Rapid resistance detection is reliable for prompt adaptation of isoniazid resistant tuberculosis management.

Objectives: Appropriate tuberculosis (TB) management requires anti-TB drugs resistance detection. We assessed the performance of rapid resistance detection assays and their impact on treatment adaptation, focusing on isoniazid resistant (Hr) TB. Methods: From 2016 to 2022, all TB cases enrolled in 3 hospitals were reviewed for phenotypic drug susceptibility testing (p-DST) and genotypic DST (g-DST) performed by rapid molecular testing, and next generation sequencing (NGS). Clinical characteristics, treatment and outcome were collected for Hr-TB patients. The concordance between g-DST and p-DST results, and delay between treatment initiation and results of g-DST and p-DST were respectively recorded to assess the contribution of DST results on Hr-TB management. Results: Among 654 TB cases enrolled, 29 were Hr-TB. Concordance between g-DST by rapid molecular methods and p-DST was 76.9 %, whilst concordance between NGS-based g-DST and p-DST was 98.7 %. Rapid resistance detection significantly fastened Hr-TB treatment adaptation (median delay between g-DST results and treatment modification was 6 days). It consisted in fluoroquinolone implementation for 17/23 patients; outcome was favourable except for 2 patients who died before DST reporting. Conclusion: Rapid resistance detection fastened treatment adaptation. Also, NGS-based g-DST showed almost perfect concordance with p-DST, thus providing rapid and safe culture-free DST alternative.

Prospective Whole-Genome Sequencing in Tuberculosis Outbreak Investigation, France, 2017-2018.

During June 2017-April 2018, active tuberculosis with Beijing SIT1 isolates was diagnosed in 14 persons living in 4 distant cities in France. Whole-genome sequencing indicated that these patients belonged to a single transmission chain. Whole-genome sequencing-based laboratory investigations enabled prompt tracing of linked cases to improve tuberculosis control.

Vitamin C and vitamin E in prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in choline deficient diet fed rats.

AIM: Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD). Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention. METHODS: Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6) - (200 mg/day), vitamin C (n = 6) (30 mg/Kg/day) or vehicle orally. RESULTS: In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 +/- 330 cpm/mg/min x 10(3)) as compared to those Vitamin E and control (2247 +/- 790; 2020 +/- 407 cpm/mg/min x 10(3), respectively) (p < 0.05). Serum levels of aminotransferases were unaltered by vitamin C or vitamin E. CONCLUSIONS: 1) Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet; 2)Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet.

BACKGROUND/AIM: The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet. METHODS: Fatty liver disease was induced in Wistar rats by a choline-deficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each--fed with a choline-deficient diet for four and twelve weeks respectively; Group III (control-G3; n=6)--fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOH-cholesteryl ester) in the liver tissue. RESULTS: We observed moderate macro- and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min x 10(3)) was significantly increased in G1 (1393-/+790) and G2 (7191-/+500) as compared to controls (513-/+170), p<0.05. The concentrations of CE-OOH were higher in G1 (5.7-/+0.9 nmol/mg protein) as compared to control (2.6-/+0.7 nmol/mg protein), p<0.05. CONCLUSION: 1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.