Supraglottic airway devices in short gynecological procedures: A randomized, clinical study comparing the Baska® mask and I-Gel® device

Background: Supraglottic airway devices are used for anesthesia in elective surgical procedures circumventing the need for intubation. We investigated the efficacy and safety of Baska® mask in comparison to an I-Gel® device. Methods: In this cross-sectional, observational study, we randomized 100 female patients (age 18–45 years, American Society of Anaesthesiologists grade I or II) undergoing elective short gynecological procedures into two groups, to receive ventilation with either Baska mask® (group 1, n = 50) or an I-Gel® device (group 2, n = 50). We excluded patients with obesity, short neck, and known systemic and upper airway disorders. The primary outcome was the oropharyngeal airway seal pressure, and the secondary outcomes were the ease of insertion and the complication rate. The results were analyzed using Mann–Whitney U-test and Fisher's exact test, and correlation analysis was done by Spearman's correlation test. Results: A total of 56 patients underwent dilatation and curettage, whereas the remaining had hysteroscopy in the study. The airway seal pressure achieved was higher with Baska® mask than I-Gel® device (35.8 ± 10.3 and 26.9 ± 7.5 of cm H2O, respectively; P 0.05). Conclusion: Baska® mask offers a superior airway seal pressure with minimum complications in comparison to an I-Gel® device. Further studies with a large number of patients in different surgical settings are required to confirm our findings

Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs

Objectives: A volunteer trial was performed to compare the pharmacokinetics of 5 drugs-warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin-when administered at a microdose or pharmacologic dose. Each compound was chosen to represent a situation in which prediction of pharmacokinetics from either animal or in vitro studies (or both) was or is likely to be problematic. Methods: In a crossover design volunteers received (1) 1 of the 5 compounds as a microdose labeled with radioactive carbon (carbon 14) (100 μg), (2) the corresponding 14C-labeled therapeutic dose on a separate occasion, and (3) simultaneous administration of an intravenous 14C-labeled microdose and an oral therapeutic dose for ZK253, midazolam, and erythromycin. Analysis of 14C-labeled drugs in plasma was done by use of HPLC followed by accelerator mass spectrometry. Liquid chromatography-tandem mass spectrometry was used to measure plasma concentrations of ZK253, midazolam, and erythromycin at therapeutic concentrations, whereas HPLC-accelerator mass spectrometry was used to measure warfarin and diazepam concentrations. Results: Good concordance between microdose and therapeutic dose pharmacokinetics was observed for diazepam (half-life t1/2 of 45.1 hours, clearance CL of 1.38 L/h, and volume of distribution V of 90.1 L for 100 μg and t1/2 of 35.7 hours, CL of 1.3 L/h, and V of 123 L for 10 mg), midazolam (t1/2 of 4.87 hours, CL of 21.2 L/h, V of 145 L, and oral bioavailability F of 0.23 for 100 μg and t1/2 of 3.31 hours, CL of 20.4 L/h, V of 75 L, and F of 0.22 for 7.5 mg), and development compound ZK253 (F = <1% for both 100 μg and 50 mg). For warfarin, clearance was reasonably well predicted (0.17 L/h for 100 μg and 0.26 L/h for 5 mg), but the discrepancy observed in distribution (67 L for 100 μg and 17.9 L for 5 mg) was probably a result of high-affinity, low-capacity tissue binding. The oral microdose of erythromycin failed to provide detectable plasma levels as a result of possible acid lability in the stomach. Absolute bioavailability for the 3 compounds examined yielded excellent concordance with data from the literature or data generated in house. Conclusion: Overall, when used appropriately, microdosing offers the potential to aid in early drug candidate selection. © 2006 American Society for Clinical Pharmacology and Therapeutics

Repeat Analysis and Incurred Sample Reanalysis: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis. With international representation from Europe, Latin America, North America and the Asia Pacific region, the team first collated common practices and guidance recommendations and assessed their suitability from both a scientific and logistical perspective. Subsequently, team members developed best practice recommendations and refined them through discussions and presentations with industry experts at scientific meetings. This review summarizes the team findings and best practice recommendations. The few topics where no consensus could be reached are also discussed. The A7 HT recommendations, together with those from the other GBC teams, provide the basis for future international harmonization of regulated bioanalytical practices

Necroptosis in stressed ovary

Abstract Stress is deeply rooted in the modern society due to limited resources and large competition to achieve the desired goal. Women are more frequently exposed to several stressors during their reproductive age that trigger generation of reactive oxygen species (ROS). Accumulation of ROS in the body causes oxidative stress (OS) and adversely affects ovarian functions. The increased OS triggers various cell death pathways in the ovary. Beside apoptosis and autophagy, OS trigger necroptosis in granulosa cell as well as in follicular oocyte. The OS could activate receptor interacting protein kinase-1(RIPK1), receptor interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) to trigger necroptosis in mammalian ovary. The granulosa cell necroptosis may deprive follicular oocyte from nutrients, growth factors and survival factors. Under these conditions, oocyte becomes more susceptible towards OS-mediated necroptosis in the follicular oocytes. Induction of necroptosis in encircling granulosa cell and oocyte may lead to follicular atresia. Indeed, follicular atresia is one of the major events responsible for the elimination of majority of germ cells from cohort of ovary. Thus, the inhibition of necroptosis could prevent precautious germ cell depletion from ovary that may cause reproductive senescence and early menopause in several mammalian species including human

Workshop Report and Follow-Up—AAPS Workshop on Current Topics in GLP Bioanalysis: Assay Reproducibility for Incurred Samples—Implications of Crystal City Recommendations

The Conference Report of the 3rd AAPS/FDA Bioanalytical Workshop (Crystal City III) endorsed the concept that assay methods supporting bioanalytical data in submissions must demonstrate assay reproducibility by using incurred samples. The present Workshop was convened to provide a forum for discussion and consensus building about incurred sample assay reproducibility for both nonclinical and clinical studies. Information about current regulatory perspectives on incurred sample reanalysis (ISR) was presented, implications of ISR for both large and small molecules were discussed, and the steering committee put forth recommendations for performing ISR. These recommendations from the Workshop, along with the subsequent evolution of approaches leading to a robust ISR program, may be used by scientists performing bioanalytical assays for regulated studies to provide additional confirmation of assay reproducibility for incurred samples