Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release Across Glucose Tolerance in Man: Lack of Correlation with β Cell Function.

Background: The aims of this study were to 1. define the responses of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin secretion.

Outpatient versus inpatient mixed meal tolerance and arginine stimulation testing yields comparable measures of variability for assessment of beta cell function.

Unlabelled: Standard practice to minimize variability in beta cell function (BCF) measurement is to test in inpatient (IP) settings. IP testing strains trial subjects, investigators, and budgets. Outpatient (OP) testing may be a solution although there are few reports on OP BCF testing variability.

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series.

Objective: Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states.

Research Design And Methods: Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT).

Arginine is preferred to glucagon for stimulation testing of β-cell function.

A key aspect of research into the prevention and treatment of type 2 diabetes is the availability of reproducible clinical research methodology to assess β-cell function. One commonly used method employs nonglycemic secretagogues like arginine (arg) or glucagon (glgn). This study was designed to quantify the insulin response to arg and glgn and determine test repeatability and tolerability.

The effects of age and gender on the pharmacokinetics and pharmacodynamics in healthy subjects of the plasminogen activator, lanoteplase.

Aims: To investigate the influence of age and gender on the intravenous pharmacokinetics and pharmacodynamics of the plasminogen activator, lanoteplase.

Methods: Forty healthy subjects (10 each of young males, elderly males, young females and elderly females) received a single bolus 10 kU kg(-1) intravenous dose of lanoteplase. Plasma from blood serially collected for 24 h post-dose was analyzed for lanoteplase (antigen), fibrinogen, plasminogen and α2-antiplasmin concentrations, plasma plasminogen activation activity (PPAA) and rapid plasminogen activator inhibitor (PAI-1).

Hormonal status, fertility, and pregnancy before and after bariatric surgery.

At the present time, the exact etiology and developmental course of obesity in many individuals is still being debated. The majority of healthcare professionals are in agreement, however, that morbidly obese persons are at risk for a wide range of health problems, both before and after bariatric surgery. Obesity is, unfortunately, a condition in which the disease as well as the available treatments have the potential to cause serious alterations in health status.

Comparison of pharmacokinetics of lanoteplase and alteplase during acute myocardial infarction.

Objective: Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of lanoteplase with those of a bolus plus two-step infusion of alteplase.

Design: Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction.

Elimination of mouse allergens in the working environment: assessment of individually ventilated cage systems and ventilated cabinets in the containment of mouse allergens.

Background: Laboratory animal allergy is an important occupational disease that is preventable by reduction of exposure to mammalian allergens.

Objective: The purpose of this investigation was to assess the efficacy of safety equipment in containing mouse urinary protein (MUP)--specifically, individually ventilated cage (IVC) systems and class I--type and class II ventilated cabinets.

Methods: Six IVC systems (which are used to house rodents) were operated at positive and negative pressure.

Pharmacodynamics and Pharmacokinetics of Irbesartan in Patients With Mild to Moderate Hypertension.

BACKGROUND: The pharmacodynamics (plasma angiotensin II [AII], plasma renin activity [PRA], renal function, blood pressure [BP], urinary excretion of major metabolites of prostacyclin [PGI(2)-M], and thromboxane A(2) [TXA(2)-M]) and pharmacokinetics of irbesartan were assessed in hypertensive patients. METHODS AND RESULTS: Twenty-four white patients with seated diastolic blood pressure 95 to 110 mmHg were randomized to double-blind irbesartan 300 mg or placebo once daily for 4 weeks, following a placebo lead-in. Irbesartan-treated patients had significantly greater 24-hour area under the curve values for mean change from baseline in AII and PRA versus placebo-treated patients on day B15 (AII [pg |mZ h/mL]: 261 +/- 515 vs 12 +/- 51; PRA [(ng/mL/h); h]:74 +/-162 vs -2 +/-14; P values >.

Effect of food on the bioavailability of stavudine in subjects with human immunodeficiency virus infection.

A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4(+) cell counts of >/=200/microliter received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments.

Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis.

The effect of hepatic impairment on the clinical pharmacology of the angiotensin II (AII) receptor antagonist irbesartan was assessed by comparing pharmacokinetic and pharmacodynamic parameters in 10 patients with hepatic cirrhosis with a matched group of 10 healthy volunteers. The pharmacokinetics and pharmacodynamics of irbesartan, 300 mg taken orally once daily, were evaluated after single- and multiple-dose (7 consecutive days) administration to normotensive subjects in an open-label, multiple-dose, parallel group study. Pharmacokinetic data obtained after administration of single and multiple doses of irbesartan showed no significant difference between the two groups in time to maximum observed plasma concentration of drug (tmax), half-life (t1/2), area under the plasma concentration-time curve (AUC), apparent oral clearance (Cl(t)/F), renal clearance (Cl(r)), and accumulation index (AI).

Pharmacokinetic and pharmacodynamic evaluation during coadministration of nefazodone and propranolol in healthy men.

Potential interactions between nefazodone (200 mg every 12 hours) and propranolol (40 mg every 12 hours) were assessed in 18 healthy male volunteers in an open-label, randomized, three-way crossover study. The nature, frequency, and severity of adverse events during coadministration of nefazodone and propranolol were similar to those observed with either treatment alone. There were no clinically significant effects on vital signs, electrocardiographic results, or laboratory parameters.

Pharmacokinetic and pharmacodynamic evaluation of warfarin and nefazodone coadministration in healthy subjects.

Nefazodone, an antidepressant with serotonin and norepinephrine receptor modulating activity, is highly protein bound and eliminated by oxidative metabolism. This study evaluated the potential for clinically significant drug interactions with warfarin and nefazodone coadministration. Eighteen subjects received warfarin daily for 14 days, achieving steady-state warfarin concentrations and a stable prothrombin ratio.