COMPARATIVE EFFECT OF BETA BLOCKERS AND ANGIOTENSIVE RECEPTOR BLOCKERS ON BLOOD GLUCOSE LEVEL IN HYPERTENSIVE PATIENTS IN UNIVERSITY HOSPITAL

Objective: There is highly co-incidence between hypertension and insulin resistance which is the important causative factor to develop diabetes mellitus (DM). There is paucity of data to establish the effect of beta-blockers and ARB on blood glucose level in Indian population. Therefore the present study was planned to search so that confederation among Indian population in a teaching hospital. Methods: The research study was carried out in 85 hypertensive patients without diabetes visiting the OPD of University teaching hospital (Majeedia hospital) New Delhi. Blood glucose levels and drug history of hypertensive patients were observed during four month of study. Results: The gender distribution of hypertensive patients reveals a higher percentage of incidences in males (53%) as compared to females (47%). Hypertensive patient without diabetes mellitus (DM) on beta blockers shows higher incidence of impaired glucose tolerance (IGT) (13.3%) and DM (5%) as compared to patient receiving ARBs as antihypertensive therapy. There was proportionate increase in incidence as the duration of therapy. None of the patients who were on angiotensin receptor blockers (ARBs) reported any incidence of IGT or DM. Conclusion: Beta blockers  may be the risk factor to develop diabetes mellitus type 2 on long term use as an antihypertensive therapy. There were no any incidence of impaired glucose tolerance or diabetes mellitus found in case of patients taking ARBs as an antihypertensive therapy so it can be safely prescribe in hypertensive patients associated with diabetes mellitus type 2. Key Words: Hypertension, Diabetes mellitus, Impaired glucose tolerance, Beta blockers and ARBs

New Paradigms of Old Psychedelics in Schizophrenia

Psychedelics such as lysergic acid diethylamide (LSD), psilocybin (magic mushrooms), and mescaline exhibit intense effects on the human brain and behaviour. In recent years, there has been a surge in studies investigating these drugs because clinical studies have shown that these once banned drugs are well tolerated and efficacious in medically supervised low doses called microdosing. Psychedelics have demonstrated efficacy in treating neuropsychiatric maladies such as difficult to treat anxiety, depression, mood disorders, obsessive compulsive disorders, suicidal ideation, posttraumatic stress disorder, and also in treating substance use disorders. The primary mode of action of psychedelics is activation of serotonin 5-HT2A receptors affecting cognition and brain connectivity through the modulation of several downstream signalling pathways via complex molecular mechanisms. Some atypical antipsychotic drugs (APDs) primarily exhibit pharmacological actions through 5-HT2A receptors, which are also the target of psychedelic drugs. Psychedelic drugs including the newer second generation along with the glutamatergic APDs are thought to mediate pharmacological actions through a common pathway, i.e., a complex serotonin–glutamate receptor interaction in cortical neurons of pyramidal origin. Furthermore, psychedelic drugs have been reported to act via a complex interplay between 5HT2A, mGlu2/3, and NMDA receptors to mediate neurobehavioral and pharmacological actions. Findings from recent studies have suggested that serotoninergic and glutamatergic neurotransmissions are very closely connected in producing pharmacological responses to psychedelics and antipsychotic medication. Emerging hypotheses suggest that psychedelics work through brain resetting mechanisms. Hence, there is a need to dig deeply into psychedelic neurobiology to uncover how psychedelics could best be used as scientific tools to benefit psychiatric disorders including schizophrenia

Comparative evaluation of doxorubicin, cyclophosphamide, 5-fluorouracil, and cisplatin on cognitive dysfunction in rats: Delineating the role of inflammation of hippocampal neurons and hypothyroidism

Chemotherapeutic agents such as doxorubicin, cyclophosphamide, fluorouracil, and cisplatin are commonly used to treat a variety of cancers and often result in chemobrain, which manifests as difficulties in learning and memory processes that can persist in the years following treatment. The current study aims to evaluate the cognitive function following treatment with these agents and the underlying mechanisms using a rat model of neuroinflammation and possible implication of thyroid toxicity in chemotherapy induced cognitive dysfunction. Wistar female rats were treated with a single dose of doxorubicin (DOX, 25 mg/kg), 5-fluorouracil (5-FU, 100 mg/kg), cisplatin (8 mg/kg), and cyclophosphamide (CYP, 200 mg/kg) by intraperitoneal injection. The cognitive performance of rats was then evaluated in spatial memory tasks using the Y-maze, novel object recognition (NOR), and elevated plus maze (EPM) tests. Serum levels of thyroid hormones (T3, T4, FT3, and FT4) and thyroid stimulating hormone (TSH) were measured, followed by estimation of TNFα, IL-6, and IL-1β in the hippocampal tissue. Results revealed that all the chemotherapeutic agents produced impairment of cognitive function, and significant increase of pro-inflammatory cytokines such as TNFα, IL-6 and IL-1β in the hippocampal tissues. There was a significant reduction in thyroid hormones (T3, FT3, and T4) and an increase in thyroid stimulating hormone (TSH) in serum, which may also have contributed to the decline in cognitive function. In conclusion, DOX, 5-FU, CYP, and cisplatin produces impairment of spatial memory possibly by inflammation of hippocampal neurons and endocrine disruption (hypothyroidism) in rats

An in-silico analysis of ivermectin interaction with potential SARS-CoV-2 targets and host nuclear importin ?

Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IMP)α directly and averts interaction with IMPβ1, leading to the prevention of nuclear localization signal (NLS) recognition. Therefore, the current study seeks to employ molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) analysis and molecular dynamics simulation studies for decrypting the binding mode, key interacting residues as well as mechanistic insights on IVM interaction with 15 potential drug targets associated with COVID-19 as well as IMPα. Among all COVID-19 targets, the non-structural protein 9 (Nsp9) exhibited the strongest affinity to IVM showing −5.30 kcal/mol and −84.85 kcal/mol binding energies estimated by AutoDock Vina and MM-GBSA, respectively. However, moderate affinity was accounted for IMPα amounting −6.9 kcal/mol and −66.04 kcal/mol. Stability of the protein-ligand complexes of Nsp9-IVM and IMPα-IVM was ascertained by 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of protein in complex with docked IVM exhibited stable root mean square deviation while root mean square fluctuations were also found to be consistent. In silico exploration of the potential targets and their interaction profile with IVM can assist experimental studies as well as designing of COVID-19 drugs

Therapeutic Properties of Vanadium Complexes

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology