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1.
J Biochem Mol Toxicol ; 37(8): e23375, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37129082

RESUMO

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2, A1B4, A4B2, A4B3, and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.


Assuntos
Antifúngicos , Bases de Schiff , Antifúngicos/farmacologia , Bases de Schiff/farmacologia , Fungos , Sulfanilamida , Linhagem Celular , Testes de Sensibilidade Microbiana
2.
Arch Pharm (Weinheim) ; 356(10): e2300302, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37541657

RESUMO

Two series of bis(1-alkylbenzimidazole)silver(I) nitrate and bis(1-alkyl-5,6-dimethylbenzimidazole)silver(I) nitrate complexes, in which the alkyl substituent is either an allyl, a 2-methylallyl, an isopropyl or a 3-methyloxetan-3-yl-methyl chain, were synthesized and fully characterized. The eight N-coordinated silver(I) complexes were screened for both antimicrobial activities against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii) and Gram-positive (Staphylococcus aureus, Staphylococcus aureus MRSA, and Enterococcus faecalis) bacteria and antifungal activities against Candida albicans and Candida glabrata strains. Moderate minimal inhibitory concentrations (MIC) of 0.087 µmol/mL were found when the Gram-negative and Gram-positive bacteria were treated with the silver complexes. Nevertheless, MIC values of 0.011 µmol/mL, twice lower than for the well-known fluconazole, against the two fungi were measured. In addition, molecular docking was carried out with the structure of Escherichia coli DNA gyrase and CYP51 from the pathogen Candida glabrata with the eight organometallic complexes, and molecular reactivity descriptors were calculated with the density functional theory-based calculation methods.

3.
Arch Pharm (Weinheim) ; 355(6): e2200041, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35352839

RESUMO

The reaction of N-substituted benzimidazole with 4-bromobutyronitrile gives the corresponding benzimidazolium salts as N-heterocyclic carbene (NHC) precursors. Silver(I) carbene complexes are synthesized by the reaction of the corresponding benzimidazolium salts with Ag2 O in dichloromethane. These new NHC precursors and Ag-NHC complexes were characterized by spectroscopy techniques and also screened for their antibacterial activities against the standard bacterial strains Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Enterococcus faecalis, and the standard fungal strains Candida albicans and Candida glabrata, and promising results were achieved. The compounds were also analyzed by density functional theory (DFT)/time-dependent DFT and docking methods.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Prata , Antibacterianos/química , Escherichia coli , Metano/análogos & derivados , Metano/química , Testes de Sensibilidade Microbiana , Sais/farmacologia , Prata/química , Prata/farmacologia , Relação Estrutura-Atividade
4.
Arch Pharm (Weinheim) ; 353(6): e2000013, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32301169

RESUMO

Catechol-containing imidazolium (four) and benzimidazolium chlorides (eight) were synthesized to evaluate their antimicrobial properties. All the compounds were fully characterized using 1 H and 13 C nuclear magnetic resonance, liquid chromatography-mass spectrometry, infrared spectroscopic methods, and elemental analyses. Antimicrobial activities of the compounds were tested against the bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, and the fungal strains Candida albicans and Candida glabrata, and promising results were achieved. The two most important benzyl-substituted benzimidazolium chlorides, 3l and 3k, showed comparable activity to vancomycin against MRSA.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Benzimidazóis/farmacologia , Catecóis/farmacologia , Imidazóis/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Catecóis/síntese química , Catecóis/química , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Imidazóis/síntese química , Imidazóis/química , Klebsiella pneumoniae/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
5.
Bioorg Med Chem ; 24(16): 3649-56, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27301680

RESUMO

Novel benzimidazolium salts were synthesized as N-heterocyclic carbene (NHC) precursors, these NHC precursors were metallated with Ag2O in dichloromethane at room temperature to give novel silver(I)-NHC complexes. Structures of these benzimidazolium salts and silver(I)-NHC complexes were characterized on the basis of elemental analysis, (1)H NMR, (13)C NMR, IR and LC-MS spectroscopic techniques. A series of benzimidazolium salts and silver(I)-NHC complexes were tested against standard bacterial strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungal strains: Candida albicans and Candida tropicalis. The results showed that benzimidazolium salts inhibited the growth of all bacteria and fungi strains and all silver(I)-NHC complexes performed good activities against different microorganisms.


Assuntos
Anti-Infecciosos/farmacologia , Benzimidazóis/farmacologia , Prata/química , Anti-Infecciosos/química , Benzimidazóis/química , Candida/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Análise Espectral/métodos , Staphylococcus aureus/efeitos dos fármacos
6.
Bioorg Med Chem ; 24(4): 643-50, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26740157

RESUMO

Eight new coumarin substituted silver(I) N-heterocyclic carbene (NHC) complexes were synthesized by the interaction of the corresponding imidazolium or benzimidazolium chlorides and Ag2O in dichloromethane at room temperature. Structures of these complexes were established on the basis of elemental analysis, (1)H NMR, (13)C NMR, IR and mass spectroscopic techniques. The antimicrobial activities of carbene precursors and silver NHC complexes were tested against standard strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungi Candida albicans and Candida tropicalis. Results showed that all the compounds inhibited the growth of the all bacteria and fungi strains and some complexes performed good activities against different microorganisms. Among all the compounds, the most lipophilic complex bis[1-(4-methylene-6,8-dimethyl-2H-chromen-2-one)-3-(naphthalene-2-ylmethyl)benzimidazol-2-ylidene]silver(I) dichloro argentate (5e) was found out as the most active one.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Cumarínicos/farmacologia , Metano/análogos & derivados , Compostos Organometálicos/farmacologia , Prata/farmacologia , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/crescimento & desenvolvimento , Cumarínicos/química , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Ligantes , Metano/química , Metano/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Prata/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade
7.
J Enzyme Inhib Med Chem ; 31(6): 1527-30, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26987046

RESUMO

This study reports the synthesis, characterisation and antimicrobial activity of five novel silver N-heterocyclic carbene (Ag-NHC) complexes obtained by N-propylphthalimide and N-methyldioxane substituted benzimidazolium salts with silver oxide. The reactions were performed at room temperature for 24 h in the absence of light. The obtained complexes were identified and characterised by (1)H and (13)C NMR, FT-IR and elemental analysis techniques. The minimum inhibitory concentration (MIC) of the complexes was determined for E. coli, P. aeruginosa, E. faecalis, S. aureus, C. tropicalis and C. albicans in vitro through agar and broth dilution. The results indicated that these complexes exhibit antimicrobial activity. In particular, complex 3 presented the significant broad spectrum antimicrobial activity.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzimidazóis/química , Metano/análogos & derivados , Prata/química , Anti-Infecciosos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Metano/síntese química , Metano/química , Metano/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética
8.
Pak J Pharm Sci ; 28(2): 611-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25730792

RESUMO

The aim of this study is synthesis of two different series of organoselenium compounds and available in vitro antioxidant and antimicrobial properties of these synthetic compounds. The synthetic compounds were identified by (1)H-NMR (300 MHz), (13)C-NMR (75.5 MHz), FT-IR spectroscopic techniques and micro analysis. Antioxidant properties of two synthetic organoselenium compounds were determined by 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical method, reducing power assay and ß-carotene bleaching method as in vitro. Antimicrobial effects of samples were assessed by the agar dilution procedure and using gram positive and gram-negative bacteria and yeast strains. Although 1,3-di-p-methoxybenzylpyrimidine-2-selenone showed better antiradical activity in DPPH test and higher protective activity on ß-carotene, 1-isopropyl-3-methylbenzimidazole-2-selenone was found to be better in reducing power and antimicrobial activity.


Assuntos
Anti-Infecciosos/síntese química , Antioxidantes/síntese química , Compostos Organosselênicos/síntese química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia
9.
Mikrobiyol Bul ; 46(2): 283-9, 2012 Apr.
Artigo em Turco | MEDLINE | ID: mdl-22639317

RESUMO

This study was aimed to isolate and identify Mycobacterium bovis and non-tuberculous mycobacteria (NTM) species in raw milk samples from cattles and to compare the diagnostic performance of the methods used for that purpose. A total of 145 raw milk samples from cattles were collected from five villages in Mersin province (located on Mediterrenean region of Turkey) between April and June 2008. Presence of mycobacteria was investigated by Ehrlich Ziehl Neelsen (EZN) staining method, culture in Löwenstein- Jensen (LJ) medium and polymerase chain reaction (PCR). Only 1 (0.7%, 1/145) raw milk sample was found to be acid fast bacilli (AFB) positive with EZN staining. Eleven (7.6%) samples were positive by culture and mycobacterial DNA was detected in 6 (4.1%) samples by PCR. Mycobacterium was isolated from both creamy and pellet layer of a culture positive sample. Identification was carried out with conventional biochemical tests, PCR-Restriction Fragment Length Polymorphisms (PCR-RFLP) and spoligotyping (spacer oligonucleotide typing) methods. One isolate was identified as Mycobacterium tuberculosis complex (MTC) and 11 isolates were identified as NTM out of 12 isolates those were isolated from culture. According to PCR-RFLP analysis of these 11 NTM isolates, 6 (54.5%) were Mycobacterium genavense, 2 (18.2%) were Mycobacterium simiae, 2 (18.2%) were Mycobacterium szulgai and 1 (9.1%) was Mycobacterium fortuitum. MTC isolate was identified as M.bovis by spoligotyping. According to the results of our study, both pellet and creamy layers from raw milk samples should be cultured to selective LJ medium (without glycerol, with 0.4% sodium pyruvate) to improve the chance of isolation and must be incubated for up to eight weeks. In our region, NTM were isolated in 6.9% and M.bovis in 0.7% of the raw milk samples from cattles and this emphasized the risk of transmission of mycobacteria to man via direct contact or ingestion of unpasteurized milk products.


Assuntos
Leite/microbiologia , Mycobacterium bovis/isolamento & purificação , Micobactérias não Tuberculosas/isolamento & purificação , Animais , Técnicas de Tipagem Bacteriana/normas , Bovinos , Meios de Cultura , DNA Bacteriano/isolamento & purificação , DNA Intergênico/análise , Mycobacterium bovis/classificação , Mycobacterium bovis/genética , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Coloração e Rotulagem/métodos , Turquia
10.
BMC Public Health ; 11: 154, 2011 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-21385458

RESUMO

BACKGROUND: Extrapulmonary tuberculosis (EPTB) has an increasing rate in Turkey. The reason remains largely unknown. A better understanding of the demographic and microbial characteristics of EPTB in the Turkish population would extend the knowledgebase of EPTB and allow us to develop better strategies to control tuberculosis (TB). METHODS: We retrospectively evaluated clinical and laboratory data of 397 bacteriologically-confirmed TB cases diagnosed during an eight year-period using by chi-square analysis and multivariate logistic regression model. RESULTS: Of the 397 study patients, 103 (25.9%) had EPTB and 294 (74.1%) had pulmonary tuberculosis (PTB). The most commonly seen two types of EPTB were genitourinary TB (27.2%) and meningeal TB (19.4%). TB in bone/joints, pleural cavity, lymph nodes, skin, and peritoneal cavity occurred at a frequency ranging from 9.7% to 10.7%. The age distribution was significantly different (P<0.01) between PTB and EPTB, with patients older than 45 years tending to have an increased risk of EPTB. Furthermore, the distribution of different types of EPTB differed significantly among age groups (P=0.03). Meningeal and bone and/or joint TB were more commonly observed among the male patients, while lymphatic, genitourinary, and peritoneal TB cases were more frequently seen among females. Unique strain infection was statistically significantly associated with EPTB (OR: 2.82, 95% CI [1.59, 5.00]) CONCLUSIONS: EPTB accounted for a significant proportion of TB cases in Malatya, Turkey between 2001 and 2007. The current study has provided an insight into the dynamics of EPTB in Malatya, Turkey. However, the risk factors for having EPTB in Malatya, Turkey remain to be assessed in future studies using population-based or randomly selected sample.


Assuntos
Demografia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mycobacterium/genética , Mycobacterium/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Tuberculose/classificação , Tuberculose/fisiopatologia , Turquia/epidemiologia , Adulto Jovem
11.
Dalton Trans ; 50(33): 11596-11603, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34355725

RESUMO

Herein, we report the synthesis, characterisation and preliminary biological evaluation of two novel silver(i) complexes of type [AgL2](NO3)3 (3 and 4) with ionic N-donor benzimidazoles. The complexes have been synthesized by the reaction of 1.5 equivalents of silver nitrate and N-donor benzimidazoles containing an imidazolium core at the 2-position (1 and 2) in ethanol. The X-ray analysis of 4 shows that it has two free imidazolium cores and the charge is balanced with three nitrate anions. A study by the combination of NMR, IR, LC-MS and elemental analysis techniques also suggests that the complexes have this structure both in the solid-state and solution. The complexes are highly soluble and stable in water. Cytotoxicity evaluation against four cancerous human cells and one non-cancerous human cell revealed that the complexes have no significant anti-growth effect. However, the complexes showed a remarkable antimicrobial effect at normalized minimum inhibitory concentrations (normalized MICs) in the range of 33-268 µM against a panel of microorganisms consisting of Gram-negative and Gram-positive bacteria, and fungi.


Assuntos
Benzimidazóis/química , Complexos de Coordenação/química , Prata/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Ligantes , Testes de Sensibilidade Microbiana , Conformação Molecular , Água/química
12.
J Clin Microbiol ; 48(9): 3301-5, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20660214

RESUMO

Drug-resistant tuberculosis (TB) presents a major challenge to global TB control. To gain a better understanding of drug-resistant TB epidemiology in Malatya, Turkey, we conducted the present study using 397 Mycobacterium tuberculosis clinical isolates collected from Malatya, Turkey, in recent years (2000-2007). Resistance to any anti-TB drug was found in 29% (114 of 397) of the study isolates, while the multidrug resistance (MDR) rate was approximately 4.5% (18 of 397). Resistances to isoniazid (15.5%) and streptomycin (13.4%) were about twice as high as resistance to rifampin (RMP) (6.3%) and ethambutol (EMB) (6.0%). Importantly, 28% (7 of 25) of the RMP-resistant isolates were non-MDR isolates, as when a significant proportion of RMP-resistant isolates in a population are non-MDR, the predictive value of molecular detection of RMP resistance for MDR can be significantly reduced. Both identical and varied drug resistance patterns were seen in the same genotyping-defined clusters, suggesting that both primary and acquired resistance have contributed to the drug-resistant TB epidemic in Malatya, Turkey. In addition, drug-resistant cases were found to be more likely to be males (odds ratio [95% confidence interval], 1.82 [1.13, 2.94]), suggesting a potential role of gender in the epidemiology of drug-resistant TB in the study population. This study demonstrates that the integration of drug susceptibility testing with genotyping and epidemiological data analysis represents a useful approach to studying the epidemiology of drug-resistant TB.


Assuntos
Antituberculosos/farmacologia , Técnicas de Tipagem Bacteriana , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Genótipo , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Turquia/epidemiologia , Adulto Jovem
13.
Molecules ; 15(4): 2203-10, 2010 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-20428038

RESUMO

Gold(I) N-heterocyclic carbene (NHC) complexes were obtained in good yields from the corresponding silver complexes by treatment with [AuCl(PPh3)] following the commonly used silver carbene transfer route. The silver complexes were synthesized from the benzimidazolium halide salts by the in situ reactions with Ag2O in dichloromethane as a solvent at room temperature. All gold complexes have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. Au-NHC complexes were evaluated for their in vitro antimicrobial activity against a variety of Gram-positive and Gram-negative bacteria and fungal species.


Assuntos
Antibacterianos/química , Antifúngicos/química , Benzimidazóis/química , Ouro/química , Metano/análogos & derivados , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ligantes , Espectroscopia de Ressonância Magnética , Metano/química , Pseudomonas aeruginosa/efeitos dos fármacos , Espectrofotometria Infravermelho , Staphylococcus aureus/efeitos dos fármacos
14.
Molecules ; 15(4): 2499-508, 2010 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-20428059

RESUMO

A series of imidazolidinium ligand precursors are metallated with Ag2O to give silver(I) N-heterocyclic carbene complexes. All compounds were fully characterized by elemental analyses, 1H-NMR, 13C-NMR and IR spectroscopy techniques. All compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and the fungi Candida albicans and Candida tropicalis. The new imidazolidin-2-ylidene silver complexes have been found to display effective antimicrobial activity against a series of bacteria and fungi.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Compostos Heterocíclicos/síntese química , Imidazolidinas/química , Metano/análogos & derivados , Prata/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Espectroscopia de Ressonância Magnética , Metano/química , Nitrogênio/química , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
15.
Mikrobiyol Bul ; 44(2): 297-302, 2010 Apr.
Artigo em Turco | MEDLINE | ID: mdl-20549966

RESUMO

The vaccine strain Mycobacterium bovis BCG may lead to disseminated infection in patients with immune deficiency. In this report a patient who developed fatal disseminated tuberculosis caused by M. bovis BCG strain was presented. One year old male patient with the previous history of recurrent lower respiratory tract infection, was admitted to the hospital with the complaints of fever, cough and diarrhea continuing for 20 days. There was no family history of tuberculosis or history of contact with a tuberculosis case. Physical examination of the case revealed growth retardation and reticular and reticulonodular infiltration was detected in his chest X-ray. The results of sweat test, cystic fibrosis gene mutation analysis and metabolic screening tests were normal. Since fever continued and infiltrations persisted in the chest X-ray despite antibiotic therapy, PPD test was applied and acid-fast bacilli (AFB) were investigated in his gastric aspirate and stool samples for three consecutive days. PPD test was negative and no AFB were detected in the microscopic examination of the clinical samples. However, growth in Lowenstein-Jensen medium was detected in the stool sample on the 38th day of incubation. The antimycobacterial susceptibility testing performed at BACTEC MGIT (Mycobacterial Growth Indicator Tube) 960 system (Becton-Dickinson, USA) revealed that the isolate was susceptible to rifampin, isoniazid, streptomicin and ethambutol. Since the isolates did not grow at PNB (para-nitro benzoic acid) medium and niacin and nitrate activities were negative, spoligotyping (spacer oligonucleotide typing) was performed and DR loci characteristic for M. bovis BCG strain were detected. However, the patient died 2 weeks before the culture results were obtained. The effective use of mycobacteriology laboratories and cooperation between laboratory and clinics provide advantages in the early diagnosis and treatment of tuberculosis cases, decreasing the morbidity and the mortality.


Assuntos
Técnicas de Tipagem Bacteriana/métodos , Mycobacterium bovis/patogenicidade , Tuberculose/microbiologia , Tosse , Diarreia , Evolução Fatal , Fezes/microbiologia , Febre , Humanos , Lactente , Masculino , Mycobacterium bovis/classificação , Mycobacterium bovis/genética , Mycobacterium bovis/isolamento & purificação , Tuberculose/diagnóstico
16.
New Microbiol ; 32(3): 255-63, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19845107

RESUMO

The aim of this study was to determine the Beijing/W family and major phylogenetic clades of Mycobacterium tuberculosis strains of tuberculosis patients in a city with a tuberculosis incidence higher than the country average. A total of 220 M. tuberculosis strains isolated over a period of more than four years were typed by spoligotyping. Spoligotyping resulted in 64 different patterns, 38 (17.3%) of which were unique, and 26 were clusters including 182 (82.7%) strains. The major shared types were ST 53 (n = 55, 25%), ST 41 (LAM7-TUR; n = 19, 8.6%), and ST 284 (n = 15, 6.8%). The major clades observed ranked in the following order: ill-defined T superfamily (n = 112, 50.9%); Latino-American-Mediterranean (LAM; n = 33, 15%); Haarlem (n = 24, 10.9%); and the S family (n = 9, 4.1%). Three strains were in the Beijing family. A high number of strains (33 strains) showed patterns that did not fall within any of the major clades described. M. tuberculosis strains in Malatya have both STs showing a widespread distribution over the world and those restricted to this city, confirming the highly diverse nature of tuberculosis. Our results suggest that the Beijing clade, which is more prevalent among the strains with MDR and isoniazid resistance, is currently not a problem in Eastern Turkey.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Tuberculose Pulmonar/microbiologia , Turquia/epidemiologia
17.
Infect Genet Evol ; 7(4): 513-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17462962

RESUMO

To highlight the transmission rate and major phylogenetic clades of drug-resistant Mycobacterium tuberculosis isolates, a total of 200 drug-resistant strains isolated in four different regions of Turkey (Marmara n=81; Mediterranean n=39; Aegean n=42; East Anatolia n=38), were typed by spoligotyping and IS6110-restriction fragment length polymorphism (RFLP). The major spoligotyping-defined shared-types (STs) and corresponding lineages were, ST 41 (22.5%, LAM7-TUR), ST53 (19.5%, ill-defined T super-family), ST 50 (6.5%, Haarlem 3), ST 1261 (4.5%, LAM7-TUR), ST 47 (3.5%, Haarlem 1), as well as two STs that belonged to undefined clades (ST 284, 3%, and ST 2067, 2.5%). The global distribution of major M. tuberculosis lineages among drug-resistant strains was as follows: T super-family (29%), Latin-American & Mediterranean (33.5%), Haarlem (14%), and the S lineage (3%). A high number of strains (n=29, 14.5%) showed patterns that did not fall within major clades described so far. A combination of spoligotyping and IS6110-RFLP fingerprinting methods resulted in a final clustering rate of 38.5% and a recent transmission rate of 25.5%. Our results underline the highly diverse nature of drug-resistant tuberculosis in our study population, as well as its ongoing transmission with lineages that are specific to these regions, the most predominant being the LAM7-TUR lineage which shows an enhanced phylogeographical specificity for Turkey.


Assuntos
Técnicas de Tipagem Bacteriana , Variação Genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Idoso , Análise por Conglomerados , Bases de Dados Genéticas , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Polimorfismo de Fragmento de Restrição , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Turquia
18.
Hepatol Res ; 34(2): 111-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16413999

RESUMO

BACKGROUND AND AIM: The aim of this study was to estimate the serum levels of endothelin-1 (ET-1) and nitric oxide (NO) and to analyze the correlation of their levels with histopathological grading and staging of the liver in patients with chronic hepatitis B (CHB) and C (CHC). METHODS: Eighty-nine patients who were either HBsAg positive (45 CHB patients, 34 inactive carriers (IC)) or had CHC (10 patients) and 36 healthy volunteers as a control group were included in this study. Fifty patients from the CHB (n=43) or CHC (n=7) groups with elevated serum alanine transaminase (ALT) levels underwent a liver biopsy. Histological activity was scored according to Ishak's activity and the fibrotic index. The ET-1 serum concentration was determined with a commercially available ELISA assay kit. Total nitrite was measured by the Griess reaction as an index for NO production. RESULTS: Serum levels of ET-1 and NO were significantly increased in CHB patients (7.67+/-4.00pg/ml and 172.44+/-50.30mumol/l, respectively) compared with the IC group (3.99+/-5.42pg/ml and 114.68+/-32.22mumol/l, respectively) and the control group (3.05+/-0.65pg/ml and 58.61+/-24.18mumol/l, respectively) (p<0.0001). The CHC patients also had significantly higher serum levels of ET-1 (5.92+/-4.24pg/ml) and NO (147.50+/-55.84mumol/l) compared to the control group (p<0.0001 and <0.001, respectively). Linear regression analysis identified that the level of ET-1 was an independent variable that correlated significantly with the stage score (r(2)=0.348, p<0.0001) in CHB patients but there was no correlation in the CHC group. CONCLUSION: ET-1 and NO levels were increased in chronic hepatitis and there was a significant correlation between the ET-1 level and the stage in CHB patients.

19.
BMC Microbiol ; 5: 44, 2005 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-16045794

RESUMO

BACKGROUND: Population-based bacterial genetics using repeated DNA loci is an efficient approach to study the biodiversity and phylogeographical structure of human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis. Indeed large genetic diversity databases are available for this pathogen and are regularly updated. No population-based polymorphism data were yet available for M. tuberculosis in Turkey, at the crossroads of Eurasia. RESULTS: A total of 245 DNAs from Mycobacterium tuberculosis clinical isolates from tuberculosis patients residing in Turkey (Malatya n = 147 or Ankara n = 98) were genotyped by spoligotyping, a high-throughput genotyping method based on the polymorphism of the Direct Repeat locus. Thirty-three spoligotyping-defined clusters including 206 patients and 39 unique patterns were found. The ST41 cluster, as designated according to the international SpolDB3 database project, represented one fourth and when gathered to three genotypes, ST53, ST50 and ST284, one half of all the isolates. Out of 34 clinical isolates harboring ST41 which were further genotyped by IS6110 and by MIRU-VNTR typing, a typical 2-copy IS6110-RFLP pattern and a "215125113322" MIRU-VNTR pattern were observed among 21 clinical isolates. Further search in various databases confirms the likely Turkish-phylogeographical specificity of this clonal complex. CONCLUSION: We described a new phylogeographically-specific clone of M. tuberculosis, designated LAM7-TUR. Further investigations to assess its frequency within all regions of Turkey and its phylogeographical origin and phylogenetic position within the global M. tuberculosis phylogenetic tree will shed new light on its endemicity in Asia Minor.


Assuntos
Mycobacterium tuberculosis/genética , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Bases de Dados de Ácidos Nucleicos , Genótipo , Geografia , Humanos , Oriente Médio , Repetições Minissatélites , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Polimorfismo de Fragmento de Restrição , Tuberculose/microbiologia , Turquia
20.
Diagn Microbiol Infect Dis ; 53(3): 201-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16243477

RESUMO

Prompt detection of drug resistance of Mycobacterium tuberculosis is essential for effective control of tuberculosis (TB). We developed a multiplex allele-specific polymerase chain reaction (MAS-PCR) that detects the most commonly observed isoniazid (INH), rifampin (RIF), and ethambutol resistance-associated mutations in a single assay. The usefulness of the newly developed method was evaluated with 174 clinical isolates of M. tuberculosis obtained from Turkey. Distinct PCR banding patterns were observed for different mutation profiles and the correlation between MAS-PCR results and DNA sequencing findings was 99.4%. With culture-based phenotypic drug susceptibility testing as a reference standard, the sensitivity and specificity of the newly developed MAS-PCR assay for drug resistance-related genetic mutation detection were determined to be 81.1% and 97.5% for INH, 93.0% and 98.9 % for RIF, and 54.5% and 68.0 % for ethambutol. MAS-PCR provides a rapid, potentially more cost-effective, method of detecting multidrug-resistant TB.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Etambutol/farmacologia , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Reação em Cadeia da Polimerase/métodos , Rifampina/farmacologia , Alelos , Meios de Cultura , DNA Bacteriano/análise , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/genética , Sensibilidade e Especificidade , Análise de Sequência de DNA
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