Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Tho...Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity its underlying mechanisms and alternative therapies for the same.展开更多
AIM:To evaluate the clinical,radiological and microbiological properties of abdominal tuberculosis (TB) and to discuss methods needed to get the diagnosis. METHODS:Thirty-one patients diagnosed as abdominal TB between...AIM:To evaluate the clinical,radiological and microbiological properties of abdominal tuberculosis (TB) and to discuss methods needed to get the diagnosis. METHODS:Thirty-one patients diagnosed as abdominal TB between March 1998 and December 2001 at the Gastroenterology Department of Kartal State Hospital, Istanbul,Turkey were evaluated prospectively.Complete physical examination,medical and family history,blood count erythrocyte sedimentation rate,routine biochemical tests, Mantoux skin test,chest X-ray and abdominal ultrasonography (USG) were performed in all cases,whereas microbiological examination of ascites,upper gastrointestinal endoscopy,colonoscopy or barium enema,abdominal tomography,mediastinoscopy,laparoscopy or laparotomy were done when needed. RESULTS:The median age of patients (14 females,17 males) was 34.2 years (range 15-65 years).The most frequent symptoms were abdominal pain and weight loss. Eleven patients had active pulmonary TB.The most common abdominal USG findings were ascites and hepatomegaly.Ascitic fluid analysis performed in 13 patients was found to be exudative and acid resistant bacilli were present in smear and cultured only in one patient with BacTec (3.2%).Upper gastrointestinal endoscopy yielded nonspecific findings in 16 patients.Colonoscopy performed in 20 patients showed ulcers in 9 (45%),nodules in 2 (10%) and,stricture,polypoid lesions,granulomatous findings in terminal ileum and rectal fistula each in one patient (5%). Laparoscopy on 4 patients showed dilated bowel loops, thickening in the mesentery,multiple ulcers and tubercles on the peritoneum.Patients with abdominal TB were divided into three groups according to the type of involvement. Fifteen patients (48%) had intestinal TB,11 patients (35.2%) had tuberculous peritonitis and 5 (16.8%) tuberculous lymphadenitis.The diagnosis of abdominal TB was confirmed microbiologically in 5 (16%) and histo- pathologically in 19 patients (60.8%).The remaining nine patients (28.8%) had been diagnosed by a positive response to antitub展开更多
Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c ...Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.展开更多
Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among...Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.展开更多
Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs...Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.展开更多
Tuberculosis(TB)is the leading cause of infectious mortality and morbidity in the world,second only to coronavirus disease 2019.Patients with chronic kidney disease and kidney transplant recipients are at a higher ris...Tuberculosis(TB)is the leading cause of infectious mortality and morbidity in the world,second only to coronavirus disease 2019.Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population.Active TB is difficult to diagnose in this population due to close mimics.All transplant candidates should be screened for latent TB infection and given TB prophylaxis.Patients who develop active TB pre-or post-trans-plantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.展开更多
AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hep...AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline(10 mL·kg-1, p.o.); hepatotoxicant(isoniazid-rifampicin, INH-RIF, 100 mg·kg-1, i.p. or 20% ethanol 5 g·kg-1, p.o.) and normal saline(10 mL·kg-1, p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg-1 p.o.; hepatotoxicant and silymarin 50 mg·kg-1 p.o.; and extract at 400 mg·kg-1 p.o.. On the 21st day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly(P < 0.05-0.001) increased the levels of alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), bilirubin, and malondialdehyde(MDA); and reduced the levels of catalase(CAT), superoxide dismutase(SOD), glutathione peroxidase(GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed(P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract(200 and 400 mg·kg-1) significantly reversed(P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens(100-400 mg·kg-1) elicited significant reduction(P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.展开更多
Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract of...Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.展开更多
文摘Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity its underlying mechanisms and alternative therapies for the same.
文摘AIM:To evaluate the clinical,radiological and microbiological properties of abdominal tuberculosis (TB) and to discuss methods needed to get the diagnosis. METHODS:Thirty-one patients diagnosed as abdominal TB between March 1998 and December 2001 at the Gastroenterology Department of Kartal State Hospital, Istanbul,Turkey were evaluated prospectively.Complete physical examination,medical and family history,blood count erythrocyte sedimentation rate,routine biochemical tests, Mantoux skin test,chest X-ray and abdominal ultrasonography (USG) were performed in all cases,whereas microbiological examination of ascites,upper gastrointestinal endoscopy,colonoscopy or barium enema,abdominal tomography,mediastinoscopy,laparoscopy or laparotomy were done when needed. RESULTS:The median age of patients (14 females,17 males) was 34.2 years (range 15-65 years).The most frequent symptoms were abdominal pain and weight loss. Eleven patients had active pulmonary TB.The most common abdominal USG findings were ascites and hepatomegaly.Ascitic fluid analysis performed in 13 patients was found to be exudative and acid resistant bacilli were present in smear and cultured only in one patient with BacTec (3.2%).Upper gastrointestinal endoscopy yielded nonspecific findings in 16 patients.Colonoscopy performed in 20 patients showed ulcers in 9 (45%),nodules in 2 (10%) and,stricture,polypoid lesions,granulomatous findings in terminal ileum and rectal fistula each in one patient (5%). Laparoscopy on 4 patients showed dilated bowel loops, thickening in the mesentery,multiple ulcers and tubercles on the peritoneum.Patients with abdominal TB were divided into three groups according to the type of involvement. Fifteen patients (48%) had intestinal TB,11 patients (35.2%) had tuberculous peritonitis and 5 (16.8%) tuberculous lymphadenitis.The diagnosis of abdominal TB was confirmed microbiologically in 5 (16%) and histo- pathologically in 19 patients (60.8%).The remaining nine patients (28.8%) had been diagnosed by a positive response to antitub
基金partly supported by Grant from the Instituto Mexicano del Seguro Social (NO.FIS/IMSS/PROT/G12/1126FIS/IMSS/PROT/G14/1341)
文摘Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.
文摘Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. Developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.
文摘Tuberculosis(TB)is the leading cause of infectious mortality and morbidity in the world,second only to coronavirus disease 2019.Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population.Active TB is difficult to diagnose in this population due to close mimics.All transplant candidates should be screened for latent TB infection and given TB prophylaxis.Patients who develop active TB pre-or post-trans-plantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.
文摘AIM: Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. METHOD: In each of the models used, seven groups were allotted. The different groups received normal saline(10 mL·kg-1, p.o.); hepatotoxicant(isoniazid-rifampicin, INH-RIF, 100 mg·kg-1, i.p. or 20% ethanol 5 g·kg-1, p.o.) and normal saline(10 mL·kg-1, p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg-1 p.o.; hepatotoxicant and silymarin 50 mg·kg-1 p.o.; and extract at 400 mg·kg-1 p.o.. On the 21st day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. RESULTS: The hepatotoxicants significantly(P < 0.05-0.001) increased the levels of alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), bilirubin, and malondialdehyde(MDA); and reduced the levels of catalase(CAT), superoxide dismutase(SOD), glutathione peroxidase(GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed(P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract(200 and 400 mg·kg-1) significantly reversed(P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens(100-400 mg·kg-1) elicited significant reduction(P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. CONCLUSION: The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action.
基金financially supported by Department of Science&Technology,Government of India,New Delhi(Grant no.GAP-274625)
文摘Objective:To assess the hepatoprotective effect of Solanum xanthocarpum(S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals.Methods:Ethanolic(50%) fruit extract ofS. xanthocarpum(100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid(I) 7.5 mg/kg, rifampicin(R) 10 mg/kg and pyrazinamide(P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatise(ALP), total bilirubin(TBL), albumin(ALB), total protein(TP), lactate dehydroginase(LDH), and serum cholesterol(CHL). Meanwhile,in vivoantioxidant activities as lipid peroxidation(LPO), reduced glutathione(GSH), superoxide dismutase(SOD) and catalase(CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination.Results:The results demonstrated that treatment withS.xanthocarpumsignificantly(P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore,S. xanthocarpumsignificantly(up toP<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpumattenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration.Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpumagainst liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.