Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans

In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg^?1 min^?1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 ± 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 ± 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 ± 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 ± 6% (P < 0.001) and 20 ± 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.     

Albumin infusion in humans does not model exercise induced hypervolaemia after 24 hours

We rapidly infused 234 ± 3 mL of 5% human serum albumin in eight men while measuring haematocrit, haemoglobin concentration, plasma volume (PV), albumin concentration, total protein concentration, osmolality, sodium concentration, renin activity, aldosterone concentration, and atrial natriuretic peptide concentration to test the hypotheses that plasma volume expansion and plasma albumin content expansion will not persist for 24 h. Plasma volume and albumin content were expanded for the first 6 h after infusion (44.3 ± 1.9–47.2 ± 2.0 mL kg^?1 and 1.9 ± 0.1–2.1 ± 0.1 g kg^?1 at pre-infusion and 1 h, respectively, P < 0.05), but by 24 h plasma volume and albumin content decreased significantly from 1 h post-infusion and were not different from pre-infusion (44.8 ± 1.9 mL kg^?1 and 1.9 ± 0.1 g kg^?1, respectively). Plasma aldosterone concentration showed a significant effect of time over the 24 h after infusion (P < 0.05), and showed a trend to decrease at 2 h after infusion (167.6 ± 32.5^?1 06.2 ± 13.4 pg mL^?1, P = 0.07). These data demonstrate that a 6.8% expansion of plasma volume and 10.5% expansion of plasma albumin content by infusion does not remain in the vascular space for 24 h and suggest a redistribution occurs between the intravascular space and interstitial fluid space.     

Potential association between endogenous leptin and sympatho‐vagal activities in young obese Japanese women

Leptin is an adipocyte‐derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho‐vagal activities in age‐ and height‐matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 ± 5.89 vs. 11.2 ± 1.10 ng · ml^?1, P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 ± 1.39 vs. 37.8 ± 8.1 ms² · ml · ng^?1, P < 0.01; SNS index per leptin: 0.04 ± 0.008 vs. 0.33 ± 0.01 ml ?· ng^?1, P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r² = 0.57, P < 0.01; SNS index per leptin r² = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced. Am. J. Hum. Biol. 15:8–15, 2003. © 2002 Wiley‐Liss, Inc.     

Influences of a dietary supplement in combination with an exercise and diet regimen on adipocytokines and adiposity in women who are overweight

The influence of a proprietary blend of modified cellulose and cetylated fatty acids (Trisynex™, Imagenetix, Inc., San Diego, CA 92127, USA) on adipocytokine and regional body composition responses to a weight loss program was examined. Twenty-two women (Supplement group (S) (n = 11): age = 36.8 ± 7.2 years; weight = 87.1 ± 6.2 kg; % body fat = 43.4 ± 4.1; Placebo group (P) (n = 11): age = 38.3 ± 6.8 years; weight = 86.9 ± 4.7 kg; % body fat = 44.3 ± 2.0) completed an 8-week placebo-controlled, double-blind study consisting of a caloric restricted diet and cardiovascular exercise. Body composition and serum insulin, leptin, and adiponectin were assessed at pre-, mid-, and post-intervention. From pre- to post-intervention, significant decreases (P < 0.05) were observed for body weight (S: 87.1 ± 6.2–77.9 ± 5.1 kg; P: 86.9 ± 4.7–82.7 ± 3.8 kg) (P < 0.05 S vs. P), % body fat (S: 43.4 ± 4.1–36.1 ± 3.6; P: 44.3 ± 2.0–40.6 ± 1.2) (P < 0.05 S vs. P), leptin (S: 28.3 ± 3.5–16.2 ± 2.6 ng ml⁻¹; P: 29.4 ± 3.2–19.9 ± 1.1 ng ml⁻¹) (P < 0.05 S vs. P), and insulin (S: 7.3 ± 0.8–5.1 ± 0.2 mU l⁻¹; P: 7.7 ± 0.9–5.1 ± 0.3 mU l⁻¹). Serum adiponectin increased (P < 0.05) (S: 12.2 ± 2.4–26.3 ± 3.0 μg ml⁻¹: 12.6 ± 2.0–21.8 ± 3.1 μg ml⁻¹) (P < 0.05 for S vs. P). Supplementation with a proprietary blend of modified cellulose and cetylated fatty acids during an 8-week weight loss program exhibited favorable effects on adipocytokines and regional body composition.     

Muscle mechanical characteristics in fatigue and recovery from a marathon race in highly trained runners

The aim of the present study was to examine muscle mechanical characteristics before and after a marathon race. Eight elite runners underwent a pre-test 1 week before the marathon and post-tests 30 min, two and five-day-post-marathon. Actual marathon race performance was 2:34:40 ± 0:04:13. Energy expenditure at marathon pace (EE_Mpace) was elevated 4% post-marathon (pre: 4,465 ± 91 vs. post 4,638 ± 91 J kg bodyweight⁻¹ km⁻¹, P < 0.05), but was lowered by 6 and 9.5% two- and five-day-post-marathon compared to EE_Mpace pre-marathon. Countermovement jump (CMJ) power decreased 13% post-marathon (pre: 21.5 ± 0.9 vs. post: 18.9 ± 1.2 W kg⁻¹; P < 0.05) and remained depressed two- (18%) and five-day (12%) post-marathon. CMJ force was unaltered across all four tests occasions. Knee extensor and plantar flexor maximal voluntary contraction (MVC) decreased from 176.6 ± 9.5 to 136.7 ± 16.8 Nm and 144.9 ± 8.7 to 119.2 ± 15.1 Nm post-marathon corresponding to 22 and 17%, respectively (P < 0.05). No significant changes were detected in evoked contractile parameters, except a 25% increase in force at 5 Hz, and low frequency fatigue was not observed. In conclusion, leg muscle power decreased acutely post-marathon race and recovered very slowly. The post-marathon increase in EE_Mpace might be attributed to a reduction in stretch shortening cycle efficiency. Finally, since MVC was reduced after the marathon race without any marked changes in evoked muscle contractile properties, the strength fatigue experienced by the subjects in this study seems to be related to central rather than peripheral mechanisms.     

Growth hormone and prolactin responses during partial and whole body warm‐water immersions

Aim: To elucidate the role of core and skin thermoreceptors in the release of growth hormone (GH) and prolactin (PRL), a sequence of two experiments using whole‐body (head‐out) and partial (one forearm) hot water immersions was performed. Methods: Experiment 1: Nine healthy men were exposed to head‐out and partial water immersions (25 min, 38–39 °C). Results: Head‐out immersion increased the core temperature (38.0 ± 0.1 vs. 36.7 ± 0.1 °C, P < 0.001) and plasma concentration of the hormones (GH, 16.1 ± 4.5 vs. 1.2 ± 0.4 ng mL^?1, P < 0.01; PRL, 9.1 ± 1.0 vs. 6.4 ± 0.4 ng mL^?1, P < 0.05). During the partial immersion the core temperature was slightly elevated (36.8 ± 0.1 vs. 36.6 ± 0.1, P < 0.001), the concentration of GH increased (4.8 ± 1.7 vs. 0.6 ± 0.3, P < 0.05), while plasma PRL decreased (7.6 ± 0.8, 6.0 ± 0.6, 5.2 ± 0.6, P < 0.01). Experiment 2: Seven volunteers immersed one forearm once in 39 °C and once in 38 °C water. The measurements were performed in 5‐min intervals. The GH concentration increased gradually from the beginning of the immersions (min 10; 39 °C: 1.9 ± 1.0 vs. 0.6 ± 0.3 ng mL^?1, P < 0.01; 38 °C: 0.19 ± 0.03 vs. 0.14 ± 0.03, P < 0.05) and peaked after their completion (39 °C: +10 min, 3.7 ± 2.0, P < 0.001; 38 °C: +15 min, 0.86 ± 0.61, P < 0.01). The core temperature was unchanged until min 15 of the 39 °C bath. Thereafter, it increased about 0.15 °C above the baseline (P < 0.01). Immersion in 38 °C water did not induce core temperature changes. Conclusions: Peripheral thermoreceptors are involved in GH release when the body is exposed to elevated environmental temperature while a substantial elevation of core temperature is a precondition of PRL release.     

Contrasting effects of platelet-derived growth factor (PDGF) isomers on mitogenesis,contraction and intracellular calcium concentration in human vascular smooth muscle

The present study was aimed at characterizing the responses of human vascular smooth muscle to all three dimeric isomers of platelet-derived growth factor (PDGF-AA, -AB and –BB) in terms of mitogenesis, contraction and intracellular calcium concentration. The potential of interaction between PDGF and endothelin-1 (ET-1) was also investigated. All three PDGF isoforms (0.1–20 ng mL^?1) stimulated DNA synthesis in cultured human coronary artery and saphenous vein vascular smooth muscle cells (VSMC), measured by [³H]thymidine incorporation. PDGF-AB and -BB elicited comparable large increases in DNA synthesis of maximum 595 ± 149% (P = 0.001, n = 9) and 576 ± 17% (P < 0.001, n = 5), respectively, whereas PDGF-AA was only weakly mitogenic (61 ± 16% increase; P < 0.05, n = 3). At a threshold concentration, PDGF acted in synergy with ET-1 to enhance DNA synthesis (816 ± 337% increase; P < 0.05, n = 7). In contrast to mitogenesis, none of the three PDGF isomers had any effect on contraction of human saphenous veins in vitro, nor did they affect the contractile response to ET-1, 5-HT or the thromboxane mimetic U46619. The effects of the three PDGF isomers on intracellular calcium ([Ca²⁺]_i) rises in cultured human VSMC were heterogeneous, with PDGF-BB inducing the largest increase in [Ca²⁺]_i (442 ± 53 nmol L^?1) vs. PDGF-AB (290 ± 28 nmol L^?1), whilst PDGF-AA had no effect. Both the responses to PDGF-AB and -BB relied upon intracellular calcium release, whilst only PDGF-AB showed additional dependence on influx of extracellular calcium. In summary, PDGF is strongly mitogenic and comitogenic with ET-1, despite not being a vasoconstrictor, for human VSMC. Also, human VSMC showed heterogeneous responses to the three PDGF isoforms. These results implicate PDGF, and in particular the PDGF receptor-β, as important role players in the development of vascular smooth muscle-mediated intimal thickening in humans.     

Plasma leptin and insulin in C57Bl/6J mice on a high-fat diet: relation to subsequent changes in body weight

It has been proposed that leptin and insulin through central effects are involved in the regulation of energy balance and body weight. Whether circulating leptin or insulin levels predict subsequent changes in body weight is, however, not known. We examined plasma leptin and insulin at 2, 3, 6, 9 and 12 months of age in C57Bl/6J mice given a normal diet (n = 12) or a high-fat diet (58% fat on a caloric base; n = 15). Plasma leptin levels increased by age and correlated with body weight in the entire material (r = 0.81, P < 0.001). Also plasma insulin increased by high-fat diet and correlated across all age periods with body weight (r = 0.56, P < 0.001). In mice, given normal diet, plasma leptin or insulin did not correlate to subsequent changes in body weight at any of the time points studied. However, in mice given the high-fat diet, plasma leptin at 6 (r = ?0.57, P = 0.027) and 9 months of age (r = ?0.56, P = 0.042) as well as plasma insulin at 6 (r = ? 0.51, P = 0.049) and 9 months (r = ?0.58, P = 0.037) correlated inversely to the change in body weight during the subsequent 3-month period. Hence, both leptin and insulin are negative predictors for future weight gain in high-fat fed mice. This suggests that when the regulation of body weight is challenged by a high-fat diet, leptin and insulin act to restrain or prevent future weight gain. This in turn may suggest that impairment of these (probably central) actions of leptin and insulin might underlie excessive increase in body weight under such conditions.     

Serial effects of high-resistance and prolonged endurance training on Na+–K+ pump concentration and enzymatic activities in human vastus lateralis

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na⁺–K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO _2peak = 45.3 ± 1.9 mL kg^?1 min^?1, mean ± SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO _2peak = 44.4 ± 6.6 mL kg^?1 min^?1, n = 7) cycled 5–6 times per week for 2 h day^?1 at 68% VO _2peak for 11 weeks. In the HRT group, Na⁺–K⁺ ATPase (pmol g^?1 wet wt), measured with the ³H-ouabain binding technique, showed no change from 0 (289 ± 22) to 4 weeks (283 ± 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 ± 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 ± 31) until 3 weeks (339 ± 29) with no further changes observed at either 9 weeks (345 ± 25) or 11 weeks (359 ± 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, β-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO _2peak, prolonged submaximal training increased VO _2peak by ≈15%. Only for prolonged exercise training was a relationship observed for VO _2peak and Na⁺–K⁺-ATPase (r = 0.59; P < 0.05). Correlations between VO _2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na⁺–K⁺ ATPase concentration, only the prolonged submaximal training programme enhances the potential for β-oxidation, oxidative phosphorylation and glucose phosphorylation.     

Contribution of pH,diprotonated phosphate and potassium for the reflex increase in blood pressure during handgrip

The relative importance of pH, diprotonated phosphate (H₂PO₄^?) and potassium (K⁺) for the reflex increase in mean arterial pressure (MAP) during exercise was evaluated in seven subjects during rhythmic handgrip at 15 and 30% maximal voluntary contraction (MVC), followed by post-exercise muscle ischaemia (PEMI). During 15% MVC, MAP rose from 92 ± 1 to 103 ± 2 mmHg, [K⁺] from 4.1 ± 0.1 to 5.1 ± 0.1 mmol L^?1, while the intracellular (7.00 ± 0.01 to 6.80 ± 0.06) and venous pH fell (7.39 ± 0.01 to 7.30 ± 0.01) (P < 0.05). The intracellular [H₂PO₄^?] increased 8.4 ± 2 mmol kg^?1 and the venous [H₂PO₄^?] from 0.14 ± 0.01 to 0.16 ± 0.01 mmol L^?1 (P < 0.05). During PEMI, MAP remained elevated along with the intracellular [H₂PO₄^?] as well as a low intracellular and venous pH. However, venous [K⁺] and [H₂PO₄^?] returned to the level at rest. During 30% MVC handgrip, MAP rose to 130 ± 3 mmHg, [K⁺] to 5.8 ± 0.2 mmol L^?1, the intracellular and extracellular [H₂PO₄^?] by 20 ± 5 mmol kg^?1 and to 0.20 ± 0.02 mmol L^?1, respectively, while the intracellular (6.33 ± 0.06) and venous pH fell (7.23 ± 0.02) (P < 0.05). During post-exercise muscle ischaemia all variables remained close to the exercise levels. Analysis of each variable as a predictor of blood pressure indicated that only the intracellular pH and diprotonated phosphate were linked to the reflex elevation of blood pressure during handgrip.     

Microsphere infusion reverses vasoconstrictor-mediated change in hindlimb oxygen uptake and energy status

The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 ± 0.1 μm, mean ± SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 ± 0.1 g muscle) oxygen uptake (V˙O ₂) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 × 10⁶) injected during vehicle, or 5-HT infusion increased V˙O ₂ (P < 0.05) but did not affect energy status. During AII, MS decreased V˙O ₂. Change in V˙O ₂ correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 × 10⁶) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 × 10⁶ microspheres were intensified by a second injection of 1.5 × 10⁶ microspheres but further injection (>3.0 × 10⁶ microspheres) began to inhibit flow. It is concluded that a finite number (≤3.0 × 10⁶) of microspheres of 11.9 μm diameter has opposite effects on V˙O ₂ depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.     

The energetics of the quiescent heart muscle: high potassium cardioplegic solution and the influence of calcium and hypoxia on the rat heart

Heart basal metabolism has been classically studied as the energy expenditure of those processes unrelated to mechanical activity and often measured by rendering the heart inactive using cardioplegic solutions (usually by increasing extracellular K concentration ([K]_e). In arterially perfused rat heart (at 25 °C), raising [K]e from 7 to 25 mM at a constant extracellular Ca concentration ([Ca]_e) (0.5 mM ), induced an increase in resting heat production (Hr) from 4.1 ± 0.3 to 5.1 ± 0.3 mol. wt g^?1. Under 25 mM K additional increase in [Ca]_e further increased Hr to 6.0 ± 0.4, 7.0 ± 0.4 and 8.3 ± 0.9 mol. wt g^?1 for 1, 2 and 4 mM Ca, respectively. While under 7 mM K perfusion Hr was not affected by 4 μM verapamil, under 25 mM K and 2 mM Ca 0.4 μM verapamil induced a decrease in Hr (?1.6 ± 0.2 mol. wt g^?1, n = 5, P < 0.001). Caffeine increased Hr under 0.5 mM Ca and 7 mM K perfusion (+0.32 ± 0.06 and +1.19 ± 0.25 mol. wt g^?1 for 1 and 5 mM caffeine respectively), but under 25 mM K conditions Hr was not affected by caffeine 2 mM . Severe hypoxia decreased Hr under both 7 and 25 mM K (3.7 ± 0.5 to 2.7 ± 0.4 mol. wt g^?1 and 7.0 ± 0.4 to 2.2 ± 0.5 mol. wt g^?1, respectively) suggesting that the increased Hr associated with the verapamil sensitive fraction of heat released is associated to a mitochondrial mechanism. Therefore, the use of high [K]_e overestimates basal values by increasing a verapamil sensitive fraction of the energy released. In addition, high [K]_e modifies a caffeine sensitive energy component probably due to a depletion of caffeine-dependent Ca stores.     

The effect of exercise on postprandial lipidemia in type 2 diabetic patients

To elucidate if postprandial exercise can reduce the exaggerated lipidemia seen in type 2 diabetic patients after a high-fat meal. Two mornings eight type 2 diabetic patients (males) (58 ± 1.2 years, BMI 28.0 ± 0.9 kg m⁻²) and seven non-diabetic controls ate a high-fat breakfast (680 kcal m⁻², 84% fat). On one morning, 90 min later subjects cycled 60 min at 57% . Biopsies from quadriceps muscle and abdominal subcutaneous adipose tissue were sampled after exercise or equivalent period of rest and arterialized blood for 615 min. Postprandial increases in serum total-triglyceride (TG) (incremental AUC: 1,702 ± 576 vs. 341 ± 117 mmol l⁻¹ 600 min), chylomicron-TG (incremental AUC: 1,331 ± 495 vs. 184 ± 55 mmol l⁻¹ 600 min) and VLDL-TG as well as in insulin (incremental AUC: 33,946 ± 7,414 vs. 13,670 ± 3,250 pmol l⁻¹ 600 min), C-peptide and glucose were higher in diabetic patients than in non-diabetic controls (P < 0.05). In diabetic patients these variables were reduced (P < 0.05) by exercise (total-TG incremental AUC being 1,110 ± 444, chylomicron-TG incremental AUC 1,043 ± 474 mmol l⁻¹ 600 min and insulin incremental AUC 18,668 ± 4,412 pmol l⁻¹ 600 min). Lipoprotein lipase activity in muscle (11.0 ± 2.0 vs. 24.1 ± 3.4 mU g per wet weight, P < 0.05) and post-heparin plasma at 615 min were lower in diabetic patients than in non-diabetic controls, but did not differ in adipose tissue and did not change with exercise. In diabetic patients, 210 min after exercise oxygen uptake (P < 0.05) and fat oxidation (P < 0.1) were still higher than on non-exercise days. In type 2 diabetic patients, after a high-fat meal exercise reduces the plasma concentrations of triglyceride contained in both chylomicrons and VLDL as well as insulin secretion. This suggests protection against progression of atherosclerosis and diabetes.     

Plasma immunoreactive atrial natriuretic peptide and vasopressin after ethanol intake in man

To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg^-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1^-l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg^-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min^-l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1^-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1^-1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1^-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ± 2 , 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min^-1 at 6 p.m. to 95 min^-1 at 12 p.m. We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.     

Comparison of the effects of sibutramine versus sibutramine plus metformin in obese women

Sibutramine and metformin are drugs commonly used to obtain weight loss. We aimed to compare the effects of sibutramine alone with that of sibutramine plus metformin combination on weight loss, insulin sensitivity, leptin and C reactive protein in obese women. Seventy obese women were included. After a diet period of month (baseline), each individual was randomly assigned to receive 15 mg sibutramine (sibutramine group; n = 36) or 15 mg sibutramine plus 1,700 mg metformin per day (sibutramine plus metformin group; n = 34) during the next 12 months. Body weight, insulin resistance by the homeostasis model assessment model (HOMA-IR), leptin and C reactive protein were measured at baseline, after 3 months and after 12 months. Mean weight losses in sibutramine and sibutramine plus metformin groups were 5.3 ± 4.0% (P < 0.001) and 6.8 ± 3.9% (P < 0.001) after 3 months, and 10.5 ± 4.4% (P < 0.001) and 15.7 ± 4.6% (P = 0.007) after 12 months, respectively. HOMA-IR value also decreased in both sibutramine (P = 0.045 and P = 0.002) and sibutramine plus metformin groups (P = 0.04 and P = 0.015) after 3 and 12 months, respectively. Similarly, serum leptin levels decreased in both sibutramine (P = 0.04, P = 0.01) and sibutramine plus metformin groups (P = 0.023, P = 0.025) after 3 and 12 months, respectively. There was also significant reductions in serum C reactive protein levels in both sibutramine (P = 0.045, P = 0.02) and sibutramine plus metformin groups (P = 0.007, P = 0.001) after 3 and 12 months, respectively. These decrements of body weight, HOMA-IR, serum leptin and C reactive protein levels were not statistical significance between these two groups both after 3 and 12 months (P > 0.05). Combination of sibutramine with metformin did not result in any further effects on weight loss, insulin resistance, leptin and C reactive protein levels when compared to sibutramine alone.     

Iron status in HIV-1 infection: implications in disease pathology

Background

There had been conflicting reports with levels of markers of iron metabolism in HIV infection. This study was therefore aimed at investigating iron status and its possible mediation of severity of HIV- 1 infection and pathogenesis.

Method

Eighty (80) anti-retroviral naive HIV-1 positive and 50 sero-negative controls were recruited for the study. Concentrations of serum total iron, transferrin, total iron binding capacity (TIBC), CD₄⁺ T -lymphocytes, vitamin C, zinc, selenium and transferrin saturation were estimated.

Results

The mean CD₄⁺ T-lymphocyte cell counts, serum iron, TIBC, transferrin saturation for the tests and controls were 319 ± 22, 952 ± 57 cells/μl (P < 0.001), 35 ± 0.8, 11.8 ± 0.9?μmol/l (P < 0.001), 58.5 ± 2.2, 45.2 ± 2.4?μmol/l (P < 0.005) and 68.8 ± 3.3, 27.7 ± 2.2%, (P <0.001), respectively, while mean concentrations of vitamin C, zinc and selenium were 0.03 ± 0.01, 0.3 ± 0.04 (P < 0.001), 0.6 ± 0.05, 11.9 ± 0.26?μmol/l (P < 0.001) and 0.1 ± 0.01, 1.2 ± 0.12?μmol/l (P < 0.001) respectively. Furthermore, CD₄⁺ T-lymphocyte cell count had a positive correlation with levels of vitamin C (r = 0.497, P < 0.001), zinc (r = 0.737, P < 0.001), selenium (r = 0.639, P < 0.001) and a negative correlation with serum iron levels (r = ?0.572, P < 0.001).

Conclusion

It could be inferred that derangement in iron metabolism, in addition to oxidative stress, might have contributed to the depletion of CD₄⁺ T cell population in our subjects and this may result in poor prognosis of the disease.

     

Effect of drink pattern and solar radiation on thermoregulation and fluid balance during exercise in chronically heat acclimatized children

The purposes of this study were to examine the thermoregulatory and body fluid balance responses in chronically heat acclimatized children, i.e., indigenous to a tropical climate, during exercise in four outdoor conditions and the effects of dehydration on their thermoregulatory response. Nine children (age = 13.3 ± 1.9 yr, VO₂max = 45.5 ± 9.2 ml · kg^?1 · min^?1) cycled at 60% VO₂max each under four conditions: sun exposure voluntary drinking (SuVD), sun exposure forced drinking (SuFD), shaded voluntary drinking (ShVD), and shaded forced drinking (ShFD). Exercise sessions consisted of four 20-min exercise bouts alternating with 25-min rest periods. Globe temperature and the WBGT index were higher during SuVD and SuFD compared to ShVD and ShFD (P < 0.05). The change in rectal temperature, metabolic heat production, and heat storage did not differ among the conditions. Total water intake (% IBW) was higher during SuFD (4.1 ± 0.01) and ShFD (3.7 ± 0.1) compared to SuVD (2.1 ± 0.1) and ShVD (1.0 ± 0.1) and during SuVD compared to ShVD (P < 0.05). Sweating rate (L · hr^?1) was higher during SuFD (0.7 ± 0.1) and ShFD (0.6 ± 0.1) compared to SuVD (0.5 ± 0.1) and ShVD (0.4 ± 0.1) (P < 0.05). Total fluid loss did not differ among conditions (SuVD = 1.7 ± 0.4; SuFD = 1.5 ± 0.4; ShVD = 2.1 ± 0.2; ShFD = 1.3 ± 0.3). Results indicate that when exercising in a tropical climate, chronically heat acclimatized children demonstrate mild voluntary dehydration and adequate heat dissipation. © 1995 Wiley-Liss, Inc.     

Low leptin concentration may identify heart failure patients with central sleep apnea

Low leptin concentration has been shown to be associated with central sleep apnea in heart failure patients. We hypothesized that low leptin concentration predicts central sleep apnea. Consecutive ambulatory New York Heart Association (NYHA ) classes I–IV heart failure patients were studied prospectively, including measurement of serum leptin, echocardiography and polysomnography. Sleep apnea was defined by type (central/mixed/obstructive) and by apnea–hypopnea index ≥5 by polysomnography. Subjects were divided into four groups by polysomnography: (1) central sleep apnea, (2) mixed apnea, (3) no apnea and (4) obstructive sleep apnea. Fifty‐six subjects were included. Eighteen subjects were diagnosed with central sleep apnea, 15 with mixed apnea, 12 with obstructive apnea and 11 with no sleep apnea. Leptin concentration was significantly lower in central sleep apnea compared to obstructive apnea (8 ± 10.7 ng mL^?1 versus 19.7 ± 14.7 ng mL^?1, P  ? 0.01) or no sleep apnea (8 ± 10.7 ng mL^?1 versus 17.1 ± 8.4 ng mL^?1, P  ? 0.01). Logistic regression showed leptin to be associated independently with central sleep apnea [odds ratio (OR ): 0.19; 95% confidence interval (CI ): 0.06–0.62; area under the curve (AUC ): 0.80, P  < 0.01]. For the detection of central sleep apnea, a cut‐off value for leptin concentration 5 ng mL^?1 yielded a sensitivity of 50% and specificity of 89%. In conclusion, a low leptin concentration may have utility for the screening of heart failure patients for central sleep apnea.     

Renal tubular transport and metabolism of carboxyamidated and glycine-extended gastrins in pigs

Renal handling of postprandial and intravenously administered gastrin was investigated in anaesthetised pigs. The fractional extraction of postprandial carboxyamidated and glycine-extended gastrin in the kidneys was 0.21 ± 0.01 and 0.16 ± 0.02, but the respective urinary clearance comprised only 0.57 ± 0.03 and 0.44 ± 0.05% of the GFR (P < 0.02). The respective total body clearance of carboxyamidated and glycine-extended gastrin-17 (gastrin-17 and gastrin-17Gly) during continuous infusion was 22.9 ± 1.5 and 19.6 ± 1.4 mL kg^?1 min^?1 (NS), and the renal fractional extraction of the peptides was 0.31 ± 0.03 and 0.29 ± 0.05, respectively. The kidneys accounted for 8% of total body clearance of gastrin-17. Renal filtration rate of gastrin-17 exceeded renal extraction rate (9.739 ± 0.487 vs. 6.407 ± 0.321 pmol min^?1). Urinary clearance of gastrin-17 and gastrin-17Gly amounted only 0.91 ± 0.16 and 0.13 ± 0.03%, respectively, of the GFR (P < 0.01), but urinary excretion rate correlated with the filtered amount of the peptides (r = 0.93, P < 0.01). Neither was a renal plasma threshold recorded nor was a T_m value for tubular uptake or degradation of gastrin achieved in spite of supraphysiological plasma levels of the peptides. The results indicate that filtered gastrin is almost completely removed in the renal tubules, primary by metabolism although part of the absorbed peptides may be returned to the circulation in intact form. The process for uptake or metabolism has a high capacity but varies with the molecular form of gastrin.