Undergraduate performance in a domestic animal laboratory taught via distance education.

The objective of this study was to determine if laboratory modules of an undergraduate animal anatomy course offered in distance education (DistEd) format were as effective as face-to-face (F2F) format in helping students learn. Students (n = 159) completed an anatomy pretest as well as a presurvey to assess prior DistEd experience. Alternating each week, laboratory topics were presented either as F2F or as virtual DistEd laboratories. Two laboratory examinations were administered and included material from both laboratory formats (DistEd and F2F). Questions from the pretest were also included and used to generate the posttest scores. At the end of the semester, students completed a postsurvey to determine if DistEd was a viable alternative to F2F. Student grades on each examination were compared using an ANOVA model that included main effects of presentation method (DistEd, F2F), semester (fall, spring), and their interaction. Learning was evaluated based on the performances of students on pre- and posttests using unpaired t-tests. There was an increase (P < 0.0001) in anatomy post- vs. pretest scores for both semesters, indicative of student learning, although there was no effect of presentation method (F2F or DistEd). On exam 1, students achieved greater scores in fall 2008 (P < 0.0001) on material presented via DistEd compared with that presented as F2F. However, in spring 2009 students scored better on material presented as F2F. There was no effect of presentation method on exam 2 scores for either semester. Based on the postsurvey, 79.3% of students in fall 2008 and 52% of students from spring 2009 agreed that DistEd laboratories were a viable alternative to F2F laboratories. The results of this study support the conclusion that anatomy material can be taught effectively by distance education methods.

Long-term effects of increased dietary polyunsaturated fat from walnuts on metabolic parameters in type II diabetes.

BACKGROUND/OBJECTIVES: Most dietary interventions have metabolic effects in the short term, but long-term effects may require dietary fat changes to influence body composition and insulin action. This study assessed the effect of sustained high polyunsaturated fatty acids (PUFA) intake through walnut consumption on metabolic outcomes in type II diabetes. SUBJECTS/METHODS: Fifty overweight adults with non-insulin-treated diabetes (mean age 54+/-8.7 years) were randomized to receive low-fat dietary advice +/-30 g per day walnuts targeting weight maintenance (around 2000 kcal, 30% fat) for 1 year. Differences between groups were assessed by changes in anthropometric values (body weight, body fat, visceral adipose tissue) and clinical indicators of diabetes over treatment time using the general linear model. RESULTS: The walnut group consumed significantly more PUFA than the control (P=0.035), an outcome attributed to walnut consumption (contributing 67% dietary PUFA at 12 months). Most of the effects were seen in the first 3 months. Despite being on weight maintenance diets, both groups sustained a 1-2 kg weight loss, with no difference between groups (P=0.680). Both groups showed improvements in all clinical parameters with significant time effects (P<0.004), bar triacylglycerol levels, but these were just above normal to begin with. The walnut group produced significantly greater reductions in fasting insulin levels (P=0.046), an effect seen largely in the first 3 months. CONCLUSIONS: Dietary fat can be manipulated with whole foods such as walnuts, producing reductions in fasting insulin levels. Long-term effects are also apparent but subject to fluctuations in dietary intake if not of the disease process.

Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects.

Potential for inhibition of CYP3A activity by simvastatin, an HMG-CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. On day 7, an intravenous injection of 3 microCi [14C N-methyl]erythromycin for the erythromycin breath test (EBT) was coadministered with a 2 mg oral solution of midazolam. The values for percent 14C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg. The 95% confidence interval was 0.97 to 1.18 for EBT and 0.99 to 1.23 for midazolam AUC. In addition, the total urinary recoveries of midazolam and its 1'-hydroxy metabolites (free plus conjugate) obtained from both treatments were not statistically different (p > 0.200). These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes.

Antiplatelet effects of MK-852, a platelet fibrinogen receptor antagonist, in healthy volunteers.

MK-852, a cyclic heptapeptide, is a potent platelet fibrinogen receptor antagonist. When administered to normal healthy male subjects by 1- and 4-hour constant rate intravenous infusions, it provides a generally well-tolerated and reversible means of inhibition of platelet function. At infusion rates of 1 microgram/kg/min for 1 hour and 0.44 microgram/kg/min for 4 hours, respectively, MK-852 extended baseline bleeding time by greater than 2.2-fold and 2.6-fold, inhibited ADP-induced platelet aggregation by 76% and 69%, and inhibited collagen-induced platelet aggregation by 65% and 67%, respectively. The pharmacokinetics of MK-852 include an elimination half-life of approximately 2 hours, total clearance of about 150 ml/min, and volume of distribution of about 18 liters. Examination of the relationship between MK-852 whole-blood concentration in vitro and inhibition of platelet aggregation showed an EC50 of about 55 ng/ml and a Hill coefficient of 1.55. The infusions were generally well tolerated, with no study drug-related changes in blood counts or biochemical profiles.

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37 degrees C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 microgram/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.

Concurrent administration of the erythromycin breath test (EBT) and oral midazolam as in vivo probes for CYP3A activity.

Given the prominent role of CYP3A in the metabolism of drugs, it is important to identify whether new chemical entities will affect this enzyme system and produce clinically relevant drug interactions. This study evaluated concomitant administration of intravenous [14C N-methyl] erythromycin (3 microCi) (erythromycin breath test; EBT) and 2 mg oral midazolam as probes of systemic and of systemic plus presystemic CYP3A activity, respectively. Twelve males received the probes in a two-period crossover fashion: one period included the probes on two occasions, 5 days apart; in the second period, 200 mg ketoconazole was given orally 2 hours prior to the probes. The within-subject CV for EBT (%14CO2/h) and midazolam AUC0-last was 4.9% and 16.9%, respectively. Ketoconazole reduced %14CO2/h by 43% and increased midazolam AUC0-last by approximately fivefold. In a nonrandomized third period (N = 5), ketoconazole was given simultaneously with midazolam (no EBT); midazolam AUC0-last was similar whether ketoconazole was given 2 hours prior to or simultaneously with the midazolam. The low midazolam dose was generally well tolerated; mild sedation was occasionally seen. Concurrent administration of the EBT and oral midazolam is a sensitive and reproducible tool to screen new chemical entities for potentially important CYP3A interactions.

Effect of multiple doses of rifampin on the [14C N-methyl] erythromycin breath test in healthy male volunteers.

The erythromycin breath test (EBT), which measures 14CO2 produced from [14C N-methyl] erythromycin, is one of the most frequently employed measures to examine drug interactions involving cytochrome P450 3A4 (CYP3A). However, the reproducibility and reliability of this test, and the effects of drugs that alter CYP3A activity, continue to be defined. In this study, the reproducibility of the EBT was evaluated in eight healthy volunteers before and after oral administration of 600 mg of rifampin daily for 8 days. Two sequential EBT determinations performed 5 days apart before rifampin administration were highly reproducible. Rifampin induced CYP3A, reflected in a mean percent (+/- standard deviation) increase in EBT values of 86 +/- 30%. Recovery of enzyme function after discontinuation of rifampin for 17 days was manifested as a return of EBT values to preinduction levels. These results support the utility of EBT as a valid, reproducible, and reliable measure of CYP3A activity in vivo.

Pharmacokinetics and pharmacodynamics of tepoxalin after single oral dose administration to healthy volunteers.

This study was conducted to examine the pharmacokinetics and pharmacodynamics of tepoxalin in healthy volunteers, an antiinflammatory compound that inhibits cyclooxygenase and lipoxygenase. Tepoxalin was absorbed after oral administration of single doses from 35 to 300 mg, after which it was rapidly converted to an acidic metabolite, RWJ 20142, which inhibits cyclooxygenase but not lipoxygenase. The areas under the concentration-time curve (AUC) of tepoxalin and RWJ 20142 in plasma increased in a dose-dependent fashion. Administration of the lowest dose of tepoxalin completely inhibited whole blood cyclooxygenase for the entire period of observation. This inhibition correlated closely with that of secretion and aggregation induced by collagen of platelets obtained from these subjects. Similarly, administration of tepoxalin was associated with significant inhibition of lipoxygenase in whole blood. Lipoxygenase was inhibited a maximum of 60% in a time-dependent fashion, and the duration of inhibition was dose-dependent. These studies demonstrate that tepoxalin inhibits whole blood cyclooxygenase, lipoxygenase, and platelet function after oral administration in humans.

Elder abuse peer support partners: a family violence prevention strategy utilizing volunteers.

The Elder Abuse Resource Centre, a program of the Winnipeg, Manitoba-based Age & Opportunity Inc., provides counselling, information/referral, community education and research and data collection services related to family violence issues that affect older adults (60+). Volunteers have been involved in every aspect of the Centre's operations since its inception in 1990 and are key to the Centre's existence. This article will describe the Elder Abuse Resource Centre's Peer Support Volunteer Program, beginning with the rationale for establishing this vital volunteer position. The primary role that training has played in maintaining a quality volunteer program will also be addressed.

Plasma elevations of histamine and a prostaglandin metabolite in acute asthma.

Recent studies of laboratory-provoked asthma have suggested that asthma is an inflammatory disease of lower airways. The purpose of this study was to measure the systemic elaboration of 2 bronchoconstrictive inflammatory mediators during naturally acquired acute asthma utilizing a prospective, serial-sampling protocol. Plasma levels of 13,14-dihydro-15-keto-PGF2 alpha and histamine were measured by radioimmunoassay and radioenzymatic assay, respectively, in 23 children with acute asthma. Mean PG metabolite and histamine values (pg/ml) before (167 +/- 72, 1,029 +/- 378) and 10 to 90 min after (377 +/- 145, 1,000 +/- 489) initial therapy were significantly higher than those of the same children after resolution of asthma (2.9 +/- 0.2, 260 +/- 42) and those of normal children (4.3 +/- 0.9, 240 +/- 14). Peak PG metabolite levels were significantly higher in children who presented with PEFR values (% predicted) less than 40% (1,234 +/- 432) compared with those who presented with greater than 40% (404 +/- 296), and in children with post-therapy improvement in PEFR of less than 20% (1,281 +/- 470) compared with those with greater than 20% (365 +/- 226). Histamine levels were significantly higher in children with post-therapy improvement in PEFR of less than 20% (2,560 +/- 1,600) compared with those with greater than 20% (475 +/- 100), and in hospitalized (3,915 +/- 1,910) compared with nonhospitalized (408 +/- 130) children. Significant differences were not observed on the basis of corticosteroid dependence, allergic disposition, or type of initial therapy. These data suggest a role for histamine and PGF2 alpha in the pathogenesis of airway inflammation in acute asthma.

High-performance liquid chromatographic determination of N-acetylcysteine in human serum following acetaminophen overdosage.

An analytical method has been developed for the determination of N-acetylcysteine in human serum following acetaminophen overdosage in humans. Serum samples were treated with dithiothreitol and the protein-freed product was derivatized with 2,4-dinitrofluorobenzene. N-Acetylhomocysteine thiolactone was used as an internal standard. Following diethyl ether extraction, the components were separated on a reversed-phase column with retention times of 7.4 and 9.9 min for N-acetylcysteine and internal standard, respectively. Ultraviolet detection at 365 nm was employed and little interference was noted from other serum components. The method has been applied to quantitation of N-acetylcysteine given as treatment for acetaminophen intoxication.

Development of ribulose 1,5-diphosphate carboxylase in nonphotosynthetic endosperms of germinating castor beans.

Ribulose 1,5-diphosphate (RuDP) carboxylase has been partially purified from dark-grown nonphotosynthetic endosperms of germinating castor beans (Ricinus communis var. Hale). The Km values for RuDP, HCO(3) (-), and Mg(2+) are 0.51, 33, and 1.78 mm, respectively. The pH optimum for the carboxylation reaction is pH 7.5. Germination is required for the development of the carboxylase in the endosperms. The enzyme reaches a maximal activity in 4- to 5-day-old dark-grown seedlings (which have an endosperm weight of approximately 0.75 g fresh weight/bean) and then declines. Total endosperm carboxylase activity is 1230 nmoles/min.g fresh weight which is 25 and 50% of the total activity developed in soybean and maize leaves, respectively. Specific activity of the carboxylase in crude soluble endosperm preparations (which contain enzymic and storage protein) is 0.05 mumole/min.mg protein. This is 5 times greater than the specific activity of RuDP carboxylase in soluble preparations from etiolated leaves. During germination the V(max) of the endosperm carboxylase for RuDP increases 10-fold. Development of the enzyme is inhibited 90% by the exposure of the endosperm to 2 mug/ml cycloheximide or 50 mug/ml chloramphenicol. Light (or phytochrome Pfr) is not required for the synthesis of the enzyme. Electron photomicrographs of dark-grown endosperm cells (with peak RuDP carboxylase activity) show proplastids with several invaginations of the inner membrane but no prolamellar-like structures.