BackgroundSerotonin reuptake inhibitors were recently reported to possess antimicrobial potentials, potentiate activity of several antibiotics, reverse multidrug resistant phenotypes of bacteria and make them susceptible to previously resistant drugs. We investigated antimicrobial potentials of sertraline (SR) against ATCC strains, clinical isolates of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa alone and in-combination with seven antibiotics. Antifungal activity was investigated against four fungal strains including Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Fusarium solani. Intrinsic antibacterial action and Minimum Inhibitory Concentrations (MICs) were determined using well assay, nutrient broth and agar dilution techniques. Disk diffusion and nutrient broth methods were used to study bacterial susceptibility to SR. Minimum Fungicidal Concentrations (MFCs) of SR were determined using Sabouraud dextrose Agar (SDA).ResultsSertraline possesses strong intrinsic antibacterial, antifungal activities and has augmented the antibacterial activities of antibiotics. For S. aureus ATCC 6538, E. coli ATCC 8739 and P. aeruginosa ATCC 9027, the MICs of SR were 20, 40 and 60 μg ml−1, respectively, whereas 55.5% clinical isolates of S. aureus and 50% of E. coli strains were inhibited at 20 and 60 μg ml−1 of SR, respectively. Among the tested fungi, 60% of A. niger and A. fumigatus were inhibited at 40 and 80 μg ml−1, respectively. MFCs were 60 and 80 μg ml−1 for A. flavus and F. solani, respectively. Antibacterial activities of all antibiotics were significantly increased (p < 0.001) with the addition of SR 100 μg ml−1 against all tested bacteria.ConclusionCombination study revealed that SR had significantly increased the activity of antibiotics, and some previously resistant strains were made susceptible. Thus antidepressants are potential sources of resistance modifying agents when used in combination.

Peptic ulceration is among the most prevalent gastrointestinal disorders characterized by pepsin and gastric acid mediated mucosal damage, as result of imbalance between defensive and offensive processes. The main objective of the current study was to investigate the antiulcer potentials of Polygonum hydropiper crude methanolic ectract (Ph.Cr) in aspirin induced ulcerogenesis using pylorus ligated rat model. In-vitro urease and Proteus mirabilis inhibitory potentials were evaluated using standard protocols. All fractions were analyzed using GC-MS to identify major components. The aspirin induced ulcerogenesis in pylorus ligated rat model was associated with significant changes in the mean ulcer score [F(5, 30) = 7.141, P = 0.0002], gastric juice volume [F(5, 30) = 8.245, P < 0.0001], gastric juice pH [F(5, 30) = 5.715, P = 0.0008], free acidity [F(5, 30) = 4.544, P = 0.0033], total acidity [F(5, 30) = 2.740, P = 0.0373], and pepsin concentration [F(5, 30) = 2.335, P = 0.0664]. Pre-treatment with Ph.Cr at 100, 200, and 400 mg/kg dose exhibited marked gastroprotective and anti-ulcerogenic effect in the aspirin induced pyloric ligation ulcerogenesis model at 100, 200, and 400 mg/kg as indicated by ulcerative biochemical parameters. In urease inhibition assay, leaves essential oil (Ph.Lo), saponins (Ph.Sp), and chloroform extract (Ph.Chf) exhibited highest activities with IC50 of 90, 98, and 520 μg/ml, respectively. Ph.Sp, Ph.Chf, ethyl acetate (Ph.EtAc), and Ph.Cr showed MICs of 25, 30, 32.25, and 40.50 μg/ml, respectively against P. mirabilis. Several compounds were identified in GC-MS analysis of samples. Significant in-vivo antiulcer, urease inhibitory as well as anti-proteus potentials of P. hydropiper solvent extracts, signify its potential use for the management of peptic ulcers and may provide scientific bases for the traditional uses of the plant.

P2X receptors are ligand-gated cation channels that mediate many of the extracellular actions of adenosine 5 -triphosphate (ATP). The genes encoding seven different P2X subunits, P2X1-7, have been cloned and when expressed alone all P2X subunits form functional receptors, except P2X6, which usually only assembles in a heteromeric form. Subunits can also interact with each other and to date seven functional heteromultimers with pharmacological and/or biophysical properties that differ from the individual homomultimers have been identified: P2X2/3, P2X4/6, P2X1/5, P2X2/6, P2X1/4, P2X1/2, and possibly P2X4/7. These are distributed widely throughout the body and are involved in many physiological and pathophysiological processes. ATP is an agonist at all subtypes and few selective agonists and no useful antagonists were available when P2X receptors were first defined. Subsequently, nonselective antagonists, such as suramin and PPADS, were discovered and since then, and particularly in the past decade, numerous potent and subtype-selective antagonists have been developed. These include NF449 and RO-1 at P2X1 receptors; PSB-1011 at P2X2 receptors; A317491, compound A, RO-3, and AF-353 at P2X3 and P2X2/3 receptors; 5-BDBD at P2X4 receptors; and A740003, A438079, A804598, GSK314181A, AZ10606120, AZ11645373, AZD-9056, CE-224535, and EVT-401 at P2X7 receptors. The therapeutic usefulness of these compounds is currently being investigated in a variety of disorders, including thrombosis (P2X1), chronic neuropathic and inflammatory pain (P2X3, P2X2/3, P2X4, P2X7), dysfunctional urinary bladder (P2X1, P2X3, P2X2/3), rheumatoid arthritis and osteoarthritis (P2X7), and depression (P2X7). 

Aims COVID-19 outbreak has created a public health catastrophe all over the world. Here, we have aimed to conduct a systematic review and meta-analysis on remdesivir use for COVID-19. Main methods We searched Pubmed, Scopus, Embase, and preprint sites and identified ten studies for qualitative and four studies for quantitative analysis using PRISMA guidelines. The quantitative synthesis was performed using fixed and random effect models in RevMan 5.4. Heterogeneity was assessed using the I-squared (I 2 ) test. Key findings Comparing 10-day remdesivir group with placebo or standard of care (SOC) group, remdesivir reduced 14 days mortality (OR 0.61, CI 0.41–0.91), need for mechanical ventilation (OR 0.73, CI 0.54–0.97), and severe adverse effects (OR 0.69, 95% CI 0.54 to 0.88). Clinical improvement on day 28 (OR 1.59, CI 1.06–2.39), day 14 clinical recovery (OR 1.48, CI 1.19–1.84), and day 14 discharge rate (OR 1.41, CI 1.15–1.73) were better among remdesivir group. Earlier clinical improvement (MD −2.51, CI −4.16 to −0.85); and clinical recovery (MD −4.69, CI −5.11 to −4.28) were seen among the remdesivir group. Longer course (10 days) of remdesivir showed a higher discharge rate at day 14 (OR 2.11, CI 1.50–2.97), but there were significantly higher rates of serious adverse effects, and drug discontinuation than the 5-day course. Significance Remdesivir showed a better 14 days mortality profile, clinical recovery, and discharge rate. Overall clinical improvement and clinical recovery were earlier among the remdesivir group. 10-day remdesivir showed more adverse outcome than 5-day course with no significant benefits.

Endogenous nucleotides have widespread actions in the cardiovascular system, but it is only recently that the P2X and P2Y receptor subtypes, at which they act, have been identified and subtype-selective agonists and antagonists developed. These advances have greatly increased our understanding of the physiological and pathophysiological functions of P2X and P2Y receptors, but investigation of the clinical usefulness of selective ligands is at an early stage. Nonetheless, the evidence considered in this review demonstrates clearly that various cardiovascular disorders, including vasospasm, hypertension, congestive heart failure and cardiac damage during ischemic episodes, may be viable targets. With further development of novel, selective agonists and antagonists, our understanding will continue to improve and further therapeutic applications are likely to be discovered.

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Rumex dentatus is well known plant of Polygonaceae family which is widely used in traditional medicine to treat gastrointestinal tract. R. dentatus at doses 250 and 500 mg/kg significance decreased (p<0.001) the elevated level of ALT, AST, ALP and bilirubin induced by paracetamol and results are comparable (p<0.001) with silymarin. The results were supported by histopathological investigations, phytochemical screening and detection of hepatoprotective active constituents e.g quercetin, kaempferol, myricetin by HPLC. So, it is concluded that R. dentatus has hepatoprotective effect against paracetamol liver damage in mice. Article InfoReceived:12