Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers

The pharmacokinetics of two brands of simvastatin 40 mg tablets were compared in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Zocor, MSD, Netherlands) and test (Simvast, Julphar, UAE) products were administered to fasted volunteers; blood samples were collected at specified time intervals, plasma separated and analyzed for simvastatin and its active metabolite (beta-hydoxy acid) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences - USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Simvast is bioequivalent to Zocor of MSD, Netherlands.     

Measuring gynecological morbidity: evaluating two different data sources from Beirut

The lack of consensus over the most appropriate source to use in assessing reproductive morbidity could, in part, explain the inadequacy of available information on the subject. To outline this situation, gynecological morbidity data collected from two different sources in Beirut, Lebanon, namely, population-based health interviews (779 ever-married women aged between 15 and 49) and private gynecologists' clinics (867 women with similar characteristics), are described. Although neither source is likely to represent the true prevalence of gynecological conditions, both agree sufficiently to shed light on the importance of some conditions such as menstrual disturbances (15% in both samples), infections/inflammations (17% in the households sample), and infertility-related concerns (12% in the clinics sample). Interestingly, despite the demographic differences, the most common conditions that the women complained about and the most common diagnoses that the gynecologists offered were similar for both samples. Therefore, given that the logistics in the gynecologists' clinic survey were easier, we recommend the use of health service data in settings where a representative sample of providers can be identified and service use is high.     

Pancreatic-derived factor (FAM3B), a novel islet cytokine,induces apoptosis of insulin-secreting beta-cells

PANDER (PANcreatic DERived factor, FAM3B), a newly discovered secreted cytokine, is specifically expressed at high levels in the islets of Langerhans of the endocrine pancreas. To evaluate the role of PANDER in beta-cell function, we investigated the effects of PANDER on rat, mouse, and human pancreatic islets; the beta-TC3 cell line; and the alpha-TC cell line. PANDER protein was present in alpha- and beta-cells of pancreatic islets, insulin-secreting beta-TC3 cells, and glucagon-secreting alpha-TC cells. PANDER induced islet cell death in rat and human islets. Culture of beta-TC3 cells with recombinant PANDER had a dose-dependent inhibitory effect on cell viability. This effect was also time-dependent. PANDER caused apoptosis of beta-cells as assessed by electron microscopy, annexin V fluorescent staining, and flow-cytometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. PANDER did not affect cytosolic Ca(2+) levels or nitric oxide levels. However, PANDER activated caspase-3. Hence, PANDER may have a role in the process of pancreatic beta-cell apoptosis.     

The use of non-heart-beating donors for isolated pancreatic islet transplantation

Recent improvements in isolated islet transplantation indicate that this therapy may ultimately prove applicable to patients with type I diabetes. An obstacle preventing widespread application of islet transplantation is an insufficient supply of cadaveric pancreata. Non-heart-beating donors (NHBDs) are generally not deemed suitable for whole-organ pancreas donation and could provide a significant source of pancreata for islet transplantation. Isolated pancreatic islets prepared from 10 NHBDs were compared with those procured from 10 brain-dead donors (BDDs). The success of the isolation for the two groups was analyzed for preparation purity, quality, and recovered islet mass. The function of NHBD and BDD islets was evaluated using in vitro and in vivo assays. On the basis of the results of this analysis, an NHBD isolated islet allograft was performed in a type I diabetic. The recovery of islets from NHBDs was comparable to that of control BDDs. In vitro assessment of NHBD islet function revealed function-equivalent BDD islets, and NHBD islets transplanted to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice efficiently reversed diabetes. Transplantation of 446,320 islet equivalents (IEq) (8,500 IEq/kg of recipient body weight) from a single NHBD successfully reversed the diabetes of a type I diabetic recipient. Normally functioning pancreatic islets can be isolated successfully from NHBDs. A single donor transplant from an NHBD resulted in a state of stable insulin independence in a type I diabetic recipient. These results indicate that NHBDs may provide an as yet untapped source of pancreatic tissue for preparation of isolated islets for clinical transplantation.     

Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable

The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.     

Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing

Background: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant.
Methods: The dose-dependent effects of adjuvant preoperative epidural tramadol on postoperative analgesia (pain scores and patient-controlled analgesia (PCA) use) and pain processing (heat pain thresholds) were prospectively studied in a double-blind, randomised, placebo-controlled 5-day trial. Forty patients undergoing knee or hip surgery received anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous PCA tramadol in all patients.
Results: Postoperative pain scores were similar in all groups. The time to first PCA use was shorter, the total dose and duration of PCA use greater, and side-effects more common with 20 mg tramadol than with 100 mg or placebo ( P <0.05). There were no differences in PCA doses required or side-effects between the tramadol 100 mg and placebo treatment groups. Heat pain tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively compared to baseline and placebo ( P = 0.01).
Conclusions: Preoperative adjuvant epidural tramadol does not improve postoperative analgesia after lidocaine epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti-analgesia and increased side-effects. While tramadol 100 mg depresses postoperative pain-processing, as measured by heat pain tolerance thresholds, this is not reflected in improved clinical pain measures.     

Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis: A population-based matched cohort study

BACKGROUND Patients with autoimmune hepatitis(AIH) require life-long immunosuppressive agents that may increase the risk of poor corona virus disease 2019(COVID-19)outcomes.There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases.AIM To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19.METHODS We conducted a population-based,multicenter,propensity score-matched cohort study with...     

Energy metabolism during transplantation rejection

The effect of transplantation rejection on energy metabolism is unknown. In order to investigate energy expenditure changes in this setting, we used an eight-cage rat indirect calorimeter to measure resting energy expenditure (REE) in the well-defined model of rat cardiac transplantation. Preoperative baseline measurements of REE were performed on Lewis recipients of allogeneic (Wistar Furth) or syngeneic (Lewis) heterotopic abdominal cardiac grafts (80.3 +/- 3.3 kcal0.75/day). Postoperatively, REE was measured on days 1 through 10, 15, and 20. An abnormal REE was defined as a greater than 10% change from the preoperative value. All cardiac allografts were rejected on postoperative day 7, whereas syngeneic hearts contracted for more than 100 days. Both groups of animals had a hypermetabolic response to surgery on postoperative day 1 compared with preoperative values (93.0 +/- 7.6 kcal/kg0.75/day, p less than 0.01). On postoperative day 2, REE normalized to preoperative baseline values in the syngeneic group and remained unchanged for the duration of the study (80.4 +/- 1.0, p = 0.49). In the allogeneic group, on postoperative days 3 through 6 an abnormal REE was recorded in 22 of 28 measurements compared with only 3 of 16 in the syngeneic group (p less than 0.001). After transplant rejection, REE normalized to preoperative values in the allogeneic group. Characteristic changes in energy expenditure occur during transplantation rejection. These changes in REE preceded rejection in this animal model.