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Objectives Levetiracetam (LEV) is an antiepileptic recommended during pregnancy. Bacopa monneri is a medicinal herb used in Ayurveda for improvement of cognition. Data on effects of LEV and Bacopa on cognition is inadequate. The study evaluated the cognitive effects of LEV on rat offspring of dams exposed to LEV and whether pretreatment with Bacopa monnieri, inhibits the potential cognitive decline by LEV. Methods Pregnant rats were allocated into four groups of three rats each. Groups 1, 2, 3 and 4 received 2% gum acacia, LEV 270 mg/kg, LEV 270 mg/kg + Bacopa 100 mg/kg and LEV 270 mg/kg + Bacopa 200 mg/kg respectively during pregnancy and lactation. Three pups from all dams were chosen at random and exposed to passive avoidance, Hebb-Williams and Morris water maze tests to check for their cognition and relevant histopathology was done. Results In the passive avoidance model groups 3 and 4, showed an increase in escape latency compared with group 2, demonstrating an improved learning (p=0.05). In Hebb-Williams maze, the time taken to reach reward chamber by group 2 increased compared to group 1, p=0.006, showing cognitive decline. Neuronal count in hippocampus and prefrontal cortex decreased significantly in group 2, which improved in group 3 & 4 however there was distortion of architecture in group 4. Conclusions LEV exposure in intrauterine and neonatal period induced cognitive decline in rat offsprings and Bacopa 100 mg/kg prevented LEV induced cognitive decline. However safety of exposure to Bacopa during the gestation period has to be evaluated.

ImportanceNovel SARS-CoV-2 virus has infected nearly half a billion people across the world and is highly contagious. There is a need for a novel mechanism to block viral entry and stop its replication.BackgroundSpike protein N terminal domain (NTD) of the novel SARS-CoV-2 is essential for viral entry and replication in human cell. Thus the S1 NTD of human coronavirus family, which is similar to a galectin binding site - human galactose binding lectins, is a potential novel target for early treatment in COVID-19.ObjectivesTo study the feasibility of performing a definitive trial of using galectin antagonist – Prolectin-M as treatment for mild, symptomatic, rRT-PCR positive, COVID-19.Main outcomes and measuresCycle threshold (Ct) value is number of cycles needed to express fluorescence, on real time reverse transcriptase polymerase chain reaction. Ct values expressed for RNA polymerase (Rd/RP) gene +Nucleocapsid gene and the small envelope (E) genes determine infectivity of the individual. A digital droplet PCR based estimation of the Nucleocapid genes (N1+N2) in absolute copies/μL determines active viral replication.Design and interventionPilot Feasibility Randomised Controlled Open-Label, parallel arm, study. Oral tablets of Prolectin-M were administered along with the best practice, Standard of Care (SoC) and compared against SoC. Voluntarily, consenting individuals, age >18 years, and able to provide frequent nasopharyngeal and oropharyngeal swabs were randomly allocated by REDCap software.The intervention, Prolectin-M was administered as a multi dose regime of 4 gram tablets. Each tablet contained 2 grams of (1-6)-Alpha-D-mannopyranosil mixed with 2 grams of dietary fibre. Each participant took a single chewable tablet every hour, to a maximum of 10 hours in a day. Tablets were administered only during the daytime, for total of 5 days.ResultsThis pilot trial demonstrated the feasibility to recruit and randomize participants. By day 7, following treatment with Prolectin-M, Ct value of Rd/Rp + N gene increased by16.41 points, 95% (CI – 0.3527 to 32.48, p=0.047). Similarly, small envelope (E) gene also increased by 17.75 points (95% CI;-0.1321 to 35.63, p = 0.05). The expression of N1, N2 genes went below detectable thresholds by day 3 (Mann Whitney U = 0.000, prRT-PCR testing done in the clinic on day 1, 7, and 14 had 3 participants (60%) turn negative by day 7 and all turned negative by day 14 and stayed negative until day 28. In the SoC group 2 participants had zero detectable viral loads at baseline, 2 participants tested negative on day 14, and the last participant tested remained positive on day 28. There were no serious adverse events, and all participants were clinically asymptomatic before day 28 with reactive immunoglobulin G (IgG).Trial relevanceThis pilot study proves that it is feasible and safe to perform a trial using a Galectin antagonist in COVID-19. This is a novel mechanism for blocking viral entry and its subsequent replication.Trial RegistrationClinical Trials.gov identifier NCT04512027; CTRI ref. CTRI/2020/09/027833

Levetiracetam (LEV) is an antiepileptic recommended during pregnancy.Pregnant rats were allocated into four groups of three rats each. Groups 1, 2, 3 and 4 received 2% gum acacia, LEV 270 mg/kg, LEV 270 mg/kg + Bacopa 100 mg/kg and LEV 270 mg/kg + Bacopa 200 mg/kg respectively during pregnancy and lactation. Three pups from all dams were chosen at random and exposed to passive avoidance, Hebb-Williams and Morris water maze tests to check for their cognition and relevant histopathology was done.In the passive avoidance model groups 3 and 4, showed an increase in escape latency compared with group 2, demonstrating an improved learning (p=0.05). In Hebb-Williams maze, the time taken to reach reward chamber by group 2 increased compared to group 1, p=0.006, showing cognitive decline. Neuronal count in hippocampus and prefrontal cortex decreased significantly in group 2, which improved in group 34 however there was distortion of architecture in group 4.LEV exposure in intrauterine and neonatal period induced cognitive decline in rat offsprings and Bacopa 100 mg/kg prevented LEV induced cognitive decline. However safety of exposure to Bacopa during the gestation period has to be evaluated.

Betulinic acid, a triterpenoid, is currently a molecule of great research interest with significant pharmacological activities including antioxidant action. In the current study we decided to study the effect of betulinic acid in a rat model of gentamicin induced renal damage. Nephrotoxicity was induced with gentamicin 80mg/kg, intraperitoneally for 8 days, and the test drug was administered at doses, 0.5, 1.5, and 3 mg/kg, per oral for 8 days, betulinic acid administered 3 days prior and concurrently with gentamicin for 5 days in wistar albino rats. Biochemical parameters studied included blood urea, serum creatinine, uric acid and blood urea nitrogen and also corroborated with histopathological examination of the kidney. The control group treated with gentamicin showed marked renotoxicity as evidenced by raised serum urea, serum uric acid, serum creatinine and blood urea nitrogen (107.5±16.92 mg/dL, 0.88±0.09 mg/dL, 3.05±0.29 mg/dL and 47.80±9.07 mg/dL resp.) when compared to the saline treated groups. Betulinic acid when given with gentamicin significantly (p < 0.05) decreased the biochemical parameters. Histopathological study revealed dilated tubules, denuded epithelium and extensive tubular necrosis in the disease control, whereas betulinic acid in higher doses showed evidence of renal tubular regeneration. To conclude, the results of the present study indicates that betulinic acid has significant nephroprotective effect in animal models of gentamicin induced renal damage