Targeting Multidrug Resistant Mycobacterium Tuberculosis HtrA2 With Identical Chemical Entities of Fluoroquinolones.

Targeting Multidrug Resistant Mycobacterium tuberculosis HtrA2 with Identical Chemical Entities of Fluoroquinolones.

Indian J Pharm Sci. 2012 May; 74(3): 217-22
Daisy P, Vijayalakshmi P, Selvaraj C, Singh SK, Saipriya K

Tuberculosis is a highly communicable and chronic respiratory disease caused by pathogenic bacterium Mycobacterium tuberculosis. The drug – resistant species of Mycobacterium tuberculosis are tough to cure due to its resistant activity toward potential drugs. Available inhibitors of tuberculosis include few antimicrobial fluoroquinolone agents like ciprofloxacin, ofloxacin, and moxifloxacin to treat resistant Mycobacterium strains. Literature study elucidates that macromolecular target namely, HtrA2 of Mycobacterium tuberculosis play a dual role of protease and chaperone. These two activities are dependent on temperature, with low temperatures promoting the chaperone function and high temperatures promoting serine protease activity. Under normal physiological conditions HtrA2 acts as a quality control factor and promotes cell survival. In the present investigation, we screened fluoroquinolone such as ciprofloxacin, moxifloxacin and ofloxacin and their analogues based on better Docking score, absorption, distribution, metabolism and excretion screening and Lipinski’s rule of 5, to find out their efficiency on resistant strain through in silico study. From the results observed, the analogues are suggested to be potent inhibitors of HtrA2 with sufficient scope for further exploration. HubMed – drug


Associations of Gender and Age with the Reporting of Drug-Induced Hepatic Failure: Data from the VigiBase™

J Clin Pharmacol. 2013 Feb 25;
Petronijevic M, Ilic K

Patient gender and age are considered to be the risk factors for developing drug-induced liver injury (DILI). The aim of this study was to analyze gender and age differences in reporting of drug-induced hepatic failure (HF) to the VigiBase™. VigiBase™ was screened for the HF reports submitted from 2000 to 2009. The information retrieved referred to the suspected drug, age, gender, and a reporting country. Variables were examined by using descriptive statistics and the binomial test. During the 10-year period there were in total 6?370 HF reports from 38 countries. After the exclusion of cases with missing gender data (379 cases), females counted for 54.03%. The largest portion of HF cases referred to age <55 (42.57%) with female predominance (56.81%), whereas age ?55 (32.57%) showed almost even gender distribution. Overall, there were 941 different drugs or their combinations reported. Females significantly predominated in HF cases associated with analgesics, antiepileptics, antiinflamatory and antirheumatic drugs, psychoanaleptics, antibacterials for systemic use, and antidiabetic drugs. Males were significantly overrepresented in HF cases associated with antivirals for systemic use. Differences between genders and/or age groups in the reporting of drug-induced HF depend on drug and/or drug class but may be influenced by multiple factors. HubMed – drug


Improving adverse drug event detection in critically ill patients through screening intensive care unit transfer summaries.

Pharmacoepidemiol Drug Saf. 2013 Feb 26;
Anthes AM, Harinstein LM, Smithburger PL, Seybert AL, Kane-Gill SL

PURPOSE: This study aimed to determine the frequency and type of adverse drug events (ADEs) identified in intensive care unit (ICU) transfer summaries and in the hospital discharge summaries to demonstrate the effectiveness of ICU transfer summary surveillance in the identification of ADEs. METHODS: A retrospective electronic medical record review was conducted for medical ICU patients admitted between January 2009 and April 2009 to a large, academic medical center. The Harvard Practice Scale and the modified Leonard Assessment Scale were used to evaluate the presence of an ADE from the ICU transfer and hospital discharge summaries. RESULTS: Two hundred and fifty-four patients were identified for inclusion with a median medical ICU length of stay of 4.5?days and hospital length of stay of 13?days. The ICU transfer summary review revealed 173 ADEs among 124 unique patients with a rate of 33.9 ADEs per 1000 hospital patient days. Sixty-nine ADEs among 63 unique patients were identified through the hospital discharge summary with a rate of 13.5 ADEs per 1000 hospital patient days. Only 23.1% of ADEs discussed in the ICU transfer summary were also discussed in the hospital discharge summary. CONCLUSIONS: The use of ICU transfer summaries is an effective tool to increase ADE detection. The use of an ICU transfer summary should be considered as an adjunct method to an existing ADE surveillance system for heightened pharmacovigilance. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug


Dynamic contrast-enhanced MRI in mice at high field: Estimation of the arterial input function can be achieved by phase imaging.

Magn Reson Med. 2013 Feb 25;
Fruytier AC, Magat J, Colliez F, Jordan B, Cron G, Gallez B

PURPOSE: Quantitative dynamic contrast-enhanced MRI requires an accurate arterial input function (AIF). At high field, increased susceptibility effects and decreased longitudinal relaxivity of contrast agents lead to predominant T(2) * effects in blood vessels, producing a dip in signal during passage of the contrast agent bolus. This study determined phase-derived AIFs in mice at 11.7 T. METHODS: AIFs were measured in aorta/vena cava for five FBV/N mice and in iliac arteries/veins for five NMRI mice with a fast low angle shot sequence, simultaneously with tumor imaging (temporal resolution: 1.19 s). Gadoterate was injected into the tail vein as a bolus (0.286 mmol Gd/kg). An in vitro study was also performed to calculate the relationship between ?? and gadolinium concentration. RESULTS: The phantom system confirmed the linear relationship between measured ?? and gadolinium concentration. In vivo, a dip in arterial magnitude signal made it impossible to quantify the AIF. With phase imaging, a clear quantifiable bolus peak was obtained; peak measured concentration in plasma was 4.9?±?0.9 mM for FBV/N mice and 8.0?±?0.6 mM for NMRI mice, close to the expected concentration of 6.8 mM. CONCLUSION: Phase imaging seems to be an appropriate means to measure the AIF of mice at high field. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc. HubMed – drug