Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans.

BACKGROUND: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide-stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. METHODS: Ten healthy male volunteers (21-28 years) participated in a placebo-controlled, double-blind, cross-over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. RESULTS: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. CONCLUSION: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.

Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity.

OBJECTIVE: To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. RESEARCH METHODS AND PROCEDURES: Twenty-one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m(2)) and 13 lean (body mass index: 20.4 to 24.7 kg/m(2)) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1-23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty-four-hour EE and substrate oxidations were measured by whole-body indirect calorimetry. SPA was assessed by microwave radar. RESULTS: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24-hour EE before (r = -0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24-hour and resting nonprotein respiratory quotient (r = -0.47, p < 0.05 and r = -0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = -0.41, p = 0.07), 16 weeks (r = -0.51, p < 0.05), and 24 weeks (r = -0.50, p < 0.05). DISCUSSION: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.

[A complicated course of Salmonella gastroenteritis during antihypertensive treatment]. / Kompliceret forløb af Salmonella-gastroenteritis under antihypertensiv behandling.

Although Salmonella gastroenteritis usually is a fairly mild and self-limiting disease, serious complications are sometimes seen. We present a case that was further complicated by treatment with enalapril. We recommend discontinuation of treatment with ACE inhibitors in patients with any kind of ongoing gastroenteritis with fluid loss in order to prevent a potentially serious outcome.

Obese male subjects show increased resting forearm venous plasma noradrenaline concentration but decreased 24-hour sympathetic activity as evaluated by thrombocyte noradrenaline measurements.

OBJECTIVE: To study resting forearm venous plasma noradrenaline (NA) and 24 h sympathoadrenal activity evaluated by measurements of thrombocyte NA and adrenaline (A) in obese male subjects before and after weight reduction. DESIGN: Blood samples were collected in obese subjects and in controls after an overnight fast. MEASUREMENTS: Fatness and fat distribution parameters, plasma and thrombocyte NA and A, lymphocyte beta 2-adrenoceptor mRNA, cAMP and lymphocyte subset composition. RESULTS: Forearm venous plasma NA at rest was significantly elevated in the obese subjects and correlated to the body mass index and diastolic blood pressure. Thrombocyte NA and A correlated, however, negatively to the body fat % in obese subjects. Further analysis showed that thrombocyte NA and A were reduced in obese subjects with body fat % above 40% but not in the other groups. Weight reduction normalized both forearm venous plasma NA and thrombocyte NA and A. beta 2-adrenoceptor mRNA correlated positively to the frequency of CD3-CD56+ and CD3+CD8+ cells in the blood and negatively to plasma A, but there was no difference in the mRNA level, cyclic AMP and lymphocyte subset composition between obese and controls. CONCLUSIONS: Sympathetic activity at rest as evaluated by forearm venous plasma NA was increased in the obese male subjects and this abnormality was related to the increase in body mass index and the arterial blood pressure. Thrombocyte NA and A, which is likely to reflect 24 h plasma catecholamine concentrations were reduced in obese subjects with a body fat % above 40%, probably due to a reduced physical activity in these subjects. Both catecholamine parameters were normalized by weight reduction.

Regulation of cAMP in a lymphocyte preparation isolated from peripheral venous blood in human subjects: the significance of residual thrombocytes, noradrenaline and prostaglandins.

1. The aim of the study was to elucidate the mechanism of the previously reported close correlation observed between noradrenaline and cAMP in a lymphocyte preparation (LP) isolated from peripheral venous blood in healthy subjects. A close correlation was also obtained in the present study between lymphocyte noradrenaline and adrenaline and cAMP both in the basal state and after stimulation with isoproterenol (P<0.05 to 0.007).2. Although 99% of the thrombocytes were removed from the LP during the washing procedure, LP contained approximately one thrombocyte per lymphocyte. The noradrenaline concentration in LP which could be ascribed to residual thrombocytes, calculated from the average noradrenaline concentration in thrombocytes and the number of thrombocytes in LP, correlated closely to noradrenaline in LP (P<0.007).3. To test the hypothesis that noradrenaline in LP was primarily derived from plasma, we studied three patients with phaeochromocytoma, who had high levels of noradrenaline and adrenaline both in plasma and in LP. 4. Further studies showed that the addition of thrombocytes to LP increased cAMP. The response was inhibited by indomethacin, whereas the addition of cimetidine and propranolol had no effect on basal or thrombocyte-stimulated cAMP.5.We conclude that noradrenaline in LP is a marker of the number of residual thrombocytes. The addition of thrombocytes to LP increased cAMP in lymphocytes. This response was not mediated by catecholamines but possibly by prostaglandins.