Search results for "Cyclic compound"
showing 10 items of 819 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…
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…
Gastric relaxation induced by apigenin and quercetin: Analysis of the mechanism of action
2009
Abstract Aims Recently, flavonoids have been shown to cause murine gastric relaxation. In the present study we examined the mechanism of action underlying gastric relaxation induced by apigenin and quercetin in isolated mouse stomach. Main methods The mechanical activity from the whole stomach was detected as changes in the endoluminal pressure and the response to increasing concentrations of both flavonoids were tested before and after different pharmacological treatments. Key findings Apigenin and quercetin-induced a concentration-dependent gastric relaxation, apigenin being more potent than quercetin. The responses were unaffected by 2′5′dideoxyadenosine, an inhibitor of adenylate cyclas…
Effects of dopamine antagonists with different receptor blockade profiles on morphine-induced place preference in male mice.
2001
The effects of dopamine (DA) antagonists with different selectivity for the DA receptors (SCH 23390, 0.5, 0.25, 0.125 mg/kg; haloperidol, 0.2, 0.1 mg/kg; raclopride, 1.2, 0.6, 0.3 mg/kg; risperidone, 0.4, 0.2, 0.1 mg/kg; U-99194A maleate, 40, 20 mg/kg; clozapine, 2.5, 1.25, 0.625 mg/kg) on the acquisition of place conditioning and morphine-induced conditioned place preference (CPP) were explored in male mice. Morphine (40 mg/kg) produced CPP while SCH 23390, haloperidol and clozapine (highest dose) and risperidone (lowest dose) produced conditioned place aversion (CPA). Raclopride and U-99194A maleate did not produce CPP or CPA. Morphine-induced CPP was reversed by the administration of SCH…
Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study).
2012
To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients.Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 μmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h …
Studies on the disposition, metabolism and hepatotoxicity of coumarin in the rat and Syrian hamster.
2002
The hepatotoxicity, metabolism and disposition of coumarin has been compared in male Sprague-Dawley rats and Syrian hamsters. The treatment of rats for 12, 24 and 42 weeks with diets containing 0.2 and 0.5% coumarin resulted in hepatotoxicity and increased relative liver weights. While levels of cytochrome P450 (CYP) and CYP-dependent enzymes were decreased, levels of reduced glutathione (GSH) and activities of UDP glucuronosyltransferase, gamma-glutamyltransferase and GSH S-transferase were increased. In contrast, coumarin produced few hepatic changes in the Syrian hamster. Following a single oral dose of 25 mg/kg [3-14C]coumarin, radioactivity was rapidly excreted by the rat and Syrian ha…
Protein gene product (PGP) 9.5 immunoreactivity in nerve fibres and pinealocytes of guinea-pig pineal gland: interrelationship with tyrosine- hydroxy…
1993
This light-microscopic (LM) immunohistochemical study has evaluated the presence and distribution of the pan-neural and neuroendocrine marker protein gene product (PGP) 9.5 in pinealocytes and nerve fibres of guinea-pig pineal gland. The pattern of PGP 9.5-immunoreactive (ir) nerve fibres has been compared with that of fibres staining for tyrosine hydroxylase (TH) or neuropeptide Y (NPY). The vast majority of pinealocytes stained for PGP 9.5, although with variable intensity. PGP 9.5 immunoreactivity was localized in pinealocytic cell bodies and processes. Double-immunofluorescence revealed that PGP 9.5 immunoreactivity was absent from glial cells identified with a monoclonal antibody again…
Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice
2015
Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single su…