Thirst and artificial heat acclimatization in man

The purpose of this study was to investigate the relationship between serum osmotic changes, water intake and water balance in four, fit young men during and after exercise in the heat, before and after artificial heat acclimatization. During exercise, before steady-state conditions were reached, voluntary water intakes generally paralleled but were not proportional to the serum osmotic pressure. In steady-state conditions, drinking was approximately proportional to the effective osmotic pressure of the serum. During the post-exercise recovery period, when serum osmolarity returned to normal levels, water intake also subsided even though there was a total body water (wt) deficit of about 3%. Body weight did not return to control levels until 62 to 86 hr following the exercise. This slow recovery could not be accounted for by a loss of water associated with glycogen utilization during exercise or by sweat electrolyte depletion. In general, the results supported Dill's hypothesis but plasma volume changes, in addition to osmotic factors,are very likely operative in the initiation and satiation of drinking under these conditions. Perhaps slower acting volume control mechanisms mediate the slow recovery of total body water.

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Zusammenfassung Untersucht wurde die Beziehung zwischen osmotischen Veränderungen im Serum, Wasseraufnahme und Wassergleichgewicht bei 4 gesunden,jungen Männern während und nach körperlicher Arbeit in der Hitze vor und nach künstlicher Hitzeakklimatisation. Die freiwillige Wasseraufnahme während der Arbeit, ehe ein steady state erreicht wurde, war im allgemeinen gleichlaufend, aber nicht proportional dem osmotischen Serumdruck. Im steady state war die Trinkmenge ungefähr proportional dem effektiven osmotischen Serumdruck. Wenn die Serumosmolarität während der Erholungsphase zur normalen Werten zurückkehrte, liess die Wasseraufnahme ebenfalls nach,obwohl das Gesamtkörperwasserdefizit ungefähr 3% betrug.Die Körpergewichte erreichten die Ausgangswerte 62–86 Std nach der Arbeit. Diese langsame Erholung war nicht bedingt durch einen Wasserverlust dur Glykogenverwertung während der Arbeit oder durch Elektrolytverluste beim Schwitzen. Die Ergebnisse stützen Dill's Hypothese, doch unter diesen Bedingungen wirken Plasmavolumen-Veränderungen zusätzlich zu osmotischen Faktoren sehr wahrscheinlich mit bei der Auslösung des Trinkens und der Sättiging mit Wasser. Vielleicht vermitteln langsamer wirkende Volumenkontrollmechanismen die langsame Wiederherstellung der Gesamtkörper-Wasservorräte.

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Resume On a examiné les relations existant chez 4 jeunes hommes sains entre les variations de la pression osmotiques du sérum d'une part,l'ingestion d'eau et l'équilibre acqueux du corps d'autre part et cela pendant et après un travail corporel à la chaleur tant avant qu'après une acclimatisation artificielle au chaud.L'ingestion volontaire d'eau évolue similairement à la pression osmotique du sérum, mais ne lui est pas proportionnel. Ce phénomène s'observe jusqu'à ce qu'un état dit stationnaire soit atteint. Dès ce moment, les quantités bues sont à peu près proportionnelles à la pression osmotique effective. Pendant la phase de récupération, la pression osmotique redevient normale et l'eau ingérée diminue bien que le déficit en eau pour le corps entier soit encore de 3% environ.Le poids du corps ne retrouve sa valeur initiale que 62 à 86 heures après la période de travail. Ce lent rétablissement n'est pas dû à des pertes d'eau par suite de l'utilisation de glycogènes pendant l'exercice ou par suite de la perte d'électrolytes par la sueur. Ces résultats viennent confirmer les hypothèses de Dill. Pourtant, dans ces conditions, les variations de volume du plasma agissent très vraisemblablement en plus des facteurs osmotiques dans le besoin de boire ou l'état de satiété. Il est possible que des mécanismes de contrôle du volume agissant plus lentement président aux phénomènes de rétablissement des réserves en eau dans son ensemble.

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Results were presented in part at the "Symposium on Nutrition and Physical Activity", The Swedish Nutrition Foundation, Tylösand, Sweden, 15–17 August,1966.     

Effects of protein malnutrition and ascorbic acid levels on drug metabolism

The duration of action of drugs (or other environmental chemicals) is dependent on their rate of metabolic deactivation and elimination from the body. Termination of activity is achieved either through excretion of the drug via the kidney and bile or, more commonly, through metabolic deactivation by enzymes of the liver and other tissues. In recent years, it has become increasingly obvious that nutritional status is one of the major factors capable of modifying the pharmacological effect of drugs. Numerous studies have indicated that the process of drug metabolism may be affected by acute starvation, undernutrition, protein nutrition, and deficiencies of minerals, vitamins, and lipids. Although most of the evidence concerning the effects of nutrition on the metabolism of drugs has been derived from studies on experimental animals, there is significant fragmentary human data to show that the same effects may occur in man. This paper will discuss the influence of nutritional status with particular references to protein and ascorbic acid on the metabolism of foreign compounds including drugs. The interrelationships of nutrition and the metabolism of drugs are an important consideration in view of the widespread recurrence of primary malnutrition in the developing countries, and of secondary malnutrition in more affluent societies, especially in debilitated chronically ill patients, in postoperative patients, and in those whose dietary manipulations are carried out in weight-reducing regimens. The effects of nutrition on drug metabolism may be viewed as an extension of the search for one of the environmental factors that modify drug action.     

Effects of bromocriptine on sweat gland function during heat acclimatization

This study examined the involvement of the hormones aldosterone and prolactin in sweat gland function during heat acclimatization. Two groups of male subjects (n = 8) were tested - one receiving a placebo (control), the other receiving bromocriptine. Both groups performed cycle ergometer exercise at 50% of maximal oxygen uptake over 10 consecutive days in an environmental chamber maintained at 39 degrees C and 30% relative humidity. Duration of exercise was 90 min on days 2-4 and 6-9, and 45 min on test days 1, 5 and 10. Electrolyte concentrations were determined by total body washdown. Prolactin increased (p less than 0.001) during exercise on day 1 in the control group but not on days 5 and 10. In contrast, prolactin was suppressed by bromocriptine and did not rise in response to exercise or heat exposure. Plasma aldosterone increased during exercise in both groups, showing no differences between groups. The sodium concentration in sweat decreased significantly (p less than 0.05) in the control group from day 1 to 10 but was unchanged in the treatment group. These data suggest that acclimatization-related changes in sweat gland function may be attenuated by increases in central dopaminergic activity and implicate prolactin in control of sweat gland function.     

LacaScore: a novel plasma sample quality control tool based on ascorbic acid and lactic acid levels

Introduction

Metabolome analysis is complicated by the continuous dynamic changes of metabolites in vivo and ex vivo. One of the main challenges in metabolomics is the robustness and reproducibility of results, partially driven by pre-analytical variations.

Objectives

The objective of this study was to analyse the impact of pre-centrifugation time and temperature, and to determine a quality control marker in plasma samples.

Methods

Plasma metabolites were measured by gas chromatography-mass spectrometry (GC–MS) and analysed with the MetaboliteDetector software. The metabolites, which were the most labile to pre-analytical variations, were further measured by enzymatic assays. A score was calculated for their use as quality control markers.

Results

The pre-centrifugation temperature was shown to be critical in the stability of plasma samples and had a significant impact on metabolite concentration profiles. In contrast, pre-centrifugation delay had only a minor impact. Based on the results of this study, whole blood should be kept on wet ice and centrifuged within maximum 3 h as a prerequisite for preparing EDTA plasma samples fit for the purpose of metabolome analysis.

Conclusions

We have established a novel blood sample quality control marker, the LacaScore, based on the ascorbic acid to lactic acid ratio in plasma, which can be used as an indicator of the blood pre-centrifugation conditions, and hence the suitability of the sample for metabolome analyses. This method can be applied in research institutes and biobanks, enabling assessment of the quality of their plasma sample collections.

     

Effects of heat on drug action in man

The pharmacological actions of many drugs may become altered as a result of physiological reactions in persons exposed to heat. With pyrexia due to inadequate thermoregulation an increase in the rate of chemical reaction and drug metabolism may affect the activity of a diverse group of substances including digitalis, caffeine, alcohol, dicumarol and the shorter acting barbiturates. Water and electrolyte disturbances can affect the responses to vaso-active drugs, diuretics and the cardiac glycosides. Unacclimatized subjects in heat tend to be hypersensitive to the actions of thyroxine and norepinephrine. A decrease in the glomerular filtration rate may decrease the clearance of drugs that are not metabolized within the body, thus increasing activity and toxicity.

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Zusammenfassung Die pharmakologische Wirkung vieler Medikamente kann als Folge der physiologischen Reaktionen von Personen bei Hitzeexponierung verändert werden.Bei Pyrexie als Folge unzureichender Wärmeregulation kann der Anstieg der Reaktionsgeschwindigkeit der chemischen Prozesse und des Medikamenten-Stoffwechsels die Aktivität verschiedener Gruppen von Medikamenten, z.B. Digitalis, Koffein, Alkohol, Dicumarol und kurz wirkende Barbiturate, beeinflussen. Wasser- und Elektrolytstörungen können die Reaktion auf gefässaktive Substanzen, Diuretika und Herzglykoside beeinflussen.Nichtakklimatisierte Personen in der Hitze neigen zu Überempfindlichkeit auf Thyroxin und Noradrenalin. Die Verminderung der Glomerulus-Filtrationsrate kann die Ausscheidung von den im Körper nicht abgebauten Medikamenten verzögern und zum Anstieg ihrer Aktivität und Toxizität führen.

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Resume Chez les sujets exposèa la chaleur, l'effet pharmacologique de bien des médicaments peut être modifié par suite de réactions physiologiques. Dans le cas de pyrexie due à une insuffisance de la thermo-régulation, on peut constater une accélération de la vitesse de réaction des processus chimiques et du métabolism des médicaments. De ce fait, l'activité d'un certain groupe de médicaments tels que la digitale, la caféine, l'alcool, le décumarol et les barbituriques à effet bref se trouve modifié. Des perturbations dand le bilan de l'eau et des électrolytes peuvent influencer la réaction de l'individu aux substances régissant les fonctions vasculaires, diurétiques, glycoside cardiaques. Les sujets non acclimatés au chaud sont généralement très sensibles à l'action de la thyroxine et de la noradrénaline. La diminution du taux de filtration glomérulaire peut retarder l'élimination de médicaments non absorbés par le métabolism du corps et conduire à une augmentation de leur activité et de leur toxicité.

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Presented during the Fourth International Biometeorological Congress at Rutgers, The State University, New Brunswick, New Jersey, 26 August – 2 September 1966.