Contribution of Fc fragment of monoclonal antibodies to tetanus toxin neutralization

Neurotoxicity Research - Monoclonal antibodies (MAbs) against neurotoxin of Clostridium tetani are considered as a novel source of immunoglobulins for passive immunotherapy of tetanus. Toxin...     

Metformin protects PC12 cells against oxygen-glucose deprivation/reperfusion injury

Oxidative stress has a causative role in ischemic reperfusion-induced cell death. Evidence has shown that metformin is capable to reduce ischemic reperfusion injuries. The current study investigated the effect of metformin on ischemia/reperfusion-induced apoptosis in PC12 cells by evaluation of Bcl-2 family proteins expression. Cells were exposed to a time-dependent in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) injury and then treated with metformin. The intracellular reactive oxygen species (ROS) levels were measured. Western blotting was used to examine the expression of anti- and pro-apoptotic proteins. Moreover, the number of apoptotic cell death was evaluated by TUNEL assay. Our results showed that metformin attenuated ROS generation, downregulated pro-apoptotic BAX expression, and upregulated expression of the Bcl-2 protein in the PC12 cells. Moreover, metformin reduced cell death under OGD/R condition which was confirmed by lower apoptotic cell death in the TUNEL assay. These findings suggest that neuroprotective effect of metformin on OGD/R-induced cell death is possibly mediated by inhibition of ROS-induced apoptosis pathway.     

Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid‐Based Solid Dispersion to Improve Rat Sperm Count

Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)‐Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P‐glycoprotein (P‐gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid‐based solid dispersion (TAF2‐SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2‐SD‐treated rats showed significantly twofold (p < 0.001) and fourfold (p < 0.001) higher sperm count than did TAF2‐treated and vehicle‐treated (control) rats, respectively. The study also demonstrated no significant in vitro ileal absorption changes of the quassinoids by P‐gp efflux inhibitors and concentration change or secondary metabolite formation upon in vitro incubation with rat liver homogenates, suggesting that P‐gp‐mediated efflux and presystemic metabolism were not limiting their bioavailability. Further study on orally TAF2‐treated rats confirmed that the area under the curve and bioavailability curve of each quassinoid in the absence and presence of ketoconazole were unchanged. Copyright © 2017 John Wiley & Sons, Ltd.     

Bariatric Surgery in the Elderly Is Associated with Similar Surgical Risks and Significant Long-Term Health Benefits

Purpose

Older age (>?60) has been considered a relative contraindication for bariatric surgery due to increased complication risk. This study examined the risks and benefits of bariatric surgery for patients older than 60 years in Canadian population.

Methods

This was a retrospective cohort study of the Ontario Bariatric Registry: a database recording peri-operative and post-operative outcomes of publicly funded bariatric surgeries across the province. Patients who completed 1 year follow-up, who underwent laparoscopic gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between January 2010 and May 2013, were divided into older (>?60) and younger (>?60) cohorts, and outcomes were compared.

Results

Between January 2010 and May 2013, 3166 registry patients underwent LRYGB or LSG and completed 1-year follow-up. Of these, 204 (6.5%) were older than 60 years, with 175 (85.8%) undergoing LRYGB and 29 (14.2%) LSG. Demographics were similar, except for a higher number of males in the older group (59 (28.9%) versus 452 (15.3%) (p?<?0.001)). No significant difference in complication rate was noted (15% for younger cohort versus 13.8% (p?=?0.889)). The average percentage of excess weight loss was significantly higher in the younger population (60.72% versus 56.25% (p?<?0.05)) overall, however not significantly in the LSG group. Reduction in medication use post-surgery for management of co-morbidities was significantly higher in the older patients (??0.91 versus ??2.03 (p?<?0.001)).

Conclusion

The older cohort who underwent LRYGB or LSG was at no greater risk for intra-operative and post-operative complications and showed greater reduction in medication use post-surgery when compared to the younger cohort.

     

Applications of engineered exosomes in drugging noncoding RNAs for cancer therapy

Noncoding RNAs (ncRNAs) are engaged in key cell biological and pathological events, and their expression alteration is connected to cancer progression both directly and indirectly. A huge number of studies have mentioned the significant role of ncRNAs in cancer prevention and therapy that make them an interesting subject for cancer therapy. However, there are several limitations, including delivery, uptake, and short half-life, in the application of ncRNAs in cancer treatment. Exosomes are introduced as promising options for the delivery of ncRNAs to the target cells. In this review, we will briefly discuss the application and barriers of ncRNAs. After that we will focus on exosome-based ncRNAs delivery and their advantages as well as the latest achievements in drugging ncRNAs with exosomes.     

Diagnosis and management of acute cholecystitis: a single-centre audit of guideline adherence and patient outcomes

BackgroundThe Tokyo Guidelines were published in 2007 and updated in 2013 and 2018, with recommendations for the diagnosis and management of acute cholecystitis. We assessed guideline adherence at our academic centre and its impact on patient outcomes.MethodsThis is a retrospective chart review of patients with acute calculous cholecystitis who underwent cholecystectomy at our institution between November 2013 and March 2015. Severity of cholecystitis was graded retrospectively if it had not been documented preoperatively. Compliance with the Tokyo Guidelines’ recommendations on antibiotic use and time to operation was recorded. Cholecystitis severity groups were compared statistically, and logistic regression was used to determine predictors of complications.ResultsOne hundred and fifty patients were included in the study. Of these, 104 patients were graded as having mild cholecystitis, 45 as having moderate cholecystitis, and 1 as having severe cholecystitis. Severity was not documented preoperatively for any patient. Compliance with antibiotic recommendations was poor (18.0%) and did not differ by cholecystitis severity (p = 0.90). Compliance with the recommendation on time to operation was 86.0%, with no between-group differences (p = 0.63); it improved when an acute care surgery team was involved (91.0% v. 76.0%, p = 0.025). On multivariable analysis, comorbidities (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.19–1.85, p < 0.001) and conversion to laparotomy (OR 13.45, 95% CI 2.16–125.49, p = 0.01) predicted postoperative complications, while severity of cholecystitis, antibiotic compliance and time to operation had no effect.ConclusionIn this study, compliance with the Tokyo Guidelines was acceptable only for time to operation. Although the poor compliance with recommendations relating to documentation of severity grading and antibiotic use did not have a negative affect on patient outcomes, these recommendations are important because they facilitate appropriate antibiotic use and patient risk stratification.