Search results for "cyclic"
showing 10 items of 2439 documents
International Normalized Ratio and Mortality Risk in Acute Heart Failure and Nonvalvular Atrial Fibrillation Patients Receiving Vitamin K Antagonists
2019
Introduction and objectives: Heart failure patients with nonvalvular atrial fibrillation (NVAF) on treatment with vitamin K antagonists (VKA) often have suboptimal international normalized ratio (INR) values. Our aim was to evaluate the association between INR values at admission due to acute heart failure and mortality risk during follow-up. Methods: In this observational study, we retrospectively assessed INR on admission in 1137 consecutive patients with acute heart failure and NVAF who were receiving VKA treatment. INR was categorized into optimal values (INR = 2-3, n = 210), subtherapeutic (INR 3, n = 267). Because INR did not meet the proportional hazards assumption for mortality, res…
Interrelationship between demethylation of p-nitroanisole and conjugation of p-nitrophenol in rat liver
1973
The metabolism of p-nitroanisole (pNA) and p-nitrophenol (pNP) was studied in isolated rat livers perfused with a hemoglobin-free medium. The activity and viability of the surviving organ was tested by recording pH, “arterial” and “venous” oxygen tension as well as the disappearance of added pNP. pNA is converted to its primary metabolite pNP which, in turn, is excreted into the perfusion medium as conjugates. The coordination of pNA oxidation and the conjugation reactions of pNP were investigated. When 50 μM pNA is added as substrate 0.4±0.1 nmoles×ml−1×(g liver)−1 are excreted as pNP-glucuronide and 3.5±0.2 nmoles×ml−1×(g liver)−1 as the sulphate within 90 min. When pNP itself (50 μM) is …
Does the NO/sGC/cGMP/PKG pathway play a stimulatory role in platelets?
2012
Nitric oxide (NO) stimulates cGMP synthesis by activating its intracellular receptor, soluble guanylyl cyclase (sGC). It is a currently prevailing concept that No and cGMP inhibits platelet function. However, the data supporting the inhibitory role of NO/sGC/cGMP in platelets have been obtained either in vitro or using whole body gene deletion that affects vessel wall function. Here we have generated mice with sGC gene deleted only in megakaryocytes and platelets. Using the megakaryocyte- and platelet-specific sGC-deficient mice, we identify a stimulatory role of sGC in platelet activation and in thrombosis in vivo. Deletion of sGC in platelets abolished cGMP production induced by either NO…
Differences in the nitric oxide/soluble guanylyl cyclase signalling pathway in the myocardium of neonatal and adult rats
2000
Abstract The effects of a nitric oxide-donor, S -nitroso- N -acetylpenicillamine, and a direct activator of soluble guanylyl cyclase, 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), on force of contraction ( F c ) and L-type Ca 2+ currents ( I Ca(L) ) were investigated in myocardial preparations from neonatal and adult rats. Since hearts from adult and neonatal animals contained 160 and 47 mg/100 g wet weight myoglobin, respectively, its possible interaction with both drugs was also investigated. Both S -nitroso- N -acetylpenicillamine (100 μM) and YC-1 (30 μM) were ineffective in myocardial preparations from adult rats but reduced the magnitude of I Ca(L) and F c in preparations fr…
Biosynthesis and transformation of 20α 21-dihydroxycholesterol by rat adrenal preparations
1979
Abstract The biosynthesis of [ 3 H]-20α, 21 dihydroxycholestderol from [ 3 H]-20α-hydroxycholesterol and its transformation to [ 3 H]-21-hydroxypregnenolone by rat adrenal preparations has been demonstrated. 20α-Hydroxycholesterol was transformed to 20α, 21-dihydroxycholesterol by microsomal preparations in the presence of NADPH and 20α-21-dihydroxycholesterol was metabolized to 21-hydroxypregnenolone by mitochondrial preparations in the presence of a NADPH-generating-system. Comparison of the Michaelis-Menten-Kinetics of the steps “20α, 21-dihydroxycholesterol → 21-hydroxycholesterol” and “20α-hydroxycholesterol → pregnenolone” revealed that both compounds behaved as analogue substrates of…
Phosphodiesterase 10A in the Rat Pineal Gland: Localization, Daily and Seasonal Regulation of Expression and Influence on Signal Transduction
2010
The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606–7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master cloc…
Reduced basal and stimulated (isoprenaline, Gpp(NH)p, forskolin) adenylate cyclase activity in Alzheimer's disease correlated with histopathological …
1991
Cyclic adenosine monophosphate (cAMP) is an adenylate cyclase borne second messenger involved in basic metabolic events. The beta-adrenoceptor sensitive adenylate cyclase was studied in post-mortem hippocampi of controls and Alzheimer patients. Virtually identical subsets of each hippocampus homogenate were stimulated by 100 mumol isoprenaline, Gpp(NH)p and forskolin, respectively, in presence of an ATP-regenerating system. The determination of cAMP formed was carried out by means of a radioassay. The observed significant 50% reduction in basal as well as in stimulated adenylate cyclase activity in Alzheimer's disease is negatively correlated with semiquantitative evaluations of amyloid pla…
Sleep in children with autistic spectrum disorder: a questionnaire and polysomnographic study.
2007
Abstract Objective To evaluate sleep in children with autistic spectrum disorder (ASD) by means of sleep questionnaires and polysomnography; moreover, to analyze their cyclic alternating pattern (CAP). Methods Thirty-one patients with ASD (28 males, 3 females, aged 3.7–19 years) and age-matched normal controls were included. ASD children were evaluated by a standard sleep questionnaire that consisted of 45 items in a Likert-type scale covering several areas of sleep disorders and by overnight polysomnography in the sleep laboratory after one adaptation night. Results The questionnaire results showed that parents of ASD children reported a high prevalence of disorders of initiating and maint…
Nitric oxide is formed in a subpopulation of rat pineal cells and acts as an intercellular messenger.
1998
In the rat pineal, formation of the second messenger cyclic GMP (cGMP) is under adrenergic control. Two important sequential steps mediate adrenergic signal transduction by cGMP, receptor-stimulated nitric oxide (NO) formation by the enzyme NO synthase I (NOS I), and NO-induced cGMP formation by the cytosolic enzyme guanylyl cyclase. With regard to the first step in cGMP transduction (i.e. NO formation) we found, by means of NOS I immunostaining and NADPH-diaphorase staining, that the presence of NOS I was restricted to a subpopulation of pineal cells, generally surrounded by NOS I-negative cells. Considering the fact that NO is able to permeate the cell membrane, the question arises whethe…
Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions?
2003
Therapeutic drug monitoring (TDM) of tricyclic antidepressants (TCA) is established in the treatment of depression to optimize outcome and safety. However, there are few reports on TDM under naturalistic clinical conditions. In the present study, we investigated a TDM group (TDM) and a randomly assigned parallel group without TDM (no-TDM) while on TCA treatment. Serum levels were analyzed in both cohorts, but feedback and dose recommendation were only provided for the TDM group. Serum levels of TCA were assessed by high-performance liquid chromatography (HPLC). The outcome was measured weekly using the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impressions Scale (CGI), and…