Impact of time interval from the last meal on glucose response to exercise in subjects with type 2 diabetes.

We evaluate the influence of the time interval from the last meal on the blood glucose response to exercise in men with type 2 diabetes. Nineteen men with type 2 diabetes participated in an exercise training program carried out at 60% of maximal oxygen uptake (VO2peak) for 1 h, 3 times a week. Capillary whole blood glucose was measured immediately before and after each exercise session, and the time interval from the last meal (breakfast, lunch, or dinner) was recorded.

Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?

Background: The present study tested the hypothesis that simple variables, such as waist circumference and fasting plasma triglyceride (TG) concentrations, could be used as screening tools for the identification of men characterized by a metabolic triad of nontraditional risk factors (elevated insulin and apolipoprotein [apo] B and small, dense LDL particles).

Methods And Results: Results of the metabolic study (study 1) conducted on 185 healthy men indicate that a large proportion (>80%) of men with waist circumference values >/=90 cm and with elevated TG levels (>/=2.0 mmol/L) were characterized by the atherogenic metabolic triad.

Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity.

The prototype "classic" over-the-counter antihistamine diphenhydramine was shown to interact with the polymorphic P450 enzyme CYP2D6. This project was undertaken to investigate (1) whether diphenhydramine inhibits the biotransformation of the clinically relevant CYP2D6 substrate metoprolol in vitro and (2) whether this in vitro interaction results in a clinically significant pharmacokinetic and pharmacodynamic drug interaction in vivo. In vitro incubations were carried out with microsomes obtained from lymphoblastic cells transfected with CYP2D6 complementary deoxyribonucleic acid to determine the type and extent of inhibition.

Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans.

According to in-vitro studies with microsomes from human livers and from yeast expression systems with high CYP2D6 activity, the major oxidation pathway of venlafaxine is catalysed by CYP2D6. In this study, we investigated the role of the CYP2D6 polymorphism and the effects of low-dose quinidine, a selective inhibitor of, CYP2D6, on the disposition of venlafaxine. Fourteen healthy men, eight with the extensive metabolizer and six with the poor metabolizer phenotype were administered venlafaxine hydrochloride 18.

Ischemia-induced action potential shortening is blunted by d-sotalol in a pig model of reversible myocardial ischemia.

The purpose of this study was to investigate, in an anesthetized pig model of low-flow myocardial ischemia, the electrophysiologic effects of the class III drug d-sotalol during myocardial ischemia. Serial monophasic action potential (MAPD90) recordings and refractory period determinations from the anterior and posterior left ventricular wall were taken in 25 pigs during baseline, after low-flow posterior wall ischemia, after d-sotalol infusion under nonischemic conditions, and after repeated posterior wall ischemia while continuing the drug. Measurements were done at 60 and 150 beats/min after radiofrequency ablation of atrioventricular conduction.

beta-adrenoceptor-stimulated lipolysis of subcutaneous abdominal adipocytes as a determinant of fat oxidation in obese men.

Background: To verify whether an impaired lipolytic capacity of subcutaneous adipocytes may contribute to low rate of fat oxidation.

Design: Relationships between adipose tissue lipolysis of subcutaneous (subc) abdominal and femoral isolated adipocytes and respiratory quotient (RQ) were investigated in 20 obese men (age: 44 +/- 5 years; means +/- SD) studied in a fasting state.

Results: Maximal isoproterenol-induced lipolysis was greater in subcutaneous abdominal than in femoral fat cells even if glycerol release was corrected for variation in cell surface area (P < 0.

Impact of left ventricular diastolic dysfunction on maximal treadmill performance in normotensive subjects with well-controlled type 2 diabetes mellitus.

Patients with type 2 diabetes often have impaired exercise capacity compared with nondiabetic subjects. Left ventricular (LV) diastolic dysfunction has been shown to limit exercise performance in nondiabetic subjects. Men with well-controlled type 2 diabetes were divided into 2 groups: normal LV diastolic function (group 1, n = 9) or LV diastolic dysfunction (group 2, n = 10) based on standard echocardiographic criteria using pulmonary veins and transmitral flow recordings.

Electrophysiological characterization of SCN5A mutations causing long QT (E1784K) and Brugada (R1512W and R1432G) syndromes.

Unlabelled: Familial long QT syndrome (LQTS) and Brugada syndrome are two distinct human hereditary cardiac diseases known to cause ventricular tachyarrhythmias (torsade de pointes) and idiopathic ventricular fibrillation, respectively, which can both lead to sudden death.

Objective: In this study we have identified and electrophysiologically characterized, in patients having either LQTS or Brugada syndrome, three mutations in SCN5A (a cardiac sodium channel gene).

Method: The mutant channels were expressed in a mammalian expression system and studied by means of the patch clamp technique.

Importance of histamine in the cytokine network in the lung through H2 and H3 receptors: stimulation of IL-10 production.

Histamine, a well-known inflammatory mediator, has been implicated in various immunoregulatory effects that are poorly understood. Thus, we tested the hypothesis that histamine inhibits the release of a proinflammatory cytokine, namely TNF, by stimulating the release of an anti-inflammatory cytokine, IL-10. Alveolar macrophages (AMs) from humans, Sprague Dawley rats, and the AM cell line, NR8383, were treated with different concentrations of histamine (10-5-10-7 M) for 2 h prior to their stimulation with suboptimal concentration of LPS (1 ng/ml) for 4 h.

Midterm follow-up of unstented biological valves.

We have used the stentless aortic biosprosthesis for aortic valve replacement during the last 10 years. Since 1988, 647 stentless aortic prosthesis were implanted: 384 unstented heterografts, 176 Ross procedures, and 87 homografts. Patients up to age 50 were offered the Ross procedure, those between the ages of 50 and 60 a homograft, and patients 60 years old and older received heterografts.

Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current.

Introduction: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time-dependent outward potassium current involved in cardiac repolarization (I(K)r).

Methods And Results: Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L.

Involvement of CYP2D6 activity in the N-oxidation of procainamide in man.

Occurrence of a lupus-like syndrome in a significant number of patients treated with procainamide has limited the clinical use of this antiarrhythmic drug. In-vitro studies conducted in our laboratory have demonstrated that CYP2D6 is the major cytochrome P450 isozyme involved in the formation of N-hydroxyprocainamide, a metabolite potentially involved in the drug-induced lupus erythematosus syndrome observed with procainamide. In the current study, we evaluated the role of CYP2D6 activity in the in-vivo oxidation of procainamide in man.

CYP2D6 mutations and therapeutic outcome in schizophrenic patients.

Study Objective: To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs).

Design: Prospective, observational study.

Myocardial blood flow regulation relative to left ventricle pressure and volume in anesthetized dogs.

The influence of left ventricle pressure and volume changes on coronary blood flow was investigated in eight anesthetized dogs. Coronary artery pressure-flow relationships were determined at two levels of left ventricular pressure and volume. The distribution of blood flow within the myocardium was also determined when these relationships varied.

Changes in left ventricular mass and function after aortic valve replacement: a comparison between stentless and stented bioprosthetic valves.

The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to the postoperative changes in left ventricular (LV) mass and function. Forty patients with aortic stenosis undergoing valve replacement with a stentless (20 patients) or a stented (20 patients) bioprosthesis were evaluated early (baseline), 1 year, and 2 years after operation. Left ventricular mass index was calculated with the corrected American Society of Echocardiography formula.

Hemodynamic and physical performance during maximal exercise in patients with an aortic bioprosthetic valve: comparison of stentless versus stented bioprostheses.

Objectives: The objective of this study was to compare stentless bioprostheses with stented bioprostheses with regard to their hemodynamic behavior during exercise.

Background: Stentless aortic bioprostheses have better hemodynamic performances at rest than stented bioprostheses, but very few comparisons were performed during exercise.

Methods: Thirty-eight patients with normally functioning stentless (n = 19) or stented (n = 19) bioprostheses were submitted to a maximal ramp upright bicycle exercise test.

Accelerometric gait analysis for use in hospital outpatients.

Objectives: To provide clinicians with a quantitative human gait analysis tool suitable for routine use.

Methods: We evaluated the reproducibility, sensitivity, and specificity of gait analysis based on measurements of acceleration at a point near the center of gravity of the body. Two accelerometers held over the middle of the low back by a semi-elastic belt were used to record craniocaudal and side-to-side accelerations at a frequency of 50 Hz.

Comparison of propafenone versus procainamide for the acute treatment of atrial fibrillation after cardiac surgery.

A prospective, randomized, double-blind study to compare the efficacy in terminating postoperative atrial fibrillation of the class Ic drug propafenone versus class Ia drug procainamide was conducted. Intravenous propafenone was superior to procainamide in achieving rapid cardioversion and a better rate control with a lower incidence of symptomatic hypotension.

Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes.

Venlafaxine is a newly introduced antidepressant agent. The drug causes selective inhibition of neuronal reuptake of serotonine and norepinephrine with little effect on other neurotransmitter systems. Cases of seizures, tachycardia, and QRS prolongation have been observed following drug overdose in humans.

Effect of respiratory syncytial virus on subsequent allergic sensitization to ovalbumin in guinea-pigs.

Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop recurrent wheezing, asthma and allergic sensitization, but the role of RSV in the pathogenesis of these sequelae is unclear. This study examined whether RSV infection potentiates subsequent allergic sensitization, airway hyperresponsiveness (AHR) and airway inflammation induced by repeated exposures to aerosolized ovalbumin (OA) in guinea-pigs. Guinea-pigs received either RSV or sham inoculum, followed by exposures to OA- or saline-containing aerosols to form the following groups: 1) noninfected, nonsensitized controls (sham/saline group); 2) RSV-infected, nonsensitized animals (RSV/ saline group); 3) noninfected, OA-sensitized animals (sham/OA group); 4) RSV infection and first OA exposure on the same day (RSV/OA group), and 5) RSV infection six days prior to first OA exposure (RSV6/OA group).

Lysophosphatidylcholine, a metabolite which accumulates early in myocardium during ischemia, reduces gap junctional coupling in cardiac cells.

Lysophosphatidylcholine (LPC) is a metabolite that accumulates rapidly during cardiac ischemia in animal and human hearts. LPC induces electrophysiological changes including action potential alterations and cardiac arrhythmias. Since there is increasing evidence that disrupted cell coupling can contribute to the generation of cardiac arrhythmias under ischemic conditions, this study was designed to assess the effects of LPC on gap junction coupling between cardiac cell pairs using the dual whole-cell voltage-clamp technique.

Modulation of HERG potassium channel properties by external pH.

We expressed the human eag-related gene (HERG), known to encode for the cardiac potassium channel IKr, in Chinese hamster ovary (CHO) cells. This study investigated effects of external pH (pHo) on HERG current properties using the whole-cell patch-clamp technique. We observed that current amplitude was decreased and kinetics of activation and deactivation were faster when pHo was lowered from 7.

Liver pathology and the metabolic syndrome X in severe obesity.

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery.

Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine.

Caffeine consumption is extensive in industrialized countries and its role in drug-drug interactions is often overlooked. CYP1A2, the major cytochrome P450 isoform involved in the metabolism of caffeine, has also been implicated in the formation of N-hydroxymexiletine, the major metabolite of mexiletine. Therefore, the objective of this study was to assess the effects of a clinically relevant dosage of caffeine on the stereoselective disposition of mexiletine.