19 research outputs found

    Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis

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    In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis

    The neuronal monoamine transporter VMAT2 is regulated by the trimeric GTPase Go(2

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    Monoamines such as noradrenaline and serotonin are stored in secretory vesicles and released by exocytosis. Two related monoamine transporters, VMAT1 and VMAT2, mediate vesicular transmitter uptake. Previously we have reported that in the rat pheochromocytoma cell line PC 12 VMAT1, localized to peptide-containing secretory granules, is controlled by the heterotrimeric G-protein Go 2. We now show that in BON cells, a human serotonergic neuroendocrine cell line derived from a pancreatic tumor expressing both transporters on large, densecore vesicles, VMAT2 is even more sensitive to G-protein regulation than VMAT1. The activity of both transporters is only downregulated by G�o 2, whereas comparable concentrations of G�o 1 are without effect. In serotonergic raphe neurons in primary culture VMAT2 is also downregulated by pertussis toxin-sensitive Go 2. By electron microscopic analysis from prefronta

    Phosphoinositide-Dependent Protein Kinase 1 (PDK1)

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    Phosphatidylinositol-3-kinase (PI3K) signaling influences susceptibility to virus infections, anoxia, obstetric complications, and cancer; which are changed in patients with schizophrenia and their first degree relatives. Therefore PI3K signaling might have impact on the pathophysiology of schizophrenia. PI3K signaling crucially involves phosphoinositide-dependent protein kinase (PDK1). Increased anxiety behavior is observed in PDK1 hypomorphic mice. Here we show enhanced prevalence of schizophrenia in carriers of the PDK1 CC genotype in human beings. Moreover, decreased parietal P300 amplitude, which is a well-studied schizophrenic endophenotype, was observed in PDK1 CC carriers. Glutamate and glutamine concentrations are increased in the frontal lobe of PDK1 dysmorphic mice and human CC individuals. Our results demonstrate that the PDK1 CC genotype is associated with increased risk to develop schizophrenia, a typical endophenotype profile observed in the disease and modified neurotransmitter concentrations in brain regions associated with the disease
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