Direct EPR Detection of Nitric Oxide in Mice Infected with the Pathogenic Mycobacterium Mycobacterium tuberculosis

It has been shown that treatment of mice preinfected with Mycobacterium tuberculosis with spin NO traps (iron complexes with diethyldithiocarbamate) enables detection of large amounts of NO in internal organs 2 and 4 weeks after infection (up to 55–57 μmol/kg of wet lung tissue accumulated with spin NO traps during 30 min). The animals were infected with the drug-sensitive laboratory strain H37Rv and a clinical isolate nonrespondent to antituberculous drugs (the multidrug-resistant strain of M. tuberculosis) obtained from a patient with an active form of tuberculosis. Two weeks after infection with the multidrug-resistant strain, the NO level in the lungs, spleen, liver and kidney increased sharply concurrently with slight lesions of lung tissue. A reverse correlation, i.e., low level of NO in the lungs and other internal organs and extensive injury of lung tissue, was established for H37Rv-infected mice. Four weeks after infection, NO production in the lungs increased dramatically for both M. tuberculosis strains resulting in 80–84% damage of lung tissue. The lesion is suggested to be due to the development of defense mechanisms in M. tuberculosis counteracting NO effects

Türkiye’de inme hastalarında atrial fibrilasyonun yönetimi: NöroTek çalışması gerçek hayat verileri

Objective: Atrial fibrillation (AF) is the most common directly preventable cause of ischemic stroke. There is no dependable neurology-based data on the spectrum of stroke caused by AF in Turkiye. Within the scope of NoroTek-Turkiye (TR), hospital-based data on acute stroke patients with AF were collected to contribute to the creation of acute-stroke algorithms.Materials and Methods: On May 10, 2018 (World Stroke Awareness Day), 1,790 patients hospitalized at 87 neurology units in 30 health regions were prospectively evaluated. A total of 929 patients [859 acute ischemic stroke, 70 transient ischemic attack (TIA)] from this study were included in this analysis.Results: The rate of AF in patients hospitalized for ischemic stroke/TIA was 29.8%, of which 65% were known before stroke, 5% were paroxysmal, and 30% were diagnosed after hospital admission. The proportion of patients with AF who received "effective" treatment [international normalization ratio >= 2.0 warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) at a guideline dose] was 25.3%, and, either no medication or only antiplatelet was used in 42.5% of the cases. The low dose rate was 50% in 42 patients who had a stroke while taking NOACs. Anticoagulant was prescribed to the patient at discharge at a rate of 94.6%; low molecular weight or unfractionated heparin was prescribed in 28.1%, warfarin in 32.5%, and NOACs in 31%. The dose was in the low category in 22% of the cases discharged with NOACs, and half of the cases, who received NOACs at admission, were discharged with the same drug.Conclusion: NoroTekTR revealed the high but expected frequency of AF in acute stroke in Turkiye, as well as the aspects that could be improved in the management of secondary prophylaxis. AF is found in approximately one-third of hospitalized acute stroke cases in Turkiye. Effective anticoagulant therapy was not used in three-quarters of acute stroke cases with known AF. In AF, heparin, warfarin, and NOACs are planned at a similar frequency (one-third) within the scope of stroke secondary prophylaxis, and the prescribed NOAC dose is subtherapeutic in a quarter of the cases. Non-medical and medical education appears necessary to prevent stroke caused by AF.Amaç: Atrial fibrilasyon (AF) iskemik inmenin doğrudan önlenebilir en sık nedendir. Ülkemizde AF nedenli inme spektrumuna dair nöroloji kaynaklı geniş ölçekte bir veri bulunmamaktadır. NöroTek-Türkiye (TR) kapsamında akut inme algoritmalarının oluşturulmasına katkı yapması beklenen AF tespit edilen akut inme hastalarına dair hastane verisi toplanmıştır. Gereç ve Yöntem: 10 Mayıs 2018 Dünya İnme Farkındalık Günü’nde 30 sağlık bölgesine yer alan 87 nöroloji biriminde yatmakta olan 1.790 hasta prospektif olarak değerlendirilmiştir. Çalışmada yer alan toplam 929 hasta [859 akut iskemik inme, 70 geçici iskemik atak (GİA)] bu analize dahil edilmiştir. Bulgular: İskemik inme/GİA sebebiyle ile interne edilmiş hastalarda AF oranı %29,8 olup bunların %65’i bilinmekte olan, %5’i paroksismal ve %30’u yeni tanıdır. AF tanısı ile gelen hastalarda “etkin” tedavi [internasyonel normalizasyon oranı ≥2,0 varfarin veya rehber dozunda non-vitamin K antagonist oral antikoagülan (NOAK)] alanların oranı %25,3 olup, %42,5 olguda ya hiç ilaç kullanılmamakta ya da sadece antiplatelet kullanılmaktaydı. Düşük doz kullanım oranı 42 NOAK alırken inme geçirmiş olguda %50 idi. Taburcu edilirken antikoagülan %94,6 (düşük molekül ağırlıklı veya non-fraksiyone heparin %28,1; varfarin %32,5 ve NOAK %31) hastaya reçete edilmişti. NOAK ile taburcu edilen olguların %22’sinde doz düşük kategoride olup gelişte NOAK almakta olan olguların yarısı aynı ilaçla taburcu edilmiştir. Sonuç: NöroTekTR ülkemizde AF’nin akut inmedeki sıklığı yanı sıra sekonder proflaksi perspektifinde yönetiminin geliştirilebilecek yönlerini ortaya koydu. Türkiye’de hastanede yatan akut inme olgularının yaklaşık üçte birinde AF saptanmıştır. AF’si bilinen akut inme olgularının dörtte üçünde etkin antikoagülan tedavi kullanılmamaktaydı. AF’de inme sekonder proflaksisi kapsamında heparin, varfarin ve NOAK planlaması benzer sıklıkta (üçte bir) olup reçete edilen NOAK dozu dörtte bir olguda subterapötiktir. AF’ye bağlı inmenin önlenebilmesi non-medikal ve medikal eğitim gerekli görünmektedir

The effect of nitric oxide combined with fluoroquinolones against Salmonella enterica serovar Typhimurium in vitro

Two regulons, soxRS and marRAB, are associated with resistance to quinolones or multiple antibiotic in Salmonella enterica serovar Typhimurium. These regulons are activated by nitric oxide and redox-cycling drugs, such as paraquat and cause on activation of the acrAB-encoded efflux pump. In this study, we investigated the effect of nitric oxide (NO) alone and in combination with ofloxacin, ciprofloxacin, and pefloxacin against S. typhimurium clinical isolates and mutant strains in vitro. We did not observe synergistic effect against clinical isolates and SH5014 (parent strain of acr mutant), while we found synergistic effect against PP120 (soxRS mutant) and SH7616 (an acr mutant) S. typhimurium for all quinolones. Our results suggest that the efficiencies of some antibiotics, including ofloxacin, ciprofloxacin, and pefloxacin are decreased via activation of soxRS and marRAB regulons by NO in S. enterica serovar Typhimurium. Further studies are warranted to establish the interaction of NO with the genes of Salmonella and, with multiple antibiotic resistance

Multicenter Evaluation Of Crystal Violet Decolorization Assay (Cvda) For Rapid Detection Of Isoniazid And Rifampicin Resistance In Mycobacterium Tuberculosis

The aim of this multicenter study was to evaluate the performance of the crystal violet decolorization assay (CVDA) for detection of multidrug resistant tuberculosis (MDR-TB). This study was performed in 11 centers in two phases. A total of 156 isolates were tested for INH and RIF resistance. In the phase I, 106 clinical isolates were tested in the Center 1-7. In the phase 2, 156 clinical isolates were tested in the center 1-6, center 8-11. Eighty six of 156 tested isolates were the same in phase I. Agreements were 96.2-96.8% for INH and 98.1-98.7% for RIF in the phase I-II, respectively. Mean time to obtain the results in the phase I was 14.3 +/- 5.4 days. In the phase II, mean time to obtain the results was 11.6 +/- 3.5 days. Test results were obtained within 14days for 62.3% (66/106) of isolates in the phase I and 81.4% (127/156) of isolates in the phase II. In conclusion, CVDA is rapid, reliable, inexpensive, and easy to perform for rapid detection of MDR-TB isolates. In addition, it could be adapted for drug susceptibility testing with all drugs both in developed and developing countries.WoSScopu