RESUMO
AIMS: There are limited data on the role of human monocyte subsets in ST-elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI. METHODS: Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase ß (IKKß, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow-up of 46 months. RESULTS: Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43-8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19-7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKß levels were associated with 10-fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6-month follow-up (P < 0.001). CONCLUSIONS: Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.
Assuntos
Insuficiência Cardíaca , Quinase I-kappa B , Monócitos , NF-kappa B , Infarto do Miocárdio com Supradesnível do Segmento ST , Biomarcadores/análise , Biomarcadores/metabolismo , Contagem de Células/métodos , Correlação de Dados , Feminino , Citometria de Fluxo , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Quinase I-kappa B/análise , Quinase I-kappa B/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/classificação , Monócitos/fisiologia , NF-kappa B/análise , NF-kappa B/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Fagocitose , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Volume SistólicoAssuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , HumanosRESUMO
Coumarin and 6-nitrocoumarin hydrazones (2a,b), respectively, were prepared via the reaction of 2-thiocoumarin (1a,b) derivatives with hydrazine hydrate. The hydrazones were used as key intermediates for the preparation of some benzopyrano[2,3-c]pyrazoles (21-24) through the reaction of different acyl halides and subsequent cyclization in N,N-dimethylaniline. Benzopyrano[2,3-c]pyrazole-3-thione (25a,b) was prepared by the reaction of 1a with CS2 on which some alkylation, acylation and Mannich reactions were studied. Alternative procedures, other reactions and biological activity of some new compounds were given.
Assuntos
Antibacterianos/síntese química , Cumarínicos/síntese química , Animais , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Antifúngicos/síntese química , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Artemia , Bacillus cereus/efeitos dos fármacos , Cumarínicos/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade MicrobianaRESUMO
2-N-Aryl/heterocyclic carboxamidomethylthio-5-p-chlorophenyl-1,3,4-oxadiazoles have been synthesized by the reaction of 1 and N-aryl/heterocyclic-2-chloracetamides in presence of basic medium. 2 and 3 react with heterocyclic thiols in ethanolic potassium hydroxide to give 3-S-substituted-mercaptomethyl-5-substituted-phenyl-1,3,4-oxadiazol-2-thione 5 and 6 respectively. Tert. amines react with 2 to yield the corresponding amino chlorides in good yield. Some of the prepared compounds were tested as antibacterials against Gram-positive and Gram-negative organism.
Assuntos
Antibacterianos/síntese química , Oxidiazóis/síntese química , Bactérias/efeitos dos fármacos , Fenômenos Químicos , Química , Oxidiazóis/farmacologiaRESUMO
The reaction between N-nitrosamides and 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (LR) at low temperature (20-50 degrees C) gives the corresponding thioamides as the main products. In the reaction between N-nitroso-2-pyrrolidone and LR, dihydro-2-(3H)-thiophenone (III) is also isolated. Mechanistic considerations for the formation of III are presented. The nitrosation of thiono compounds gives the corresponding oxo analogues. N-Nitroso-2-pyrrolidone is obtained after nitrosation of 2-pyrrolidinethione. A kinetic investigation of this reaction has been performed using the theory of consecutive reactions with 2-pyrrolidone as an intermediate. The rate constants for these two reactions are found to be k1 = 0.055 s-1 for the formation of 2-pyrrolidone, using a first order plot of the change of 2-pyrrolidinethione; for the formation of N-nitroso-2-pyrrolidone, the rate constant obtained by computer simulation is k2 = 0.032 mol(-1)1 s-1.