum. By itself, postnatal stress similarly decreased trophic factor expression in prefrontal cortex while evoking stimulation elsewhere. Gestational stress altered the pattern of FGF-2 expression in response to adult stress, completely reversing the pattern in the prefrontal cortex (stimulatory instead of inhibitory), blunting the response in the entorhinal cortex and desensitizing the response in the striatum. These effects point to a unique interference of chronic prenatal stress with both ongoing FGF-2 expression and its responses to subsequent stressors, lasting into adulthood. Given the multifaceted role of FGF-2 in synaptic development, maintenance and plasticity, these data provide detailed mechanistic evidence as to how prenatal stress elicits lifelong effects on synaptic function. The abnormal modulation of FGF-2 gene expression in specific brain regions in response to subsequent stress in adulthood may impair the normal adaptive responses of the cell to challenging situations.
Acute Disease↗
Evaluation of cardiovascular demands of game play and practice in women's ice hockey.
Preparation for the physical demands of competition often involves game simulation during practice. This paradigm is thought to promote physiological adaptations that enhance maximal performance. However, a mismatch between practice intensity and actual competition intensity may not provide adequate training to achieve optimal game-play fitness. The purpose of this study was to evaluate the effectiveness of practice in meeting the cardiovascular demands of a women's ice hockey game. Heart rate (HR) data from 11 U.S. National Women's Ice Hockey team members were collected (5-second intervals) during a game and a typical practice session. Data was normalized to individual HRmax determined during Vo(2)max testing. Working time was defined as a game shift or practice-working interval. Mean working HR was greater during the game than the practice, 90 +/- 2% and 76 +/- 3% of HRmax, respectively (p < 0.05). Mean percent session time (game or practice) >90% HRmax was also longer during the game than the practice, 10.5 +/- 4.1% and 5.6 +/- 3.5% (p < 0.05), respectively. Mean session HR, percent time >80% HRmax, and mean resting HR were not different between game and practice (68 +/- 7% vs. 69 +/- 5%, 23.2 +/- 5.3% vs. 26.1 +/- 9.2%, and 59 +/- 8% vs. 56 +/- 5%, respectively). Elite women hockey players experience significantly greater cardiovascular load during game play than during practice. This mismatch in cardiovascular demand may prevent players from achieving "game shape," thus affecting competition play.
Adult↗
Sensitization, subjective health complaints, and sustained arousal.
The purpose of this presentation is to discuss the possibility that sensitization is a psychobiological mechanism underlying not only multiple chemical sensitivity (MCS), but a much more general cluster of illness, referred to as "subjective health complaints". Sustained arousal, or sustained "stress" responses, may be an important factor for the development of these conditions. Patients with subjective complaints without objective changes are sometimes referred to as having "fashionable diagnoses" or "unexplained symptoms". They may be given diagnoses like MCS, epidemic fatigue, chronic fatigue syndrome, burnout, stress, a variety of intoxications, environmental illness, radiation, multiple chemical hypersensitivity, food intolerance, functional dyspepsia, irritable bowel, myalgic encephalitis, postviral syndrome, yuppie flu, fibromyalgia, or vital exhaustion. One issue is whether this is one general condition or separate entities. Another issue is whether sensitization may be the psychobiological mechanism for most or all of these conditions. Finally, is it likely that sustained arousal may facilitate the development of sensitization in some or many neural circuits? In this review, the main emphasis will be on musculoskeletal pain. This is the most frequent and most expensive condition for sickness compensation and disability. The comorbidity of other complaints, however, will also be taken into account.
Adaptation, Physiological↗
Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition.
The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Telemetry augments the validity of the rat as a model for heat acclimation.
Repeated exposure to heat stress results in physiological adaptations which increase tolerance to heat stress. Core temperature (Tc) and heart rate (HR), two indices of successful heat acclimation, are both increased by the handling and restraint usually required to measure these variables in the rat. This study compares measurement of these variables in telemetry- and nontelemetry-equipped heat-acclimated rats. Four groups of male Sprague-Dawley rats were used: CAC (24, control for acclimated), HAC (24, heat acclimated), TCAC (3, telemetry implanted control for acclimation), and THAC (3, telemetry implanted, heat acclimated). The CAC and TCAC rats were maintained at 26 degrees C for 2 weeks; HAC and THAC groups were maintained at 32-33 degrees C for 2 weeks. The telemetry rats were surgically implanted with transmitters which measured activity, temperature, blood pressure (BP), and ECG. Following acclimation, the rats were subjected to a heat-stress test as follows: animals were placed in a chamber maintained at 41.5 degrees C until a Tc of 41.5 degrees C was reached, when the animals were removed to a 26 degrees C chamber to recover. The Tc of the CAC and HAC rats was manually measured with a rectal probe every 15 min. The TCAC and THAC rats had Tc, HR, and BP monitored electronically every 2.5 min from 30 min prior to heat stress through 30 min after heat. The THAC rats maintained lower Tc, HR, and BP than the TCAC rats throughout the heat stress. The CAC and HAC rats had higher Tc and slower rates of cooling after heat than either of the telemetry groups. Simultaneous measurement of HR, BP, and Tc has not previously been reported in unrestrained heat-acclimated rats. Measurement of these variables without the confounding effects of restraint or handling has increased the validity of the rat as a model for human heat acclimation.
Animals↗
Health-related quality-of-life assessment in patients with cutaneous T-cell lymphoma.
OBJECTIVE: To measure and evaluate the health-related quality of life (HRQOL) in patients with cutaneous T-cell lymphoma (CTCL), a visible cutaneous malignancy that may have a profound effect on patients' lives. DESIGN: Monocenter, cross-sectional study. SETTING: The Skin Oncology Program, Department of Dermatology, and the Photopheresis Unit of Boston Medical Center. PATIENTS: A total of 22 adult patients with confirmed CTCL. MAIN OUTCOME MEASURES: (1) Evaluation of general oncologic and skin disease-specific HRQOL using, respectively, the Functional Assessment of Cancer Therapy-General (FACT-G) and Skindex-29 profiles; (2) assessment of HRQOL association with disease stage (early stage, IA-IIA; late stage, IIB-IVB). RESULTS: Patients with more advanced CTCL stages reported more effects on general health (FACT-G), particularly in the physical, emotional, and functional domains (P < .05). Patients with early-stage CTCL reported better skin-specific HRQOL overall (Skindex-29; P = .002) and for each specific domain than did patients with late-stage disease. The Skindex-29 scales had high internal consistency, and the confirmatory factor structure was similar to that of previous studies. CONCLUSIONS: The HRQOL of patients with CTCL can be evaluated using the Skindex-29 and FACT-G instruments. Patients with more advanced stages of CTCL had lower HRQOL scores.
Adaptation, Physiological↗
Health-related quality of life and appropriateness of knee or hip joint replacement.
BACKGROUND: We studied the association between explicit appropriateness criteria for total hip joint replacement (THR) and total knee replacement (TKR) with changes in health-related quality of life of patients undergoing these procedures. METHODS: Prospective observational study of 1576 consecutive patients with diagnoses of osteoarthritis on waiting lists to undergo THR or TKR. Explicit appropriateness criteria using the RAND appropriateness method were applied. Patients completed 2 questionnaires that measured health-related quality of life, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), before the procedure and 6 months afterward. RESULTS: Patients who were considered appropriate candidates for these procedures had greater improvements than those who were considered inappropriate candidates in all 3 WOMAC domains (pain, functional limitation, and stiffness; THR: 43.0, 40.6, and 40.4 vs 14.7, 19.1, and 15.9; TKR: 34.9, 32.5, and 30.2 vs 23.2, 18.9, and 17.1; P<.001 for all comparisons). Patients who underwent THR and were judged to be appropriate candidates had greater improvements in the physical function, role-physical, bodily pain, and social function domains of the SF-36 than those judged to be inappropriate candidates (34.4, 35.1, 33.1, and 26.6 vs 19.6, 9.2, 5.7, and 7.0; P = .04, P = .03, P < .001, and P < .001, respectively). Appropriate candidates for TKR demonstrated greater improvement in the social function domain of the SF-36 after the procedure than those deemed inappropriate candidates (19.9 vs 7.9; P = .004) but not in the other domains of functional status. CONCLUSIONS: These results suggest a direct relationship between explicit appropriateness criteria and better health-related quality-of-life outcomes after THR and TKR surgery. Our results support the use of these criteria for clinical guidelines or evaluation purposes.
Activities of Daily Living↗
The nature of man's adaptation to his total environment and the relation of this to illness.
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Acclimatization↗
17-OHCS levels in combat. Special forces "A" team under threat of attack.
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17-Hydroxycorticosteroids↗
Personal differences in perceptual deprivation.
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Adaptation, Physiological↗
Control of states of consciousness. I. Attainment through control of psychophysiological variables.
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Adaptation, Physiological↗