MICROBIAL OXIDATION OF FINASTERIDE WITH MACROPHOMINA PHASEOLINA(KUCC 730)

Objectives: New  microbial oxidative derivatives of Finasteride [17β-(N-tert-butylcarbamoyl)-4-aza-5α-androst-1-en-3-one] (1) has been investigated with Macrophomina phaseolina (ATCC730).Methods: Fermented media of  Macrophomina phaseolina (ATCC730) was prepared to cultivate the fungal cultures . Substrate 1 was incubated in liquid media for 16 days. After sixteen days, filtration and extraction of the fermented media was carried out with 9 L DCM in three portions. Resulting organic extract was dried using anhydrous (Na2SO4), and evaporated to afford a brown gum (950 mg). This on chromatographic purification with MeOH in CH2Cl2 afforded the metabolites 2-4 . Results: Three oxidised metabolites of finasteride (1) which were identified as 15-oxo-finasteride (2), 11a-hydroxyfinasteride (3), and 15β-hydroxyfinasteride (4). Metabolite 2 was found to be new. The structure of the oxidised metabolites were elucidated by 1-D (1H, 13C) and 2-D NMR (COSY, HMBC, HMQC, NOESY) techniques and MS analyses.Conclusion: As a result of these study, oxidation at C-7, C-11 and C-15 positions were found. Metabolite 2 was identified as a new metabolite

Acute toxicity study of a polysaccharide based hydrogel from linseed for potential use in drug delivery system

Linseed hydrogel (LSH) was evaluated by acute toxicity for its potential application in oral drug delivery design. White albino mice and rabbits were divided in four groups (I–IV) and different doses of LSH (1, 2 and 5 g/kg body weight) were given except to the control group (I) that was left untreated. Rabbits were monitored for eye irritation, acute dermal toxicity and primary dermal irritation, whereas, body weight, food and water consumption, hematology and clinical biochemistry, gross necropsy and histopathology of vital organs were scrutinized in mice. LSH was considered safe after eye irritation test as no adverse signs or symptoms were seen in the eye. In dermal toxicity and irritation study, skin of treated rabbits was found normal in color without any edema or erythema. After oral administration, there was no sign of any abnormalities in treated group animals (II–IV). The hematology and clinical biochemistry of treated group animals was comparable with the control group. Histopathology of vital organs has not shown any lesion or abnormalities. In the light of these outcomes, it can be concluded that LSH is not a hazardous biomaterial and could be incorporated as an excipient in oral and dermal preparations

Variation of Peak Expiratory Flow Rate with Body Mass Index in Medical Students of Karachi, Pakistan

OBJECTIVE: The primary aim of our study was to assess the variation of PEFR with BMI in normal medical students of Karachi, PakistanDESIGN: Cross-sectional studySetting: Medical students of Karachi Medical and Dental CollegeParticipants: 138 non-smoker healthy medical students composed of 111 females and 27 males. VARIABLE PARAMETERS: They include mean age, body height and body weight and PEFR. They were marked separately for each genderRESULTS: The mean BMI in females was found out to be 18.54±2.10 corresponding with that of mean PEFR value 431.62±56.62 whereas in males the mean BMI was 25.07±2.96 corresponding with that of mean PEFR value 533.70±23.22. Also there is a statistically significant variation in PEFR with an increase in BMI.CONCLUSION: The study concludes that PEFR is affected positively by variation in BMI. Also young males have more BMI and PEFR values than their young female counterparts. A large sample size with accurate peak flow meter is required along with ethnic consideration of the study population for better and accurate result

Variation of PEFR with height, weight and waist-hip ratio in medical students

OBJECTIVE: The primary aim of our study was to assess the variation of PEFR with various medical students of Karachi, PakistanDESIGN: Cross-sectional studySetting: Medical students of Karachi Medical and Dental CollegeParticipants: 276 non-smoker healthy medical students composed of 168 females and 108 males.VARIABLE PARAMETERS: They include mean age, body height and body weight and PEFR. They were marked separately for each genderRESULTS: The mean waist hip ratio in females was observed to be 0.843±0.111in relation with that of mean PEFR value 452.97±65.84 L/min, whereas in males the mean waist hip ratio was 0.864±0.028 in relation with that of mean PEFR value 445.93±66.49 L/min. Also there is a statistically significant variation in PEFR with an increase in waist hip ratio. The mean height of males was 173.63 ±7.5 cm and weight was 61.81 ±11.25 Kg while mean height of females was 158.56±7.3 cm and weight was 49.33±9.04 Kg. PEFR is positively correlated with increase in height and weight up to a certain limit.CONCLUSION: The study concludes that PEFR is affected positively by variation in waist hip ratio; moreover young females have more waist hip ratio and PEFR values than their young male counterparts. A large sample size with accurate peak flow meter is required along with ethnic consideration of the study population for better, accurate and clear results

Concordance of clinical, histopathologic and direct Immunofluorescence findings in patients with intraepidermal immunobullous disorders

Objective: To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders. Method: The prospective cross-sectional study was conducted at the Institute of Skin Diseases, Karachi, from December 2020 to December 2022, and comprised adult patients of either gender presenting with complaints of bullae, vesicles, pustules and crusts on the skin or mucous membrane. Diagnostic findings of each patient as obtained by clinical assessment, microscopy and direct immunofluorescence were compared. Data was analysed using SPSS 19. Results: Of the 81 patients, 41(50.6%) were males and 40(49.4%) were females. The overall median age was 35 years (interquartile range: 23 years), with 66(75%) patients aged 19-55 years. The predominant body site involved was the trunk 49(60.5%), followed by mucosa 26(32.1%). Clinical diagnosis detected 80(98.7%) cases, compared to 76(93.8%) by microscopy and 81(100%) by direct immunofluorescence. Conclusion: Direct immunofluorescence was found to be the gold standard for a confirmatory diagnosis of intraepidermal immunobullous disorders, especially when clinical and histopathology findings were inconclusive. Key Words: Intraepidermal immunobullous disorders, Pemphigus vulgaris, Histopathology, Direct immunofluorescence

Molecular Screening of Bioactive Compounds of Garlic for Therapeutic Effects against COVID-19

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was conducted to discover potential antiviral compounds from Allium sativum. Twenty-five phytocompounds of this plant were selected from the literature and databases including 3-(Allylsulphinyl)-L-alanine, Allicin, Diallyl sulfide, Diallyl disulfide, Diallyl trisulfide, Glutathione, L-Cysteine, S-allyl-mercapto-glutathione, Quercetin, Myricetin, Thiocysteine, Gamma-glutamyl-Lcysteine, Gamma-glutamylallyl-cysteine, Fructan, Lauricacid, Linoleicacid, Allixin, Ajoene, Diazinon Kaempferol, Levamisole, Caffeicacid, Ethyl linoleate, Scutellarein, and S-allylcysteine methyl-ester. Virtual screening of these selected ligands was carried out against drug target 3CL protease by CB-dock. Pharmacokinetic and pharmacodynamic properties defined the final destiny of compounds as drug or non-drug molecules. The best five compounds screened were Allicin, Diallyl Sulfide, Diallyl Disulfide, Diallyl Trisulfide, Ajoene, and Levamisole, which showed themselves as hit compounds. Further refining by screening filters represented Levamisole as a lead compound. All the interaction visualization analysis studies were performed using the PyMol molecular visualization tool and LigPlot+. Conclusively, Levamisole was screened as a likely antiviral compound which might be a drug candidate to treat SARS-CoV-2 in the future. Nevertheless, further research needs to be carried out to study their potential medicinal use

Evaluation of in vitro antibacterial activity and phytochemical screening of nigella sativa leaves extracts against human pathogenic bacteria

Objective: The current study objective was to explore the antimicrobial activity and phytochemical screening (Alkaloids, Flavonoid, Saponins, Phenolic compounds, terpenoid) of leaves extract of Nigella sativa. Study Design: Experimental study Place and duration of study: The current study was performed in Department Medical Laboratory Technology (MLT) at the University of Haripur. Haripur, Khyber Pakhtunkhwa, Pakistan from March 2021 to February 2022. Methods: Antimicrobial susceptibility test was done on Muller Hinton agar (MHA) using the disk diffusion method. Screening of N. sativa leaves extracts against Gram-positive bacteria Methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria Pseudomonas aeruginosa, Salmonella species, Escherichia coli and Klebsiella pneumonia were carried out using standard methods. Results: The results showed that ethanol, chloroform, hexane extract of nigella sativa had the best antimicrobial activity against P. aeruginosa, Methicillin-resistant S. aureus, Salmonella species, E. coli and K. pneumonia. Leaves extract of N. sativa were found to contain terpenoid, flavonoid, alkaloids, phenolic compounds except for saponins. Nigella sativa leaves showed good antibacterial activity against clinical multi-drug resistant bacteria. Conclusions: The results of this study provide useful bioactive compounds that show strong antibacterial activity against different multi drug resistant (MDR) including gram negative and gram positive bacteria

Molecular epidemiology of β-thalassemia in Pakistan: Far reaching implications

Background: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. Aim: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. Materials and Methods: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. Results: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles. Conclusions: Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations