Orexin A decreases lipid peroxidation and apoptosis in a novel hypothalamic cell model

Current data support the idea that hypothalamic neuropeptide orexin A (OxA; hypocretin 1) mediates resistance to high fat diet-induced obesity. We previously demonstrated that OxA elevates spontaneous physical activity (SPA), that rodents with high SPA have higher endogenous orexin sensitivity, and that OxA-induced SPA contributes to obesity resistance in rodents. Recent reports show that OxA can confer neuroprotection against ischemic damage, and may decrease lipid peroxidation. This is noteworthy as independent lines of evidence indicate that diets high in saturated fats can decrease SPA, increase hypothalamic apoptosis, and lead to obesity. Together data suggest OxA may protect against obesity both by inducing SPA and by modulation of anti-apoptotic mechanisms. While OxA effects on SPA are well characterized, little is known about the short- and long-term effects of hypothalamic OxA signaling on intracellular neuronal metabolic status, or the physiological relevance of such signaling to SPA. To address this issue, we evaluated the neuroprotective effects of OxA in a novel immortalized primary embryonic rat hypothalamic cell line. We demonstrate for the first time that OxA increases cell viability during hydrogen peroxide challenge, decreases hydrogen peroxide-induced lipid peroxidative stress, and decreases caspase 3/7 induced apoptosis in an in vitro hypothalamic model. Our data support the hypothesis that OxA may promote obesity resistance both by increasing SPA, and by influencing survival of OxA-responsive hypothalamic neurons. Further identification of the individual mediators of the anti-apoptotic and peroxidative effects of OxA on target neurons could lead to therapies designed to maintain elevated SPA and increase obesity resistance.     

Improvement of Oral Bioavailability and Anti-Tumor Effect of Zingerone Self-Microemulsion Drug Delivery System

This study sought to prepare a self-microemulsion drug delivery system containing zingerone (Z-SMEDDS) to improve the low oral bioavailability of zingerone and anti-tumor effect. Z-SMEDDS was characterized by particle size, zeta potential and encapsulation efficiency, while its pharmacokinetics and anti-tumor effects were also evaluated. Z-SMEDDS had stable physicochemical properties, including average particle size of 17.29 ± 0.07 nm, the zeta potential of -22.81 ± 0.29 mV, and the encapsulation efficiency of 97.96% ± 0.02%. In vitro release studies have shown the release of zingerone released by Z-SMEDDS was significantly higher than free zingerone in different release media. The relative oral bioavailability of Z-SMEDDS was 7.63 times compared with free drug. Meanwhile, the half inhibitory concentration （IC50）of Z-SMEDDS and free zingerone was 8.45 μg/mL and 13.30 μg/mL, respectively on HepG2. This study may provide a preliminary basis for further clinical research and application of Z-SMEDDS.     

The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis

BACKGROUND AND AIMS: The evidence that proton pump inhibitor (PPI) therapy affects symptoms of nonulcer dyspepsia is conflicting. We conducted a systematic review to evaluate whether PPI therapy had any effect in nonulcer dyspepsia and constructed a health economic model to assess the cost-effectiveness of this approach. METHODS: Electronic searches were performed using the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, and SIGLE until September 2002. Dyspepsia outcomes were dichotomized into cured/improved versus same/worse. Results were incorporated into a Markov model comparing health service costs and benefits of PPI with antacid therapy over 1 year. RESULTS: Eight trials were identified that compared PPI therapy with placebo in 3293 patients. The relative risk of remaining dyspeptic with PPI therapy versus placebo was .86 (95% confidence interval, .78-.95; P = .003, random-effects model) with a number needed to treat of 9 (95% confidence interval, 5-25). There was statistically significant heterogeneity between trials (heterogeneity chi(2) = 30.05; df = 7; P < .001). The PPI strategy would cost an extra US dollar 278/month free from dyspepsia if the drug cost US dollar 90/month. If a generic price of US dollar 19.99 is used, then a PPI strategy costs an extra US dollar 57/month free from dyspepsia. A third-party payer would be 95% certain that PPI therapy would be cost-effective, provided they were willing to pay US dollar 94/month free from dyspepsia. CONCLUSIONS: PPI therapy may be a cost-effective therapy in nonulcer dyspepsia, provided generic prices are used.     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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Termination of Living Anionic Polymerization of Butyl Acrylate with α‐(Chloromethyl)acrylate for End‐Functionalization and Application to the Evaluation of Monomer Reactivity

Anionic polymerization of n‐butyl acrylate (nBA) in toluene initiated with a binary initiator, isopropyl α‐lithioisobutyrate/ethylaluminum bis(2,6‐di‐tert‐butylphenoxide) at ?60 °C, is terminated with ethyl α‐(chloromethyl)acrylate (ECMA) to afford a poly(nBA) possessing an acryloyl group at the terminal with 80% of termination efficiency. The reactivity of nBA against a polymer anion of methyl methacrylate formed under identical conditions is estimated relative to the termination with ECMA by reacting a mixture of nBA and ECMA followed by ¹H NMR spectroscopic chain‐end analysis; the relative reactivity of nBA is found 80 times or more higher than ECMA.

     

“大肠者传道之官”新识

在过去相当长的一段时期内,中医学界仅把大肠视为排泄器官。但大肠与神经传导、神经系统病变之间存在紧密联系,以"大肠主神志传导"补释"大肠者传道之官",而不使用"肠脑相通"新理论主要是因为以下2点:①中医学的发展要以经典为主线,凡是能够在原有理念下依附存在的学说,没有必要也不应该作为新的理论提出。②尚有很多周围神经病变的病位并不在中枢神经系统,无法用"肠脑相通"理论解释。"大肠主神志传导"一说旨在提出"神经系统病变从肠论治",更符合中医学整体、互联、恒动的观念。