Many researches are undertaken to develop antibiotics to treat resistant tuberculosis. This review discusses new trends in research undertaken on new antituberculars reported to date, with a particular attention on th...Many researches are undertaken to develop antibiotics to treat resistant tuberculosis. This review discusses new trends in research undertaken on new antituberculars reported to date, with a particular attention on their synthesis and analysis.展开更多
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
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
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 antituberculous treatment. CONCLUSION:Neither clinical signs,laboratory,radiological and endoscopic methods nor bacteriological and histopathological findings provide a gold standard by themselves in the diagnosis of abdominal TB.However,an algorithm of these diagnostic methods leads to considerably higher precision in the diagnosis of this insidious disease which primarily necessitate a clinical awareness of this serious health problem.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
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
Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ...Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.展开更多
A series of 5-substituted-3-[{5-（6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-oxadiazol-2-yl}-imino] -1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-t...A series of 5-substituted-3-[{5-（6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-oxadiazol-2-yl}-imino] -1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-tubercular and antimalarial activity.展开更多
This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide der...This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.展开更多
Tuberculosis caused by Mycobacterium(M.)tuberculosis remains a global public health threat.Over the last few decades,anti-tubercular research mainly focused on mechanisms of identifying by which activated macrophages ...Tuberculosis caused by Mycobacterium(M.)tuberculosis remains a global public health threat.Over the last few decades,anti-tubercular research mainly focused on mechanisms of identifying by which activated macrophages can slaughter or the proliferation of M.tuberculosis bacilli prevented in a cell-dependent manner.In this regard,for disease resolution,inflammatory cytokines are very crucial.Here,we demonstrate how macrophages act as the first line of defense against the M.tuberculosis.Studies have revealed a dual role in M.tuberculosis infection played by macrophages.It is worth mentioning that the macrophages are the crucial immune effector and antigen-presenting cells that play the anti-tubercular response,which is the habitat of M.tuberculosis,hence,followed by progressing the disease protecting M.tuberculosis.This dual role can be correlated with the different macrophage polarization statuses,namely,M1 and M2.Herein,we have stated how the several polarization conditions of macrophages are directly linked to the immune responses during host and M.tuberculosis pathogen interactions.We have proposed that macrophage polarization and repolarization are of paramount significance for the anti-tubercular immune response that may involve a sterile cure of the disease.This article summarizes the immune response to M.tuberculosis,the polarization states of macrophages during M.tuberculosis and the repolarization of macrophages by some agents during some diseases including M.tuberculosis,which may be an important factor in the World Health Organization's target to cure tuberculosis by 2035.展开更多
BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of ...BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of spinal tuberculosis after organ transplantation. METHOD: Two cases were diagnosed as spinal tuberculosis after liver transplantation and were treated with socarboxazide, rifampicin, streptomycin and ethambutol for more than one year. RESULTS: After treatment with anti-tuberculosis drugs for several months, the symptoms of both patients clearly improved. Back pain disappeared, and erythrocyte sedimentation and body temperature returned to normal. CONCLUSIONS: We should highly suspect spinal tuberculosis if notalgia and night sweats are present after organ transplantation. Anti-tuberculosis therapy is an effective treatment for spinal tuberculosis after organ transplantation.展开更多
Objective:To investigate the inhibitory activity of the chloroform extract,petroleum ether and chloroform sub-extracts,lead-acetate treated chloroform extract,fractions and secondary metabolites of Uvaria rufa(U.rufa)...Objective:To investigate the inhibitory activity of the chloroform extract,petroleum ether and chloroform sub-extracts,lead-acetate treated chloroform extract,fractions and secondary metabolites of Uvaria rufa(U.rufa) against Mycobacterium tuberculosis(M.tuberculosis) H_(37)Rv. Methods:The antituberculosis susceptibility assay was earried out using the colorimetric Microplate Alamar blue assay(MABA).In addition,the cytotoxicity of the most active fraction was evaluated using the VERO cell toxicity assay.Results:The in vitro inhibitory activity against M.tuberculosis H_(37)Rv increased as purification progressed to fractionation(MIC up to 23μg/mL). The chloroform extract and its sub-extracts showed moderate toxicity while the most active fraction from chloroform sub-extract exhibited no cytotoxicity against VERO cells.Meanwhile, the lead acetate-treated crude chloroform extract and its fractions showed complete inhibitions (100%) with MIC values up to 8μg/mL.Phylochemical screening of the most active fraction showed,in general,the presence of terpenoids,steroids and phenolic compounds.Evaluation of the antimycobacterial activity of known secondary metabolites isolated showed no promising inhibitory activity against the test organism.Conclusions:The present results demonstrate the potential of U.rufa as a phytomedicinal source of compounds that may exhibit promising antituberculosis activity.In addition,elimination of polar pigments revealed enhanced inhibition against M.tuberculosis H_(37)Rv.While several compounds known for this plant did not show antimycobacterial activity,the obtained results are considered sufficient reason for further study to isolate the metabolites from U.rufa responsible for the antitubercular activity.展开更多
A series of Mannich products bearing quinoline nucleus was synthesized, characterized, and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The results showed that compoun...A series of Mannich products bearing quinoline nucleus was synthesized, characterized, and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The results showed that compounds 4b, and 4d found most active with percentage inhibition of 95, and 96, respectively, at minimum inhibitory concentration (MIC) of >6.25 μg/mL, among the synthesized compounds. Whereas, compounds 4a, 4c, 4e, and 4f exhibited considerable antitubercular activity with percentage inhibition of 71, 79, 55, and 68, respectively, at MIC of >6.25 μg/mL. The structures of synthesized compounds were elucidated by various spectroscopic tools like IR, 1H NMR, 13C NMR, mass and elemental analysis.展开更多
Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB...Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB i.e. multiple-drug resistance tuberculosis, XDR-TB i.e. extensively-drug resistance tuberculosis & TDR-TB i.e. total-drug resistance tuberculosis has forwarded an urgent need to discover novel antitubercular agents. The current work is aimed at combining two previously well-known pharmacophores (pyrazoline and benzoxazole nucleus) in order to design and synthesize a series of novel benzoxazole-based pyrazoline derivatives. The synthesized target compounds were structurally confirmed by LCMS, 1H-NMR and 13C-NMR analysis. The target compounds were In vitro evaluated against M. tuberculosis H37Rv strain, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. The In vitro screening results depicted that majority of the target compounds displayed potent activity with MIC in a range of ~0.8 to 6.25 μg/mL. Many compounds were found to be more potent than isoniazid against MDR-TB with MIC value 3.12 μg/mL and XDR-TB with MIC value 12.5 μg/mL. Cytotoxicity assay of these active compounds on VERO cell lines also displayed good selectivity index.展开更多
A series of 2-amino-4H-pyran-3-carbonitrile derivatives were designed and synthesized. Their antitubercular activities were evaluated against autoluminescent M. tuberculosis H37Ra and standard strain M. tuberculosis H...A series of 2-amino-4H-pyran-3-carbonitrile derivatives were designed and synthesized. Their antitubercular activities were evaluated against autoluminescent M. tuberculosis H37Ra and standard strain M. tuberculosis H37Rv. No obvious antitubercular activities could be observed (MIC > 10 ug/mL). The results are in sharp contrast with the previously reported data.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
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
This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/ or hyster...This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/ or hysteroscopy. This study included 78 patients with infertility and who were diagnosed with GTB through laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015? The recruited patients were divided into ATT and nonATT groups on the basis of ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy outcomes of the patients were determined at follow-up. Among the 78 patients, 46 received ATT and 32 did not receive ATT. The menstrual volumes of patients in the ATT group significantly decreased relative to those of patients in the nonATT group. GTB did not recur among all patients regardless of treatment. A total of 11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT group were observed. Pregnancy rates significantly differed (P = 0.002) between the two groups.ATT may decrease the menstrual volume and pregnancy rates of patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In addition, ATT did not improve the prognosis of patients with chronic GTB.展开更多
Tuberculosis is a serious threat to public health throughout the world.A series of new l3-n-nonylprotoberberine derivatives was designed,synthesized and evaluated for anti-mycobacterial activity against Mycobacterium ...Tuberculosis is a serious threat to public health throughout the world.A series of new l3-n-nonylprotoberberine derivatives was designed,synthesized and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis strain H_(37)Rv.Several compounds(2,11a-c,11g,13d,15c)exhibited excellent anti-tubercular activity with an MIC below 1.0μg/mL.Notably,compound 13d showed potential antibacterial effect against both drug-susceptible and multidrug-resistant(MDR)M.tuberculosis with MIC ranges of 0.0625-1.0μg/mL.These results suggest a mode of action different from that of the current anti-mycobacterial drugs rifampicin and isoniazid.Hence,compound 13d is an attractive lead compound for the development of new antitubercular agents.展开更多
文摘Many researches are undertaken to develop antibiotics to treat resistant tuberculosis. This review discusses new trends in research undertaken on new antituberculars reported to date, with a particular attention on their synthesis and analysis.
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.
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 antituberculous treatment. CONCLUSION:Neither clinical signs,laboratory,radiological and endoscopic methods nor bacteriological and histopathological findings provide a gold standard by themselves in the diagnosis of abdominal TB.However,an algorithm of these diagnostic methods leads to considerably higher precision in the diagnosis of this insidious disease which primarily necessitate a clinical awareness of this serious health problem.
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.
文摘Tuberculosis(TB)has been a human disease for centuries.Its frequency is increased manyfold in patients with liver cirrhosis.The gold standard of TB management is a 6-mo course of isoniazid,rifampicin,pyrazinamide and ethambutol.Although good results are seen with this treatment in general,the management of patients with underlying cirrhosis is a challenge.The underlying depressed immune response results in alterations in many diagnostic tests.The tests used for latent TB have many flaws in this group of patients.Three of four first-line antitubercular drugs are hepatotoxic and baseline liver function is often disrupted in patients with underlying cirrhosis.Frequency of hepatotoxicity is increased in patients with liver cirrhosis,frequently leading to severe liver failure.There are no established guidelines for the treatment of TB in relation to the severity of liver disease.There is no consensus on the frequency of liver function tests required or the cutoff used to define hepatotoxicity.No specific treatment exists for prevention or treatment of hepatotoxicity,making monitoring even more important.A high risk of multidrug-resistant TB is another major worry due to prolonged and interrupted treatment.
文摘A series of 5-substituted-3-[{5-（6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl）-1,3,4-oxadiazol-2-yl}-imino] -1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-tubercular and antimalarial activity.
基金National Institute of Technology Karnataka,India for the financial support and laboratory facility
文摘This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.
文摘Tuberculosis caused by Mycobacterium(M.)tuberculosis remains a global public health threat.Over the last few decades,anti-tubercular research mainly focused on mechanisms of identifying by which activated macrophages can slaughter or the proliferation of M.tuberculosis bacilli prevented in a cell-dependent manner.In this regard,for disease resolution,inflammatory cytokines are very crucial.Here,we demonstrate how macrophages act as the first line of defense against the M.tuberculosis.Studies have revealed a dual role in M.tuberculosis infection played by macrophages.It is worth mentioning that the macrophages are the crucial immune effector and antigen-presenting cells that play the anti-tubercular response,which is the habitat of M.tuberculosis,hence,followed by progressing the disease protecting M.tuberculosis.This dual role can be correlated with the different macrophage polarization statuses,namely,M1 and M2.Herein,we have stated how the several polarization conditions of macrophages are directly linked to the immune responses during host and M.tuberculosis pathogen interactions.We have proposed that macrophage polarization and repolarization are of paramount significance for the anti-tubercular immune response that may involve a sterile cure of the disease.This article summarizes the immune response to M.tuberculosis,the polarization states of macrophages during M.tuberculosis and the repolarization of macrophages by some agents during some diseases including M.tuberculosis,which may be an important factor in the World Health Organization's target to cure tuberculosis by 2035.
文摘BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of spinal tuberculosis after organ transplantation. METHOD: Two cases were diagnosed as spinal tuberculosis after liver transplantation and were treated with socarboxazide, rifampicin, streptomycin and ethambutol for more than one year. RESULTS: After treatment with anti-tuberculosis drugs for several months, the symptoms of both patients clearly improved. Back pain disappeared, and erythrocyte sedimentation and body temperature returned to normal. CONCLUSIONS: We should highly suspect spinal tuberculosis if notalgia and night sweats are present after organ transplantation. Anti-tuberculosis therapy is an effective treatment for spinal tuberculosis after organ transplantation.
文摘Objective:To investigate the inhibitory activity of the chloroform extract,petroleum ether and chloroform sub-extracts,lead-acetate treated chloroform extract,fractions and secondary metabolites of Uvaria rufa(U.rufa) against Mycobacterium tuberculosis(M.tuberculosis) H_(37)Rv. Methods:The antituberculosis susceptibility assay was earried out using the colorimetric Microplate Alamar blue assay(MABA).In addition,the cytotoxicity of the most active fraction was evaluated using the VERO cell toxicity assay.Results:The in vitro inhibitory activity against M.tuberculosis H_(37)Rv increased as purification progressed to fractionation(MIC up to 23μg/mL). The chloroform extract and its sub-extracts showed moderate toxicity while the most active fraction from chloroform sub-extract exhibited no cytotoxicity against VERO cells.Meanwhile, the lead acetate-treated crude chloroform extract and its fractions showed complete inhibitions (100%) with MIC values up to 8μg/mL.Phylochemical screening of the most active fraction showed,in general,the presence of terpenoids,steroids and phenolic compounds.Evaluation of the antimycobacterial activity of known secondary metabolites isolated showed no promising inhibitory activity against the test organism.Conclusions:The present results demonstrate the potential of U.rufa as a phytomedicinal source of compounds that may exhibit promising antituberculosis activity.In addition,elimination of polar pigments revealed enhanced inhibition against M.tuberculosis H_(37)Rv.While several compounds known for this plant did not show antimycobacterial activity,the obtained results are considered sufficient reason for further study to isolate the metabolites from U.rufa responsible for the antitubercular activity.
文摘A series of Mannich products bearing quinoline nucleus was synthesized, characterized, and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The results showed that compounds 4b, and 4d found most active with percentage inhibition of 95, and 96, respectively, at minimum inhibitory concentration (MIC) of >6.25 μg/mL, among the synthesized compounds. Whereas, compounds 4a, 4c, 4e, and 4f exhibited considerable antitubercular activity with percentage inhibition of 71, 79, 55, and 68, respectively, at MIC of >6.25 μg/mL. The structures of synthesized compounds were elucidated by various spectroscopic tools like IR, 1H NMR, 13C NMR, mass and elemental analysis.
文摘Various recent reports on Tuberculosis have alarmed an increase in the patient class and subsequent death rates across the globe. Over and above the spread of more dangerous and fatal forms of tuberculosis like MDR-TB i.e. multiple-drug resistance tuberculosis, XDR-TB i.e. extensively-drug resistance tuberculosis & TDR-TB i.e. total-drug resistance tuberculosis has forwarded an urgent need to discover novel antitubercular agents. The current work is aimed at combining two previously well-known pharmacophores (pyrazoline and benzoxazole nucleus) in order to design and synthesize a series of novel benzoxazole-based pyrazoline derivatives. The synthesized target compounds were structurally confirmed by LCMS, 1H-NMR and 13C-NMR analysis. The target compounds were In vitro evaluated against M. tuberculosis H37Rv strain, multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. The In vitro screening results depicted that majority of the target compounds displayed potent activity with MIC in a range of ~0.8 to 6.25 μg/mL. Many compounds were found to be more potent than isoniazid against MDR-TB with MIC value 3.12 μg/mL and XDR-TB with MIC value 12.5 μg/mL. Cytotoxicity assay of these active compounds on VERO cell lines also displayed good selectivity index.
文摘A series of 2-amino-4H-pyran-3-carbonitrile derivatives were designed and synthesized. Their antitubercular activities were evaluated against autoluminescent M. tuberculosis H37Ra and standard strain M. tuberculosis H37Rv. No obvious antitubercular activities could be observed (MIC > 10 ug/mL). The results are in sharp contrast with the previously reported data.
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.
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This retrospective study aims to demonstrate the effect of antitubercular treatment (ATT) on the pregnancy outcomes and prognoses of patients with genital tuberculosis (GTB) who had received laparoscopy and/ or hysteroscopy. This study included 78 patients with infertility and who were diagnosed with GTB through laparoscopy and/or hysteroscopy over the period of November 2005 to October 2015? The recruited patients were divided into ATT and nonATT groups on the basis of ATT duration. The GTB recurrence rates, menstrual patterns, and pregnancy outcomes of the patients were determined at follow-up. Among the 78 patients, 46 received ATT and 32 did not receive ATT. The menstrual volumes of patients in the ATT group significantly decreased relative to those of patients in the nonATT group. GTB did not recur among all patients regardless of treatment. A total of 11 pregnancies (36.7%) in the ATT group and 19 pregnancies (63.3%) in the nonATT group were observed. Pregnancy rates significantly differed (P = 0.002) between the two groups.ATT may decrease the menstrual volume and pregnancy rates of patients who were diagnosed with GTB through laparoscopy and/or hysteroscopy. In addition, ATT did not improve the prognosis of patients with chronic GTB.
基金This work was supported by the National Natural Science Fund for Young Scientists(81102312)the National S&T Major Special Projecton Major New Drug Innovation(2012ZX09301002-001).
文摘Tuberculosis is a serious threat to public health throughout the world.A series of new l3-n-nonylprotoberberine derivatives was designed,synthesized and evaluated for anti-mycobacterial activity against Mycobacterium tuberculosis strain H_(37)Rv.Several compounds(2,11a-c,11g,13d,15c)exhibited excellent anti-tubercular activity with an MIC below 1.0μg/mL.Notably,compound 13d showed potential antibacterial effect against both drug-susceptible and multidrug-resistant(MDR)M.tuberculosis with MIC ranges of 0.0625-1.0μg/mL.These results suggest a mode of action different from that of the current anti-mycobacterial drugs rifampicin and isoniazid.Hence,compound 13d is an attractive lead compound for the development of new antitubercular agents.
