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.     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, verapamil SR 240 mg plus indapamide 2.5. mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg, patients with sitting diastolic blood pressures of 95--115 mm Hg were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. (Patients with diastolic BP < 95 mm Hg on this initial treatment were excluded from further study.) Efficacy assessed after 16 weeks or at the end point showed all three treatments significantly reduced sitting diastolic blood pressure from baseline levels. Compared with Group I (low-dose) verapamil SR treatment, there was a reduction in Group III combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction in Group II high-dose verapamil SR therapy of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Efficacy results were independent of age or body weight. Patients who were poor responders to lead-in verapamil SR 240 mg daily prior to randomization tended to have a greater response to combination therapy than to high-dose verapamil SR. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving high-dose verapamil (Group II), exceeding the withdrawal from the other two treatment groups (8.5% from Group II and 4% from Group I). The most frequent adverse experiences in Group II were constipation and peripheral edema; headache was most common in Groups I and III. This trial demonstrates that adding indapamide to low-dose verapamil SR enhances efficacy and is well tolerated.     

Could Helicobacter pylori play an important role in axonal type of Guillain-Barré Syndrome pathogenesis?

In this case-control study, ELISA and Western blot with whole bacterial protein lysate were performed on serum and cerebrospinal fluid (CSF) of 15 controls and 15 patients. According to Griffin subtypes, 10 of our patients were in acute inflammatory demyelinating polyradiculoneuropathy (AIDP) group, 3 in acute motor axonal neuropathy (AMAN) group, and 2 in acute motor sensory axonal neuropathy (AMSAN) subtype. 86.6% of patients were positive for Helicobacter pylori (H. pylori) IgG. Serum anti-H. pylori IgG of patients and controls were significantly different. CSF anti-H. pylori IgG was significantly higher in patients than controls. In patients, the titer of anti-H. pylori IgG in serum was significantly higher than CSF, which may indicate extra-neural antibody synthesis. CSF IgG titer was higher in patients having axonal pattern. Western blot was positive in CSF of 13 patients and negative in all controls. There was a correlation between the number of antibody types against H. pylori particles and the titer of anti-H. pylori IgG in CSF and serum. Also, antibody against cytotoxin associated protein (CagA) was associated with primary axonal pattern.     

A novel automated cell‐seeding device for tissue engineering of tubular scaffolds: design and functional validation

Obtaining an efficient, uniform and reproducible cell seeding of porous tubular scaffolds constitutes a major challenge for the successful development of tissue‐engineered vascular grafts. In this study, a novel automated cell‐seeding device utilizing direct cell deposition, patterning techniques and scaffold rotation was designed to improve the cell viability, uniformity and seeding efficiency of tubular constructs. Quantification methods and imaging techniques were used to evaluate these parameters on the luminal and abluminal sides of fibrous polymer scaffolds. With the automated seeding method, a high cell‐seeding efficiency (~89%), viability (~85%) and uniformity (~85–92%) were achieved for both aortic smooth muscle cells (AoSMCs) and aortic endothelial cells (AoECs). The duration of the seeding process was < 8 min. Initial cell density, cell suspension in matrix‐containing media, duration of seeding process and scaffold rotation were found to affect the seeding efficiency. After few days of culture, a uniform longitudinal and circumferential cell distribution was achieved without affecting cell viability. Both cell types were viable and spread along the fibres after 28 h and 6 days of static incubation. This new automated cell‐seeding method for tubular scaffolds is efficient, reliable and meets all the requirements for clinical applicability. Copyright © 2011 National Research Council Canada and John Wiley & Sons, Ltd.     

A positron emission tomography approach to visualize flow perfusion in hollow-fiber membrane bioreactors

Despite the success of hollow-fiber membrane bioreactors in tissue engineering, few evaluations of steady- and pulsatile-flow perfusion through these bioreactors have been made. Such evaluations are vital to the optimization of bioreactor culture conditions. In this study, positron emission tomography (PET) was proposed and used to visualize steady- and pulsatile-flow perfusion in hollow-fiber membrane bioreactors for tissue-engineering applications. PET is a noninvasive method that allows measuring the spatial distribution of a radioactive tracer by detecting its activity within porous scaffolds. A radioactive tracer, 18-fluoro-deoxy-glucose (¹⁸FDG), was injected into a fluid circuit having a hollow-fiber membrane bioreactor with gel-devoid or gel-filled extracapillary space. Dynamic PET scans of the inlet section were acquired and followed by volumetric PET scans of the whole bioreactor. Results were used to reconstruct dynamic and volumetric two- and three-dimensional images. Pulsatile inlet flow improved the uniformity of perfusion flow within the bioreactor in comparison to the steady inlet flow. Pulsatile flow also reduced the accumulation of radioactive tracer for both gel-devoid and gel-filled bioreactors compared to the steady flow. The stability of the radioactive tracer for both conditions was evaluated. The potential of the PET approach was demonstrated by the quantification of the imaging results for steady- and pulsatile-flow perfusions that can be used for the development of bioreactors for tissue-engineering applications.     

Eradication of methicillin-resistant Staphylococcus aureus infection by nanoliposomes loaded with gentamicin and oleic acid

Context: Methicillin-resistant Staphylococcus aureus (MRSA) infection with its high incidence is responsible for nosocomial infections. MRSA strains resistant to multiple antibiotics have emerged increasingly. Recently, combination therapy and efficient drug delivery systems are developed to treat infections.

Objective: The aim of the present study was to evaluate antibacterial activities of combination of oleic acid and gentamicin against MRSA, in both free and liposomal forms, and in comparison with vancomycin.

Materials and methods: The antibacterial activities against MRSA ATCC 43300 were assessed by the determination of minimum inhibitory concentration (MIC), MBC, and Fractional Inhibitory Concentration Index (FICI). The time-kill assays were performed to evaluate the potency of antibacterial agents. Nanoliposomal formulations of gentamicin, oleic acid, and combination of gentamicin with oleic acid were prepared by the dehydration–rehydration (DRV) method and characterized for size, zeta potential, and encapsulation efficiency.

Results: MIC values of gentamicin and oleic acid were 19.5 and >250?µg/ml, respectively. Synergetic effects were observed by the gentamicin and oleic acid combination; FICI was 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 15- and 27-fold, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective formula in time-kill study.

Discussion and conclusion: Liposomal formulation showed a higher antibacterial activity in comparison with the free forms and vancomycin. These carriers can improve antimicrobial activity as well as reducing the effective concentration required and inducing rapid bacterial clearance.     

Computational study of culture conditions and nutrient supply in a hollow membrane sheet bioreactor for large-scale bone tissue engineering

Successful bone tissue culture in a large implant is still a challenge. We have previously developed a porous hollow membrane sheet (HMSh) for tissue engineering applications (Afra Hadjizadeh and Davod Mohebbi-Kalhori, J Biomed. Mater. Res. Part A [2]). This study aims to investigate culture conditions and nutrient supply in a bioreactor made of HMSh. For this purpose, hydrodynamic and mass transport behavior in the newly proposed hollow membrane sheet bioreactor including a lumen region and porous membrane (scaffold) for supporting and feeding cells with a grooved section for accommodating gel-cell matrix was numerically studied. A finite element method was used for solving the governing equations in both homogenous and porous media. Furthermore, the cell resistance and waste production have been included in a 3D mathematical model. The influences of different bioreactor design parameters and the scaffold properties which determine the HMSh bioreactor performance and various operating conditions were discussed in detail. The obtained results illustrated that the novel scaffold can be employed in the large-scale applications in bone tissue engineering.     

Early maladaptive schemas,behavioral inhibition/approach systems,and defense styles in the users of natural and synthetic substances and healthy subjects

Factors contributing to abusing various substances may be different. The aim of the present study was to study the comparison of early maladaptive schemas (EMSs), behavioral inhibition system (BIS)/behavioral approach system (BAS), and defense styles among Iranian natural and synthetic substance users at the start of their treatment and healthy subjects in Shiraz, Iran, since July 2014 to September 2015. In a cross-sectional comparative design, 1056 participants including 704 users of natural (n = 352) and synthetic (n = 352) substances (mean_age = 29) and healthy subjects (n = 352, mean_age = 29) were selected and they completed the demographic questionnaire, Young Maladaptive Schemas Questionnaire-Short Form, Carver & White BIS/BAS scale, and Defense Style Questionnaire. Results revealed that there were significant differences between the natural and synthetic substance users with healthy subjects in EMSs, BIS, BAS subscales, and defense styles. Also, the users of natural substances showed higher means in EMSs, BIS, and immature defense style, while the synthetic substance users earned higher scores on BAS subscales and neurotic defense style, and healthy subjects gained higher scores on mature defense style than natural and synthetic substances. We concluded that there were significant differences among two groups in EMSs, BIS, BAS subscales, and defense styles.