Clastogenic effect of fenfluramine in mice bone marrow cells in vivo

Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.     

Spreadsheets for Automated Data Collection, Analysis, and Report Generation for Diagnostic Medical Physics: Publicly Available on the World Wide Web

A library of spreadsheets has been developed to facilitate the practice of diagnostic physics quality assurance. Each spreadsheet follows a standard template and uses the highest ranking controlling authority (within the United States) for pass/fail criteria and testing procedures. Sheets are now available for CT (computed tomography), MR (magnetic resonance), US (ultrasound), screen-film mammography, stereotactic breast, radiographic, fluoroscopic, computed radiography, film digitizer, and display quality control. Use is made of spreadsheet "workbooks" so that each testing event is a single sheet in the workbook. Thus, results over the lifetime of the device are gathered in a single file, and historical control charts are gathered on the first sheet. The spreadsheets are available at http://radweb.mcis.washington.edu/~sglanger, and are released under the Gnu (a recursive acronym. Gnu's Not Unix) public license. It is expected that others will add improvements, and they are expected and requested to submit them back to the author to be shared with the diagnostic physicist community at large.     

ELAV inhibits 3'-end processing to promote neural splicing of ewg pre-mRNA

The embryonic lethal abnormal visual system (ELAV) is a gene-specific regulator of alternative pre-mRNA processing in neurons of Drosophila. Here we define a functional in vivo binding site for ELAV in neurons through the development of a reporter gene system in transgenic animals in combination with in vitro binding assays. ELAV binds to erect wing (ewg) RNA 3' of a polyadenylation site in the terminal intron 6. At this polyadenylation site, ELAV inhibits 3'-end processing in vitro in a dose-dependent and sequence-specific manner, and ELAV binding is necessary in vivo to promote splicing of ewg intron 6. Further, the AAUAAA poly(A) complex recognition sequence, together with ELAV, is required to regulate neural 3' splice site choice in vivo. In addition, the use of segmentally labeled RNA substrates in UV cross-linking assays suggest that ELAV does not inhibit or redirect binding of cleavage factor dCstF64 at the regulated polyadenylation site on ewg RNA. These data indicate that binding of 3'-end processing factors, together with ELAV, can regulate alternative splicing.     

Formation and specification of ventral neuroblasts is controlled by vnd in Drosophila neurogenesis

During Drosophila neural development, neuroblasts delaminate from the neuroectoderm of each hemisegment in a stereotypic orthogonal array of five rows and three columns (ventral, intermediate, and dorsal). Prevailing evidence indicates that the individual neuroblast fate is determined by the domain-specific expression of genes along the dorsoventral and anteroposterior axis. Here, we analyze the role of Vnd, a NK-2 homeodomain protein, expressed initially in the ventral neuroectoderm adjacent to the ventral midline, in the dorsoventral patterning of the neuroectoderm and the neuroblasts. We show that in vnd null mutants most ventral neuroblasts do not form and the few that form do not develop ventral fates, but instead develop intermediate-like fates. Furthermore, we demonstrate that Vnd influences the gene expression patterns in the ventral proneural clusters and neuroectoderm, and that its action in neuroblast formation includes, but is not exclusive to the activation of proneural AS-C genes. Through the use of GAL4/UAS gene-expression system we show that ectopic Vnd expression can promote ventral-like fates in intermediate and dorsal neuroblasts and can suppress certain normal characteristics of the intermediate and dorsal neuroectoderm. Our results are discussed in the context of the current evidence in dorsoventral patterning in the Drosophila neuroectoderm.     

Correction to: Efficient photodynamic therapy against drug-resistant prostate cancer using replication-deficient virus particles and talaporfin sodium

Lasers in Medical Science - After publication of this paper, the authors determined an error in Fig. 1.     

An improved model of galactosamine-induced fulminant hepatic failure in the pig

Fulminant hepatic failure is a serious condition with very high mortality. Development of new therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of fulminant hepatic failure in the pig by administration of an aminosugar d-galactosamine hydrochloride. Galactosamine in a dose of 1.0 g/kg was dissolved in 5% dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of galactosamine or D5W alone, under general anesthesia. Neurological data were recorded at the same intervals before inducing anesthesia. Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of galactosamine, with death resulting from fulminant hepatic failure characterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histology showed massive hepatocellular necrosis in all seven galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans.     

SYNTHESIS OF THE RIGID ANALOGUES OF AN SSRI BENZENEPROPANAMINE

Several 1-(substituted phenoxy)-3-{[4-(4-trifluoromethyl) phenoxy] piperidin-1-yl} propan-2-ols (str.II) were prepared in a six-step reaction sequence starting from methylamine and ethyl acrylate and evaluated for antidepressant activity. The compounds were fully characterized by spectral and elemental analyses, and were tested for their effect on gross behavior, antireserpine and anorexigenic activity. No effect was observed on gross behavior and some of them showed fluoxetine like antireserpine and anorexigenic activity.     

Reasons for delay in cataract surgery in patients with advanced cataracts during the COVID-19 pandemic

Purpose:To analyze the reasons for delay in cataract surgery in patients with advanced cataracts during the COVID-19 pandemic.Methods:This was a prospective, cross-sectional, multicenter questionnaire study which included patients with mature cataract, nuclear sclerotic cataract grade IV, and cataracts with best corrected visual acuity (BCVA) <5/60, during the COVID-19 pandemic from December 2020 to April 2021. Reasons for delay in presentation to the hospital were analyzed.Results:One thousand four hundred seventy two patients were recruited with advanced cataracts. Absence of ophthalmic care nearby (44.2%), lack of awareness regarding elective surgeries (42.6%), lack of public transportation (37%), fear of contracting COVID-19 (23.4%), and waiting for outreach camps (20.4%) were found to be the reasons behind the delay in cataract surgery. 53.7% of the patients had worsening of defective vision and 55.3% of them had difficulty in carrying out activities of family living. 30.8% of the patients faced difficulty in commuting and 8.4% of the patients suffered a fall during this pandemic due to worsening of the visual acuity.Conclusion:The lockdown imposed during the pandemic has created a significant backlog of patients who are progressing to advanced cataracts due to lack of ophthalmic care nearby, lack of awareness regarding elective surgeries, lack of public transportation, and no outreach camps. Proactive measures to deal with this backlog are of utmost need to prevent blindness due to cataract.