Tuberculosis(TB) is a symbolic menace to mankind,infecting almost one third of the world's populace and causing over a million mortalities annually.Mycobacterium tuberculosis(M.tuberculosis) is the key pathogen of...Tuberculosis(TB) is a symbolic menace to mankind,infecting almost one third of the world's populace and causing over a million mortalities annually.Mycobacterium tuberculosis(M.tuberculosis) is the key pathogen of TB that invades and replicates inside the host's macrophage.With the emerging dilemma of multi-drug resistant tuberculosis(MDR-TB) and extensivelydrug resistant tuberculosis(XDR-TB),the exigency for developing new TB drugs is an obligation now for worldwide researchers.Among the propitious antimycobacterial agents examined in last few decades,anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity,selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action.In this review,we epitomized the current advances in the anti-tubercular peptides,focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides.The review investigates the current anti-tubercular peptides exploited not only from human immune cells,human non-immune cells,bacteria and fungi but also from venoms,cyanobacteria,bacteriophages and several other unplumbed sources.The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within M.tuberculosis.The present context also describes the several cases that manifested the severe side effects of extant antiTB drugs.The downfall,failure to reach clinical trial phases,inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides.Keeping in view of the emerging trends of drug resistant M.tuberculosis globally and unexampled mycobactericidal characteristics of peptides,the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicatc TB in future by developing new therapeutic drugs.展开更多
Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their manageme...Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.展开更多
A series of indazol-2-yl（pyridin-4-yl）methanones, 4 were acquired from 2,6-bisbenzylidene cyclohex- anones, 3 and anti-tubercular drug （isoniazid）, and their anti-tubercular impacts were screened. Among the test c...A series of indazol-2-yl（pyridin-4-yl）methanones, 4 were acquired from 2,6-bisbenzylidene cyclohex- anones, 3 and anti-tubercular drug （isoniazid）, and their anti-tubercular impacts were screened. Among the test compounds used against Mycobacterium tuberculosis H37 Ra cell line in the microplate alamar blue assay, the compounds 4g-j revealed moderate anti-tubercular activity with MIC 12.5 μg/mL, comparable to standard drugs （streptomycin, MIC, 6.25 μg/mL, pyrazinamide, isoniazid and ciprofloxacin with MICs of 3.125 μg/mL）.展开更多
A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as wel...A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as well as cytotoxicity. All benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids exhibited considerable in vitro anti-mycobacterial activities against the tested three MTB strains, and all of them also showed acceptable cytotoxicity. The most active hybrid 7f was >4.8 and >51 folds more potent than the first line anti-TB agents RIF and INH against both drug-sensitive MTB H_(37)Rv and MDR-TB isolates, respectively. The results demonstrated the potential utility of benzofuran-isatin-hydroxylimine/-thiosemicarbazide hybrids as anti-TB agents.展开更多
AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS A retrospective study of clinical outcome among children treated with...AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS A retrospective study of clinical outcome among children treated with thalidomide was conducted. All patients had evidence of tuberculosis infection with a failure of anti-tuberculosis treatment for more than one year,and were subsequently diagnosed with CD. All the patients received thalidomide treatment with a starting dose of 1.2-2.5 mg/kg per day. Remission was defined as pediatric CD activity index less than or equal to 10.RESULTS Ten patients with CD were treated with thalidomide at an average age of 7.2 years and followed up for a median of 22.2 mo. Clinical remission rate was 60% after 9-12 mo of thalidomide treatment. One patient with no response had an interleukin-10 receptor alpha gene mutation. Erythrocyte sedimentation rate,C-reactive protein and platelet count showed a dramatic decrease; hemoglobin level and weight improved significantly after thalidomide treatment when compared with the baseline values.CONCLUSION Thalidomide is an effective and safe drug for remission of CD in pediatric patients who have been treated for tuberculosis.展开更多
Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear po...Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.展开更多
A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized u...A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.展开更多
Miliary tuberculosis (MTB) of the liver can present non-specifically, which often leads to a diagnostic delay. The objective of this clinical case report is to highlight an unusual presentation of miliary TB in a youn...Miliary tuberculosis (MTB) of the liver can present non-specifically, which often leads to a diagnostic delay. The objective of this clinical case report is to highlight an unusual presentation of miliary TB in a young female patient, who was admitted to hospital with right upper quadrant tenderness and constitutional symptoms. Most of her investigations yielded little to support the diagnosis until a subsequent positive TB Elispot test and CT chest, abdomen and pelvis with contrast were done. Features of this case are discussed, together with anti-tubercular treatment (ATT) strategy utilized for miliary TB with hepatic involvement.展开更多
基金supported by Maulana Azad National Fellowship(Fl17.1/2015-16/MANF-2015-17-BIH-60730),University Grants Commission,Delhi,India
文摘Tuberculosis(TB) is a symbolic menace to mankind,infecting almost one third of the world's populace and causing over a million mortalities annually.Mycobacterium tuberculosis(M.tuberculosis) is the key pathogen of TB that invades and replicates inside the host's macrophage.With the emerging dilemma of multi-drug resistant tuberculosis(MDR-TB) and extensivelydrug resistant tuberculosis(XDR-TB),the exigency for developing new TB drugs is an obligation now for worldwide researchers.Among the propitious antimycobacterial agents examined in last few decades,anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity,selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action.In this review,we epitomized the current advances in the anti-tubercular peptides,focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides.The review investigates the current anti-tubercular peptides exploited not only from human immune cells,human non-immune cells,bacteria and fungi but also from venoms,cyanobacteria,bacteriophages and several other unplumbed sources.The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within M.tuberculosis.The present context also describes the several cases that manifested the severe side effects of extant antiTB drugs.The downfall,failure to reach clinical trial phases,inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides.Keeping in view of the emerging trends of drug resistant M.tuberculosis globally and unexampled mycobactericidal characteristics of peptides,the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicatc TB in future by developing new therapeutic drugs.
文摘Introduction: The adverse drug events (ADEs) to second-line anti-TB drugs are one of the major reasons for the patients default on treatment. A general awareness of various adverse drug events (ADE) and their management is essential for the effective management of tuberculosis. Identification of adverse drug reaction profile of patients can be useful for the early detection, management and prevention of adverse drug events. Material and methods: It was a prospective observational study conducted after approved Institutional Ethics Committee. A total of 104 drug resistant tuberculosis patients registered from 1st November 2012 to 31st October 2013 started with second line anti-tubercular drugs under PMDT-RNCP after taking written informed consent. Adverse drug reaction during treatment recorded and assessed by Hart wig and WHO scale. Results: 87% patients experienced adverse drug reactions. Total 346 ADR were reported. Most common were gastritis (65%) and arthralgia (60.6%), others were nausea (35.6%), vomiting (32.7%), hyperuricemia (30.8%), giddiness (27%), anorexia (17.3), generalized weakness (15.4), insomnia (10.6%), psychosis (8.6%), hearing impairment (6.7%), hypersensitivity reaction (5.8%), peripheral neuropathy (4.8%), visual disturbance (3.8%), nephrotoxicity (2.9%), forgetfulness (2.9%), gynaecomastia (1.9%), hypothyroidism (1%), seizure (1%), and thrombocytopenia (1%). Conclusion: Majority of patients experienced wide range adverse drug reactions. Most of patients faced the problem within 2 - 3 months of initiation of treatment and managed by symptomatic. Early identification, prompt management and standardized reporting adverse drug reactions at all the level of healthcare are needed.
基金VIT University for providing us with research funding and laboratory facilitiesMaratha Mandal Dental College,Belgaum for biological screening support
文摘A series of indazol-2-yl（pyridin-4-yl）methanones, 4 were acquired from 2,6-bisbenzylidene cyclohex- anones, 3 and anti-tubercular drug （isoniazid）, and their anti-tubercular impacts were screened. Among the test compounds used against Mycobacterium tuberculosis H37 Ra cell line in the microplate alamar blue assay, the compounds 4g-j revealed moderate anti-tubercular activity with MIC 12.5 μg/mL, comparable to standard drugs （streptomycin, MIC, 6.25 μg/mL, pyrazinamide, isoniazid and ciprofloxacin with MICs of 3.125 μg/mL）.
文摘A series of novel benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids were designed, synthesized and evaluated for their in vitro anti-TB activities against drug-sensitive MTB H_(37)Rv and MDR-TB isolates as well as cytotoxicity. All benzofuran-isatin-hydroxylimine/thiosemicarbazide hybrids exhibited considerable in vitro anti-mycobacterial activities against the tested three MTB strains, and all of them also showed acceptable cytotoxicity. The most active hybrid 7f was >4.8 and >51 folds more potent than the first line anti-TB agents RIF and INH against both drug-sensitive MTB H_(37)Rv and MDR-TB isolates, respectively. The results demonstrated the potential utility of benzofuran-isatin-hydroxylimine/-thiosemicarbazide hybrids as anti-TB agents.
基金Supported by Medical Science and Technology Planning Project of Zhejiang Province,China,No.2015KYB430(to Hong Y)
文摘AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS A retrospective study of clinical outcome among children treated with thalidomide was conducted. All patients had evidence of tuberculosis infection with a failure of anti-tuberculosis treatment for more than one year,and were subsequently diagnosed with CD. All the patients received thalidomide treatment with a starting dose of 1.2-2.5 mg/kg per day. Remission was defined as pediatric CD activity index less than or equal to 10.RESULTS Ten patients with CD were treated with thalidomide at an average age of 7.2 years and followed up for a median of 22.2 mo. Clinical remission rate was 60% after 9-12 mo of thalidomide treatment. One patient with no response had an interleukin-10 receptor alpha gene mutation. Erythrocyte sedimentation rate,C-reactive protein and platelet count showed a dramatic decrease; hemoglobin level and weight improved significantly after thalidomide treatment when compared with the baseline values.CONCLUSION Thalidomide is an effective and safe drug for remission of CD in pediatric patients who have been treated for tuberculosis.
文摘Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.
文摘A new series of quinazolin-4（3H）-one derivatives containing a（1 3-diphenyl-1H-pyrazol-4-yl） core with substituents at the 2-position and aromatic or heteroaromatic substituents at the 3-position were synthesized using an L-proline catalyzed one-pot multi-component reaction approach.All the synthesized compounds were characterized and screened for their antimicrobial,antifungal and anti-tubercular activities.
文摘Miliary tuberculosis (MTB) of the liver can present non-specifically, which often leads to a diagnostic delay. The objective of this clinical case report is to highlight an unusual presentation of miliary TB in a young female patient, who was admitted to hospital with right upper quadrant tenderness and constitutional symptoms. Most of her investigations yielded little to support the diagnosis until a subsequent positive TB Elispot test and CT chest, abdomen and pelvis with contrast were done. Features of this case are discussed, together with anti-tubercular treatment (ATT) strategy utilized for miliary TB with hepatic involvement.
基金Project supported by National Science and Technology Project of China(2009ZX09102-054)the Global Alliance for TB Drug Development financial support of this project
