A comparative pH-dissolution profile study of selected commercial levothyroxine products using inductively coupled plasma mass spectrometry

Levothyroxine (T4) is a narrow therapeutic index drug with classic bioequivalence problem between various available products. Dissolution of a drug is a crucial step in its oral absorption and bioavailability. The dissolution of T4 from three commercial solid oral dosage forms: Synthroid^® (SYN), generic levothyroxine sodium by Sandoz Inc. (GEN) and Tirosint^® (TIR) was studied using a sensitive ICP-MS assay. All the three products showed variable and pH-dependent dissolution behaviors. The absence of surfactant from the dissolution media decreased the percent T4 dissolved for all the three products by 26-95% (at 30 min). SYN dissolution showed the most pH dependency, whereas GEN and TIR showed the fastest and highest dissolution, respectively. TIR was the most consistent one, and was minimally affected by pH and/or by the presence of surfactant. Furthermore, dissolution of T4 decreased considerably with increase in the pH, which suggests a possible physical interaction in patients concurrently on T4 and gastric pH altering drugs, such as proton pump inhibitors. Variable dissolution of T4 products can, therefore, impact the oral absorption and bioavailability of T4 and may result in bioequivalence problems between various available products.     

Rapamycin, an mTOR inhibitor, disrupts triglyceride metabolism in guinea pigs

This study was designed to define some of the mechanisms by which rapamycin (RAPA), an mTOR inhibitor, induces hypertriglyceridemia when used as an immunosuppressive or antiproliferative agent and to determine whether low doses result in less undesirable side effects. Thirty male guinea pigs (n=10 per group) were randomly assigned to control (no RAPA), low-RAPA (0.08 mg/d), or high-RAPA (0.85 mg/d) treatment for 3 weeks. Rapamycin treatment resulted in more than a 2-fold increase in plasma triglycerides (TG) (P<.01), whereas no differences were observed in plasma cholesterol between RAPA and control groups. Low-RAPA treatment resulted in lower concentrations of cholesterol in the aorta (28.6%) and lower hepatic acyl-CoA cholesteryl acyltransferase activity compared to control and high-RAPA groups (P<.01). In addition, acyl-CoA cholesteryl acyltransferase activity was positively correlated with aortic cholesterol (r=0.43, P<.05). In contrast, aortic TG concentrations were higher in RAPA-treated guinea pigs than in control (P<.01). Very low density lipoprotein and low-density lipoprotein particles isolated from guinea pigs treated with RAPA were larger in size and contained more TG molecules than particles from control animals. Interestingly, plasma free fatty acids and fasting plasma glucose were 65% and 72% higher in the high-RAPA group than in control (P<.01). Tumor necrosis factor-alpha concentrations in the aorta were 3.6- and 10.4-fold higher in the low-RAPA and high-RAPA groups than in control guinea pigs (P<.01). These results suggest that RAPA interferes with TG metabolism by altering the insulin signaling pathway, inducing increased secretion of very low density lipoprotein and promoting deposition of TG in the aorta. Low RAPA was found to decrease cholesterol accumulation in tissue (liver and aorta) compared to high RAPA, suggesting that lower doses could be less detrimental to transplant patients.     

WriteSim TCExam - An open source text simulation environment for training novice researchers in scientific writing

Background  

The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers)     

Cholecystectomy Concomitant with Laparoscopic Gastric Bypass: A Trend Analysis of the Nationwide Inpatient Sample from 2001 to 2008

Background  

Gallstone formation is common in obese patients, particularly during rapid weight loss. Whether a concomitant cholecystectomy should be performed during laparoscopic gastric bypass surgery is still contentious. We aimed to analyze trends in concomitant cholecystectomy and laparoscopic gastric bypass surgery (2001–2008), to identify factors associated with concomitant cholecystectomy, and to compare short-term outcomes after laparoscopic gastric bypass with and without concomitant cholecystectomy.     

Eftozanermin alfa (ABBV-621) monotherapy in patients with previously treated solid tumors: findings of a phase 1, first-in-human study

Investigational New Drugs - Eftozanermin alfa (eftoza), a second-generation tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) agonist, induces apoptosis in tumor cells by...     

Evaluation of existing and candidate measures of obesity for detection of insulin resistance and cardiometabolic risk among Asian Indians: Development of two clinically useful models

BackgroundThe optimal measure of obesity continues to be debated. The objective of this study was to evaluate existing and candidate measures of obesity for detecting the presence of cardiometabolic risk and insulin resistance among Asian Indians.MethodsAnthropometry, detailed body composition analysis, blood pressure, lipids, fasting blood glucose and fasting serum insulin were measured in a cross-sectional study involving 507 subjects from North India.ResultsIn females, all indices of obesity, except waist-to-hip ratio (WHR) and total body fat (TBF) to waist circumference (WC) ratio and in men, all indices of obesity including fat mass index and WHR, were significantly associated with insulin resistance and cardiovascular risk factors (p < 0.05). Using stepwise logistic regression, two models were developed excluding WC and WHR, respectively. In model 1, subscapular skinfold thickness, WHR and age in males, and waist circumference to square of height ratio (WS²R) and age in females; and in model 2, subscapular skinfold thickness, WS²R and visceral adiposity index in males, and TBF to WC ratio, WS²R and age in females showed strong and significant association with the presence of cardiovascular risk factors or insulin resistance.ConclusionsThe clinical models for measurement of obesity developed by us would help in detecting cardiometabolic risk in Asian Indians.     

Antimicrobial stewardship programs: interventions and associated outcomes

Guidelines regarding antimicrobial stewardship programs recommend an infectious diseases-trained physician and an infectious diseases-trained pharmacist as core members. Inclusion of clinical microbiologists, infection-control practitioners, information systems experts and hospital epidemiologists is considered optimal. Recommended stewardship interventions include prospective audit and intervention, formulary restriction, education, guideline development, clinical pathway development, antimicrobial order forms and the de-escalation of therapy. The primary outcome associated with these interventions has been the associated cost savings; however, few published investigations have taken into account the overall cost of the intervention. Over the past 5 years, there has been an increased focus upon interventions intended to decrease bacterial resistance or reduce superinfection, including infections associated with Clostridium difficile colitis. Few programs have been associated with a reduction in antimicrobial drug adverse events. Antimicrobial stewardship programs are becoming increasingly associated with clear benefits and will be integral in the in-patient healthcare setting.