Potent ROS inhibitors from Zanthoxylum armatumDC of Nepali origin.

A bioassay-guided isolation on the plant Zanthoxylum armatum DC yielded compounds tambulin (1), and prudomestin (2), from ethyl acetate fraction which showed the highest ROS inhibiting activity (IC50 = 17.8 ± 1.1 µg/mL). Structure elucidation of pure compounds was done using mass and NMR spectroscopic techniques. Compounds 1 and 2 revealed potent ROS inhibition with IC50 = 7.5 ± 0.3 and 1.5 ± 0.3 µg/mL, respectively, as compared to standard ibuprofen (IC50 = 11.2 ± 1.9 µg/mL). Likewise, both compounds 1 and 2 showed potent antioxidant activity with IC50 = 32.65 ± 0.31 and 26.96 ± 0.19 µg/mL, respectively. In vitro studies were supported by molecular docking and drug-likeliness properties. In silico studies of 1 and 2 with cyclooxygenase-2 (COX-2) showed perfect binding affinity with binding energies of -8.4 and -8.6 kcal/mol, respectively, comparable to standard ibuprofen (-7.7 kcal/mol). Drug likeness and ADMET showed higher gastrointestinal absorption of 1 and 2 and no toxic impact.

Use of Unannounced Standardized Patient to Assess Quality of Care in Community Pharmacies / Medicine Shops: A Pilot, Cross-Sectional Study.

BACKGROUND: Community pharmacies are the most accessible healthcare providers l which plays a key role in primary healthcare services managing minor ailment and ensure the quality use of drugs. Our study aimed to assess the quality care from community pharmacies using unannounced standardized patient. METHODS: All community pharmacies from three municipalities of Kavrepalanchowk district were visited by unannounced standardized patients presenting with acute dysentery, seasonal influenza, acute gastritis, acute diarrhea and pulmonary tuberculosis. Responses were audio-recorded and checked using standard checklist. Descriptive analysis was performed and data were presented as frequencies and percentages. RESULTS: A total of 40 visits were performed for each case of acute dysentery, seasonal influenza and acute gastritis and 41 visits for acute diarrhea and pulmonary tuberculosis. During visits, on average, 17.7% (±12.3) of recommended questions were asked by the community pharmacies. Among the drug dispensed, on average, 1.9 (± 0.6) drugs were dispensed. All the community pharmacies 40 (100.0%) provided correct drugs in acute gastritis followed by 34 (85.0%) in acute dysentery, 31 (77.5%) in acute diarrhea and 21 (52.5) in seasonal influenza, whereas no pharmacies provided correct drug in the case of pulmonary TB. None of the pharmacies counseled on potential adverse effects. CONCLUSIONS: The study showed a high rate of drug dispensed without sufficient inquiry of the recommended symptoms for proper diagnosis and counseling regarding drug use was low. The study recommends a need for continuous training by concerned bodies to improve the quality of professional practice in the community pharmacies.

A Rare Case Report of Giant Urinary Bladder Stone Causing Recurrent Dysuria in a Woman.

Background: Large urinary bladder stones are not common and even less common in females. We report a case of large bladder stone presented with acute retention of urine in a female patient. Case Report. A 62-year-old female presented in emergency department with retention of urine for 12 hours with history of recurrent UTIs for last 1 year. She was also complaining of mild dull lower abdominal pain for last 6 months. She had no history of incontinence of urine and fever. On physical examination, hard mass was palpable on suprapubic region on palpation of abdomen. Urine culture shows Escherichia coli for which antibiotics was given. An X-ray kidney ureter bladder showed a radio-opacity in the pelvic region measuring 9 × 8 cm in size. Ultrasonography revealed bilateral mild hydronephrosis with a large bladder stone. Open cystolithotomy was performed, and the stone was taken out. Stone biochemical analysis showed predominantly urate crystals. Patient had uneventful postoperative course, and she was discharged on 4th postoperative day and was followed up for 1 months after operation. Conclusions: Large urinary bladder stones are not common and even less common in females. Clinician should have think regarding large bladder stone as a cause of recurrent lower urinary tract symptoms like dysuria and should assess renal function for proper treatment. Open cystolithotomy is choice of operation in large bladder stone.

Antioxidant, Antibacterial, Antidiabetic Potential, and In silico Analysis of Rhus chinensis from Western Nepal.

BACKGROUND: Rhus chinensis Mill, indigenous wild fruit primarily found in the hilly region of Nepal. The ripe fruit is very sour and considered medicinal as a remedy for colic pain. In addition, their astringent and styptic qualities are used internally to treat illnesses such as diarrhea and hemorrhage. Also, they are used as a common component of polyherbal medications for diabetic mellitus. OBJECTIVES: This work aimed to determine the total phenolic and flavonoid content, antioxidant, antibacterial, α-glucosidase, and α-amylase inhibition activity of the crude extract and fractions of Rhus chinensis Mill. Additionally, molecular docking of compounds from Rhus chinensis was performed. METHODS: Folin Ciocalteu's (FC) reagent was used to estimate total phenolic content. Likewise, the aluminium trichloride method was applied to determine total flavonoid content. A 2,2-diphenyl-1- picrylhydrazyl (DPPH) free radical scavenging assay was performed for the antioxidant activity. Furthermore, the substrate-based enzyme inhibition assay was carried out for α-glucosidase and α- amylase inhibition activity of R. chinensis. P-nitrophenyl-α-D-glucopyranoside (PNPG) and 2- Chloro-4-Nitrophenyl-α-D-Maltotrioside (CNPG3) were used as substrates for α-glucosidase and α- amylase inhibition assay, respectively. Similarly, the well-diffusion method was used for the antibacterial activity. Autodock vina was used to perform molecular docking. RESULTS: The total phenolic and flavonoid content of R. chinensis fruit were 117.092±1.1 mg GAE/g and 62.41±1.23 mg QE/g, respectively. The IC50 value for antioxidant activity of the crude extract and its fractions ranged from 3.12±1.15µg/mL to 50.85±2.10µg/mL. Similarly, the IC50 for α- glucosidase inhibition ranged from2.33±1.01µg/mL to 28.34±2.79µg/mL. Likewise, The IC50 of R. chinensis crude methanolic extract against α-amylase was 120.3±1.382µg/mL. The antibacterial activity of R. chinensis was effective against gram-positive bacteria; Staphylococcus aureus (ZOI=11.0) and Bacillus subtilis (ZOI=9.0). Quercetin-3-O-rhamnoside and Myricetin-3-Orhamnoside showed excellent binding to the active site of protein with binding energy -9.4kcal/mol and -9.6kcal/mol, respectively. CONCLUSION: Rhus chinensis Mill is a potent antioxidant and inhibits enzymes; α-glucosidase and α- amylase. In addition, the methanolic extract of this plant shows antibacterial activity. However, further research is required to determine the inhibiting compounds.

Nepal measles outbreak response immunization during COVID-19: A risk-based intervention strategy.

In 2020, National Immunization Programme (NIP) of Nepal implemented a measles outbreak response immunization (ORI) campaign, which was additional to an ongoing preventive measles-rubella SIA campaign. Both campaigns were implemented during ongoing COVID-19 transmission. By April, 220 measles cases and two deaths were confirmed from eight districts of Nepal. The NIP triangulated information from surveillance (measles and COVID-19), measles immunization performance and immunity profile, programme capacities and community engagement and applied a logical decision-making framework to the collated data to inform 'Go/No-Go' decisions for ORI interventions. This was reviewed by the National Immunization Advisory Committee (NIAC) for endorsement. Outbreak response with non-selective immunization (ORI), vitamin-A administration and case management were implemented in affected municipalities of four districts, while in the remaining districts outbreak response without ORI were undertaken. The structure and iterative application of this logical framework has been described. ORI was implemented without interrupting the ongoing measles-rubella vaccination campaign which had targeted children from 9 to 59 months of age. The age group for ORI was same as SIA in one sub-district area, while for the other three sub-district areas it was from 6 months to 15 years of age. More than 32,000 persons (97% coverage) were vaccinated in ORI response. Overall measles incidence decreased by 98% after ORI. The daily incidence rate of measles was 94 times higher (95% confidence interval: 36.11 - 347.62) before the ORI compared to two weeks after ORI until year end. Close attention to surveillance and other data to inform actions and seamless collaboration between NIP and core immunization partners (WHO, UNICEF), with guidance from NIAC were key elements in successful implementation. This was an example of feasible application of the global framework for implementation of a mass vaccination campaign during COVID-19 through application of a simple decision-making logical framework.