Comparative bioavailability study with two amiodarone tablet formulations administered with and without food in healthy subjects.

Objective: The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of amiodarone (CAS 19774-82-4) in healthy volunteers of both sexes, with and without food.

Methods: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval, in two groups, with and without food. Plasma samples were obtained for up to 240 h post dose.

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results.

Dihydroergotoxine is a mixture of semi-synthetic ergot alkaloids mainly used for age-related cognitive impairment. In this study, dihydroergotoxine (30 microM) was added to incubates of rat and bovine liver microsomes, and the resulting major metabolites were identified as hydroxy-dihydroergocornine, hydroxy-dihydroergocryptine and hydroxy-dihydroergocristine on the basis of molecular mass measurements, determined with a time-of-flight mass spectrometer. The relevance of these to humans was then investigated by simultaneously monitoring dihydroergotoxine and its hydroxy-metabolites in human plasma by LC-MS/MS after oral dosing of dihydroergotoxine mesylate (27 mg) to a healthy volunteer (male, age 45, height 1.

Simultaneous quantification of GMP, AMP, cyclic GMP and cyclic AMP by liquid chromatography coupled to tandem mass spectrometry.

Phosphodiesterases are drug targets for treating various diseases. Inhibition of these can increase cAMP and cGMP levels, which can affect a variety of physiological responses. Here we report a new method for determining PDE activity by combining high-performance liquid chromatography and tandem mass spectrometry.

Helicobacter pylori and epigenetic mechanisms underlying gastric carcinogenesis.

Gastric carcinogenesis is a multistep process triggered by Helicobacter pylori and characterized by accumulation of molecular alterations. Two mechanisms are implicated in cancer-related molecular alterations: genetic and epigenetic. The former includes changes in the DNA sequence, the latter occurs without changes of DNA sequence.

Is screening for and surveillance of atrophic gastritis advisable?

Gastric cancer remains a leading cause of cancer-related deaths in many parts of the world. At present, prevention seems to be the most effective means to reduce its the incidence and mortality rate. Gastric atrophy is considered the first relevant step in the histogenesis of gastric adenocarcinoma.

Pharmacokinetic profile of atenolol aspirinate.

We report microwave-assisted synthetic routes, the pharmacokinetic profile along with results from ulcerogenicity and mutagenicity studies of atenolol aspirinate, and an already described derivative, in which acetyl salicylic acid (aspirin) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t(1/2) = 7.6 min).

Effect of topic defibrillation on serum markers of myocardial damage.

Serum levels of cardiac enzymes and troponins after external cardioversion (ECV) for atrial defibrillation and atrial flutter, and after endocardiac cardioverter defibrillation by implantable cardioverter defibrillator (ICD), have been well investigated. The aim of this study was to assess the effects of topic defibrillation (TD), after cardiac surgery, on cardiac enzymes in patients with uncomplicated clinical course. Biochemical markers were analyzed prospectively for 20 patients after TD (group A) and for 20 patients that were not defibrillated (Control group).

Vascular effects of long-term propranolol administration after chronic nitric oxide blockade.

Long-term propranolol treatment reduces arterial blood pressure in hypertensive individuals mainly by reducing peripheral vascular resistance, but mechanisms underlying their vasodilatory effect remain poorly investigated. This study aimed to investigate whether long-term propranolol administration ameliorates the impairment of relaxing responses of aorta and mesenteric artery from rats made hypertensive by chronic nitric oxide (NO) deficiency, and underlying mechanisms mediating this phenomenon. Male Wistar rats were treated with N(omega)-Nitro-L-arginine methyl ester (L-NAME; 20 mg/rat/day) for four weeks.

A bioequivalence study of gliclazide based on quantification by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry.

Objective: The aim of this study was to evaluate, in human volunteers, the performance of one gliclazide tablet formulation (gliclazide 80 mg tablet from EMS Indústria Farmacêutica Ltda.) against two reference gliclazide tablet formulations (Diamicron 80 mg tablet from Servier do Brazil Ltda. and Diamicron 80 mg tablet from Servier (Ireland) Industries Limited).

Differential protein expression patterns obtained by mass spectrometry can aid in the diagnosis of Hodgkin's disease.

More than 90% of patients with cancer, if diagnosed early, can be promptly treated; however diagnosis usually occurs after cancer cells have metastasized. Recent technological advances in mass spectrometry challenges the field of machine learning to model such high dimensional datasets for clinical diagnosis and prognosis. Here we use support vector machines recursive feature elimination to hunt for protein expression patterns in the serum mass spectra of Hodgkin's disease (HD) patients and control subjects (CS) that could aid in diagnosing-the disease.

Pharmacokinetics and pharmacodynamics of a nitric oxide-releasing derivative of enalapril in male beagles.

1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles.

Anastrozole quantification in human plasma by high-performance liquid chromatography coupled to photospray tandem mass spectrometry applied to pharmacokinetic studies.

A rapid, sensitive and specific method for quantifying the aromatase inhibitor (anastrozole) in human plasma using dexchlorpheniramine as the internal standard (I.S.) is described herein.

Effect of BAY 41-2272 in the pulmonary hypertension induced by heparin-protamine complex in anaesthetized dogs.

1. BAY 41-2272 is a potent activator of the nitric oxide-independent site of soluble guanylate cyclase and has been recently introduced as a new therapeutic agent to treat chronic pulmonary hypertension (PH) in neonatal sheep. Because the in vivo heparin-protamine interaction may lead to severe PH, the aim of the present study was to evaluate the effects of BAY 41-2272 in the PH induced by heparin-protamine interaction in anaesthetized dogs.

Clonazepam quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry in a bioequivalence study.

A rapid, sensitive and specific method for quantifying clonazepam in human plasma using diazepam as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using a hexane/diethylether (20 : 80, v/v) solution. The extracts were analysed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS-MS).

Reactivity of mesenteric and aortic rings from trained rats fed with high caloric diet.

A strong association between the benefits of physical exercise on the cardiovascular disease with an improvement of the endothelium-derived relaxing factor production has been consistently shown. The purpose of this study was to evaluate the effect of exercise training associated with high caloric diet in the reactivity of rat mesenteric and aortic rings. Experimental protocol consisted of 4 weeks of high caloric diet consumption previous to 4 weeks of run training (1.

Purification, sequencing and structural analysis of two acidic phospholipases A2 from the venom of Bothrops insularis (jararaca ilhoa).

Bothrops snake venoms contain a variety of phospholipases (PLA(2)), some of which are myotoxic. In this work, we used reverse-phase HPLC and mass spectrometry to purify and sequence two PLA(2) from the venom of Bothrops insularis. The two enzymes, designated here as BinTX-I and BinTx-II, were acidic (pI 5.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion.

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks.

Effects of neonatal capsaicin treatment in the neutrophil production, and expression of preprotachykinin-I and tachykinin receptors in the rat bone marrow.

Bone marrow is richly innervated with both myelinated and non-myelinated nerve fibers, but the role of this innervation on hemopoiesis is poorly understood. Therefore, the aim of this study was to investigate the role of C-fibers on hematopoiesis. Wistar rats were neonatally injected with either capsaicin or its vehicle, and used at adult ages (8-10 weeks).

Bioequivalence of two lithium formulations in healthy volunteers.

Objective: The purpose of this study was to compare the maximum exposure and extent of bioavailability of two lithium carbonate (CAS 554-13-2) containing 300 mg tablet formulations (test and reference) for oral administration.

Method: This bioequivalence study was conducted in a 2-period crossover design with a washout phase of 7 days. Plasma samples were obtained by blood sampling over 72 h in each period.

Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats.

Staphylococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.

Protective effect of prior physical conditioning on relaxing response of corpus cavernosum from rats made hypertensive by nitric oxide inhibition.

The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min.

Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals.

Our objectives were to quantitate insulin-stimulated inward glucose transport and glucose phosphorylation in forearm muscle in lean and obese nondiabetic subjects, in lean and obese type 2 diabetic (T2DM) subjects, and in normal glucose-tolerant, insulin-resistant offspring of two T2DM parents. Subjects received a euglycemic insulin (40 mU.m(-2).

Endocarditis caused by Lactococcus lactis subsp. lactis in a patient with atrial myxoma: a case report.

We report a case of subacute endocarditis in a 55-year-old patient affected by left atrial myxoma and with a severe mitral regurgitation. Lactococcus lactis subsp. lactis was isolated from blood cultures and infection was eliminated by treatment with amoxicillin-clavulanic acid.

Characterization of the SPECT 5-HT2A receptor ligand 123I-R91150 in healthy volunteers: part 2--ketanserin displacement.

Unlabelled: As part of the radioiodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]5-iodo-2-methoxybenzamide ((123)I-R91150) characterization study, ketanserin challenges were performed on healthy volunteers with the aim of assessing the specificity of (123)I-R91150 binding to subtype 2A of the 5-hydroxytryptamine receptor (5-HT(2A)), the sensitivity of (123)I-R91150 SPECT in measuring ligand displacement, the relationship between ketanserin plasma concentrations and (123)I-R91150 displacement, and the suitability of the cerebellum as a reference region for quantification.

Methods: Dynamic SPECT was performed on 6 healthy men (mean age +/- SD, 21 +/- 0.89 y) from the time of (123)I-R91150 injection until 470 min afterward.

Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: a role for nitric oxide and calcium entry blockade.

1. Propranolol has been prescribed successfully to patients with cardiovascular diseases, but the exact mechanisms by which it reduces peripheral vascular resistance have been poorly investigated. 2.