Hypericin: a potential antiglioma therapy

Journal ArticleHYPERICIN, A POLYCYCLIC aromatic dione isolated from plants, is presently being clinically evaluated as an antiviral agent in the treatment of human immunodeficiency virus (HIV) infection. In addition, it is known to be a potent protein kinase C inhibitor. To evaluate its potential as an inhibitor of glioma growth, an established (U87) and low-passage glioma line (93-492) were treated with hypericin in tissue culture for a period of 48 hours after passage. Hypericin inhibited the glioma growth in a dose-related manner, with a marked inhibition of growth in the low-micromolar concentration range (e.g., in line U87 and low-passage line 93-492 , a concentration of hypericin of 10 pmol/L produced 62 and 76% decreases in [3H]thymidine uptake, respectively). Because the reported inhibitory effects of protein kinase Care enhanced by visible light, [3H]thymidine uptake was measured in both the presence and the absence of visible light. In glioma line A172, the presence of light slightly increased the inhibitory effect of hypericin. Moreover, an apoptosis (i.e., programmed cell death) assay was performed to determine whether the treatment of glioma cells with hypericin was cytostatic or cytocidal. Cells were harvested, and purified deoxyribonucleic acid (DNA) was analyzed by agarose gel electrophoresis. DNA from cells treated with hypericin for 48 hours exhibited a classical "ladder" pattern of oligonucleosome-sized fragments characteristic of apoptosis. These data suggest that the proven safe drug hypericin may have potential as an antiglioma agent; we suggest clinical trials

Laboratory Column flotation studies for reduction of alumina and silica in iron ore slimes of an operating plant

A typical iron ore washing plant for treating iron ore fines (<10 mm) consist of sizing of the ore by dry / wet screening, washing, classification by screw classifiers followed by single or multi-stage hydrocycloning of screw classifiers overflow. The underflow of the hydrocyclones forms the concentrate which is suitable for pellets making. Since the cut-point of hydrocyclones is usually at 20 µm or less, relatively lower diameter cyclones in a cluster with parallel feeding are used. This is found to, often, result in choking of the spigots, at times, by extraneous material reporting along with the slurry. It is observed to lead to sub-optimum performance of the cyclones with loss of iron values into cyclone overflow and thereafter into tailings. Analysis of the data of an operating beneficiation plant (Beneficiation plant - 1) of M/s Jindal South West (JSW) Steel Limited, Karnataka, India over a period of one year indicated that weight recovery of the concentrate from two-stage hydrocycloning was 45.9% (with respect to feed to the cyclones) and assaying 63.43% Fe, 4.43% SiO2 and 2.23% Al2O3. Considering the fineness of the slimes (d80: 40.5 µm), generated as screw classifier overflow, flotation is thought to be better alternative vis-à-vis hydrocyclones to recover iron values from it. The present study aims at improving the recovery of the iron values from the screw classifier overflow by adopting reverse cationic column flotation technology. After selecting a suitable collector, process parameters like collector and depressant dosages are optimized by statistically designed experiments on a Denver D12 flotation cell. Later, the effect of important operating parameters of flotation column like air flow-rate, froth depth and wash water on the separation process is studied and optimized. It was established that a typical screw classifier overflow analyzing 60.43% Fe, 6.88% SiO2 and 3.26% Al2O3 could be improved to 63.30% Fe, 4.04% SiO2 and 2.32% Al2O3 with 59.10% weight and 61.70% Fe recovery. This is an improvement of 29% in weight recovery of the concentrate at equivalent metallurgy compared to what is being obtained, by two-stage cycloning

Right-handed Sneutrinos as Nonthermal Dark Matter

When the minimal supersymmetric standard model is augmented by three right-handed neutrino superfields, one generically predicts that the neutrinos acquire Majorana masses. We postulate that all supersymmetry (SUSY) breaking masses as well as the Majorana masses of the right-handed neutrinos are around the electroweak scale and, motivated by the smallness of neutrino masses, assume that the lightest supersymmetric particle (LSP) is an almost-pure right-handed sneutrino. We discuss the conditions under which this LSP is a successful dark matter candidate. In general, such an LSP has to be nonthermal in order not to overclose the universe, and we find the conditions under which this is indeed the case by comparing the Hubble expansion rate with the rates of the relevant thermalizing processes, including self-annihilation and co-annihilation with other SUSY and standard model particles.Comment: 17 pages v.2: References adde

Perspectives of Teachers at Medical Colleges Across India regarding the Competency based Medical Education Curriculum – A Qualitative, Manual, Theoretical Thematic Content Analysis

Background: Competency-based medical education (CBME) curriculum has been implemented in India since 2019 with a goal to create an “Indian Medical Graduate” (IMG) possessing requisite knowledge, skills, attitudes, values, and responsiveness. Objectives: To explore teachers’ perceptions across India at medical colleges on the newly implemented competency-based medical education curriculum. Methods: This was a qualitative cross?sectional study conducted among teachers working at medical colleges across India, between February and April 2022 (n = 192). The data collection was done using Google forms online survey platform on teachers’ perception regarding CBME, its specific components, and perceived bottlenecks. We analyzed this qualitative data using manual, theoretical thematic content analysis following the steps endorsed in Braun and Clarke’s six-phase framework. Results: The majority of the teachers (64.1%) have positively responded to the CBME curriculum’s implementation. However, it came with a caution that the curriculum should continuously evolve and adapt to regional demands. The foundation course, early clinical exposure, and the family adoption program were the specific components of CBME curriculum over which the teachers raised concerns. The need for additional teachers in each department (department-specific teacher or faculty per hundred students ratio to be worked out) and the need for enabling faculty preparedness through adequate training was highlighted. Concerns were also raised regarding implementing CBME with teachers without a medical background (especially in preclinical departments). Conclusion: It is the need of the hour for the curriculum to incorporate a systematic feedback mechanism built into the system, though which such critical appraisals can be meaning collated and acted upon, to ultimately evolve, thereby creating an “Indian Medical Graduate” for the needs of todays’ society

Young voices and visions for tropical restoration science in the UN Decade on Ecosystem Restoration

Funder: Oxford India Centre for Sustainable DevelopmentFunder: Rhodes TrustFunder: Gates Cambridge Trust; Id: http://dx.doi.org/10.13039/50110000537

Comparative in vivo study of pure drug and fast dissolving tablets of Simvastatin

The objective of this study was to investigate differences in the pharmacokinetic patterns between pure drug and an optimized&nbsp; formulation of fast dissolving tablets&nbsp; of Simvastatin. The formulations were administered to 2 groups of white New Zealand rabbits (n=6) following cross over design pattern and the plasma levels were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each formulation. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels.&nbsp; The highest mean Cmax value was observed for optimized fast dissolving tablets (68.33 ± 0.42ng/ml) compared to&nbsp; pure drug (27.72 ± 0.31ng/ml). The mean time taken to peak plasma concentration for (Tmax) following administration of pure drug&nbsp; was &nbsp;11.53 ± 0.011hours, while it was 6.09 ± 0.072 hour following administration of selected optimized fast dissolving tablets.The elimination rate constant (Kel) for pure drug and optimized fast dissolving tablets were found to be 0.58 ± 0.012h-1and 0.53 ± 0.014 h-1&nbsp;respectively.&nbsp; The absorption rate constant (Ka) for pure drug and optimized fast dissolving tablets were found to be 1.68 ± 0.01h-1and 5.53 ± 0.02h-1&nbsp;respectively. The AUC0-αvalues observed with optimized fast dissolving tablets686.1.±2.07 nghr/ml in compared to pure drug values 191 ± 1.43 nghr/ml. Thus, the results of pharmacokinetic studies indicated rapid and higher oral absorption of Simvastatin when administered as its fast dissolving tablets. Both Ka and AUC were markedly increased by fast dissolving tablets. Keywords: LC-MS/MS, Simvastatin, fast dissolving, In-vivo studies, pharmacokinetic parameters

Calcium ion binding to δ- and to β-crystallins. The presence of the "EF-hand" motif in δ-crystallin that aids in calcium ion binding

Abnormal levels of endogenous calcium ions are known to induce eye lens opacity, and a variety of causative factors has been proposed, including calcium-mediated aggregation and precipitation of the lens proteins crystallins. We have specifically looked in some detail at the interaction of Ca2+ with various crystallins and its consequences. Lenses incubated in solutions containing 10 mM Ca2+ or 5 mM Tb3+ opacified. Fluorescence titration of crystallins with TbCl3 revealed that this ion binds to &#948;- and &#946;-crystallins in solution. Equilibrium dialysis showed that four Ca2+ ions bind to one &#948;-crystallin tetramer with an affinity of 4.3 &#215; 103 M-1. Analysis of the amino acid sequence of &#948;-crystallin reveals the presence of a calmodulin-type "helix-loop-helix" or "EF-hand" calcium ion binding conformational motif in the region comprising residues 300-350. This is a novel feature of the molecule not reported so far. No other crystallins appear to have this motif. &#946;-Crystallin also binds four Ca2+ ions/aggregate unit of mass 160 kDa, with an affinity of 2.6 &#215; 103 M-1, presumably in the midregion of the molecule that is rich in anionic and polar residues. Circular dichroism spectroscopy shows that the binding of calcium ion leads to subtle conformational changes in the molecules, notably in the tertiary structure

Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic

Importance The rapidly expanding novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged the medical community to an unprecedented degree. Physicians and health care workers are at added risk of exposure and infection during the course of patient care. Because of the rapid spread of this disease through respiratory droplets, health care workers who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures, such as otolaryngologists–head and neck surgeons, are particularly at risk. A set of safety recommendations was created based on a review of the literature and communications with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic. Observations A high number of health care workers were infected during the first phase of the pandemic in the city of Wuhan, China. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for health care workers without jeopardizing the care of patients. The most common procedures related to the examination and treatment of upper aerodigestive tract diseases were reviewed. Each category was reviewed based on the potential risk imposed to health care workers. Specific recommendations were made based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in patients with COVID-19. Conclusions and Relevance Preserving a highly skilled health care workforce is a top priority for any community and health care system. Based on the experience of health care systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of health care workers could be greatly reduced while providing high levels of care. The provided recommendations, which may evolve over time, could be used as broad guidance for all health care workers who are involved in the care of patients with COVID-19