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Physiological adaptations to fasting in an actively wintering canid, the Arctic blue fox (Alopex lagopus).

This study investigated the physiological adaptations to fasting using the farmed blue fox (Alopex lagopus) as a model for the endangered wild arctic fox. Sixteen blue foxes were fed throughout the winter and 32 blue foxes were fasted for 22 d in Nov-Dec 2002. Half of the fasted blue foxes were food-deprived again for 22 d in Jan-Feb 2003. The farmed blue fox lost weight at a slower rate (0.97-1.02% body mass d(-1)) than observed previously in the arctic fox, possibly due to its higher initial body fat content. The animals experienced occasional fasting-induced hypoglycaemia, but their locomotor activity was not affected. The plasma triacylglycerol and glycerol concentrations were elevated during phase II of fasting indicating stimulated lipolysis, probably induced by the high growth hormone concentrations. The total cholesterol, HDL- and LDL-cholesterol, urea, uric acid and total protein levels and the urea:creatinine ratio decreased during fasting. Although the plasma levels of some essential amino acids increased, the blue foxes did not enter phase III of starvation characterized by stimulated proteolysis during either of the 22-d fasting procedures. Instead of excessive protein catabolism, it is liver dysfunction, indicated by the increased plasma bilirubin levels and alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase activities, that may limit the duration of fasting in the species.

Acclimatization↗

Physiological adaptations and activity recorded at a polar base.

Physiological parameters and activity were recorded monthly on 19 men wintering at a polar base. A comparison was made between those in their first Antarctic winter (Group A, n = 13) and those in their second consecutive Antarctic winter (Group B, n = 6). Group A were more active (p less than 0.001) and spent more time outside (p less than 0.001) during the summer months than during the darker and colder winter period. Combined data showed no correlation between total activity and meteorological conditions, but a clear (p less than 0.001) negative correlation with time spent outside and wind speed. In the first part of the year group A became fitter (as shown by a lower heart rate at a VO2 1.51 min-1), increased basal oxygen uptake under standard conditions and put on body and fat mass. These changes were not demonstrated in group B living and working under identical conditions. Lean body mass of both groups rose throughout the year (A, p less than 0.001; B, p less than 0.05). These data suggested that the changes in physiological parameters in group A were in response to the life style and activity of a polar base, rather than to the Antarctic climate per se.

Adaptation, Physiological↗

The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment.

It is clear from the literature reviewed that modifications in membrane lipid composition play a major role in the adaptation of diverse organisms to specific environments and physiological circumstances. Acyl chain and molecular species restructuring in phospholipids are the most ubiquitous adaptations to environmental insult, being implicated in membrane adjustments to temperature, pressure, water activity, pH and salinity. In contrast, other adaptations (e.g. modulation of anionic phospholipids (salinity adaptation), trehalose content (dehydration) and the PC/PE ratio (temperature acclimation] appear to be more context specific. Although the volume of correlative data relating membrane composition to environmental state is impressive, several questions must be explicitly addressed in future research if a mechanistic understanding of the role of lipids in fine tuning membrane function is to be achieved. These include: (1) Adaptation thresholds--How much environmental variation is required before an acclimatory response is initiated, and is the extent of membrane perturbation induced by such minimally effective stimuli similar for different stress vectors? Interspecific comparisons of the Na+/K(+)-ATPase of fish collected at different depths indicate that species must be separated in depth by a distance corresponding to a pressure difference of 20 MPa before pressure adaptation is evident. Assuming a dT/dP value of 0.23 (Table 1), a 20 MPa change in pressure corresponds to ca. a 5 degrees C change in temperature, which agrees well with the minimal temperature change required to elicit changes in the lipid composition of plasma membranes in kidney tissue of thermally-acclimating trout. A pressure of 20 MPa also corresponds approximately to the maximum depth from which deep sea animals survive being brought to the surface. Collectively, these observations suggest that the minimally effective stimuli for both temperature and pressure adaptation are similar. Comparable data are not available for other environmental variables. (2) Signal transduction--What signals are being sensed and how are they transduced into an adaptational response? In some cases, it is clear that the enzymes of lipid metabolism respond directly (either by a variation in catalytic rate or substrate preference) to variations in the physical environment in an apparently adaptive manner (e.g. refer Sections VI.A.1 and VI.B.2). It seems unlikely, however, that such direct effects can explain the totality of the adaptive capacity of organisms, especially given the evidence for the induction of desaturase synthesis in cold adaptation (refer to Section VI.A.2).(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

Creatine depletion elicits structural, biochemical, and physiological adaptations in rat costal diaphragm.

To elucidate adaptations elicited by creatine (Cr) depletion in the costal diaphragm (Dia), 16 12-wk-old male Fisher 344 rats had 2% beta-guanidinopropionic acid (beta-GPA), a competitive inhibitor of Cr transport into muscle, added to their food; a control group (Con) of 16 rats ate normal rat chow. After 18 wk, beta-GPA and Con Dia did not differ histochemically with respect to fiber-type distribution; however, the cross-sectional area of type II(b + x) fibers was 33% less in beta-GPA than Con Dia. Biochemically, the proportion of myosin heavy chain IIb in beta-GPA Dia was decreased 42% from Con Dia, whereas the proportions of myosin heavy chains I and IIa were increased. Physiologically, both peak twitch tension and tetanic tension in beta-GPA Dia were decreased 40% from Con. To assess fatigability, we used the protocol of Kelsen and Nochomovitz (J. Appl. Physiol. 53; 440-447, 1982) for 2-6 min duration; the percentage of initial force exhibited by beta-GPA Dia was approximately twice that of Con Dia. We conclude that these structural, biochemical, and physiological adaptations elicited by Cr depletion can all be explained by selective atrophy of IIb muscle fibers in the Dia.

Acclimatization↗

Physiological adaptations of the intertidal rockpool teleost Blennius pholis L., to aerial exposure.

Gas exchange, metabolism, ventilation, circulation and acid-base balance in water and air were investigated in Blennius pholis. The rates of gas exchange in water and air were similar with the RQ remaining around 0.8. Aerial gas exchange was equally divided between the head/gills and the tail region. Ventilatory adaptations involved a reduction in rate in air and the mode of ventilation changed from flow-through to tidal, with closed opercula. A transient bradycardia developed on transition to air before heart frequency (fH) returned to aquatic levels. During aerial exposure PvCO2 rose only by 1 Torr with a concomitant decrease in pH of 0.19 pH-units. At the same time a metabolic acidosis was observed which could not be fully accounted for by the formation of lactic acid in the blood, although tissue lactate levels did not change significantly. No histological evidence was found for the presence of carbonic anhydrase in the epithelial cells of the skin or the oesophagus to aid aerial CO2 excretion. Inhibition of CA activity by addition of methazolamide to blood, however, caused PvCO2 to rise by 3 Torr and pHv to decrease by 0.4 pH unit. It is concluded that B. pholis is physiologically well adapted to aerial exposure through adjustments in ventilation and circulation and that erythrocytic carbonic anhydrase plays a major role in CO2 transfer.

Acid-Base Equilibrium↗

Biochemical and physiological adaptation to chronic propranolol treatment in the rat.

The biochemical and physiological aspects of isoprenaline sensitivity in normotensive rats were examined during and after abrupt withdrawal of chronic propranolol treatment. Serum propranolol concentrations in rats chronically treated for one month (0.125% propranolol in drinking water: 75-100 mg/kg/day) ranged from 7 to 23 ng/ml. At the height of the blockade, rats showed a decreased responsiveness in vivo to isoprenaline-induced increase in heart rate and fall in blood pressure; the ED50 values for isoprenaline being increased some 20- and 4-fold respectively. There was a 180% increase in beta-receptor number in sarcolemmal membranes isolated from ventricular muscle of these animals, together with increased basal (290%), fluoride- (100%), forskolin- (80%) and isoprenaline-stimulated (125%) adenylate cyclase activity. Twenty-four hours after propranolol withdrawal, serum propranolol concentrations were reduced by over 95%. At this time rats exhibited increased chronotropic and blood pressure responses to i.v. isoprenaline, indicated by the reduced ED50 values (2-fold and 12-fold respectively compared to controls). In addition, cardiac sarcolemmal beta-receptor number and adenylate cyclase activities were still significantly elevated above those of controls; 35% increase in beta-receptor number and increases of 96, 26, 13 and 37% in basal, fluoride-, forskolin- and isoprenaline-stimulated adenylate cyclase activities respectively. Forty-eight hours after drug withdrawal serum propranolol concentrations were only just detectable at 0.5 +/- 0.1 ng/ml. Although sarcolemmal beta-receptor numbers were still elevated (23%) isoprenaline-stimulated adenylate cyclase activity had returned to control values. However, both the fluoride- and forskolin-stimulated enzyme activities were decreased below control values by 12 and 23% respectively, suggestive of a reduction in the catalytic capacity of the adenylate cyclase complex. In parallel with the reduction in beta-receptor number and adenylate cyclase activity, the chronotropic response to i.v. isoprenaline had also returned to control values. In contrast, the blood pressure response to i.v. isoprenaline was still elevated in these animals indicated by the 5-fold reduction in the ED50 value compared with control animals.

Adaptation, Physiological↗

Regulated endocytosis of opioid receptors: cellular mechanisms and proposed roles in physiological adaptation to opiate drugs.

Opiate drugs such as morphine and heroin are among the most effective analgesics known. Prolonged or repeated administration of opiates produces adaptive changes in the nervous system that lead to reduced drug potency or efficacy (tolerance), as well as physiological withdrawal symptoms and behavioral manifestations such as craving when drug use is terminated (dependence). These adaptations limit the therapeutic utility of opiate drugs, particularly in the treatment of chronically painful conditions, and are thought to contribute to the highly addictive nature of opiates. For many years it has been proposed that physiological tolerance to opiate drugs is associated with a modification of the number or functional activity of opioid receptors in specific neurons. We now understand certain mechanisms of opioid receptor desensitization and endocytosis in considerable detail. However, the functional roles that these mechanisms play in the complex physiological adaptation of the intact nervous system to opiates are only beginning to be explored.

Adaptation, Physiological↗

Theoretical and semantic aspects of the modular physiological adaptation.

Adaptation is a fundamental concept in biology. The use of this notion in physiology presents a special problem, on the one hand, due to its widespread application to practically all physiologic phenomena of organic economy, on the other hand, because there is no formal definition providing a demarcation between adaptive processes and secondary processes without relating them with adaptation. Therefore, the objective of this work is to formalize a modular definition of adaptation that allows a differentiation between adaptive processes and non adaptive ones. I conclude that the use of the concept of 'module' in the definition of adaptation makes it possible to demarcate adaptive processes. Furthermore, the proposed definition lets us eliminate the use of notions such as those of 'features' and 'characteristics' and solve a methodological problem encountered at organizational levels.

Adaptation, Physiological↗

Homeostatic theory of drug tolerance: a general model of physiological adaptation.

At the heart of homeostatic theory is the idea that explicit or implicit behavioral demands placed on physiological systems are required for the biological detection of homeostatic disturbances. The detection of drug-induced disturbances is required to drive the development of all systemic tolerance, both associative and nonassociative (i.e., both forms of tolerance are behaviorally contingent). A wide range of findings ranging from morphine-induced analgesia to ethanol-induced hyposexuality shows that contingent tolerance is pervasive and may be universal. The theory also stipulates that behavioral demands placed on the target system will govern the loss of both associative and nonassociative tolerance (physiological). The present formulation integrates contingent, associative, and nonassociative tolerance and drug-opposite withdrawal reactions within a unified theory.

Adaptation, Physiological↗

Metabolite profiles of nodulated alfalfa plants indicate that distinct stages of nodule organogenesis are accompanied by global physiological adaptations.

An effective symbiosis between Sinorhizobium meliloti and its host plant Medicago sativa is dependent on a balanced physiological interaction enabling the microsymbiont to fix atmospheric nitrogen. Maintenance of the symbiotic interaction is regulated by still poorly understood control mechanisms. A first step toward a better understanding of nodule metabolism was the determination of characteristic metabolites for alfalfa root nodules. Furthermore, nodules arrested at different developmental stages were analyzed in order to address metabolic changes induced during the progression of nodule formation. Metabolite profiles of bacteroid-free pseudonodule extracts indicated that early nodule developmental processes are accompanied by photosynthate translocation but no massive organic acid formation. To determine metabolic adaptations induced by the presence of nonfixing bacteroids, nodules induced by mutant S. meliloti strains lacking the nitrogenase protein were analyzed. The bacteroids are unable to provide ammonium to the host plant, which is metabolically reflected by reduced levels of characteristic amino acids involved in ammonium fixation. Elevated levels of starch and sugars in Fix(-) nodules provide strong evidence that plant sanctions preventing a transformation from a symbiotic to a potentially parasitic interaction are not strictly realized via photosynthate supply. Instead, metabolic and gene expression data indicate that alfalfa plants react to nitrogen-fixation-deficient bacteroids with a decreased organic acid synthesis and an early induction of senescence. Noneffective symbiotic interactions resulting from plants nodulated by mutant rhizobia also are reflected in characteristic metabolic changes in leaves. These are typical for nitrogen deficiency, but also highlight metabolites potentially involved in sensing the N status.

Adaptation, Physiological↗

Physiologic adaptations of pregnancy.

Normal pregnancy changes include physiologic anemia, leukocytosis, and thrombocytopenia. Cardiac rate and stroke volume increase, vascular resistance falls, and creatinine clearance markedly rises. Thyroid binding globulin and cortisol binding globulin both increase, as do complement proteins and fibrinogen, the latter resulting in a normally high erythrocyte sedimentation rate. Estrogen and progesterone rise dramatically. Low back pain, hip and sacroiliac complaints are common. The cytolytic activity of natural killer (NK) cells is decreased, as are adhesion and chemotaxis of phagocytic cells. Antibody responses are normal. CD4 cells proportionately decrease. A large number of circulating proteins suppression lymphocyte proliferation, and T-cell interleukin-2 (IL-2) production may be suppressed. In studies of pregnant patients, controls must include normal pregnant women.

Female↗

Aspergillus hyphae in infected tissue: evidence of physiologic adaptation and effect on culture recovery.

Microbiologic cultures of fungi are routinely incubated at ambient temperatures in room air, and the rate of recovery of Aspergillus species from clinical specimens is poor. Failure of current culture methods to mimic the physiologic temperature and low-oxygen environment found in hypha-laden infected tissue may underlie this poor recovery. Experiments were performed to compare the recovery of Aspergillus spp. incubated at 35 degrees C in 6% O(2)-10% CO(2) with that at 25 degrees C in room air. The samples tested included Aspergillus-infected tissue specimens from a dog model and human autopsies, experimental anaerobically stressed Aspergillus inocula, and 10,062 consecutive clinical specimens. Culture at 35 degrees C in 6% O(2)-10% CO(2) significantly enhanced the recovery of Aspergillus spp. from the infected autopsy tissue samples. Incubation at 35 degrees C alone resulted in approximately 10-fold-improved culture recovery from the experimentally stressed hyphae, and the 6% O(2)-10% CO(2) atmosphere independently favored growth under temperature-matched conditions. Finally, incubation at 35 degrees C (in room air) improved the overall recovery of Aspergillus spp. from clinical specimens by 31%. Culture at 35 degrees C in a microaerobic atmosphere significantly enhances the recovery of Aspergillus spp. from various sources. Aspergillus hyphae growing in infected tissue appear to be adapted to the physiologic temperature and hypoxic milieu.

Adaptation, Physiological↗

Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress?

Overtraining syndrome (OTS) is a condition wherein an athlete is training excessively, yet performance deteriorates. This is usually accompanied by mood/behavior changes and a variety of biochemical and physiological alterations. Presently, there is no global hypothesis to account for OTS. The present paper will attempt to provide a unifying paradigm that will integrate previous research under the rubric of the cytokine hypothesis of overtraining. It is argued that high volume/intensity training, with insufficient rest, will produce muscle and/or skeletal and/or joint trauma. Circulating monocytes are then activated by injury-related cytokines, and in turn produce large quantities of proinflammatory IL-1beta, and/or IL-6, and/or TNF-alpha, producing systemic inflammation. Elevated circulating cytokines then co-ordinate the whole-body response by: a) communicating with the CNS and inducing a set of behaviors referred to as "sickness" behavior, which involves mood and behavior changes that support resolution of systemic inflammation: b) adjusting liver function, to support the up-regulation of gluconeogenesis, as well as de novo synthesis of acute phase proteins, and a concomitant hypercatabolic state; and c) impacting on immune function. Theoretically, OTS is viewed as the third stage of Selye's general adaptation syndrome, with the focus being on recovery/survival, and not adaptation, and is deemed to be "protective," occurring in response to excessive physical/physiological stress. Recommendations are made for potential markers of OTS, based on a systemic inflammatory condition.

Acute-Phase Proteins↗

A cell biologist's perspective on physiological adaptation to opiate drugs.

Opiate drugs such as morphine and heroin are among the most effective analgesics known but are also highly addictive. The clinical utility of opiates is limited by adaptive changes in the nervous system occurring after prolonged or repeated drug administration. These adaptations are believed to play an important role in the development of physiological tolerance and dependence to opiates, and to contribute to additional changes underlying the complex neurobehavioral syndrome of drug addiction. All of these adaptive changes are initiated by the binding of opiate drugs to a subfamily of G protein-coupled receptors that are also activated by endogenously produced opioid neuropeptides. It is increasingly evident that opiate-induced adaptations occur at multiple levels in the nervous system, beginning with regulation of opioid receptors themselves and extending to a complex network of direct and indirect modifications of "downstream" signaling machinery. Efforts in my laboratory are directed at understanding the biochemical and cell biological basis of opiate adaptations. So far, we have focused primarily on adaptations occurring at the level of opioid receptors themselves. These studies have contributed to defining a set of membrane trafficking mechanisms by which the number and functional activity of opioid receptors are controlled. The role of these mechanisms in affecting adaptation of "downstream" neurobiological substrates, and in mediating opiate-induced changes in whole-animal physiology and behavior, are exciting questions that are only beginning to be explored.

Adaptation, Physiological↗