Transforming growth factor-beta 3 alters intestinal smooth muscle function: implications for gastroschisis-related intestinal dysfunction.

BACKGROUND: Gastroschisis (GS) is a congenital abdominal wall defect that results in the development of GS-related intestinal dysfunction (GRID). Transforming growth factor-ß, a pro-inflammatory cytokine, has been shown to cause organ dysfunction through alterations in vascular and airway smooth muscle. The purpose of this study was to evaluate the effects of TGF-ß3 on intestinal smooth muscle function and contractile gene expression. METHODS: Archived human intestinal tissue was analyzed using immunohistochemistry and RT-PCR for TGF-ß isoforms and markers of smooth muscle gene and micro-RNA contractile phenotype. Intestinal motility was measured in neonatal rats ± TGF-ß3 (0.2 and 1 mg/kg). Human intestinal smooth muscle cells (hiSMCs) were incubated with fetal bovine serum ± 100 ng/ml of TGF-ß 3 isoforms for 6, 24 and 72 h. The effects of TGF-ß3 on motility, hiSMC contractility and hiSMC contractile phenotype gene and micro-RNA expression were measured using transit, collagen gel contraction assay and RT-PCR analysis. Data are expressed as mean ± SEM, ANOVA (n = 6-7/group). RESULTS: GS infants had increased immunostaining of TGF-ß3 and elevated levels of micro-RNA 143 & 145 in the intestinal smooth muscle. Rats had significantly decreased intestinal transit when exposed to TGF-ß3 in a dose-dependent manner compared with Sham animals. TGF-ß3 significantly increased hiSMC gel contraction and contractile protein gene and micro-RNA expression. CONCLUSION: TGF-ß3 contributed to intestinal dysfunction at the organ level, increased contraction at the cellular level and elevated contractile gene expression at the molecular level. A hyper-contractile response may play a role in the persistent intestinal dysfunction seen in GRID.

Chronic antiplatelet therapy and mortality among patients with infective endocarditis.

Whether antiplatelet therapy is associated with better outcomes among patients with infective endocarditis (IE) remains controversial. A retrospective study was conducted concerning all patients with IE, treated in a tertiary-care centre of Canada between 1991 and 2006, who satisfied the modified Duke criteria for a definite or possible IE. The primary outcome was all-cause mortality within 90 days of diagnosis. A secondary outcome was the development of major systemic embolism. In total, 241 patients satisfied the inclusion criteria, 75 of whom had been on chronic antiplatelet therapy prior to developing endocarditis. Seventy-one (29.5%) patients died. According to multivariate analysis, age, a high Charlson score, aortic valve involvement, myocardial infarction and presence of a perivalvular abscess were strongly associated with mortality. Undergoing valvular replacement (adjusted OR (AOR) 0.28, 95% CI 0.09-0.84) and chronic antiplatelet therapy before IE (AOR 0.27, 95% CI 0.11-0.64) correlated with lower mortality. There was a trend for lower mortality among patients started on antiplatelet drugs after admission (AOR 0.29, 95% CI 0.08-1.13). The effect of aspirin on mortality was much the same in patients who received 325 or 80 mg daily. Chronic antiplatelet therapy was not associated with a significantly lower risk of major embolism. In conclusion, chronic antiplatelet therapy was associated with lower mortality among patients with IE, independently of any effect on major embolism. Whether or not a beneficial effect could be replicated by initiating antiplatelet therapy at the time of diagnosis remains unproven.

Aqueous solubility and Daphnia magna chronic toxicity of di(2-ethylhexyl) adipate.

A water solubility of 5.5 (+/-0.22) microg/L for di(2-ethylhexyl) adipate (DEHA) was measured using the slow-stir method. This value is consistent with computer estimations and over two orders of magnitude lower than that previously determined using the shake-flask method. We performed a 21-day chronic Daphnia magna limit test at an average exposure of 4.4 microg/L in laboratory diluent water to avoid insoluble test material and avoid physical entrapment. One hundred percent of the DEHA-treated organisms survived compared to 90% survival in both the controls and solvent controls. Mean neonate reproduction was 152, 137, and 148 and mean dry weight per surviving female was 0.804, 0.779, and 0.742 mg in the DEHA treatment, control, and solvent control, respectively. No adverse effects were observed.

Toxicity of benzotriazole and benzotriazole derivatives to three aquatic species.

Benzotriazole and its derivatives comprise an important class of corrosion inhibitors, typically used as trace additives in industrial chemical mixtures such as coolants, deicers, surface coatings, cutting fluids, and hydraulic fluids. Recent studies have shown that benzotriazole derivatives are a major component of aircraft deicing fluids (ADFs) responsible for toxicity to bacteria (Microtox). Our current research compared the toxicity of benzotriazole (BT), two methylbenzotriazole (MeBT) isomers, and butylbenzotriazole (BBT). Acute toxicity assays were used to model the response of three common test organisms: Microtox bacteria (Vibrio fischeri), fathead minnow (Pimephales promelas) and water flea (Ceriodaphnia dubia). The response of all the three organisms varied over two orders of magnitude among all compounds. Vibrio fischeri was more sensitive than either C. dubia or P. promelas to all the test materials, while C. dubia was less sensitive than P. promelas. The response of test organisms to unmethylated benzotriazole and 4-methylbenzotriazole was similar, whereas 5-methylbenzotriazole was more toxic than either of these two compounds. BBT was the most toxic benzotriazole derivative tested, inducing acute toxicity at a concentration of < or = 3.3 mg/l to all organisms.

Adverse effect of helicopter flight on the ability to palpate carotid pulses.

STUDY OBJECTIVE: To determine if the air medical helicopter environment compromises the ability to palpate carotid pulses. DESIGN: Using a carotid pulse model, flight nurses were tested for their ability to palpate the simulated carotid pulse at normal (120/80 mm Hg) and low (80/60 mm Hg) blood pressures on the ground and during helicopter flight. SETTING: Palpation tests were performed during flight in an MBB BO-105 twin-turbine engine, single-rotor air medical helicopter; control palpation tests were performed on the ground. TYPE OF PARTICIPANTS: Ten flight nurses. MEASUREMENTS AND MAIN RESULTS: Tracings of pulsatile pressure from the carotid pulse model verified its ability to simulate a wide range of arterial pressures. Analyses of variance for repeated measures, including polynomial contrasts, were performed to compare the number of correct detections of the presence or absence of pulse pressures in flight with the number of correct detections in the two control conditions for both carotid pulse pressures. The mean in-flight number of correct detections was lower than both the preflight and postflight control tests, which were themselves nearly equal, at each simulated carotid pulse pressure. The quadratic terms for both the 120/80 mm Hg trial (F1,14 = 9.28; P = .0087) and the 80/60 mm Hg trial (F1,18 = 5.69; P = .0283) were statistically significant. CONCLUSION: Factors associated with transport of patients in an MBB BO-105 helicopter impair the ability of flight nurses to detect carotid pulses in a simulated physiologic model.

Training community developmental disabilities associates: a collaborative model.

Direct care staff play critical roles in contributing to the successful community adjustment of individuals with developmental disabilities. The current shortage of qualified personnel for these positions, however, will hinder future community integration efforts, particularly as individuals with more intensive needs attempt to live in the community. Improvements, both in the training of staff and in the pay and other incentives they receive, are needed. One response to this growing need is associate degree training that is being provided by a few community colleges and technical schools throughout the country. This article briefly describes the implementation and major components of such a program now being offered through Wisconsin's Vocational, Technical, and Adult Education System. Developed in response to local needs and representing an ongoing collaborative effort among the academic, advocacy, and service communities, the program also illustrates an important role the University Affiliated Facility can play in promoting exemplary training.