Combination Of Isoniazid Research Articles

Early Bactericidal Activity of AZD5847 in Patients with Pulmonary Tuberculosis.

AZD5847 is an oxazolidinone antibiotic with in vitro activity against Mycobacterium tuberculosis The objective of this study was to evaluate the antimycobacterial activity, safety, and pharmacokinetics of AZD5847 in patients with pulmonary tuberculosis. Groups of 15 treatment-naive, sputum smear-positive adults with pulmonary tuberculosis were randomly assigned to receive AZD5847 at one of four doses (500 mg once daily, 500 mg twice daily, 1,200 mg once daily, and 800 mg twice daily) or daily standard chemotherapy. The primary efficacy endpoint was the mean daily rate of change in the log10 number of CFU of M. tuberculosis per milliliter of sputum, expressed as the change in log10 number of CFU per milliliter of sputum per day. The mean 14-day activity of the combination of isoniazid, rifampin, ethambutol, and pyrazinamide (-0.163 log10 CFU/ml sputum/day; 95% confidence interval [CI], -0.193, -0.133 log10 CFU/ml sputum/day) was consistent with that found in previous studies. AZD5847 at 500 mg twice daily significantly decreased the number of CFU on solid medium (-0.039; 95% CI, -0.069, -0.009; P = 0.0048). No bactericidal activity was detected at doses of AZD5847 of 500 mg once daily (mean early bactericidal activity [EBA], 0.02 [95% CI, -0.01, 0.05]), 1,200 mg once daily (mean EBA, 0.02 [95% CI, -0.01, 0.05]), and 800 mg twice daily (mean EBA, 0.02 [95% CI, -0.01, 0.05]). AZD5847 at doses of both 500 mg and 800 mg twice daily also showed an increase in the time to a positive culture in MGIT liquid culture medium. Two serious adverse events (grade 4 thrombocytopenia and grade 4 hyperbilirubinemia) occurred in patients receiving AZD5847 at higher doses. AZD5847 dosed twice daily kills tubercle bacilli in the sputum of patients with pulmonary tuberculosis and has modest early bactericidal activity. (This study has been registered at ClinicalTrials.gov under registration no. NCT01516203.).

Comparative evaluation of manuka honey with honey in antitubercular drug-induced hepatotoxicity in rats

Objective: The objective of this study is to compare the effect of manuka honey with honey in hepatotoxicity induced by antitubercular drugs in rats. Materials and Methods: Hepatotoxicity was induced in rats by a combination of isoniazid, rifampicin, and pyrazinamide given orally as suspension for 30 days. Treatment groups received honey and manuka honey along with anti-tubercular drugs. Liver damage was assessed by biochemical and histological parameters. Results: Concurrent administration of manuka honey along with anti-tubercular drugs significantly prevented the rise in levels of serum alanine aminotransferase, serum aspartate aminotransferase, and tissue malondialdehyde. It reduced inflammation, degeneration, and necrotic changes in hepatocytes. Similarly, manuka honey significantly prevented fall in serum total protein and superoxide dismutase as compared to the group receiving anti-tubercular drugs alone. However, the effects produced by manuka honey were not statistically different from those of honey and silymarin. Conclusion: Manuka honey is effective as a hepatoprotective agent as it significantly prevented the hepatotoxic damage induced by antitubercular drugs in rats. However, the comparison between the effects produced by manuka honey and honey or silymarin showed that the difference was not statistically significant. Hence, contrary to the popular belief, it is only as good and effective as honey.

Effect of homogenates of avocado pear (<i>Persea americana</i>) seeds and fluted pumpkin (<i>Telfairia occidentalis</i>) leaves coadministered with anti-tuberculosis drugs on liver enzymes of albino rats

This study evaluated the effects of aqueous homogenates of avocado pear ( Persea americana ) seeds and fluted pumpkin ( Telfairia occidentalis ) leaves co-administered with anti-tuberculosis drug on liver enzymes of albino rats. Twenty (20) albino rats were divided into five (5) groups (of four rats each) designated as I, II, III, IV and V (which is the normal control). A dose of 5.14mg/kg body weight of a first line anti-tuberculosis drug (a combination of isoniazid, rifampicin, pyrazinamide and ethambutol) was administered orally to two (2) rats in group I, II, III, and IV for seven (7) days and the remaining two rats in each group for fourteen (14) days. The homogenates of avocado pear seeds (at a dose of 250mg/kg body weight), fluted pumpkin leaves (at a dose of 250mg/kg BW) and a mixture of avocado pear seeds and fluted pumpkin leaves (at a dose of 250mg/kg BW, and 125mg/kg BW respectively) were co-administered with the anti-TB drug to groups II, III and IV respectively. Group I rats served as the positive control (i.e. treated with only 5.14mg/kg BW of anti-TB drug). The results indicated that the activities of serum AST, ALT and ALP were significantly higher (P<0.05) in rats administered with 5.14 mg/kg BW first line anti-TB drugs only when compared with that of the rats co-administered with the same anti-TB drug and 250mg/kg BW plant homogenates (avocado pear seeds, fluted pumpkin leave, and a combination of the two homogenates). The mean serum AST, ALT and ALP activities were found to have decrease (P<0.05) in groups II, III, and IV rats from the beginning to the end of the treatment periods. Similarly, mean serum activities of AST, ALT and ALP in group III rats decreased (P<0.05) significantly when compared with that of group II rats. Moreover, the serum activities of these enzymes were significantly lower (P<0.05) in group V rats compared to that of groups II and III rats. The rise in the mean serum activities of liver enzymes in group I rats when compared to that of group V rats indicated that the anti-TB drug is hepatotoxic. The findings of this research work predicts that the aqueous homogenates of both avocado pear seeds and fluted pumpkin leaves have hepatoprotective abilities but, the combination of these plant parts shows more hepatoprotective function (i. e. exhibits synergy). Key words : Avocado pear, fluted pumpkin, homogenates, anti-tuberculosis, isoniazid.

Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats

Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Liver damage was assessed using biochemical and histological parameters. Administration of goat milk (20 mL/kg) along with antitubercular drugs (Group III) reversed the levels of serum alanine aminotransferase (82 ± 25.1 vs. 128.8 ± 8.9 units/L) and aspartate aminotransferase (174.7 ± 31.5 vs. 296.4 ± 56.4 units/L, p<0.01) compared with antitubercular drug treatment Group II. There was a significant decrease in serum alanine aminotransferase (41.8 ± 4.1 vs. 128.8 ± 8.9 ​ units/L, p<0.01) and aspartate aminotransferase (128.8 ± 8.54 vs. 296.4 ± 56.4 units/L, p<0.001) levels in Group IV (goat milk 40 mL/kg) compared with antitubercular drug treatment Group II. Goat milk (20 mL/kg and 40 mL/kg) was effective in reversing the rise in malondialdehyde level compared with the antitubercular drug suspension groups (58.5 ± 2 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001 and 69.7 ± 0.78 vs. 89.88 ± 2.42 μmol/mL of tissue homogenate, p<0.001, respectively). Similarly, both doses of milk significantly prevented a fall in superoxide dismutase level (6.23 ± 0.29 vs. 3.1 ± 0.288 units/mL, p<0.001 and 7.8 ± 0.392 vs. 3.1 ± 0.288 units/mL, p<0.001) compared with the group receiving antitubercular drugs alone. Histological examination indicated that goat milk reduced inflammation and necrotic changes in hepatocytes in the treatment groups. The results indicated that goat milk prevented the antitubercular drug-induced hepatotoxicity and is an effective hepatoprotective agent.

Tubercular Meningitis, A Tale of 50 Years.

Whyth in 1768 for his treatise ‘Dropsy in the brain’ [2]. The patho-physiology of TBM was unravelled by Arnold Rich and McCordock in 1933 [3]. Before the mid-20th century, childhood TB was uniformly fatal. The introduction of isoniazid in early 1950’s revolutionized the treatment of TB. For nearly two decades, the standard treatment comprised of combination of isoniazid and streptomycin, following which rifampicin was introduced. Still, the mortality was very high, and significant proportions were left with physical and mental disabilities due to delay in treatment initiation and poor compliance. To strengthen the fight against TB, the Government of India launched “District Tuberculosis Control Programme” in 1962 which focussed on prevention, control and management of the disease in both urban as well as rural areas. At the time of publication of this article [1], there existed wide disparity in the reported incidence (0.5-13%) of TBM in India, and its true situation was difficult to determine because of diagnostic uncertainties and poor case notification. In most cases, the diagnosis was presumptive, based on clinical suspicion and circumstantial evidence as bacteriological confirmation was often not possible.

A sterilizing tuberculosis treatment regimen is associated with faster clearance of bacteria in cavitary lesions in marmosets.

Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P = 0.035) and also significantly reduced uptake of [(18)F]-2-fluoro-2-deoxyglucose by positron emission tomography (P = 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P = 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.

Risk Factors and Pattern of Changes in Liver Enzymes Among the Patients With Anti-Tuberculosis Drug-Induced Hepatitis

Background: Hepatotoxicity is one of the most frequent adverse events that occurs during tuberculosis treatment and is associated with mortality of 6% - 12% if drugs are continued after the appearance of symptoms. In most of the cases, hepatitis is evident within three months after induction of anti-tuberculosis treatment. Objectives: The current study aimed to define the pattern of changes in liver transaminases and the associated risk factors among the patients with anti-tuberculosis drug-induced hepatitis who admitted to Boo-Ali Hospital in Zahedan, Southeastern Iran. Patients and Methods: The current descriptive cross-sectional study reviewed all files of the patients with anti-tuberculosis Drug-Induced Hepatitis (DIH) who referred to Boo-Ali Hospital in Zahedan, Southeastern Iran, in five years. All patients were above 14 years, and were treated with the standard regimen (a combination of isoniazid, rifampin, pyrazinamide, and ethambutol ± streptomycin). Hepatotoxicity was defined when the liver transaminases were more than five, the Upper Limit of Normal (ULN), or had clinical symptoms with an increase of liver transaminases ≥ 3 ULN. Results: Among the 946 patients with tuberculosis disease (44% men; 56% women), 52 (5.5%) cases had drug-induced hepatotoxicity. Only 25% of the patients with anti-tuberculosis drug-induced hepatitis were below 52; 50% of the cases occurred within the first two weeks after the treatment onset. Conclusions: Anti-tuberculosis drugs-induced hepatotoxicity caused treatment interruption in 5.5% of the patients with tuberculosis. The majority of the patients with DIH were above fifty, and 50% the cases occurred during the first two weeks after treatment onset. Physicians must carefully and closely monitor such patients.

Drug-induced hepatitis and the risk factors for liver injury in pulmonary tuberculosis patients.

Introduction:Short-course chemotherapy containing rifampicin and isoniazid in combination has proved to be highly effective in the treatment of tuberculosis, but one of its adverse effects is hepatotoxicity. Various risk factors have been found to be associated with drug-induced liver injury (DILI) in general population. The study aimed to determine the prevalence of drug-induced hepatitis and the risk factors associated with the DILI among the patients of pulmonary tuberculosis in Indian patients.Setting and Design:Prospective nested case control study.Materials and Methods:Out of the cohort of 3900 tuberculosis patients who were initiated on anti-tubercular therapy, 150 patients who developed drug-induced liver injury due to short-course chemotherapy under RNTCP were included in the analysis. Thirty cases were being followed up in our hospital and other 120 were referred to us for the management of drug-induced hepatitis from the primary health centers. The diagnostic criteria's for DILI were made according to the American Thoracic Society criteria. Analyses of various risk factors were done for the development of DILI.Results:The prevalence of DILI in the present study was 3.8%. It was observed that DILI patients were older and their serum albumin levels were lower, and they had multiple co-morbid conditions. Regular alcohol intake, more extensive disease associated with radiological and female gender were observed to be independent risk factors for the development of DILI.Conclusions:Of the various risk factors analyzed, advanced age, hypoalbuminemia, regular alcohol intake and advanced nature of the disease were independent risk factors for the development of DILI. The risk of development of hepatitis is increased in the presence of one or more of these risk factors.

Primary Laryngeal Tuberculosis

Primary laryngeal tuberculosis is rare. It can manifest as a malignancy delaying the diagnosis and the therapeutic management. We report the case of a 34-year-old immunocompetent man whose plaints were fever, sweat and dysphonia. There were no adenopathy, nor hepatosplenomegaly. Several blood cultures were negative. Laboratory studies showed an inflammatory syndrome. In addition, the bacteriological examinations of sputum and urine in search of Mycobacterium tuberculosis were negative. Laryngoscopy confirmed the presence of a thickness of the right vocal cord and an ulcer in the hemilarynx. The histological examination revealed tuberculoid granulomas suggestive of tuberculosis. The culture from vocal cord tissue for Mycobacterium tuberculosis was positive. No other focus of tuberculosis was found on X-ray and computed tomography. Treatment by a combination of isoniazid, rifampicin, pyrazinamide induced a total resolution of symptoms.

English

Hepatoprotective effect of Garcinia kola seed extract on oxidative stress and hepatotoxicity biomarkers of rats exposed to antitubercular drugs was investigated to evaluate its potential to ameliorate drug-induced hepatotoxicity. Six groups of five animals each were used. Combination of Isoniazid (7.5 mg/kg bodyweight) and Rifampicin (10 mg/kg bodyweight) was administered intraperitoneally to a group. Drug combination was co-administered with G. kola seed extracts (40, 60 and 80 mg/kg bodyweight) to three other groups for 35 days. Control group received saline and the last group received G. kola alone (60 mk/kg bodyweight). Plasma oxidative stress biomarkers (superoxide dismutase, glutathione, glutathione peroxidase, catalase and malondialdehyde) and hepatotoxicity biomarkers (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) were assayed after treatment. The antitubercular drugs significantly increased levels of hepatotoxicity biomarkers. The increase was mitigated by treatment with G. kola, with reduction in levels of the hepatotoxicity biomarkers upon G. kola co-administration. Similarly, the antitubercular drugs reduced the activities of oxidative stress biomarkers. Histomorphological analysis of the liver showed that the G. kola extract administered at 60 mg/kg offered significant protection from exposure to the hepatotoxic drugs. The study concluded that G. kola extract at 60 mg/kg significantly protected the animals from the damages occasioned by exposure to hepatotoxic antitubercular drugs. &nbsp; Key words: Isoniazid, rifampicin, tuberculosis, hepatotoxicity, hepatoprotection, histomorphology.

Isoniazid‐specific T‐cell Responses in patients with anti‐tuberculosis drug related liver injury

Background A combination of isoniazid (INH), rifampicin, pyrazinamide and/or ethambutol (anti-tuberculosis drugs, ATDs) is commonly used for the treatment of tuberculosis. A significant clinical problem is that drug treatment is associated with mild elevations of liver enzymes that occasionally develop into severe liver injury. The culprit drug(s) and mechanistic basis of the reaction has not been defined. Thus, the aims of this study were to (1) explore whether drug-responsive T-lymphocytes were detectable in patients with ATD-related liver injury, (2) identify the drug(s) that activate T-cells and (3) characterize the nature of the T-cell response.

Increased incidence of liver enzymes abnormalities in patients treated with isoniazid in combination with disease modifying and/or biologic agents

Reactivation of latent tuberculosis (LTB) has been described with the use of anti-TNFs. Combined treatment of isoniazid (INH) and disease modifying antirheumatic drugs (DMARDs) can potentially increase the risk of hepatotoxicity. The goal of this study was to investigate the risk of hepatotoxicity in rheumatic patients taking INH while on DMARDs and/or biologics. We reviewed the Institut de Rhumatologie de Montréal database (Rhumadata®) for rheumatic patients with positive tuberculin skin test or quantiFERON who took INH between August 2001 and April 2011. Liver function tests (LFTs) were collected at baseline and during therapy, and LFTs up to 9 months prior to INH initiation were used as controls. Of 922 patients screened for LTB, 87 patients tested positive. During INH treatment, 75.9 % were taking DMARDs, 82.8 % were taking biologics. A total of 375 LFTs performed while on INH were compared to 211 available tests collected prior to INH therapy. Twenty-four percent of the patients had abnormal LFTs during INH compared to 12.1 % prior to INH (p = 0.0481). Most of these abnormalities were mild or transient, but 8 % (seven patients) had significant abnormalities leading to INH discontinuation. Among these patients, mean (min, max) was 241 (52, 617) for AST and 262 (92, 669) for ALT. Although the use of INH therapy in combination with DMARDs and/or biologics was generally well tolerated, the rate of LFT abnormalities was higher when patients were exposed to INH, and significant abnormalities were more frequent than reported in the INH literature. It is prudent to closely follow the LFTs of these patients.

Hepatoprotective potential of Cassia auriculata roots on ethanol and antitubercular drug-induced hepatotoxicity in experimental models

Context: Tarvada [Cassia auriculata Linn. (Caesalpiniaceae)] is used against liver ailments in Indian folk medicine, but there is a lack of scientific evidence for this traditional claim.Objective: The present study investigated the protective effect of methanol extract of tarvada (MECA) roots on ethanol and antitubercular drug induced hepatotoxicity in rats.Materials and methods: In the therapeutic model, ethanol (40%, 4 g/kg b.w., p.o.) was administered to rats for 21 days and the intoxicated rats were treated with MECA (300 and 600 mg/kg, b.w.) and silymarin (100 mg/kg, b.w.) for next 7 days. In the prophylactic model, MECA and silymarin were administered simultaneously along with a combination of isoniazid (27 mg/kg, b.w.), rifampicin (54 mg/kg, b.w.) and pyrazinamide (135 mg/kg, b.w.) for 30 days. After the study duration, serum levels of AST, ALT, ALP, total bilirubin, total cholesterol, total protein, albumin were estimated along with hepatic catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and liver histopathology in each group.Results: Administration of tarvada root extract significantly (p < 0.01 and p < 0.05) lowered the elevated levels of serum AST, ALT, ALP, total bilirubin, total cholesterol, total protein and restored the abnormal levels of enzymatic antioxidants and MDA in liver due to toxicant administration in a dose-dependent manner. These results were confirmed by histopathological analysis.Discussion and conclusion: Results suggest that tarvada root extract possess potent hepatoprotective activity against ethanol and antitubercular drug-induced hepatotoxicity in rats, which could be due to an inhibition of hepatic metabolizing enzymes and antioxidant activity.

On contradictions in clinical guidelines on chemotherapy of patients with pulmonary tuberculosis in Russian Federation according to evidence!based medicine: meta!analysis and systematic review

Aim. The aim of this study was an analysis of published data in order to develop evidencebased clinical recommendations on chemotherapy of newly diagnosed pulmonary tuberculosis with high primary and secondary multidrug resistance. Methods. Metaanalysis and systematic review was carried out of all published randomized clinical trials on this topic. Results. Several experimental, bacteriological and clinical trials, which had performed in 1998–2003, showed a high efficacy of fluoroquinolones in patients with newly diagnosed pulmonary tuberculosis; a new effective chemotherapeutic regimen for regions with high rate of multidrug resistant tuberculosis was developed and could be administered before results of drug resistance tests are obtained. This regimen consisted of of isoniazid, rifampicin, pyrazynamide, etambutol, fluoroquinolone and kanamycin or amikacin; it was welltolerated and did not increase a rate of antibacteri al resistance of Mycobacterium tuberculosis. Conclusion . Given primary (5–10 %) and secondary (15–30 %) multidrug resistance of Mycobacterium tuberculosis in Russian Federation, the most effective chemotherapeutic regimen for patients with pulmonary tuberculosis is the combination of isoniazid, rifampicin, pyrazynamide, etam butol, fluoroquinolone and kanamycin or amikacin. A proven microbiological method for individual control of drug sensitivity of M.tuberculosis and response to chemotherapy is culturing of sputum or another biomaterial on solid or liquid media using the BACTEC MGIT equipment.

Lack of liver injury in Wistar rats treated with the combination of isoniazid and rifampicin

Isoniazid (INH) can cause serious idiosyncratic liver injury. An animal model would greatly facilitate mechanistic studies, but it is essential that the mechanism in the model be similar to the liver injury that can occur in humans. We attempted to replicate a previous study in which Wistar rats treated with INH and rifampicin (RMP) developed liver injury, which was promising because of its delayed onset similar to the liver injury that can occur in humans. Wistar rats were treated with either a high dose of INH (150 mg/kg/day) or a combination of INH and RMP (75 mg/kg/day and 50 mg/kg/day, respectively) for up to 4 weeks. However, we did not observe any liver injury or evidence of an inflammatory infiltrate as had been reported; rather, we observed an increase in CTLA4-positive cells in the cervical lymph nodes as well as a decrease in serum CXCL1 and MCP-1. In short, we were unable to reproduce a previously reported model of delayed onset INH-induced liver injury in Wistar rats.

Risk Factors For Drug Induced Hepatitis Under Dots Programme In General Population

Background: Short course chemotherapy containing rifampicin and isoniazid in combination has proved to be highly effective under DOTS regimens in the treatment of tuberculosis, but one of its adverse effects is hepatotoxicity. Little however has been published regarding drug induced hepatitis (DH) under general programme conditions. In this study, we aimed to determine the prevalence of drug induced hepatitis and the risk factors associated with the development of hepatitis over a period of 5 years. Methodology: This was a prospective study done from 2007 to 2011 in a tertiary care hospital. A total of 116 patients were included in the study that presented with hepatitis due to short course chemotherapy and were being treated under various categories of drug regimens. Fourty cases were being followed up and other 76 were seen at the hospital for the first time after the development of hepatitis. The diagnostic criteria’s for drug-induced hepatitis were made according to the ATS criteria’s. Various risk factors were analyzed for the development of DH. Results: The prevalence of DH in the present study was 3.6%. It was observed that DH patients were older and their serum albumin levels were lower. Regular alcohol intake, more extensive disease radiologically and female gender were observed to be independent risk factors for the development of DH. No other risk factors analyzed had any signifi cant association with DH. Conclusion: Of the various risk factors analyzed, advanced age, hypoalbuminaemia, regular alcohol intake and advanced nature of the disease were independent risk factors for the development of DH. The risk of hepatitis in the presence of one or more of these risk factors may be increased. SAARC Journal of Tuberculosis, Lung Diseases &amp; HIV/AIDS; 2013; X(1); 19-26 DOI: http://dx.doi.org/10.3126/saarctb.v10i1.8673

Compliance with treatment of latent Tuberculosis infection in healthcare workers

Healthcare workers are at higher risk of exposure to tuberculosis than the general population and screening upon hire and periodically for latent tuberculosis (TB) infection is required for work in healthcare institutions. Treatment of latent TB infection (LTBI) is strongly recommended in healthcare workers, but despite evidence that shows benefit, the adherence to treatment remains suboptimal. In our retrospective study of healthcare employees at a large, academic, tertiary care institution we found that only 73% were compliant with treatment of LTBI. Side effects and duration of therapy were major reasons for lack of adherence. Closer follow up during the treatment course, and the use of an alternative regimen such as the combination of isoniazid and rifapentine under direct observation for a shorter duration may improve compliance rates in healthcare workers in the future.

A Study of Liver Function Tests in Patients Receiving Four Drugs Regimen in Initial Two Months as Antitubercular Drugs

Biochemical monitoring of liver function is essential because Anti Tubercular Therapy (ATT) induced hepatotoxicity can cause permanent injury to liver and death. This cross-sectional comparative study was conducted in department of Biochemistry of Chittagong Medical College during the period of July 2009- Jun 2010 to determine the association of Anti-TB treatment to alter the liver function in patients of intensive phase of tuberculosis taking Four Fixed Dose Combination of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. A total of 100 subjects were enrolled in this study. They were divided into two groups. Group A (case) was diagnosed case of tuberculosis and had taken anti TB drugs (four Fixed dose combination) at least for fifteen days and group B (control) was consisting of normal subjects. Serum ALT, AST, Bilirubin and prothrombin time were measured. It was found, that out of 70 subjects 20% had increased level of serum ALT, 17.1% had increased level of serum AST, 20% had increased level of serum bilirubin and only 2.9% had increased level of prothrombin time in case group. Finally, determination of liver functions in patients receiving Anti TB therapy (in intensive phase) should be done irrespective of presence or absence of established risk factors, to minimize not only the incidence but also the morbidity and mortality.&#x0D; JCMCTA 2012 ; 23 (2): 27-29

Treating BCG-induced disease in children

Bacillus Calmette-Guerín (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global expanded immunisation programme. Given intradermally, it can cause adverse reactions, including local, regional, distant and disseminated manifestations that may cause parental distress. Rarely, it can cause serious illness and even death. Among those patients with immunocompromised conditions, such as the human immunodeficiency virus (HIV) infection, the complication rate is even higher. To assess the effects of different interventions for treating BCG-induced disease in children. The following databases were searched: the Cochrane Infectious Diseases Group Specialized Register and Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (The Cochrane Library 2012, Issue 4); MEDLINE (1966 to November 2012); EMBASE (1947 to November 2012); and LILACS (1980 to November 2012).The metaRegister of Controlled Trials (mRCT) and the WHO trials search portal. Conference proceedings for relevant abstracts and experts were also contacted to identify studies. No language restrictions were applied. Randomized controlled trials (RCTs) comparing any medical or surgical treatment modality for BCG-induced disease in children. Two authors independently evaluated titles, applied inclusion criteria, and assessed the risk of bias of studies. The primary outcomes were the failure rate of therapies for all types of BCG vaccine-induced complications and the time to resolution of illness measured in months. The secondary outcomes were death from BCG vaccine-induced disease and the all-cause mortality. Risk ratios (RRs) were used as measure of effect for dichotomous outcomes and mean differences for continuous outcomes. Five RCTs analysing 341 children addressed the primary outcomes and were included. Four arms compared oral antibiotics to no intervention or placebo, one arm evaluated needle aspiration compared to no intervention, and another evaluated the use of locally instilled isoniazid versus oral erythromycin.Two small studies evaluated oral isoniazid; we are uncertain of whether this intervention has an effect on clinical failure (RR 1.48; 95% Confidence Interval (CI) 0.79 to 2.78; 54 participants, two studies, very low quality evidence). Similarly, for oral erythromycin, we are uncertain if there is an effect (clinical failure RR 1.03; 95% CI 0.70 to 1.53; 148 participants, three studies, very low quality evidence), and for oral isoniazid plus rifampicin (clinical failure, RR 1.20; 95% CI 0.51 to 2.83; 35 participants, one study, very low quality evidence).In patients with lymphadenitis abscess, needle aspiration may reduce clinically persistent BCG-induced disease at 6 to 9 months of follow-up (RR 0.13; 95% CI 0.03 to 0.55; 77 participants, one study, low quality evidence). In another study of patients with the same condition, aspiration plus local instillation of isoniazid reduces time to clinical cure compared to aspiration plus oral erythromycin (mean difference 1.49 months less; 95% CI 0.82 to 2.15 less; 27 participants, one study).No RCTs of HIV-infected infants with a BCG-induced disease evaluated the use of antibiotics or other therapies for reducing the rate of clinical failure or the time to clinical resolution. No data on mortality secondary to the interventions for treating BCG-induced disease were reported. It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.

Ameliorative Effect of Leaves of Carica papaya in Ethanol and Antitubercular Drug Induced Hepatotoxicity

Aims: The leaves of Carica papaya Linn. (Caricaceae) have been traditionally used as a medicine against some forms of liver diseases. Its hepatoprotective activity against hepatotoxicants like CCl4 and paracetamol has been scientifically proved in animals. The aim of the present study is to examine the hepatoprotective effect of C. papaya leaves against ethanol and anti-tubercular drug-induced liver damage, the two clinically relevant animal models. Study Design: The aqueous extract of leaves of the plant was administered orally to rats and effects on hepatic marker enzymes, tissue antioxidants and liver histology were determined. Place and Duration of Study: The study was performed in Rayat Institute of Pharmacy, Railmajra, Dist. S.B.S. Nagar, Punjab, between Dec’ 2011 to July 2012. Materials and Methods: The study was performed by administering the aqueous extract of C. papaya leaves at the dose of 400 mg/kg in rats prior to administration of ethanol or combination of Isoniazid and Rifampicin. The effects on the levels of serum indicators of liver damage (ALT, AST, alkaline phosphatase and total bilirubin) and tissue antioxidant parameters like TBARS, GSH and SOD were determined. Histopathology of liver was also performed to study the influence of drug on tissue integrity. Results: Hepatoprotective activity of leaves of C. papaya was evident by the significant reduction in the levels of all serum markers in both the models. The extract also significantly increased the levels of SOD, GSH and total protein; and decreased the levels of TBARS, indicating its antioxidant effect. The results obtained were also confirmed by improvements in the histopathology of liver. Conclusion: The results obtained in the current study justify the use of Carica papaya leaves in the prevention of liver damage induced by commonly consumed hepatotoxicants, namely ethanol and anti-tubercular drugs.