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PubMed2002

Evaluation of tributyltin subchronic effects in tropical freshwater fish (Astyanax bimaculatus, Linnaeus, 1758).

Tributyltin (TBT) is widely used as a biocide in antifouling paints. Astyanax bimaculatus adult fish were acclimatized in a laboratory and isolated in groups of eight individuals. Two groups were used as a control (similar handling and corn oil control) and one group was exposed to TBTCI dissolved in corn oil (0.0688 +/- 0.0031 microg TBT.g(-1)) every 6 days for 32 days. Light and transmission electron microscopy were used to investigate the morphological effects on liver. A muscle fragment was excised for the determination of the acetylcholinesterase activity and blood smears were obtained for differential white cell counts. The results indicated nuclear irregular shapes, chromatin condensation, presence of intranuclear lipid bodies, and degenerative nuclei. Acetylcholinesterase activity was not affected by TBT exposure. The increasing number of neutrophils may represent cytotoxic and stress conditions facilitating the invasion of opportunist organisms. According to the authors' data, TBT was confirmed as a powerful aquatic contaminant to fish in tropical ecosystem.

Acetylcholinesterase↗
PubMed1999

Echocardiographic and survival studies in mice undergoing endotoxic shock: effects of genetic ablation of inducible nitric oxide synthase and pharmacologic antagonism of platelet-activating factor.

Evidence implicating inducible nitric oxide synthase (iNOS) in the alterations of cardiac function characteristic of septic shock has come mostly from studies on anesthetized animals, isolated hearts, cultured myocytes, or hosts treated with pharmacologic inhibitors that lack complete specificity for iNOS. Platelet-activating factor (PAF) can participate in the induction of iNOS and has also been implicated in cardiac dysfunction in sepsis. The present studies assessed cardiac function in a model of sepsis in awake mice in which the gene for iNOS was either normal or selectively disrupted. Mice of each genotype were treated with parenteral fluids or with a highly specific antagonist of PAF. Endotoxic shock was induced by challenge with bacterial lipopolysaccharide (LPS) after priming with heat-killed Propionobacterium acnes. Wild-type mice increased stroke volume and cardiac output in response to LPS. These changes were absent in iNOS-deficient mice. When treated with parenteral fluids, LPS-challenged wild-type and iNOS-deficient mice both had a marked reduction in cardiac output. Antagonism of PAF had no effect on echocardiographic indices in wild-type mice, but selectively overcame the bradycardia and reduced cardiac output elicited by fluid administration in LPS-shocked, iNOS-deficient mice. Thus, there are major cardiovascular effects of PAF that are shared by rather than mediated by iNOS. Neither complete iNOS deficiency nor antagonism of PAF improved survival, whether tested as single or combined intervention. On the contrary, complete deficiency of iNOS was detrimental to survival. Finally, we tested the hypothesis that iNOS deficiency might improve survival if the deficiency were specific but partial. For this, we used mice with one normal and one disrupted gene for iNOS. No survival advantage was evident for these iNOS heterozygotes. Thus, partial or complete inhibition of iNOS, with or without antagonism of PAF, afforded no evident benefit beyond the previously demonstrated reduction in hypotension. Finally, these studies demonstrate that echocardiography preceded by acclimatization is feasible in unanesthetized mice, a finding which should expand the value of genetically manipulated animals for analysis of cardiac function.

Animals↗
PubMed2006

Chronic hypoxia modulates endothelium-dependent vasorelaxation through multiple independent mechanisms in ovine cranial arteries.

Acclimatization to chronic hypoxia involves numerous compensatory changes in many tissues, including blood vessels. The present data demonstrate that in addition to well-documented changes in contractility, chronic hypoxia also produces important changes in the mechanisms mediating endothelium-dependent vasodilatation. At the level of the endothelium, hypoxia attenuates endothelial release of NO and this appears to be mediated through reductions in eNOS specific activity; chronic hypoxia has little effect on eNOS abundance. In contrast, chronic hypoxia depresses the abundance of sGC, which functions as the downstream vascular receptor for NO released from the endothelium. The decreased abundance of sGC produced by chronic hypoxia occurs without changes in sGC specific activity and results in decreased rates of NO-induced cGMP synthesis. Nonetheless, the vasodilator efficacy of NO is enhanced in hypoxic arteries, which suggests that mechanisms downstream from sGC are upregulated by hypoxia. Consistent with this view, chronic hypoxia significantly depresses PDE activity, which serves to prolong cGMP half-life and enhance its vasodilator effects. It remains possible that chronic hypoxia may also enhance PKG activity and/or the abundance of its substrates; this possibility remains a promising topic for future investigation. Overall, it is important to recognize that the mechanisms of adaptation to chronic hypoxia identified in the present study may be somewhat unique to adult carotid arteries. Adaptive responses to chronic hypoxia can vary considerably between small and large arteries, and also between immature and adult arteries . Still, the present data clearly demonstrate that both the endothelium and vascular smooth muscle of major arteries are profoundly influenced by chronic hypoxia, and thereby participate fully in whole-body adaptation to reduced oxygen availability.

Animals↗
PubMed2003

Cardio-pulmonary interactions at high altitude. Pulmonary hypertension as a common denominator.

The purpose of this review is to find the evidence that a disproportionate pulmonary vasoconstriction persisting for days, weeks and years during residence at high altitude is the common pathophysiologic mechanism of high altitude pulmonary edema (HAPE), subacute mountain sickness and chronic mountain sickness. A recent finding in early HAPE suggests that transmission of excessively elevated pulmonary artery pressure to the pulmonary capillaries leading to alveolar hemorrhage as the pathophysiologic mechanism of HAPE. The elevated incidence of HAPE in Indian soldiers led the Indian Army to extend the acclimatization period from a few days to 5 weeks. Using this protocol, HAPE was prevented, but after several weeks of residence at an altitude of 6000m dyspnea, anasarca and pleuro-pericardial effusion developed. Clinical examination revealed severe congestive right heart failure. This condition has been previously described in long-term high altitude residents of the Himalaya and the Andes. In rats, smooth muscle cells appear in normally non-muscular arterioles within days of simulated altitude. Rapid remodeling of the small precapillary arteries may prevent HAPE but increase pulmonary vascular resistance leading to pulmonary hypertension in long-term high altitude residents. Symptoms and signs of HAPE, subacute mountain sickness and chronic mountain sickness reverse completely after residents are transfered to low altitude. In conclusion, these findings strongly suggest that pulmonary hypertension at high altitude, which could be named "high altitude pulmonary hypertension", is the principal and common pathogenic factor of all three cardio-pulmonary manifestations of high altitude illness. Accordingly, subacute mountain sickness and chronic mountain sickness could be renamed in "acute-" and "chronic right heart failure of high altitude", respectively.

Altitude↗
PubMed1999

Are arterial, muscle and working limb lactate exchange data obtained on men at altitude consistent with the hypothesis of an intracellular lactate shuttle?

The "Lactate Shuttle" Hypothesis posits that lactate removal requires exchange among producing and consuming cells. The "Intra-cellular Lactate Shuttle" hypothesis posits that lactate exchange occurs among compartments within cells, and that mitochondria are the major sites of cellular lactate disposal. Thus, cells with high mitochondrial densities (cardiocytes, myocytes, hepatocytes) are those which participate in lactate clearance. The model of an Intracellular Lactate Shuttle recognizes that the Keq for LDH is 3.6 x 10(4) M-1; thus, glycolysis results in cytosolic lactate production regardless of the intracellular PO2. The model also requires presence of a mitochondrial monocarboxylate transporter (MCT) that allows uptake of lactate as well as pyruvate, and intra-mitochondrial LDH whose function is linked to the ETC, and which permits lactate-->pyruvate conversion and oxidation. Recently, we have shown that liver, heart and muscle mitochondria readily oxidize lactate and contain LDH and MCT1. Accordingly, we have concluded that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. The model of an "Intra-cellular Lactate Shuttle" is consistent with many of the observations on men at sea level and altitude. The observations include: oxidation is the primary fate of lactate disposal during rest and exercise; lactate production and oxidation occur simultaneously within resting and working muscle; increasing [lactate]a increases muscle lactate extraction, and that by increasing SaO2 acclimatization reduces blood [lactate].

Animals↗
PubMed2001

Weight loss at high altitude.

Loss of appetite and weight are frequently observed at altitudes above 5000 m. However, the pathophysiology behind changes in body composition at extreme altitude is still not fully understood. Proper acclimatization to altitude and high caloric intake minimizes, but can not completely prevent significant weight loss under the influence of hypobaric hypoxia. The discovery of leptin in 1994 has initiated a new research area investigating molecular networks that connect peripheral organs with the central nervous system to sense and regulate energy intake as well as energy expenditure. Since then, a whole microcosm of new hormones, neurotransmitters and receptors has been discovered and studied with respect to body weight control. Those agents include neuropeptide Y (NPY), agouti-related protein (AGRP), melanocortin receptors (MC-R), cocaine-amphetamine regulated transcript (CART), pro-opiomelanocortin (POMC), orexin A and B (hypocretins), melanin-concentrating hormone (MCH) and ghrelin (endogenous ligand of the growth hormone secretagogue receptor). This overview will introduce the current concepts of the molecular control of energy homeostasis and attempt to reexamine the effects of altitude on appetite and body composition in light of these concepts. An overview of studies on changes of appetite and body composition at high altitude will be followed by the presentation of recent data on changes of endocrine parameters at hypobaric hypoxia that could be involved in the pathophysiology of weight loss.

Altitude↗
PubMed2001

Genetic lessons from high altitude.

What lessons can we learn from mountain sickness or wellness that may apply to our patients? Does hypoxia affect us similarly regardless of its cause? Millions of individuals are as hypoxic from congenital or acquired heart or lung disease as healthy individuals may be at altitude. Certain adjustments enable many of such patients to lead nearly normal lives. I will compare their adjustments to those seen in the acclimatization of healthy persons to altitude. Some living organisms use strategies which enable them to tolerate a degree of hypoxia lethal to man. Are there lessons we can learn from them? In my short talk I will raise a few provocative questions, and these will lead me to discuss the relevance of basic research to the resolution of vexing human ailments. When does commercialization of research become a form of intellectual prostitution?

Altitude↗
PubMed1991

Cold prevents the light induced inactivation of pineal N-acetyltransferase in the Djungarian hamster, Phodopus sungorus.

In the Djungarian hamster seasonal acclimatization is primarily controlled by photoperiod, but exposure to low ambient temperature amplifies the intensity and duration of short day-induced winter adaptations. The aim of this study was to test, whether the pineal gland is involved in integrating both environmental cues. Exposure of hamsters to cold (0 degrees C) reduces the sensitivity of the pineal gland to light at night and prevents inactivation of N-acetyltransferase (NAT). The parallel time course of NAT activity and plasma norepinephrine content suggests that circulating catecholamines may stimulate melatonin synthesis under cold load.

Acetyltransferases↗
PubMed1989

Demonstration of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the salt gland of the Pekin duck.

A novel peptide hormone, atrial natriuretic factor/cardiodilatin (ANP/CDD), was recently isolated and characterized from mammalian heart. Its presence has been demonstrated in several organs that contribute to water and sodium homeostasis, such as salivary glands. This study demonstrates the presence of ANP/CDD immunoreactivity in the salt gland of Pekin ducks by high performance liquid chromatography, radioimmunoassay and immunocytochemistry, using a specific antibody against atriopeptide I. A small number of distinct, ovoid or cuboid shaped ANP/CDD-immunoreactive cells were localized in the connective tissue surrounding and separating the central secretory tubules, whereas no immunostaining was observed in the peripheral tubules. Salt glands of ducks that were adapted to salt water revealed a significant hypertrophy of their secretory lobules. However, no differences were found between the number or localization of immunoreactive cells in the salt gland of salt water-acclimatized ducks and nonstimulated glands of ducks that were housed with ad libitum access to fresh water. Our results indicate that ANP/CDD may play a role in the regulation of sodium secretion in the salt gland of aquatic birds.

Animals↗
PubMed1976

The manipulation of circadian rhythms.

In a study on male Wistar (TNO) rats kept under phase-shifted light-dark (12:12) conditions, it was demonstrated that the circadian rhythms of the following functions were effectively synchronized to the new lighting regimen: (a) body temperature, gross motor activity (after 1 week of acclimatization); (b) stomach weight, liver weight, liver glycogen, liver protein and acid phosphatase activity; serum corticosterone, glucose, total protein and inorganic phosphatase (after 4-6 weeks; as concluded from the data pooled of a sex of identical experiments); (c) the in vivo toxicity of approximately LD50 amounts (i.p.) for antimycin A and of E 600. In the individual experiments the various normal functions appeared to be different with respect to sensitivity to light. The overall pooled results indicated that, except for glycogen, the 24-h means of the normal values in the stomach, liver and serum were slightly decreased when compared to the respective means obtained from standard LD (= light: 6:00-18:00)-conditioned control groups (P less than 0.001 for liver weight, liver protein, serum protein and inorganic phosphate). The experimental animals revealed an intermediate or persisting decrease of the growth rate. From the serial biological and toxicological studies performed in the course of 1 year, it is concluded that the synchronizing effect of an altered lighting regiment may be influenced by seasonal factors...

Animals↗
PubMed1993

Responses to whole body and finger cooling before and after an Antarctic expedition.

Eight subjects, who were indoor workers and not habitually exposed to cold, spent 53 days in Antarctica. They did mainly geological field work often requiring the use of bare hands. The effects of the expedition on responses to a whole body cold exposure test, a finger blood flow test and a cold pressor test were studied. After the expedition, during whole-body cooling the time for the onset of shivering was delayed by 36 min (P < 0.001) and forearm and thigh temperatures were 1.5 degrees C higher (P < 0.05) at the end of exposure. During local cooling of the finger with 10 degrees C perfusion, finger vascular resistance was 14.9 (SEM 6.6) mmHg.ml-1.min.100 ml (P < 0.05) lower and finger temperature 3.9 (SEM 0.8) degrees C higher (P < 0.01). However, the decrease in rectal temperature during whole-body cooling was unaltered and the response to a cold pressor test was unchanged. The data would indicate that partial acclimatization to cold had been developed. Changes in forearm temperature were correlated with the duration of cold exposure of the hands (P < 0.05) and finger vascular resistance and finger temperature were correlated with responses to cooling before the expedition (P < 0.001 and P < 0.01, respectively). Because the ambient temperature was not clearly lower in Antarctica in comparison to Finland, the reason for the changes developed seems to be the increased exposure to the outdoor climate in Antarctica.

Adult↗
PubMed1980

Alterations in aerobic-anaerobic proportions of metabolism during work in heat.

With a view to investigating the aerobic and anaerobic proportions of oxygen supply during different grades of muscular activity in varying thermal stress, studies have been conducted on six young healthy Indians naturally acclimatized to heat. The subjects were given submaximal exercises of 400, 500, and 600 kgm/min (equivalent to 65.40, 81.75, and 98.10 W) for 6 min on a bicycle ergometer in three different simulated conditions, i.e., comfortable, hot humid, and very hot humid. Their O2 consumption (VO2), pulmonary ventilation (VE) and heart rate (HR) were measured during rest and throughout the exercise period (6 min) and for 30 min post exercise. Blood lactate level (LA) was measured during rest and recovery. From these, the total O2 cost with aerobic and anaerobic proportions were calculated. Results indicated a significant increase in the total O2 cost for each exercise with increasing thermal stress, along with a significant increase in the anaerobic fraction and a decrease in the aerobic fraction. The increase in anaerobic contribution to the energy supply processes was further confirmed by a significant increase in relative O2 debt (l/kg) and in blood lactate level at each work load. Thus, a highly significant correlation (P < 0.001) was found between O2 debt contracted and increase in thermal stress. A significant fall in VO2 max was also observed in hot humid and very hot humid conditions as against comfortable temperature, with no change in HR max and VE max.

Adult↗
PubMed1975

Temperature, time, and the influence of volatiles on phialospore germination in Verticillium malthosei Ware.

Phialospores of verticillium malthousei Ware were atomized onto acclimatized water agar and incubated for 3, 6, 9, 12, and 24 hr at 12 to 36 degrees C intervals. Germination occurred at all temperatures exclusive of 36 degrees C with maximum germination (90-98%) occurring in 24 hr at 12 degrees C, 12 degrees C, 12 HR at 18 degrees C, 9 hr at 24 degrees and 30 degrees C. Volatiles from: 1) horse manure compost colonized by Agaricus bisporus; 2) mycellium impregnated casing (soil); or 3) casing supporting mature and immature mushrooms had no statistically significant effect on spore germination of V. malthousei when measured after 12 hr at 24 degrees C. However, a tendency towards inhibition after 6 and 12 hr at 24 degrees and 12 degrees C, respectively, suggests the inhibition is temperature and time dependent. This dependency was noted with two substrates, colonized compost and casing which supported sporocarps.

Agaricales↗
PubMed1983

Thyroid state and mitochondrial population during cold exposure.

Young rats exposed to the cold (4 degrees C) for 15-25 days exhibit remarkable modifications in their thyroid state and in the mitochondrial population of target organs such as liver. The serum total and free T3 levels more or less doubled (from 77 +/- 7 to 130 +/- 7 ng/100 ml and from 350 +/- 25 to 530 +/- 25 pg/100 ml, respectively) after 2 h of exposure while the serum total T4 levels underwent a limited and transitory increase; mitochondrial alpha-glycerophosphate dehydrogenase activity increased. On re-exposure to room temperature the thyroid state returned to normal. Cold exposure diminished the cellular volumes of hepatic cells, while the successive warm re-exposure increased the number of liver cells. The number of mitochondria per nucleus increased after 5 days of cold exposure and doubled after 10 days (from 1,200 +/- 120 to 2,400 +/- 130), while the mean protein content per organelles exhibited an exactly contrary trend. These results suggest that during cold acclimatization, the thyroid, the thyroid plays a role in inducing an augmentation of mitochondrial membrane surfaces per cell by stimulation of the mitochondrial protein synthesizing mechanism. At present, it is not possible to establish whether these effects are due to transcriptional modifications of the nuclear genome only or, more likely, to a dual action at nuclear and mitochondrial level.

Animals↗
PubMed1991

Convertible adipose tissue in mice.

Ability to express uncoupling protein (UCP) and establish UCP-dependent thermogenesis was analyzed in anatomical areas of mice that are generally considered to be white adipose tissue: mesenterial, perimetral, epididymal, inguinal, and superficial layer of interscapular white adipose tissue. The mice were acclimatized for 1 week to 4 degrees C; the following week they were exposed to cold stress (1 h at -20 degrees C, 2-3 times daily). In such conditions in inguinal adipose tissue, slot-blot analysis detected significant amount of UCP mRNA and lipoprotein lipase mRNA. Immuno-electron-microscopic localization of UCP showed that developed mitochondria of cold-stressed inguinal adipocytes contained UCP in the same amount as uncoupled (UC)-mitochondria of brown adipocytes. Morphological and morphometrical analysis showed that such inguinal adipose tissue appeared as brown adipose tissue. Since in control mice, inguinal adipose tissue was UCP-negative and tissue appeared as white adipose tissue, the duration of this white-to-brown adipose tissue conversion was analyzed. Mice, cold stressed for 1 week, were rewarmed at 28 degrees C and their inguinal adipose tissue was analyzed in comparison with interscapular brown adipose tissue and epididymal white adipose tissue for another 37 days. During that time inguinal adipocytes ceased expressing UCP mRNA; UC-mitochondria in inguinal adipocytes were destroyed and replaced with common, C-mitochondria; and UCP was undetectable immunohistochemically. Adipocytes accumulated lipids, and the tissue morphologically once again resembled white adipose tissue. Described changes showed that besides typical brown and white adipose tissue in mice, there existed a third type of adipose tissue described as convertible adipose tissue.

Adipose Tissue↗
PubMed1987

Thermal stress and physiological strain in the glass bangle industry.

A preliminary survey of the few units of the small-scale glass bangle industry in Firozabad, Agra District, Uttar Pradesh, indicated that the workers were exposed to severe degrees of heat stress during various operations in the manufacturing processes. A more detailed study in eight glass bangle units was therefore undertaken to make quantitative estimates of heat stress on exposed workers in the summer season. The thermal data collected confirmed that the heat stress on the workers was severe but measurement of certain physiological indicators revealed relatively low levels of strain amongst the exposed workers. The findings could be attributable to high degrees of acclimatization, but further observations in the field supplemented by studies on simulated exposures of volunteers in a climatic chamber seem to be warranted.

Adolescent↗
PubMed1987

Effect of photoperiod and melatonin on cold resistance, thermoregulation and shivering/nonshivering thermogenesis in Japanese quail.

The effect of photoperiod and melatonin treatment on cold resistance and thermogenesis of quails was studied. The birds were acclimated for 8 weeks to short day (8L:16D) or long day (16L:8D) conditions, and 8 of 16 quails in each group were implanted with melatonin capsules. One group of quails was maintained outside in an aviary during winter. Oxygen consumption (VO2), body temperature (Tb, recorded with temperature transmitters) and shivering (integrated pectoral EMG) were recorded continuously, and samples of heart rate and breathing rate were picked up when ambient temperature was decreased stepwise from 27 down to -75 degrees C. Heat production maximum (HPmax), cold limit, lower critical temperature, basal metabolic rate (BMR) and thermal conductance were determined. The results show that short day, cold and melatonin treatment improved cold resistance and thermal insulation of quails when compared with quails acclimated to long day conditions. An increase in HPmax was induced only by melatonin treatment. The results suggest that the acclimatization of quails is under control of the pineal gland. The linear increase of shivering intensity with VO2 at moderate cold load shows that shivering is the primary source for thermoregulatory heat production in the quail. At Ta's below -40 degrees C shivering remained constant although VO2, heart rate and breathing rate continued to increase with increasing cold load. This could indicate the existence of a nonshivering thermogenesis in birds. Unlike to mammals, this non-shivering thermogenesis in birds would serve as secondary source of heat supporting shivering thermogenesis in severe cold.

Animals↗
PubMed1994

Interactive effects of temperature and photoperiod on the daily activity and energy metabolism of pouched mice (Saccostomus campestris: Cricetidae) from southern Africa.

The daily activity and energy metabolism of pouched mice (Saccostomus compestris) from two localities in southern Africa was examined following warm (25 degrees C) and cold (10 degrees C) acclimation under long (LD 14:10) and short (LD 10:14) photoperiod. There was no differential effect of photoperiod on the daily activity or metabolism of pouched mice from the two localities examined, which suggests that reported differences in photoresponsivity between these two populations were not the result of differences in daily organisation. Nevertheless, there was a significant increase in metabolism at 10 degrees C, irrespective of photoperiod, even though seven cold-acclimatized animals displayed bouts of spontaneous torpor and saved 16.4-36.2% of their daily energy expenditure. All but one of these bouts occurred under short photoperiod, which suggests that short photoperiod facilitated the expression of torpor and influenced the daily energy metabolism of these individuals. As expected for a nocturnal species, the amount of time spent active increased following acclimation to short photoperiod at 25 degrees C. However, there was a reduction in mean activity levels under short photoperiod at 10 degrees C, possibly because the stimulation of activity by short photoperiod was masked by a reduction in activity during bouts of spontaneous torpor. Cold temperature clearly had an overriding effect on the daily activity and metabolism of this species by necessitating an increase in metabolic heat production and eliciting spontaneous torpor which over-rode the effect of short photoperiod on activity at an ambient temperature of 10 degrees C.

Activity Cycles↗