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English Journal
- Salicylanilide pyrazinoates inhibit in vitro multidrug-resistant Mycobacterium tuberculosis strains, atypical mycobacteria and isocitrate lyase.
- Krátký M1, Vinšová J2, Novotná E3, Stolaříková J4.Author information 1Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: martin.kratky@faf.cuni.cz.2Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: jarmila.vinsova@faf.cuni.cz.3Department of Biochemical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. Electronic address: eva.novotna@faf.cuni.cz.4Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic. Electronic address: jirina.stolarikova@zu.cz.AbstractThe development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial active salicylanilides and pyrazinoic acid (POA), an active metabolite of pyrazinamide, in which these esters are likely hydrolysed without presence of pyrazinamidase/nicotinamidase. Minimum inhibitory concentrations (MICs) of the esters were within the range 0.5-8μmol/l for Mycobacterium tuberculosis and 1-32μmol/l for nontuberculous mycobacteria (Mycobacterium avium, Mycobacterium kansasii). All esters showed a weak inhibition (8-17%) of isocitrate lyase at the concentration of 10μmol/l. The most active pyrazinoates showed MICs for multidrug-resistant tuberculosis strains in the range of 0.125-2μmol/l and no cross-resistance with clinically used drugs, thus being the most in vitro efficacious salicylanilide esters with 4-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate superiority (MICs⩽0.25μmol/l). This promising activity is likely due to an additive or synergistic effect of released POA and salicylanilides. Selectivity indexes for the most active salicylanilide pyrazinoates ranged up to 64, making some derivatives being attractive candidates for the next research; 4-bromo-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl pyrazine-2-carboxylate showed the most convenient toxicity profile.
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Mar 12;53:1-9. doi: 10.1016/j.ejps.2013.12.001. Epub 2013 Dec 10.
- The development of antimicrobial agents represents an up-to-date topic. This study investigated in vitro antimycobacterial activity, mycobacterial isocitrate lyase inhibition and cytotoxicity of salicylanilide pyrazinoates. They may be considered being mutual prodrugs of both antimycobacterial activ
- PMID 24333643
- Atypical mycobacterial cutaneous infections in Egyptians: A clinicopathological study.
- El-Khalawany MA.Author information Department of Dermatology, Al-Azhar University, Cairo, Egypt.AbstractAtypical mycobacteria comprise an uncommon heterogenous non-tuberculous group of acid-fast bacteria that rarely involve skin. The pattern of atypical mycobacterial cutaneous infections (AMCI) has not been previously studied in Egypt. The aim of this study was to describe the clinical characteristics, pathological features and species profile of AMCI among Egyptian patients. A retrospective study included 46 cases, diagnosed with AMCI during the period 2002 to 2012. The study included 34 males (73.9%) and 12 females (26.9%). The average age of patients was 39 years while the average duration of lesions was 15 months. The lesions were mostly located on the extremities (91.3%) and there was predominance of single (65.2%) and nodular (41.4%) lesions. History of trauma was confirmed in 91.3%. Histologically, the granulomas were mostly superficial (67.4%) with predominance of nodular suppurative pattern (84.8%). Other significant histological findings included epidermal hypertrophy (100%), presence of large-sized multinucleated giant cells (87%) and intrafollicular neutrophilic abscesses (84.8%). The diagnosis was proved by direct smear in 6.5%, skin biopsy in 10.9%, tissue culture in 47.8% and polymerase chain reaction (PCR) in 34.8%. Isolated species included Mycobacterium marinum (84.8%), Mycobacterium fortuitum (10.9%) and Mycobacterium kansasii (4.3%). Although the results of this study recommend that the diagnosis of AMCI is based mainly on culture and PCR, other clinicopathological features such as history of trauma, acral location of the lesion and suppurative granulomatous reaction with intrafollicular abscesses could be helpful clues in suspecting AMCI.
- The Journal of dermatology.J Dermatol.2014 Feb 18. doi: 10.1111/1346-8138.12391. [Epub ahead of print]
- Atypical mycobacteria comprise an uncommon heterogenous non-tuberculous group of acid-fast bacteria that rarely involve skin. The pattern of atypical mycobacterial cutaneous infections (AMCI) has not been previously studied in Egypt. The aim of this study was to describe the clinical characteristics
- PMID 24533920
- Lithium inhibits growth of intracellular Mycobacterium kansasii through enhancement of macrophage apoptosis.
- Sohn H1, Kim K, Lee KS, Choi HG, Lee KI, Shin AR, Kim JS, Shin SJ, Song CH, Park JK, Kim HJ.Author information 1Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea.AbstractMycobacterium kansasii (Mk) is an emerging pathogen that causes a pulmonary disease similar to tuberculosis. Macrophage apoptosis contributes to innate host defense against mycobacterial infection. Recent studies have suggested that lithium significantly enhances the cytotoxic activity of death stimuli in many cell types. We examined the effect of lithium on the viability of host cells and intracellular Mk in infected macrophages. Lithium treatment resulted in a substantial reduction in the viability of intracellular Mk in macrophages. Macrophage cell death was significantly enhanced after adding lithium to Mk-infected cells but not after adding to uninfected macrophages. Lithium-enhanced cell death was due to an apoptotic response, as evidenced by augmented DNA fragmentation and caspase activation. Reactive oxygen species were essential for lithium-induced apoptosis. Intracellular scavenging by N-acetylcysteine abrogated the lithium-mediated decrease in intracellular Mk growth as well as apoptosis. These data suggest that lithium is associated with control of intracellular Mk growth through modulation of the apoptotic response in infected macrophages.
- Journal of microbiology (Seoul, Korea).J Microbiol.2014 Feb 17. [Epub ahead of print]
- Mycobacterium kansasii (Mk) is an emerging pathogen that causes a pulmonary disease similar to tuberculosis. Macrophage apoptosis contributes to innate host defense against mycobacterial infection. Recent studies have suggested that lithium significantly enhances the cytotoxic activity of death stim
- PMID 24535745
Japanese Journal
- 画像診断 肺カンサシ症の治療中にムコール症を合併した1例
- 日本呼吸器学会誌 = Annals of the Japanese Respiratory Society 5(3), 154-157, 2016-05-10
- NAID 40020845845
- 厚生労働省研究班の疫学調査から (特集 非結核性抗酸菌症の今)
- 症例 Mycobacterium kansasiiによる胸膜炎の1例
- 日本呼吸器学会誌 = Annals of the Japanese Respiratory Society 4(5), 413-416, 2015-09-10
- NAID 40020592970
Related Links
- [infections caused by M. kansasii]非 光発色菌であり,暗所で培養した集落は着色がないが,光に当てることによって,鮮やかなレモン黄色に変化する性質をもつM. kansasiiによる感染症である。男性の罹患が圧倒的に多く,M. avium ...
- (2)M.kansasii症の治療(図2) この菌は比較的毒力が強く、結核と同じ様な症状を来しやすいことや、性別では圧倒的に男性に多いのが特徴です。無治療で自然軽快したという報告もありますが、下記のように結核に準じて治療すれば ...
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