Endurance running acutely raises plasma osteoprotegerin and lowers plasma receptor activator of nuclear factor kappa B ligand.

Abstract The balance of the 2 cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa B ligand (soluble (s)RANKL), is known to have considerable influence on bone formation and degradation. Plasma concentrations of OPG and (s)RANKL were determined in a total of 31 long-distance runners before and immediately after running distances of either 15 or 42.195 km, respectively. In both groups of endurance runners, a significant decrease of sRANKL was observed during the run, the extent of which correlated to the running distance. Furthermore, OPG increased only in runners covering the marathon distance of 42.195 km. We hypothesize that the known positive effect of long-distance running on the skeletal mass may be mediated by the OPG/sRANKL system.

The cholinergic system controls ghrelin release and ghrelin-induced growth hormone release in humans.

The stomach-derived peptide hormone ghrelin induces appetite and GH release. Several ghrelin actions are possibly mediated and modulated by the central cholinergic system. The aim of this study was to investigate the influence of the unspecific cholinergic antagonist atropine and the acetylcholine esterase inhibitor pyridostigmine, a cholinergic enhancer on ghrelin plasma concentrations and ghrelin-induced GH release. We investigated plasma ghrelin concentrations, ghrelin-induced GH release, and glucose and insulin concentrations after administration of atropine or pyridostigmine, and ghrelin (in two different doses, 0.25 and 1 microg/kg body weight), alone and in combination in a randomized, double-blind, placebo-controlled, crossover study design on 12 young, healthy male volunteers. Atropine alone significantly reduced fasting ghrelin levels by 25%, whereas under pyridostigmine alone ghrelin levels were unaltered. Ghrelin in combination with atropine induced significantly reduced GH concentrations compared with ghrelin administration alone for both ghrelin doses, whereas ghrelin-induced GH peak concentrations and areas under the curve were not enhanced by pyridostigmine treatment. These results suggest that, in humans, fasting ghrelin concentrations might be under cholinergic control and that the cholinergic system appears to modulate ghrelin-induced GH release.

Effects of 12 months of recombinant growth hormone therapy on parameters of bone metabolism and bone mineral density in patients on chronic hemodialysis.

BACKGROUND: Renal osteodystrophy is common in patients with chronic renal failure (CRF) on hemodialysis (HD), leading to reduced bone mineral density (BMD) and higher bone fracture incidences. Since growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are known to enhance bone metabolism and BMD, and CRF patients exhibit GH and IGF-1 resistance, recombinant human GH (rhGH) therapy could be beneficial for these patients. METHODS: This study evaluated the effects of a 12-month rhGH therapy on bone metabolism parameters; alkaline phosphatase (AP), osteocalcin (OC), procollagen I carboxyterminal propeptide (PICP), telopeptide ICTP, serum crosslaps, n-terminal propeptide of type III procollagen (PIIINP) and intact parathyroid hormone (iPTH), as well as on BMD of the lumbar spine and the femoral neck in 19 malnourished HD patients (10 females, 9 males) with a mean age of 59.3 +/- 13.4 yrs. Fourteen patients completed the 12-month study. RhGH (0.25 IU/kg) was given subcutaneously 3x/week after each dialysis session. RESULTS: IGF-1 concentrations rose significantly from 169.2 +/- 95.6 to 262.9 +/- 144.4 ng/mL (p<0.01) after 3 months, followed by a slight decline over the next 9 months. PICP as a bone formation marker significantly increased after 3 months from 250.1 +/- 112.6 to 478.5 +/- 235.2 ug/L (p<0.01), as well as PIIINP, whereas OC and bone resorption parameters like ICTP showed only a slight increase (ICTP: 50.3 +/- 18.5 to 70.0 +/- 39.5 ug/L after 3 months (ns)). All bone metabolism parameters slightly declined in the following 9 months, but remained above baseline values after 12 months. PTH rose from 198.0 +/- 139.2 to 456.0 +/- 268.7 ng/ml, p<0.01 after 6 months. BMD of the lumbar spine showed a significant reduction after 3-month rhGH therapy (0.80 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, p<0.01), but returned to baseline values after 12 months. BMD of the femoral neck remained stable during the entire study. CONCLUSIONS: In summary, 12-month rhGH treatment in patients on chronic HD caused a significant increase in IGF-1, together with an increase in bone turnover. In addition, there was a temporary reduction in BMD of the lumbar spine seen, which returned to baseline values after 12 months.

Normal regulation of elevated plasma ghrelin concentrations in dialysis patients.

BACKGROUND: Chronic renal failure is often associated with malnutrition, and malnourished patients are subject to increased morbidity and mortality. Therefore plasma concentrations of the stomach-derived peptide hormone ghrelin, which has been shown to exert potent GH-releasing and appetite-stimulating effects, were determined and correlated with nutritional parameters. METHODS: Twenty-four patients (15 male, 9 female) undergoing hemodialysis (HD) were studied. In addition, six patients were studied before and one hour after ingestion of a meal and five were studied immediately before and at the end of the dialysis session. RESULTS: Chronic renal insufficiency was associated with significantly elevated ghrelin levels (320.1 +/- 57 fmol/mL vs. 75.6 +/- 12.4 fmol/mL in controls; p < 0.007). Plasma ghrelin concentrations were also significantly higher in the 16 normal-weight patients than in the eight overweight or obese patients (399.6 +/- 76.3 fmol/mL vs. 161.1 +/- 41.3 fmol/mL; p < 0.03). Ingestion of food induced a decrease in five out of six patients tested (mean 242.3 +/- 66.5 fmol/mL vs. 186 +/- 30.7 fmol/mL; n.s.). HD also resulted in a significant decrease of elevated ghrelin concentrations: ghrelin was in the normal range at the end of HD in four of the five patients tested. Plasma ghrelin concentrations did not correlate with nutritional parameters except for cholinesterase which was negatively correlated to ghrelin. CONCLUSION: Plasma ghrelin concentrations are elevated in HD. The fact that ghrelin concentrations are higher in normal-weight than in overweight or obese HD patients and suppressed after ingestion of a meal suggests that the regulation of ghrelin release is retained in HD patients, albeit shifted to a higher level.

Estudo multicêntrico com três doses diferentes de ketanserin em hipertensäo arterial essencial / Multicenter study with 3 different doses of ketanserin in essential arterial hypertension

Os autores avaliaram em estudo randomizado, simples-cego, com grupos paralelos, a atividade anti-hipertensiva de ketanserin, um novo medicamento bloqueador dos receptores 5-HT2 de serotonina, em comprimidos de 40 mg. Noventa e um pacientes de ambulatório, portadores de hipertensäo arterial essencial näo complicada, após receberem placebo por período de 4 semanas, foram incluídos aleatoriamente em um de três grupos: 40 mg uma vez, duas vezes ou três vezes ao dia. O tratamento com ketanserin foi mantido durante 12 semanas. As três doses de ketanserin reduziram a pressäo arterial, havendo pequenas diferenças entre os esquemas escolhidos. Da mesma maneira, näo ocorreu diferença apreciável entre a incidência e a natureza das reaçöes adversas entre os grupos