BACKGROUND: Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan. METHODS: We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete. FINDINGS: Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication. INTERPRETATION: Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis. FUNDING: European Union Horizon 2020 and Health Data Research UK. TRANSLATIONS: For the Bengali and Urdu translations of the abstract see Supplementary Materials section.

• MeSH
• alkaloidy terapeutické užití   MeSH
• azociny terapeutické užití   MeSH
• chinoliziny terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• odvykání kouření metody   MeSH
• poruchy vyvolané užíváním tabáku psychologie   terapie   MeSH
• psychoterapie krátká MeSH
• tuberkulóza epidemiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Bangladéš MeSH
• Pákistán MeSH

Sirtuin activating compounds (STACs) attenuate various type of liver insults through mechanisms which are not fully understood. In the present study, we investigated the ameliorative potential of quercetin (natural polyphenol) and SRT1720 (synthetic SIRT1 activator) against D-galactosamine/lipopolysaccharide-induced hepatotoxicity (an experimental model of acute liver failure). Moreover, we compared and contrasted the roles of stress responsive enzymes, sirtuin 1 (SIRT1) and heme oxygenase 1 (HO-1) in hepatoprotection/ hepatotoxicity. Liver injury was induced in male Wistar rats by intraperitoneal injection of D-galactosamine (400 mg/kg) and lipopolysaccharide (10 microg/kg). Some animals were pretreated with quercetin (50 mg/kg i.p.) or SRT1720 (5 mg/kg i.p.). Twenty-four hours later, the effects of these treatments were evaluated by biochemical studies and Western blot. D-GalN/LPS treatment upregulated HO-1 expression, downregulated SIRT1 expression, decreased AST: ALT ratio and markedly increased bilirubin, catalase and conjugated diene levels. Pretreatment of D-GalN/LPS rats with either quercetin or SRT1720 returned SIRT1 expression, HO-1 expression and all the aforementioned markers towards normal. Collectively, these findings suggest that elevated HO-1 and low SIRT1 expressions are involved in the pathogenesis of D-GalN/LPS-induced hepatotoxicity. Drugs that downregulate HO-1 and/or upregulate SIRT1 seem to have antihepatotoxic effects and need further exploration.

• MeSH
• galaktosamin toxicita   MeSH
• hemová oxygenasa (decyklizující) antagonisté a inhibitory   metabolismus   MeSH
• heterocyklické sloučeniny tetra- a více cyklické farmakologie   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• lékové postižení jater farmakoterapie   metabolismus   MeSH
• lipopolysacharidy toxicita   MeSH
• náhodné rozdělení MeSH
• potkani Wistar MeSH
• sirtuin 1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• qPCR, neinvazivní markery, supernatant,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * klasifikace   moč   MeSH
• nádorové biomarkery * moč   MeSH
• nádory močového měchýře * diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výzkum MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH