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High-altitude acclimatization and proteinuria in East Africa.

Seven climbers spent 6 weeks in the East African mountains, at heights of up to 5890 m. The mean protein urine concentration in morning specimens was over 100 mg/100 ml after climbs during the first 12 days but fell to 15 mg/100 ml during subsequent climbs. The highest concentrations (100-300 mg/100 ml) were in 5 climbers with peripheral oedema, 3 with obvious high-altitude illness. The findings implicate the kidney in high altitude acclimatization and illness.

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Trace elements in the sweat of acclimatized persons.

Sweat samples were collected from the arms of 15 normal, healthy subjects while they exercised on a cycle ergometer at room temperature. Samples were analysed for copper, zinc, manganese, nickel, cadmium and aluminium by atomic absorption spectrophotometry. Mean sweat levels determined for each element were as follows: 358.1 micrograms/l for Zn, 486.8 micrograms/l for Cu, 3.10 micrograms/l for Mn and 1.91 micrograms/l, 69.9 micrograms/l and 15.0 micrograms/l for Cd, Ni and Al, respectively. It appears that substantial quantities of trace elements are excreted in the sweat of those sweating habitually. Our findings suggest that the influence of diet in replenishing the body stores of trace elements and the conservation of these elements by the kidneys may play a part in preventing the occurrence of chronic deficiency states in acclimatized persons.

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Acclimatization to hypoxia alters cerebral convective and diffusive O2 delivery.

Ventilatory acclimatization (VA) to hypoxia alters cerebrovascular responses to arterial blood gas perturbations. For example, after VA, cerebral blood flow (CBF) is elevated, at a given arterial CO2 tension (PaCO2), compared to CBF before VA. This experiment examined the effects of VA to 72 h of normobaric hypoxia [arterial O2 tension (PaO2) approx. 40 mmHg, O2 saturation in arterial blood approx. 50%] on total and regional cerebrovascular resistance (CVR and rCVR) and cerebral O2 extraction fraction (OEF) in 32 conscious sheep. Four different O2-CO2 gas combinations were sequentially administered to each sheep before and after VA. CVR and rCVR were calculated from CBF (radiolabeled microspheres) and arterial and cerebral downstream pressures; OEF was calculated from arterial and cerebral venous O2 contents. After VA, during hyperoxia, CVR and rCVR tended to be lower during both hypocapnia and hypercapnia. During hypoxia, although CVR and rCVR were slightly less during hypocapnia, CVR and rCVR during hypercapnia were surprisingly increased. The post-VA increases in mean CVR and mean rCVR during hypoxic gas combinations differed from the post-VA decreases during hyperoxic gas combinations (0.04 less than or equal to P less than or equal to 0.11). In contrast, although VA decreased OEF during three of four gas combinations (P less than or equal to 0.003), there was a greater mean post-VA decrease in OEF during hypercapnic gas combinations than during hypocapnic gas combinations (P = 0.025); decreases in OEF were correlated with decreases in cerebral O2 consumption. The post-VA CVR responses may reflect altered neurocirculatory control by the arterial chemoreflex; the OEF responses suggest relative cerebral hyperperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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The effect of acclimatization on blood flow and its distribution in normothermic and hyperthermic domestic fowl.

Blood flow and its distribution was examined in summer and winter acclimatized normothermic and hyperthermic domestic hens. A clear trend of season on normothermic blood flow distribution was not noted; however, a significant tendency towards increased flow in summer was recorded. In 22 out of 28 organs or tissues examined, blood flow was lower in winter than in summer: pectoral muscle, adrenal and jejunum winter to summer ratios were 36, 64 and 76%, respectively (P less than 0.05). During hyperthermia, blood flow to visceral organ decreased in both groups; in summer this reduction was less severe in parts of the digestive system and more pronounced in parts of the reproductive system.

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Peroxisome proliferator-activated receptors as regulators of lipid metabolism; tissue differential expression in adipose tissues during cold acclimatization and hibernation of jerboa (Jaculus orientalis).

Brown (BAT) and white (WAT) adipose tissues play a key role in the body energy balance orchestrated by the central nervous system. Hibernators have developed a seasonal obesity to respond to inhospitable environment. Jerboa is one of the deep hibernator originated from sub-desert highlands. Thus, this animal represents an excellent model to study cold adaptation mechanism. We report that the adipogenic factor PPARgamma exhibits a differential expression between BAT and WAT at mRNA level. A specific induction was only seen in WAT of pre-hibernating jerboa. Interestingly, PPAR beta/delta is specifically induced in BAT and brain of pre-hibernating jerboa, highlighting for the first time the possible key role of this ubiquitous isoform in the cold adaptation of this true hibernator. Inductions of PPARgamma(2) in WAT and PPAR beta/delta in BAT are blunted by a hypolipemic drug, the ciprofibrate. These changes may be correlated with hibernation arrest and death of treated jerboa. Mitochondrial acyl-CoA dehydrogenase and peroxisomal acyl-CoA oxidase activities in brown and white adipose tissues are decreased up to 85% during cold acclimatization (without food privation). These enzyme activities are subject to a strong induction in BAT and in WAT (3.4-7.5 fold) during the hibernation period. The BAT thermogenesis marker is also largely induced (approximately 4 fold of UCP1 mRNA level) during pre-hibernation period. Unexpectedly, treatment with ciprofibrate deeply affects lipolysis in BAT by increasing acyl-CoA dehydrogenase activity (3.4 fold) and acyl-CoA oxidase at both activity and mRNA levels (2.8 and 3.8 fold, respectively) and enhances strongly UCP1 mRNA level (9.5 fold) during pre-hibernation.

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Correlation of seasonal acclimatization in metabolic enzyme activity with preferred body temperature in the Eastern red spotted newt (Notophthalmus viridescens viridescens).

Eastern red spotted newts, as aquatic adults, are active year round. They are small and easy to handle, and thus lent themselves to a laboratory study of seasonal changes in preferred body temperature and biochemical acclimatization. We collected newts in summer (n=20), late fall (n=10) and winter (n=5). Ten each of the summer and late fall newts were subjected to an aquatic thermal gradient. Summer newts maintained higher cloacal temperatures than late fall newts (26.8+/-0.5 degrees C and 17.2+/-0.4 degrees C, respectively). In addition, the activity of three muscle metabolic enzymes (cytochrome c oxidase (CCO), citrate synthase (CS) and lactate dehydrogenase (LDH)) was studied in all newts collected. Newts compensated for lower late fall and winter temperatures by increasing the activity of CCO during those seasons over that in summer newts at all assay temperatures (8, 16 and 26 degrees C). The activity of CS was greater in winter over summer newts at 8 and 16 degrees C. No seasonal differences in LDH activity were demonstrated. These data in newts indicate that this amphibian modifies some muscle metabolic enzymes in relation to seasonal changes and can modify its behavioral in a way that correlates with those biochemical changes.

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Ventilatory acclimatization in awake guinea pigs raised at high altitude.

To determine if laboratory strains of guinea pigs bred at sea level (SL) are "pre-adapted" to high altitude (HA), we raised litter-matched weanling Hartley guinea pigs for 4 months at SL, intermediate altitude (IA, 1250 m) or HA (3800 m) and exposed them acutely to 100, 21 and 12% inspired O2 at their respective altitude of residence. Control animals raised at SL were also exposed acutely to 10 and 8% inspired O2. In awake spontaneously breathing guinea pigs raised at SL, resting minute ventilation and tidal volume increased significantly when inspired O2 tension fell below about 60 mm Hg. In guinea pigs raised at IA or HA, ventilation was higher at any given inspired O2 tension in direct relationship to the altitude of residence. Resting hematocrit was also higher in animals raised at HA than at SL. We conclude that the pattern of ventilatory acclimatization to HA exposure in Hartley guinea pigs is similar to that in laboratory rats and human lowlanders; therefore laboratory guinea pigs are not pre-adapted and are suitable animals for the study of adaptation to high altitude.

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Regulation of body weight and thermogenesis in seasonally acclimatized Brandt's voles (Microtus brandti).

Seasonal changes in an animal's morphology, physiology, and behavior are considered to be an adaptive strategy for survival and reproductive success. In the present study, we examined body weight and several behavioral, physiological, hormonal, and biochemical markers in seasonally acclimatized Brandt's voles (Microtus brandti) to test our hypothesis that Brandt's voles can decrease energy intake associated with decrease in body weight, body fat content, serum leptin level, and increasing thermogenesis in winter conditions. We found that the body weight of Brandt's voles was lowest in winter (December to February) and highest in spring and early summer (May to June). This seasonal variation in body weight was associated with changes in other markers examined. For example, the winter decrease in body weight was accompanied by increased energy intake and enhanced nonshivering thermogenesis (NST) as well as by decreased body fat mass and reduced levels of circulating leptin. Further, circulating levels of leptin were positively correlated with body weight and body fat mass, and negatively correlated with energy intake and uncoupling protein 1 contents. Together, these data do not support our hypothesis and suggest that leptin may be involved in this process and serve as a starvation signal in Brandt's voles.

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Central nervous system mechanisms of ventilatory acclimatization to hypoxia.

Ventilatory acclimatization to hypoxia is the time-dependent increase in ventilation that occurs with chronic exposure to hypoxia. Despite decades of research, the physiological mechanisms that increase the hypoxic ventilatory response during chronic hypoxia are not well understood. This review focuses on adaptations within the central nervous system (CNS) that increase the hypoxic ventilatory response. Although an increase in CNS responsiveness had been proposed many years ago, only recently has strong experimental evidence been provided for an increase in the CNS gain in the rat, which has proved to be a good model of VAH in humans. Within the CNS, several neuroanatomical sites could be involved as well as changes in various neurotransmitters, neuromodulators or signalling mechanisms within any of those sites. Lastly, adaptations within the CNS could involve both direct effects of decreased P(O(2)) and indirect effects of increased afferent nerve activity due to chronic stimulation of the peripheral arterial chemoreceptors.

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Carotid body mechanisms in acclimatization to hypoxia.

Most studies oriented toward examining mechanisms increasing carotid body (CB) sensitivity to hypoxia during ventilatory acclimatization (VAH) have focussed on the role of known neuromodulators of CB function. Two general categories of the neuromodulatory agents studied most extensively could be considered: those thought to be primarily inhibitory to CB function: dopamine, norepinephrine, nitric oxide and those thought to be primarily excitatory: substance P, endothelin. There is evidence that these putative inhibitory agents are up-regulated in the first weeks of chronic hypoxia and that substance P is down-regulated. All these changes would favor a decrease in CB sensitivity to hypoxia. There are data suggesting that CB endothelin activity is up-regulated in rats subjected to chronic hypoxia, a direction suggesting increased CB sensitivity to hypoxia. Dopamine may have an excitatory as well as an inhibitory role on the CB, but there is not yet evidence to indicate that an excitatory role for DA exists in chronic hypoxia. Ion channel studies of type I CB cells suggest increased excitability after prolonged hypoxia. The role of excitatory CB nicotinic receptors and putative serotonin type 3 receptors should be examined further for their potential role in VAH. It is suggested that a balance of excitatory and inhibitory modulation is responsible for increased CB sensitivity to hypoxia during VAH.

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Intracarotid dopamine infusion does not prevent acclimatization to hypoxia.

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation that occurs during sustained exposure to hypoxia. The mechanism for VAH remains elusive. We sought to determine whether a deficiency in the availability of carotid body dopamine is the mechanism of increased ventilatory responsiveness to hypoxia during VAH in awake goats. This was based on the evidence that dopamine (DA) is primarily an inhibitory neuromodulator of carotid body (CB) function. The hypothesis was tested by intracarotid infusion of DA (5.0 micrograms kg-1 min-1) throughout VAH. VAH was not prevented by DA infusion, failing to support the hypothesis. We conclude that a deficiency in the availability of inhibitory DA release within the CB is probably not responsible for VAH. However, increased ventilatory responses to acute hypoxia after either prolonged DA infusion or hypoxia may have similar CB mechanisms.

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Coral bleaching--capacity for acclimatization and adaptation.

Coral bleaching, i.e., loss of most of the symbiotic zooxanthellae normally found within coral tissue, has occurred with increasing frequency on coral reefs throughout the world in the last 20 years, mostly during periods of El Nino Southern Oscillation (ENSO). Experiments and observations indicate that coral bleaching results primarily from elevated seawater temperatures under high light conditions, which increases rates of biochemical reactions associated with zooxanthellar photosynthesis, producing toxic forms of oxygen that interfere with cellular processes. Published projections of a baseline of increasing ocean temperature resulting from global warming have suggested that annual temperature maxima within 30 years may be at levels that will cause frequent coral bleaching and widespread mortality leading to decline of corals as dominant organisms on reefs. However, these projections have not considered the high variability in bleaching response that occurs among corals both within and among species. There is information that corals and their symbionts may be capable of acclimatization and selective adaptation to elevated temperatures that have already resulted in bleaching resistant coral populations, both locally and regionally, in various areas of the world. There are possible mechanisms that might provide resistance and protection to increased temperature and light. These include inducible heat shock proteins that act in refolding denatured cellular and structural proteins, production of oxidative enzymes that inactivate harmful oxygen radicals, fluorescent coral pigments that both reflect and dissipate light energy, and phenotypic adaptations of zooxanthellae and adaptive shifts in their populations at higher temperatures. Such mechanisms, when considered in conjunction with experimental and observational evidence for coral recovery in areas that have undergone coral bleaching, suggest an as yet undefined capacity in corals and zooxanthellae to adapt to conditions that have induced coral bleaching. Clearly, there are limits to acclimatory processes that can counter coral bleaching resulting from elevated sea temperatures, but scientific models will not accurately predict the fate of reef corals until we have a better understanding of coral-algal acclimatization/adaptation potential. Research is particularly needed with respect to the molecular and physiological mechanisms that promote thermal tolerance in corals and zooxanthellae and identification of genetic characteristics responsible for the variety of responses that occur in a coral bleaching event. Only then will we have some idea of the nature of likely responses, the timescales involved and the role of 'experience' in modifying bleaching impact.

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Protein flexibility acclimatizes photosynthetic energy conversion to the ambient temperature.

Adjustment of catalytic activity in response to diverse ambient temperatures is fundamental to life on Earth. A crucial example of this is photosynthesis, where solar energy is converted into electrochemical potential that drives oxygen and biomass generation at temperatures ranging from those of frigid Antarctica to those of scalding hot springs. The energy conversion proceeds by concerted mobilization of electrons and protons on photoexcitation of reaction centre protein complexes. Following physicochemical paradigms, the rates of imperative steps in this process were predicted to increase exponentially with rising temperatures, resulting in different yields of solar energy conversion at the distinct growth temperatures of photosynthetic mesophiles and extremophiles. In contrast, here we show a meticulous adjustment of energy conversion rate, resulting in similar yields from mesophiles and thermophiles. The key molecular players in the temperature adjustment process consist of a cluster of hitherto unrecognized protein cavities and an adjacent packing motif that jointly impart local flexibility crucial to the reaction centre proteins. Mutations within the packing motif of mesophiles that increase the bulkiness of the amino-acid side chains, and thus reduce the size of the cavities, promote thermophilic behaviour. This novel biomechanical mechanism accounts for the slowing of the catalytic reaction above physiological temperatures in contradiction to the classical Arrhenius paradigm. The mechanism provides new guidelines for manipulating the acclimatization of enzymes to the ambient temperatures of diverse habitats. More generally, it reveals novel protein elements that are of potential significance for modulating structure-activity relationships in membrane and globular proteins alike.

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Lobster haemocyanin. Influence of acclimatization on subunit composition and functional properties.

Haemocyanin from the lobster Palinurus elephas has been shown to change in its subunit composition according to the time of year. In contrast, in Palinurus mauritanicus, a lobster living at greater depth, no seasonal changes in subunit composition have been observed. The results obtained from a set of experiments performed on some Palinurus mauritanicus acclimatized in an aquarium have clearly indicated that modifications of haemocyanin subunit composition may be involved in the adaptation of arthropods to environmental change.

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Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m.

To investigate the effect of acclimatization to hypoxia on substrate utilization, eight sea level residents were studied during exercise at the same relative (rel) and absolute (abs) work rate as at sea level (SL), under acute (AH), and after 4 weeks exposure to 4100 m altitude (CH). Carbohydrate (CHO) and fat oxidation during exercise at SL were 2.0 +/- 0.2 and 0.3 +/- 0.0 g min(-1), respectively. At AHabs and CHabs CHO oxidation increased (P < 0.05) to 2.5 +/- 0.2 and 2.3 +/- 0.1 for CHO, and fat oxidation decreased (P < 0.05) to 0.2 +/- 0.01 and 0.2 +/- 0.01 g min(-1), respectively. Exercise in AHrel and CHrel did not cause a change in the relative CHO and fat oxidation compared with SL, the absolute rate of CHO oxidized being 1.7 +/- 0.1 and 1.7 +/- 0.02 g min(-1), respectively, and fat oxidation was 0.2 +/- 0.02 g min(-1) in ACrel and 0.3 +/- 0.02 g min(-1) in CHrel. In conclusion, substrate utilization is unaffected by AH and CH, when the work rate is matched to the same relative intensity as at SL.

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Pre-acclimatization to high altitude using exercise with normobaric hypoxic gas mixtures.

Pre-acclimatization was conducted using a new method elaborated in our laboratory, combining high intensity exercise while breathing hypoxia normobaric gas mixtures. The training consisted in a daily training during three weeks, 6 days a week, two hours a day, on bicycle ergometer. Eighteen subjects aging 22.2 +/- 1.4 years (11 males, 7 females) were matched in two similar groups: one group trained in normoxic conditions (NG) while the other group (HG) trained with a progressive decrease of the fraction of inspired oxygen (from 12.2% to 10.0%). Maximal oxygen uptake (VO2max) were measured before and after the protocol period in both hypoxic (VO2max H, FIO2 = 10.4%) and normoxic (VO2max N) conditions, for the 2 groups. Training induced a similar O2max N increase in the two groups. The ratio VO2max H/VO2max N was calculated. As expected, in NG group, this ratio decreased significantly (from 63.9 +/- 4.3 to 57.5 +/- 3.1%, p < 0.01) after the training period compared to the initial value, diminution associated with an elevation of VO2max N (from 48.4 +/- 9.0 to 52.9 +/- 9.0 ml.min-1 x kg-1, p < 0.01). Conversely, in HG group, this ratio was not significantly diminished (from 61.7 +/- 3.8 to 60.5 +/- 5.2%, NS) in spite of a similar increase of VO2max N (from 47.5 +/- 5.5 to 50.7 +/- 4.9 ml.min-1 x kg-1, p < 0.01). This does not follow the diminution of the ratio usually described when VO2max N reach higher values.(ABSTRACT TRUNCATED AT 250 WORDS)

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Acclimatization and maximum number of functioning sweat glands in Hindu and Dutch females and males.

The number and distribution of thermally (hot water bath method) activated eccrine sweat glands have been measured in Dutch, Hindu and Bushnegro males and in Dutch and Hindu females in Surinam. Results are compared with those for Dutch and Hindu males and females in the Netherlands. The results suggest that the maximum number of functioning sweat glands (F.S.G.) changes during natural acclimatization and that probably the relative magnitude of this change depends on the percentage of "recruitment type" adapters within each racial group. This change was not apparent for all sixteen body areas studied. In these experiments high relative humidity had no influence on the number of functioning sweat glands. No sex differences were observed in body density or in pattern of regional distribution. Only the Hindu and Dutch males differed significantly in body density. A positive relationship was observed between body density and extremities-weight ratio in the three male groups.

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Fetal cardiac and cerebrovascular acclimatization responses to high altitude, long-term hypoxia.

In response to high altitude long-term hypoxemia, the heart of fetal sheep shows a decrease in cardiac output that is secondary to a decrease in myocardial cell contractile function. The intracellular mechanisms responsible for these reductions might include reduced myofibrillar Mg(2+)-activated ATPase. There is also a decrease in beta(1)-adrenergic receptor stimulated augmentation of myocardial contraction. An overproduction of cAMP by beta(1)-adrenergic receptor stimulation, resulting in overphosphorylation of troponin I, may reduce calcium binding by troponin C. Fetal coronary arteries have a reduced contractile response to K(+) depolarization and a reduced sensitivity to a thromboxane A(2) receptor agonist-stimulated contraction. Cerebral arteries of adult sheep (but not the fetus) show decreased responses to both K(+)-depolarization and norepinephrine-induced contraction. Nonetheless, cerebral arteries in the long-term hypoxic fetus demonstrated a number of significant changes from control. For the cerebral arteries in general, high altitude hypoxia is associated with augmented or upregulation of presynaptic functions. In contrast, postsynaptic functions tend to be significantly depressed or downregulated. The results emphasize the role of high altitude, long-term hypoxemia in modulating adrenergic- and serotonergic-mediated signal transduction in the cerebral vasculature. They specifically highlight the significant differences in acclimatization responses between the fetus and adult.

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