Drug resistance pattern of Mycobacterium tuberculosis isolates from patients of five provinces of Iran

Objective:To determine the patterns of resistance to first line anti-tuberculosis(TB)drugs among a collection of Mycobacterium tuberculosis(MTB)isolates from 5 provinces of Iran.Methods:A total of the 6 426 clinical specimens from patients suspected of active TB were collected from March 2010 to June 2012.All specimens were subjected for microscopy and culture tests in the TB centers of studies provinces.Drug susceptibility testing to the first line anti-TB drugs for culture positive MTB was performed on Lwenstein-Jensen(LJ)medium using proportion method.Results:Of 6 426 clinical specimens,261 were culture positive for mycobacteria,of which 252 were MTB and 9 were MOTT(mycobacteria other than tuberculosis).Of 252 MTB isolates.211(83.7%)were pan-susceptible and 41(16.3%)were resistant to at least one drug.Resistance was most common to streptomycin.30 isolates(12.0%),followed by isoniuzid,20isolates(8.0%),rifampin,15 isolates(6.0%)and ethambutol,14 isolates(5.5%).Sixteen(6.3%)MTB isolates were MDR.A clear evidence of heterogeneity amongst the 5 provinces in the proportions with resistance to one or more drugs was observed[χ~2=12.209(4 degrees of freedom),P values=0.015 9].Conclusions:The prevalence of drug resistance in this study area underscoring the need for further enforcement of TB control strategies in the Iran.Drug susceptibility testing for all TB cases to provide optimal treatment,establishing advanced diagnostic facilities for rapid detection of MDR-TB and continuous monitoring of drug resistance are recommended for prevention and control of drug-resistant TB.     

A method for quantitative characterization of growth in the 3-D structure of rat pulmonary arteries

Understanding mechanisms causing pulmonary vascular disease (PVD) frequently requires a thorough understanding of the underlying structural changes in the pulmonary circulation. Animal models have been used extensively to study different forms of PVD but conventional experimental techniques are limited in their ability to allow the study of the whole pulmonary vasculature at once. In this study, we introduce novel techniques of arterial casting, high-resolution imaging and tree analysis to study the pulmonary circulation in rodent models. Male Sprague-Dawley rats were used at 20, 36, 52, 100 and 160 days of age. A technique involving arterial casting with Microfil silicone polymer, high-resolution micro-computed tomography (micro-CT) at 12.5 μm resolution and image data analysis involving segmentation and skeletonization was developed to both qualitatively and quantitatively describe the changes in the pulmonary vasculature with increasing age. Parameters identified to affect the quality of pulmonary arterial casting included polymer flow rate, total injected volume, polymer viscosity and polymerization time. By optimizing these parameters, we successfully created arterial casts of the pulmonary circulation in rats of different ages and demonstrated the feasibility of quantitatively characterizing the changes in the number of vessels with postnatal growth. These preliminary data suggest that the number of vessels with lumen diameters of 50-200 μm increases rapidly in both lungs between 52 and 100 days of age. With this new technique, the pulmonary vasculature can now be studied in a whole lung animal model to better understand the global effects of disease on vascular structure.     

Probing chelation motifs in HIV integrase inhibitors

A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.     

Oral Nitrate Reductase Activity and Erosive Gastro-esophageal Reflux Disease: A Nitrate Hypothesis for GERD Pathogenesis

Background  

Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. “Nitrate reductase” of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake.     

Serum adenosine deaminase may predict disease activity in rheumatoid arthritis

To determine the relationship between serum adenosine deaminase (ADA) and disease activity, and to develop a new disease activity index based on serum ADA in rheumatoid arthritis (RA). Seventy RA patients were included. Disease activity based on Disease Activity Score 28-ESR (DAS28-ESR) and Disease Activity Score 28-CRP (DAS28-CRP) and serum ADA were measured. There were correlations when serum ADA compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.014, 0.175, respectively, P values?<?0.00). New disease activity index was developed by replacing ADA with ESR and CRP in DAS28-ESR and DAS28-CRP. There were strong correlations when new model compared with DAS28-ESR and DAS28-CRP. (R ²?=?0.94 and 0.95, respectively, P values?<?0.00) The best new model values corresponding to DAS28-ESR values of 2.6, 3.2, and 5.1 were 2.79, 3.4, and 4.82, respectively; and new model values corresponding to DAS28-CRP values of 2.3, 2.7, and 4.1 were 2.1, 2.9, and 4, respectively. There were agreements when the new model compared with DAS28-ESR and DAS28-CRP for determination of patients in different disease activity categories. (Kappa?=?0.81 and 0.71, respectively, P values?<?0.00). The new disease activity index that applies serum ADA may help in predicting disease activity in RA.     

Traumatic brain injury and adrenal insufficiency: morning cortisol and cosyntropin stimulation tests

Introduction

Adrenal insufficiency (AI) has a great impact on the prognosis of patients with traumatic brain injury. There is a lack of consensus regarding the diagnostic criteria of AI. In these patients with acute stress we compared fasting cortisol, low and high dose cosyntropin stimulation tests to assess adrenal function in patients with moderate to severe traumatic brain injury.

Material and methods

This multicenter, cross-sectional study recruited 50 consecutive patients (aged between 15 and 70 years old) with moderate to severe traumatic brain injury who survived more than 5 days after the event. The patients’ adrenal function was assessed using the fasting cortisol, 1 and 250-µg ACTH stimulation tests.

Results

More cases of AI were detected by the 1-µg ACTH stimulation test compared to those detected by the basal serum cortisol level and 250-µg ACTH stimulation test. The κ test showed no agreement between these tests. The incidence of AI in the first 10 days after traumatic brain injury varied from 34% to 82% according to the various definitions of AI. The incidence of hypotension and need for vasopressors was higher in the patients diagnosed by the 250-µg ACTH stimulation test (p < 0.0001).

Conclusions

The incidence of secondary AI in moderate to severe traumatic brain injury seems to be high. A combination of stimulation test (either 250 or 1 µg) and basal cortisol level may improve diagnostic ability compared to either test alone. Hence performing both tests for the assessment of adrenal function in patients with traumatic brain injury is recommended.