Virtual Screening of a Series of Phytocompounds from Polygonum cuspidatum for Identification of Potential Antibacterial Drug Candidates: an In-silico and Drug Design Approaches

In recent times, the emergence of Clostridium perfringens has posed a significant challenge to public health due to its antibiotic resistance and the formation of biofilms. It is the neuraminidase enzyme that supplies toxin secretion from C. perfringens. Since the sialic acid bond is a target recognition point for bacteria, new molecules are needed to treat infections caused by dangerous pathogens such as C. perfringens.The present work focused on an alternative strategy using compounds from Polygonum cuspidatum Sieb. et Zucc. Nine bioactive compounds derived from this plant emodin, physcion, emodin-1-O-β-D-glucopyranoside, emodin-8-O-β-D-glucopyranoside, physcion-8-O-β-D-glucopyranoside, 2-methoxy-6-acetyl-7-methyl juglone, torachrysone-8-O-β-D-glucoside, polydatin and resveratrol were used as ligands and coupled. The neuraminidase enzyme from C. perfringens was chosen as the target protein. The optimal ligand insertion score and ADMET parameters were determined by employing the Lipinski rules as selection criteria. Emodin-8-O-β-D-glucopyranoside and physcion-8-O-β-D-glucopyranoside exhibited drug-like characteristics in their ability to inhibit neuraminidase, as evidenced by a chelation score of −11.9. A comparison was conducted between emodin-8-O-β-D-glucopyranoside and physcion-8-O-β-D-glucopyranoside, and the positive control quercetin.A comprehensive analysis of the drug-like properties of emodin-8-O-β-D-glucopyranoside and physcion-8-O-β-D-glucopyranoside revealed that exhibited superiority over quercetin across multiple aspects. Quercetin showed a binding affinity of −9.9, while emodin-8-O-β-D-glucopyranoside and physcion-8-O-β-D-glucopyranoside showed a binding affinity of −11.9. The results showed acceptable differential kinetic properties of emodin-8-O-β-D-glucopyranoside and physcion-8-O-β-D-glucopyranoside compared to quercetin. It has been shown to inhibit the neuraminidase enzyme from C. perfringens.

Administration of tranexamic acid for victims of severe trauma within pre-hospital care ambulance services (PHCAS) in Malaysia

@#Introduction: Trauma is a Global threat and the 5th highest cause of all-cause mortality in Malaysia caused predominantly due to road traffic accidents. Majority of trauma victims are young adults aged between 21-40 years old. In Malaysia, 24 out of 100,000 population die annually due to trauma, rating us amongst the highest in South East Asia. These alarming figures justify aggressive preventive and mitigation strategies. The aim of this paper is to promote the implementation of evidence-based interventions that will reduce the rate of preventable death because of trauma. Tranexamic acid is one of the few interventions in the early management of severe trauma with level-one evidence. Tranexamic acid has been proven to reduce all causes of mortality and mortality due to bleeding. Evidence proves that it is most effective when administered early, particularly within the 1st hour of trauma. This proposed guideline is formulated based upon quality evidence from multicentre studies, clinical practices in other countries and consideration of the local demographic factors with the intent of enabling an easy and simple pathway to administer tranexamic acid early in the care of the severely injured. Conclusion: The guideline highlights select pre-hospital criteria’s and the methods for drug administration. The authors recognise that some variants may be present amongst certain institutions necessitating minor adaptations, nevertheless the core principles of advocating tranexamic acid early in the course of pre-hospital trauma should be adhered to.

Frequency of vancomycin resistant staphylococcus aureus among clinical isolates of MRSA collected from tertiary care hospitals of Lahore, Pakistan

Objective: To determine the frequency of vancomycin resistant Staphylococcus aureus [VRSA] among clinical isolates of methicillin resistant Staphylococcus aureus [MRSA]. Study Design: Descriptive study. Place and Duration of Study: Department of Microbiology, University of Health Sciences, Lahore from Jul 2014 to Dec 2014

Material and Methods: A total of 240 [n=240] clinical isolates of MRSA were collected by consecutive sampling from different tertiary care hospitals of Lahore. Re-confirmation of MRSA was done by the standard microbiological methods using disc diffusion technique according to Clinical Laboratory Standards Institute [CLSI] guidelines 2014. Minimum inhibitory concentration [MIC] of the vancomycin was done by agar dilution method

Results: It was found that vancomycin inhibited MRSA strains in the range of 1.0-2.0 microg/ml. Ninety percent [90%] of the strains inhibited at 1 microg/ml while 25 [10.41%] strains showed growth at 1 microg/ml which indicates that their MIC was 2 microg/ml. No vancomycin resistant [VRSA] or intermediate strains [VISA] of MRSA were found during the study but there were significant numbers of isolates having >/=1 microg/ml MIC of vancomycin

Conclusion: Vancomycin has until now excellent activity against clinical isolates of Methicillin-resistant Staphylococcus aureus

Analysis of toll-like receptors-9 [TLR9] gene polymorphism [rs5743836] in Pakistani patients with HCV

Toll-like receptors [TLRs] are innate immune receptors that mediate the inflammatory response during HCV infections. The goal of this study was to evaluate the association of TLR9 gene polymorphism [rs5743836] in Pakistani patients infected with genotype 3a of HCV. Total 500 subjects were recruited, 400 HCV patients and 100 healthy individuals. Genotyping of TLR9 [-1237T/C, rs5743836] was carried out in 400 HCV patients [323 interferon responders and 77 interferon nonresponder] and control group by applying High resolution melting [HRM] curve assay. No remarkable differences in distribution of genotype between HCV [p<0.0001; OR= 3.21, 95% CI= [2.514.12] and control groups [p<0.0001; OR=0.092, 95%CI= [0.0580.14] were observed. In conclusion TLR9-1237T/C gene polymorphism may not be considered as a molecular risk for patients with HCV in Pakistan

Prevalence of torus mandibularis among various ethnic groups in Karachi City: a cross sectional study

The aim of this study was to determine the prevalence of torus mandibularis in dental patients with regard to ethnic population in Karachi city. This study was undertaken at a dentistry teaching hospital of Karachi. Eight hundred subjects were clinically examined, presenting for their common dental health issues with the diagnosis of torus mandibularis [TM]. This study was conducted from January 2011 to March 2012. The location, position and clinical presentation of torus mandibularis were recorded, related to age and sex of various ethnic populations. Subjects participated in the study were 365[45.6%] males and 435[54.3%] females. Its overall prevalence in the study subjects was 8.6%. The mean age of patient was 41.79 and STD +/- 16.61. Torus mandibularis was observed in both genders with females having predominance. Urdu speaking population showed higher frequency of TM as compared to other ethnic sample

Value of Shock Index in Prognosticating The Short Term Outcome of Death for Patients Presenting With Severe Sepsis and Septic Shock in The Emergency Department

Introduction: The importance of early recognition and treatment of sepsis and its effects on short-term survival outcome have long been recognized. Having reliable indicators and markers that would help prognosticate the survival of these patients is invaluable and would subsequently assist in the course of effective dynamic triaging and goal directed management. Study Objectives: To determine the prognosticative value of Shock Index (SI), taken upon arrival to the emergency department and after 2 hours of resuscitation on the shortterm outcome of severe sepsis and septic shock patients. Methodology: This is a retrospective observational study involving 50 patients admitted to the University of Malaya Medical Centre between June 2009 and June 2010 who have been diagnosed with either severe sepsis or septic shock. Patients were identified retrospectively from the details recorded in the registration book of the resuscitation room. 50 patients were selected for this pilot study. The population comprised 19 males (38%) and 31 females (62%). The median (min, max) age was 54.5 (17.0, 84.0) years. The number of severe sepsis and septic shock cases were 31 (62%), and 19 (38%) respectively. There were 17 (34%) cases of pneumonias, 13 (26%) cases of urological sepsis, 8 (16%) cases of gastro intestinal tract related infections and 12 (24%) cases of other infections. There were a total of 23 (46%) survivors and 27 (54%) deaths. The value of the shock index is defined as systolic blood pressure divided by heart rate was calculated. Shock Index on presentation to ED (SI 1) and after 2 hours of resuscitation in the ED (SI 2). The median, minimum and maximum variables were tested using Mann-Whitney U and Chi square analysis. The significant parameters were re-evaluated for sensitivity, specificity and cut-off points. ROC curves and AUC values were generated among these variables to assess prognostic utility for outcome. Results: Amongst all 7 variables tested, 2 were tested to be significant (p: < 0.05). From the sensitivity, specificity and ROC analysis, the best predictor for death was (SI 2) with a sensitivity of 80.8%, specificity of 79.2%, AUC value of 0.8894 [CI95 0.8052, 0.9736] at a cut-off point of ≥1.0. Conclusion: (SI 2) may potentially be utilized as a reliable predictor for death in patients presenting with septic shock and severe sepsis in an emergency department. This parameters should be further analyzed in a larger scale prospective study to determine its validity.

Uric acid profile in patients with chronic nonspecific musculoskeletal pain

The present study was undertaken to determine the uric acid profile in patients with unexplained chronic musculoskeletal complaints, and to establish any possible causal role for altered uric acid profile in such patients. Method: A comparative study of 36 patients and 36 controls of both sexes and ages between 25-60 years was carried out at Shaikh Zayed Hospital, Lahore from November 2001-May 2002. Patient included were those who had at least 4-24 weeks duration of complaints. Uric acid profile for serum uric acid, uric acid excretion, uric acid clearance and total uric acid production was done. Additional tests included renal functions test, liver function test, cardiac enzymes, haematology and serology to exclude other underlying causes of complaints. Mean serum uric acid levels were higher in patients as compared to controls [p=0.05], with 9 [25%] patients showing hyperuricemia. Uric acid clearance [female patients 5.86+0.42 ml/min, female controls 8.06+0.24 ml/min] and daily uric acid excretion [female patients 412.38+28.52 mg/24 hours, female controls 487.79+18.64 mg/24 hours] in female patients was significantly lower than control females [P=0.034 and P<0.001 respectively]. Twenty patients [55.55%, 3 males and 17 females] were classified as under excretors of uric acid, while there were no under excretors in the control group [p<0.001]. We conclude that abnormalities of uric acid profile, particularly under excretor status may be an underlying biochemical abnormality in a significant number of patients. Female patients appear more predisposed to abnormal uric acid profile such as hyperuricemia and under excretor status