OBJECTIVES: Methotrexate (MTX) is a broadly used anticancer. Its major side effect is hepatotoxicity. Gossypin is a flavonoid has a hepatoprotective effect as well as antitumor property. The study aimed at inspecting the protective effect of gossypin against MTX hepatotoxicity. MATERIALS AND METHODS: Twenty-four adult male rats arranged into four groups (six rats each): control, gossypin control, MTX, and MTX+ gossypin. Animals were orally administered gossypin at 10 mg kg^-1 day^-1 for 7 days. MTX was injected i.p. (20 mg/kg^-1 once) on 5^th day. Liver enzyme and oxidative stress markers were assessed. BAX, transforming growth factor-beta (TGF-β) gene expressions, and P-glycoprotein (P-gp) were assessed. The histopathological study as well as the immunohistochemical study for hepatic caspase 3 and nuclear factor kappa-B (NFκ-B) was done. RESULTS: MTX produced a significant increase of liver enzymes and distortion of hepatic architecture alongside with increased the hepatic collagen content. MTX administration significantly increased the oxidative stress markers and upregulated the pro-apoptotic BAX and the pro-fibrogenic TGF-β. MTX increased caspase 3 and NFκ-B expression, while diminished the expression of P-gp. Gossypin pretreatment improved the previous parameters, restored the normal hepatic architecture, reduced the hepatic fibrosis, and regained nearly normal expressions for BAX, TGF-β, caspase 3, and NFκ-B. Gossypin caused more reduction in P-gp hepatic expression. CONCLUSIONS: Gossypin may be a valuable adjuvant therapy that protects the liver against MTX toxicity through antioxidant, anti-inflammatory, antiapoptotic mechanisms, and mediated P-gp expression reduction.

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OBJECTIVE: The study assessed the efficacy, safety, pharmacokinetic (PK), and immunogenicity profiles of denosumab-biosimilar and denosumab-reference in postmenopausal osteoporotic women from India. MATERIALS AND METHODS: In this randomized, assessor-blind, active-control, multicenter trial, 114 patients were randomly allocated to receive denosumab-biosimilar (n = 58) or denosumab-reference (n = 56) at a subcutaneous dose of 60 mg every 6 months, for a year. Vitamin D and oral calcium were given daily. Lumbar spine bone mineral density (BMD) change was the primary end point. RESULTS: Of 114 randomized patients, 111 (denosumab-biosimilar, n = 56; denosumab-reference, n = 55) completed the study. All 114 patients were part of safety and immunogenicity analyses, 110 (denosumab-biosimilar, n = 56; denosumab-reference, n = 54) were part of efficacy analysis, and 20 (denosumab-biosimilar, n = 10; denosumab-reference, n = 10) were part of PK analysis. The bone mineral density (BMD) (lumbar spine) percent change at 1 year with denosumab-biosimilar and denosumab-reference (7.22 vs. 7.62; difference:−0.40; 95% confidence interval: −5.92, 5.12) showed no statistically relevant difference. Likewise, alkaline phosphatase (bone-specific) and PK parameters also did not show statistically relevant differences. Adverse events were reported in 44.83% of patients on denosumab-biosimilar versus 33.93% of patients on denosumab-reference; most events were mild or moderate and not related to the study drugs. No patients showed anti-denosumab antibody positivity. CONCLUSIONS: Denosumab-biosimilar and denosumab-reference showed biosimilarity in osteoporotic postmenopausal women. Availability of denosumab-biosimilar provides a treatment alternative for patients.

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COVID-19 pandemic led to an unprecedented collaborative effort among industry, academia, regulatory bodies, and governments with huge financial investments. Scientists and researchers from India also left no stone unturned to find therapeutic and preventive measures against COVID-19. Indian pharmaceutical companies are one of the leading manufacturers of vaccine in the world, are utilizing its capacity to its maximum, and are one among the forerunners in vaccine research against COVID-19 across the globe. In this systematic review, the information regarding contribution of Indian scientists toward COVID-19 research has been gathered from various news articles across Google platform apart from searching PubMed, WHO site, COVID-19 vaccine tracker, CTRI, clinicaltrials.gov, and websites of pharmaceutical companies. The article summarizes and highlights the various therapeutic and vaccine candidates, diagnostic kits, treatment agents, and technology being developed and tested by Indian researcher community against COVID-19.

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INTRODUCTION: Pharmacogenomics is a growing field of science that explores the genetic contributions in an individual's response to the drug, so as to choose the right drug in the right doses tailored to a patient's genetic makeup. Although pharmacogenomics information is incorporated in chapters discussing relevant drugs, it has not been materialized into clinical practice yet and still, it remains a challenge due to limited knowledge and accessibility of the pharmacogenomic tests to diagnose these polymorphisms. With this background, the objective of the study was to assess the knowledge and perception of pharmacogenomics among second-year MBBS students and to sensitize them regarding pharmacogenomics. MATERIALS AND METHODS: A cross-sectional study was done in which 138 medical students responded to a preformed semi-structured assessment tool. It comprised two main components (1) knowledge and (2) relevance of pharmacogenomics in medical education and clinical practice. RESULTS: Ninety-five percent students defined pharmacogenomics correctly, but only 54% were aware of genetic variations in drug targets, metabolizing enzymes, and transporters affecting drug therapy. Only 15% knew about the availability of pharmacogenomics tests in India. Eighty-four percent of students felt that incorporating pharmacogenomics education in the MBBS curriculum is a must for precision medicine. CONCLUSION: Second-year MBBS students had good knowledge of pharmacogenomics, but knowledge about the application in clinical practice and interpretation of pharmacogenomics was limited. Therefore, we recommend (1) basic pharmacogenomic education at all levels of medical curricula, (2) development of case-based knowledge application modules, (3) regular continuing medical education to update about available screening tools/biomarkers, and (4) patient and public awareness programs so that they receive personalized/precision medicine with optimum efficacy and reduced side effects and health-care costs.

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OBJECTIVES: This research was aimed to find out the effects of 3',4'-dihydroxyflavonol (DiOHF) on apoptosis, DNA damage, and tumor necrosis factor-α (TNF-α) levels in the frontal cortex of rats with induced experimental brain ischemi reperfusion. MATERIALS AND METHODS: A total of 38 Wistar albino male rats were used. Groups were created as 1-Sham; 2-Ischemia-reperfusion (I/R); 3-I/R + DiOHF (10 mg/kg); 4-Ischemia + DiOHF + reperfusion; 5-DiOHF + I/R. I/R was performed by carotid artery ligation for 30 min in anesthesized animals. Following experimental applications, blood samples were taken from anesthetized rats to obtain erythrocyte and plasma. Later, the rats were killed by cervical dislocation, and frontal cortex samples were taken and stored at − 80^oC for the analysis. RESULTS: In the ischemic frontal cortex tissue sections degenerate neuron numbers, Terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) positive cell ratio and caspase-3 positive cell ratio increased. Malondialdehyde, TNF-α, and 8-OHdG levels were increased in both plasma and tissue in ischemia group, whereas tissue and erythrocyte glutathione levels were significantly suppressed. However, these values were significantly reversed by DiOHF treatment. CONCLUSION: The results of the study showed that I/R significantly increased apoptosis, TNF-α, and DNA damage in rats with brain I/R. However, 10 mg/kg intraperitoneal DiOHF treatment improved deterioted parameters.

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AIM: The present study explored Cynodon dactylon hydro-ethanolic extract (CDE) effect on scopolamine-induced amnesic rats. MATERIALS AND METHODS: C. dactylon extract was subjected to antioxidant (DPPH and H₂O₂) and acetylcholinesterase enzyme tests by in vitro methods. Scopolamine (1 mg/kg, i.p) was administered to rats except for normal control. Donepezil (3 mg/kg, p.o), CDE (100, 200, and 400 mg/kg p.o) were administered to treatment groups. Behavioral paradigm: Morris water maze (MWM), elevated plus maze (EPM), and passive avoidance test (PAT) were conducted. Later, rats were sacrificed and brain homogenate was tested for levels of acetylcholinesterase, glutathione, and lipid peroxidase. Histopathology examination of cortex and hippocampus of all the groups was done. STATISTICAL METHOD: The statistical methods used were ANOVA and Tukey's post hoc test. RESULTS: CDE antioxidant activity was demonstrated by decreasing DPPH and H₂O₂ levels confirmed through in vitro analysis. Treatment group rats reversed scopolamine induced amnesia by improvement in spatial memory, decreased transfer latency and increased step through latency significantly (P<0.001) in behavior models such as morris water maze, elevated plus maze and passive avoidance task respectively. CDE modulated acetylcholine transmission by decreased acetylcholinesterase enzyme level (P < 0.001) and scavenging scopolamine-induced oxidative stress by increased reduced glutathione levels and decreased lipid peroxidation levels in the rat brain. CDE and donepezil-treated rats showed mild neurodegeneration in comparison to scopolamine-induced severe neuronal damage on histopathology examination. CONCLUSION: C. dactylon extract provides evidence of anti-amnesic activity by the mechanism of decreased acetylcholinesterase enzyme level and increased antioxidant levels in scopolamine-induced amnesia in rats.

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AIM: The current work establishes an easy, reliable technique for the estimation of serum Olanzapine concentration which correlates it clinically. SUBJECTS AND METHODS: The work was agreed in 61 schizophrenic patients who were on olanzapine. Serum drug amount was estimated by normal-phase high-performance liquid chromatography and brief psychiatry rating scale was used to determine disease progression. RESULTS: Samples provided 61 patients, 40 were under sub-therapeutic range, 18 were under therapeutic range and 3 were above the therapeutic range. CONCLUSION: Therapeutic drug monitoring must be a part of clinical practice in psychiatric hospitals for optimizing the dose of an individual patient along with the correlation of serum concentration with the clinical assessment scales.

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OBJECTIVES: This study was aimed to determine in vitro human whole blood-to-plasma ratio (K_WB/_P) of THJ-018 by gas chromatography/mass spectrometry (GC/MS). MATERIALS AND METHODS: The samples (human blood) were sprayed with THJ-018 and an internal standard and extracted using solid-phase extraction. THJ-018 was determined in the final extracts by GC/MS. RESULTS: The value for K_WB/_P was 1.56 (1.38–1.81), and red blood cell partitioning was 1.01 (1.01–1.02). The distribution of THJ-018 between whole blood and plasma was observed to be affected by temperature. CONCLUSION: The data analysis supports the proposition that the ratio of the plasma to whole blood concentrations (1.56) is a suitable parameter characterizing THJ-018 distribution in whole blood. For toxicological analysis, it would be best to refrain from converting any drug concentration measured in whole blood to that anticipated in plasma or serum; however, toxic and therapeutic concentrations should be determined for the individual specimens collected.

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Intravenous amiodarone treatment may cause hepatic toxicity. N-acetylcysteine (NAC) is a powerful antioxidant, reduces the level of free radicals by increasing glutathione levels, and is used in acetaminophen intoxication. An 83-year-old female Caucasian patient who had congestive heart failure and implantable cardioverter-defibrillator was admitted to the hospital with palpitations and confusion. After analysis of ICD device, ventricular tachycardia, ventricular fibrillation runs of patient and intervention of ICD device with electric shocks were noticed. Intravenous 1200 mg amiodarone infusion was administered as treatment. Later, her transaminase levels increased dramatically. Hepatic injury due to intravenous administration of amiodarone was diagnosed and 1200 mg/day intravenous NAC was given. After 72 h of NAC treatment, hepatic enzymes were found to be recovering. After parenteral amiodarone administration, patients must be monitored for acute hepatotoxicity. This article accentuates the benefits of NAC treatment in drug-induced liver injury.

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BACKGROUND: Studies have shown that there is a critical time period to start hormone therapy after the loss of ovarian function during menopause. The length of estrogen deprivation may evolve different pathophysiological manifestations. OBJECTIVE: The aim of the present study was to investigate behavioral, biochemical, and molecular alterations at different time points after surgical menopause with an aim and identify various pathophysiological targets to exploit “window of opportunity” and to design newer therapeutic modalities for menopause-associated neurobehavioral and vascular deficits. MATERIALS AND METHODS: Bilateral ovariectomy was performed to induce surgical menopause and estrogen deficiency state. Menopause-associated neuronal and vascular dysfunctions were noted after 1, 2, and 3 months of the study. RESULTS: Neuronal and vascular endothelial dysfunction post ovariectomy revealed that behavioral, biochemical, molecular, and vascular endothelial dysfunction appeared after 1 month of ovariectomy except hyperglycemia, which occurs after 3 months. CONCLUSIONS: Time-response studies measuring behavioral, biochemical, and molecular markers at various time points after ovariectomy reveal that there is a fast onset of neuronal and vascular complications, but the duration of insulin resistance is a relatively late phenomenon.

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