FABRICATION AND EVALUATION OF HERBAL OINTMENT FORMULATIONS OF MORINGA OLEIFERA FOR TOPICAL DELIVERY

Objective: Traditional medicine is an important source of potentially useful new compounds for the development of chemotherapeutic agents. Moringa oleifera Lam. is a multipurpose and exceptionally nutritious vegetable tree with a variety of potential uses. It is distributed in many countries of the tropics and subtropics. Ointments are semisolid systems which behave as viscoelastic materials when shear stress is applied. They contain medicaments and are intended to be applied externally to the body or to the mucous membrane. Methods: In present study the Morenga oleifera leaves extract was used to formulate four different ointment formulations with different bases like cetostearyl alcohol, hard paraffin, and liquid paraffin. Formulations were evaluated for different parameters such as general appearance, spreadability, pH, extrudability, centrifugation,   irritancy, loss on drying, stability study etc. Results: All formulations were found to be free of grittiness, homogeneous, without phase separation with green colour with a smooth homogeneous texture and glossy appearance. Viscosity of the ointment formulations was in the range of 32.21±0.51 to 35.3±0.4. Formulations were found to be stable at different temperature. Conclusion: On the basis of results it can be concluded that ointment preparations with extract of Morenga oleifera leaves indicated the suitability of method for the production of ointments. Peer Review History: Received 13 June 2018;   Revised 27 August; Accepted 1 September, Available online 15 September 2018 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:        Reviewer's Comments: Average Peer review marks at initial stage: 3.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Jennifer Audu-Peter, University of Jos, Nigeria, [email protected] Dr. Emmanuel O. Olorunsola, Department of Pharmaceutics & Pharmaceutical Technology, University of Uyo, Nigeria, [email protected] Similar Articles: A RECENT OVERVIEW OF LOCALLY ADMINISTERED TOPICAL OTIC DOSAGE FORM

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Β-SITOSTEROL: ISOLATION FROM MUNTINGIA CALABURA LINN BARK EXTRACT, STRUCTURAL ELUCIDATION AND MOLECULAR DOCKING STUDIES AS POTENTIAL INHIBITOR OF SARS-CoV-2 Mpro (COVID-19)

Objecive: A novel human coronavirus (HCoV), labelled as SARS-CoV-2 (COVID-19), causing pneumonia is spreading around the world. At present, there are no specific treatments for COVID-19. β-sitosterol is well known for its multiple biological actions. The aim of this research is to isolate and study binding affinity of β-sitosterol for SARS-CoV-2 (COVID-19) main protease (Mpro). Methods: Extraction and Column chromatography was performed to isolate the β-sitosterol from n-hexane extract of Muntingia calabura bark followed by thin layer chromatography (TLC), HPTLC, FTIR and UV-Visible Spectroscopy. The molecular docking studies were performed on SARS-CoV-2 Mpro to determine the binding affinity of the β-sitosterol by using PyRx Virtual Screening Tool. Results: In present study, preliminary phytochemical screening showed presence of carbohydrate, steroid, terpenoid and flavonoid compounds. Total 115 fractions were collected from column chromatography by using benzene as solvent by isocratic elution technique. HPTLC Fingerprinting analysis showed the presence of β-sitosterol under 366 nm. FTIR characterization was performed of the same fraction which clearly gives the absorption peaks which resembles to β-sitosterol structure. Conclusion: The overall study concludes this method can be considered as a standard method for isolation of β-sitosterol from Muntingia calabura bark. Favipiravir have less binding affinity i.e. -5.7 kcal/mol than β-sitosterol which has -6.9 kcal/mol. The no. of hydrogen bonds formed by the Favipiravir is much more i.e. 04 than β-sitosterol which formed only 01 hydrogen bond with SARS-CoV-2 Mpro

Mutations in <i>MINAR2</i> encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice

Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report on DNA variants in MINAR2 , encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities. MINAR2 is a recently annotated gene with limited functional understanding. We detected three MINAR2 variants, c.144G > A (p.Trp48*), c.412_419delCGGTTTTG (p.Arg138Valfs*10), and c.393G > T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The c.393G > T variant is shown to disrupt a splice donor site. We show that Minar2 is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein ( Minar2 tm1b/tm1b ) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. We conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study

BACKGROUND: There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. METHODS: We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of χ(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. FINDINGS: We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. INTERPRETATION: Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009–10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation