Measurement Of Plasma Verapamil Levels By High-performance Liquid Chromatography

[No abstract available]26775376

Bioavailability Of Four Pharmaceutical Formulations Of Metronidazole Tested On Normal Healthy Volunteers

[No abstract available]24121251126

Nitric Oxide: Properties And Therapeutic Use [Óxido Nítrico: Propriedades E Potenciais Usos Terapêuticos]

Nitric oxide (•NO) is a substance that acts as a second-messenger and is associated with a number of important physiological functions such as regulation of the vascular tonus, immune modulation and neurotransmission. As a physiological mediator, alteration of its concentration level may cause pathophysiological disfunctions such as hypertension, septic shock and impotence. Possible therapeutic approaches are being developed to control NO levels in vivo. We review herein the main physical and chemical properties of •NO, its biological functions and available chemical interventions to reduce and increment its physiological concentration levels. Recent developments in the field are also highlighted.28610461054http://www.nobel.se/nobel/alfred-nobel/biographical/ringertzFurchgott, R.F., (1999) Angew. Chem., Int. Ed., 38, p. 1870Ignarro, L.J., (1999) Angew. Chem., Int. Ed., 38, p. 1882Murad, F., (1999) Angew. Chem., Int. 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Neutrophils And Mononuclear Cells From Patients With Chronic Granulomatous Disease Release Nitric Oxide

Chronic granulomatous disease (CGD) is a group of genetic disorders characterised by recurrent severe suppurative infections due to impaired microbial killing. The principal biochemical defect is an impairment in the production of reactive oxygen intermediates by phagocytes. Nitric oxide (NO) is synthesised from the guanidino nitrogen atom(s) of L-arginine and has recently been proposed to be involved in defence mechanisms. The aim of this study was to investigate the involvement of the oxidative burst in the biosynthesis of NO by neutrophils and mononuclear cells from patients with CGD. NO synthesis was assayed by the ability of neutrophils and mononuclear cells to inhibit thrombin-induced washed platelet aggregation while superoxide anion (O2-) production was measured spectrophotometrically by the superoxide dismutase inhibitable reduction of cytochrome c. Neutrophils and mononuclear cells from patients with CGD released NO. This release was inhibited by nitro-L-arginine methyl ester but could be reversed by L-arginine. Zymosan- and PMA-induced O2- production was less than 10% as compared with health controls. These results indicate that O2- production is not essential for NO synthesis in human leucocytes.35548549

Bioequivalence Study Of Two Enalapril Maleate Tablet Formulations In Healthy Male Volunteers: Pharmacokinetic Versus Pharmacodynamic Approach

Objective: Two different conventional release enalapril maleate tablet formulations were evaluated for their relative bioavailability (Eupressin tablets 10 mg, Biosintetica as the test formulation vs Renitec tablets 10 mg Merck Sharp and Dhome, as the reference formulation). A single 20 mg oral dose of each preparation was administered to 18 healthy male adult volunteers and their bioequivalence was assessed by comparing the serum enalaprilat and total enalapril (enalaprilat plus enalapril maleate) concentration-time curves. Angiotensin converting enzyme (ACE) activity was also quantified in each serum sample. Results: The pharmacokinetic parameters obtained for each formulation were the area under the time-concentration curve from 0 to 24 h (AUC[0-24]), maximum concentration C(max) and the time at which it occurred (t(max)). When serum enalaprilat concentration-time curves were employed to assess bioequivalence, the formulations were bioequivalent in the extent but not in the rate of absorption. However, no difference in either the extent or the rate of absorption were observed when serum total enalapril vs time curves were analysed. ACE activity-time curves were similar for both formulations and showed that ACE was 90% inhibited 3-5 h after enalapril administration, and till approximately 50% after 24 h. At that time, circulating enalaprilat and total enalapril levels were less than the tenth of C(max). Conclusion: The results show that complete bioequivalence of the two formulations can be concluded from serum total enalapril concentration data, and that serum ACE activity is not a suitable pharmacodynamic variable for assessing bioequivalence.505399405Todd, P.A., Goal, K.I., Enalapril: A reappraisal of its pharmacology and therapeutic use in hypertension (1992) Drugs, 43, pp. 346-383Todd, P.A., Heel, R.C., Enalapril: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure (1986) Drugs, 31, pp. 198-248Ferguson, R.K., Vlasses, P.H., Swanson, B.N., Mojaverian, P., Hichens, M., Effects of enalapril, a new converting enzyme inhibitor, in hypertension (1982) Clin Pharmacol Ther, 32, pp. 48-53Sánchez, R.A., Marcó, E., Gilbert, H.B., Raffaele, P., Brito, M., Moledo, L.I., Natriuretic effect and changes in renal haemodynamics induced by enalapril in essential hypertension (1985) Drugs, 30 (1 SUPPL.), pp. 49-58Sánchez, R.A., Ramírez, A.J., Muscará, M.N., Gilbert, H.B., Marcó, E., Moledo, L.I., Inhibitory effects of enalapril on serum aldosterone in essential hypertension (1987) Medicina (Bs. 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Daily Cycling Of Nitric Oxide Synthase (nos) In The Hippocampus Of Pigeons (c. Livia)

Background: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. 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