the Indian Journal of Pharmacy最新文献

Background: Human metapneumovirus (HMPV) is an emerging respiratory pathogen affecting children, elderly individuals, and immunocompromised patients. Despite its disease burden, no antiviral treatment has been approved to date.

Objective: The present study aimed to identify the Food and Drug Administration-approved drugs with potential for repurposing against HMPV by targeting its key structural proteins-fusion (F) and nucleoprotein (N).

Materials and methods: The crystallographic structures of HMPV fusion (Protein Data Bank [PDB] ID: 5WB0) and nucleoprotein (PDB ID: 5FVD) were retrieved, validated, and subjected to molecular docking. Ligands with favorable binding scores were further evaluated using molecular dynamics simulations and binding-free-energy calculations. Pharmacokinetic and toxicity profiles were predicted to assess their translational viability.

Results: For the fusion protein, rutin, carbetocin, and acarbose showed strong binding affinities and stable molecular interactions. For the nucleoprotein, mobocertinib, lapatinib, and levetiracetam emerged as top candidates, with mobocertinib showing the most favorable binding energy. Among all, levetiracetam displayed the most drug-like characteristics, including high gastrointestinal absorption, no major cytochrome P450 inhibition, and no violations of Lipinski's rule.

Conclusion: The study highlights mobocertinib, rutin, and levetiracetam as promising repurposed drugs against HMPV. While mobocertinib exhibited the strongest predicted binding affinity, levetiracetam demonstrated the best pharmacokinetic profile, making it a particularly viable candidate for further experimental validation. These results validate the usefulness of in silico drug repurposing in addressing unmet antiviral needs and warrant preclinical studies to evaluate therapeutic efficacy.

Objective: The purpose of this study was to determine the in vitro synergistic effect of meropenem and sulbactam drug combinations through checkerboard assay against Carbapenem-resistant Acinetobacter baumannii (CRAB) to establish potential treatment options.

Materials and methods: CRAB was cultured from the clinical samples of Endotracheal aspirate, blood, pus, throat swab, and urine specimens from 80 patients with suspected nosocomial infection in 1 year. Minimum inhibitory concentration (MIC) was determined for meropenem and sulbactam drugs individually. Synergism was determined for meropenem + sulbactam combinations using checkerboard assay.

Results: All the 80 CRAB isolates were found to be resistant (>16 MIC) for Meropenem drug and 64 out of 80 showed resistant (>16 MIC) to sulbactam, 14 isolates displayed intermediate (8 MIC), and 2 of them were found to be sensitive (<2 MIC). The checkerboard assay showed 66.25% of synergism between meropenem and sulbactam followed by 25% of additivity and 8.75% of them were found to be indifferent.

Conclusion: In the current checkerboard assay, we observed potential synergistic activity between meropenem and sulbactam against CRAB isolates which indicates that this combination can be an appealing strategy in the treatment of nosocomial infections caused by CRAB isolates.

Abstract: Aspirin as an agent for thromboprophylaxis in patients with total knee replacement (TKR) and total hip replacement (THR) is gaining a lot of importance owing to its efficacy and safety in preventing venous thromboembolism (VTE) complications. The current guidelines do not recommend aspirin over other anticoagulants as the data from the meta-analysis of randomized controlled trails (RCTs) lacked a significant sample to draw conclusive results. The present study was aimed to carry out a systematic review and meta-analysis of nonrandomized studies (NRSs) to determine the effect of aspirin as prophylaxis for VTE. A complete electronic search was conducted at PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar for relevant articles published till March 2021. Any postsurgical VTE event (deep vein thrombosis and/or pulmonary embolism) is considered the primary outcome and adverse events as secondary outcomes. Both efficacy and safety outcomes were reported as pooled risk estimates with 95% confidence interval (CI) with a level of significance at P < 0.05. A total of 21 studies were identified for the analysis. The overall risk of occurrence of VTE among the patients taking aspirin was not significantly different from anticoagulants (risk ratio [RR]: 0.78, 95% CI: 0.52-1.15). Patients who underwent THR had a higher risk for VTE with aspirin (RR: 1.50, 95% CI: 1.35-1.61), whereas the patients who underwent TKR showed a lower risk of VTE with aspirin (RR: 0.80, 95% CI: 0.75-0.85). Meta-analysis of NRS advocates the role of aspirin as a prophylactic agent for VTE, especially for patients who are in need for TKR. Further RCTs are required to reestablish the role of aspirin, especially in patients undergoing THR.

Background: Tinnitus or "phantom sound" continues to be a significant health problem without a uniformly accepted treatment. Numerous pharmaceutical options have been investigated, but satisfactory results are yet to be obtained.

Objectives: The objectives of this study were to study and compare the efficacy, safety, and cost-effectiveness of caroverine alone, caroverine combined with ginkgo biloba and betahistine alone in patients of moderate tinnitus.

Materials and methods: In this prospective, observational, hospital-based study, wherein 72 patients were distributed equally across three groups - Group A received caroverine 20 mg twice daily, Group B received caroverine 20 mg combined with ginkgo biloba 120 mg twice daily, and Group C received betahistine 8 mg thrice daily for 12 weeks. Efficacy was zanalyzed assessing the changes in tinnitus handicap inventory (THI), tinnitus functional index (TFI), Visual Analog Scale (VAS) score, and pure tone audiometry values from baseline at 4, 8 and 12 weeks. The cost-effectiveness analysis was done at the end of 12 weeks zutilizing the incremental costeffectiveness ratio. The Chi-square test and one-way ANOVA were used to evaluate the statistical significance of the results.

Results: The reduction in the THI, TFI and VAS scores was maximum in Group B followed by Group A and Group C. All the drugs were well-tolerated, and the adverse effects encountered were mild and nonserious. Combination therapy of caroverine with gingkgo biloba was the most expensive.

Conclusion: Caroverine and ginkgo biloba combination therapy was the most effective in reducing the handicap of moderate tinnitus.

Abstract: Once incurable and chronic devastating diseases of chromomycosis is now curable with, debulking, intralesional amphotericin B and oral terbinafine (DAT). Debulking methods ranged from electrocautery to total surgical excision according to the size and the site of the lesion; a diluted solution of 1 mg/mL of amphotericin B (AMB) was injected weekly at the edge of the lesion; and simultaneous treatment with daily 500 mg oral terbinafine. Voriconazole 200 mg twice daily was added in one patient who had infection spread along the right lower limb for more than 20 years. DAT therapy was continued until complete clinical clearance where 14 out of 16 (87.5%) were cured using intralesional AMB 4-8 weeks (mean 5.8, mode 7) and oral terbinafine 6-12 weeks (mean 9.6, mode 12). Two patients who had lesions for 10 years and 20 years had to continue treatments for 14 weeks and 34 weeks, respectively, leaving scarring, chronic lymphedema, or depigmentation to a lesser degree. Early initiation of treatment gives an optimal outcome in a shorter period of time without residual sequelae.

Background: Exosomes derived from adipose-derived stem cells (ADSCs) have garnered significant attention for their therapeutic potential in various diseases. These vesicles are capable of transporting bioactive molecules such as noncoding RNAs and proteins. Among these noncoding RNAs, circular RNAs (circRNAs) are characterized as end-to-end circular structures, which are notably enriched within exosomes.

Objective: This study aims to investigate the impact of the circHIPK3 delivered via ADSC-derived exosomes on ovarian aging.

Materials and methods: ADSCs were isolated, and exosomes were obtained from a cell culture medium. The exosomes were labeled with PKH26, and uptake by primary granulosa cells (pGCs) was detected. ADSCs were transfected with circHIPK3 siRNAs, and the exosomes were isolated for the treatment of aging female mice. Ovary weight was recorded, and HE staining, Masson's trichrome, and TUNEL staining were performed to detect tissue morphology and apoptosis in ovary tissues. In addition, the senescence and apoptosis of pGCs were evaluated using the S-β-gal staining kit and Annexin V/PI detection kit. Further experiments included immunoprecipitation and RNA pulldown, determined the ubiquitination of p38 protein under circHIPK3 alteration.

Results: Results showed that ADSC-derived exosomes effectively delivered circHIPK3 to pGCs. Treatment with these exosomes significantly increased ovary weight and enhanced follicular development in aged mice. Conversely, the depletion of circHIPK3 reversed these effects, promoting cell apoptosis. ADSC-derived exosomes also mitigated senescence and apoptosis in pGCs, while circHIPK3 depletion hindered these benefits.

Conclusion: Exosomal circHIPK3 modulated the ubiquitination of p38 in pGCs to improve ovarian function in aging mice and to promote pGC cell viability.

Background: Our study explores nosodes (potentized medicines derived from microbes), as alternative antimicrobial measures against infections. Different nosodes were tested for efficacy against pathogens in clinical urine samples, comparing them with Gentamicin.

Objective: Evaluating the efficacy of potentized medicines against microbes found in urine samples.

Materials and methods: The test samples were added to the sterile 96 well plates with 150 μL of sterile media followed by bacteria-positive clinical urine samples (10 μL), and the plate was incubated at 37°C. After 72 h, optical density was measured. Reduction in bacterial growth was calculated as the antibacterial potential of the drugs.

Results: Escherichia coli poly-nosode 100C exhibited the highest efficacy at 93.79%, followed by Neisseria gonorrhoeae 100C (89.27%), E. coli 200C (79.61%), and Syphilinum 30C (78.76%) against Klebsiella pneumoniae. The average efficacy against Pseudomonas aeruginosa for the 27 test samples studied was 72.32%, (verses Gentamicin 74.25%). The highest efficacy at 92.79% was observed with E. coli poly-nosode followed by methicillin-resistant Staphyloccus aureus (MRSA) 30C (92.29%), N. gonorrhoeae 50C (92.29%), Cantharis 30C (90.95%), and Salmonella typhi 30C poly-nosode (81.35%). Cantharis 30C at 86.53% and E. coli 200C at 78.02% were effective against the mixed infection of E. coli + Candida albicans. The average efficacy of nosodes against this mixed infection was 63.53%, while Gentamicin demonstrated 61.97% efficacy. MRSA 100C showed the highest efficacy at 52.37% against E. coli, and an average efficacy of 44.5% was noted with test samples.

Conclusions: Our study unveils the therapeutic potential of homeopathic medicines against antibiotic-resistant bacterial strains.