Search results for "Heterocyclic compound"
showing 10 items of 382 documents
Characterization of a Ryanodine Receptor inPeriplaneta Americana
1997
Specific binding sites for the alkaloid ryanodine were characterized in membrane preparations from sarcoplasmatic reticulum of Periplaneta americana skeletal muscle. Binding of [3H]ryanodine was optimal at pH 8 and at CaCl2 concentration of about 300 mumol l-1. The Ca-chelating agents EGTA (100 mumol l-1) and EDTA (100 mumol l-1) abolished 95% and 90% of the [3H]ryanodine binding respectively. Preincubation with Ca2+ (100 mumol l-1) restored the ryanodine binding in presence of up to 300 mumol l-1 EGTA. Radioligand binding experiments showed one class of high affinity binding sites for ryanodine. Determination of rate constants revealed 7.05 x 10(6) l mol-1 min-1 for associating and 3.77 x …
Regulation of noradrenergic coerulean neuronal firing mediated by 5-HT2 receptors: involvement of the prepositus hypoglossal nucleus.
1991
Abstract Previous studies have indicated a 5-HT2-mediated inhibitory influence on unit activity in the locus coeruleus. In the present work, attempts were made to determine which area(s) of the brain is (are) involved in this effect: (1) Microiontophoretic application of serotoninergic compounds (quipazine, ketanserin, RU 24969 (Roussel Uclaf), 8-hydroxy-2(di-n-propylamino) tetralin (8-OH-DPAT), metergoline, serotonin) in the locus coeruleus, did not alter the coerulean discharge. Local microinjection of quipazine or ketanserin in the area of the locus coeruleus, as well as in one of its major afferents, the prepositus hypoglossi, had no effect on the unit activity in the locus coeruleus. 1…
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…
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…
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…
Absence of lipid peroxidation as determined by ethane exhalation in rats treated with 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).
1985
The exhalation of ethane is widely used as an indicator of in vivo lipid peroxidation. To test the hypothesis that lipid peroxidative events are involved in the toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), we administered a lethal dose of TCDD (60 μg/kg), IP to male Sprague Dawley rats (160–180 g) and measured by gas chromatography the exhalation of ethane into the atmosphere of a closed all-glass exposure chamber. TCDD-treated rats exhaled only slightly more ethane than control rats at a single time point 7 days following TCDD administration. Since the exhalation of ethane is the net result of the endogenous production of the gas and its metabolic degradation, the latter was …
COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.
2020
ABSTRACT Background Little evidence on COVID‐19 in people living with HIV (PLWH) is currently available. Material and Methods We reported clinical and viro‐immunological data of all HIV‐positive patients admitted to our centre with COVID‐19 from March 1 to May 12,2020. Results Overall, five patients were included: all were virologically‐suppressed on antiretroviral therapy and CD4+ count was >350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. SARS‐CoV‐2‐RNA was never detected from nasopharyngeal swabs in two patients, whereas, in the others, viral clearance occurred within a maximum of 43 days. IgG prod…