EVALUATION OF THE STABILITY OF VIGABATRIN IN HOSPITALAR EXTEMPORANEOUS FORMULATIONS

The aim of this study was to analyze the chemical stability of the anticonvulsant vigabatrin extemporaneous formulation from tablets in storage conditions of different temperatures and types of packaging used. The analysis of vigabatrin extemporaneous formulations were performed by high-performance liquid chromatography (HPLC). The method described in British Pharmacopoeia was co-validated for specificity, linearity, precision and accuracy. Vigabatrin extemporaneous solutions were prepared in triplicate and placed in amber glass and PET bottles, which were stored under three different conditions: at room temperature (15 to 30 °C), under refrigeration (2 to 8 °C), and oven (40 °C). Samples of solutions stored at room temperature and refrigeration were collected every 7 days along 35 days. The same was done for solutions kept at 40 °C, but for a period of 28 days. It was also analyzed the solutions pH in each sampling time. Vigabatrin extemporaneous solutions showed variations within the limits of British Pharmacopoeia 2016 up to 21 days in amber PET and glass bottles at room and refrigerated temperatures. Vigabatrin content for formulations kept in oven decreased above 10% after 7 days of study. The lowest pH change occurred in amber glass bottle stored under refrigeration. Results of this study will be applied as a reference for vigabatrin extemporaneous formulation in hospital, once it was demonstrated the reliability of storage time interval and proper conditions for the use. Thus, pediatric patients with fractionated doses or use of nasogastric probe will have adequately prepared extemporaneous formulations, reducing the risk of dilution errors and microbiological contamination, improving the efficacy and safety, and enabling more time for nursing assistance. 

In vitro toxic evaluation of two gliptins and their main impurities of synthesis

Background: The presence of impurities in some drugs may compromise the safety and efficacy of the patient’s treatment. Therefore, establishing of the biological safety of the impurities is essential. Diabetic patients are predisposed to tissue damage due to an increased oxidative stress process; and drug impurities may contribute to these toxic effects. In this context, the aim of this work was to study the toxicity, in 3 T3 cells, of the antidiabetic agents sitagliptin, vildagliptin, and their two main impurities of synthesis (S1 and S2; V1 and V2, respectively). Methods: MTT reduction and neutral red uptake assays were performed in cytotoxicity tests. In addition, DNA damage (measured by comet assay), intracellular free radicals (by DCF), NO production, and mitochondrial membrane potential (ΔψM) were evaluated. Results: Cytotoxicity was observed for impurity V2. Free radicals generation was found at 1000 μM of sitagliptin and 10 μM of both vildagliptin impurities (V1 and V2). A decrease in NO production was observed for all vildagliptin concentrations. No alterations were observed in ΔψM or DNA damage at the tested concentrations. Conclusions: This study demonstrated that the presence of impurities might increase the cytotoxicity and oxidative stress of the pharmaceutical formulations at the concentrations studied

BMP Signaling Modulates Hepcidin Expression in Zebrafish Embryos Independent of Hemojuvelin

Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

Remaking Movie Making: The Environmental Impacts of the Film Industry in Southern California

The film and television industry is integral to the economics and culture of the Southern California region. It is also a major contributing factor to the environmental problems in the region. Currently the Motion Picture, Television, and Commercial Industries Act of 1984 is the only regulation written specifically for the entertainment industry. This regulation was created with the purpose of streamlining the film permitting process to prevent run-away production, taking production out of state, and encourage growth. A change in this regulation is needed since studios routinely fail to meet environmental standards or work towards improvement during on-location filming. Amendments to this regulation requiring permits to contain environmental conditions would improve environmental conditions and stay true to the original purpose of the act

Evaluating the validity of a German translation of an uncanniness questionnaire

When researching on the acceptance of robots in Human-Robot-Interaction the Uncanny Valley needs to be considered. Reusable and standardized measures for it are essential. In this paper one such questionnaire got translated into German. The translated indices got evaluated (n=140) for reliability with Cronbach's alpha. Additionally the items were tested with an exploratory and a confirmatory factor analysis for problematic correlations. The results yield a good reliability for the translated indices and showed some items that need to be further checked

Creative Writing Panel #4: Crime & Punishment

Student Session “The Case of Colonel Warburton’s Madness” - Sarah Wingert “Supersonic Man” - Ellie Zumbach “Saints of Little Odessa” - Jamie Hudall

Targeted metabolic profiling of methionine cycle metabolites and redox thiol pools in mammalian plasma, cells and urine

The concentration of thiol and thioether metabolites in plasma has diagnostic value in genetic diseases of B-vitamin metabolism linked to methionine utilization. Among these, cysteine/cystine (Cys/CSSC) and glutathione/oxidized glutathione (GSH/GSSG) act as cellular redox buffers. A new LC-MS/MS method was developed for the simultaneous detection of cystathionine (Cysta), methionine (Met), methionine sulfoxide (MSO), creatinine and the reduced and oxidized pairs of homocysteine (Hcy/HSSH), cysteine (Cys/CSSC) and glutathione (GSH/GSSG). A one-step thiol-blocking protocol with minimal sample preparation was established to determine redox thiol pairs in plasma and cells. The concentrations of diagnostic biomarkers Hcy, Met, Cysta, and Cys in a cohort of healthy adults (n = 53) agreed with reference ranges and published values. Metabolite concentrations were also validated in commercial samples of human, mouse, rat and Beagle dog plasma and by the use of a standardized ERNDIM quality control. Analysis of fibroblasts, endothelial and epithelial cells, human embryonic stem cells, and cancer cell lines showed cell specificity for both the speciation and concentration of thiol and thioether metabolites. This LC-MS/MS platform permits the fast and simultaneous quantification of 10 thiol and thioether metabolites and creatinine using 40 µL plasma, urine or culture medium, or 500,000 cells. The sample preparation protocols are directly transferable to automated metabolomic platforms