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Pediatr Cardiol ; 35(7): 1108-15, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24714980


Cardiopulmonary bypass (CPB) reduces coagulation factor levels through hemodilution and consumption. Differences in CPB-induced alterations of factor XIII (FXIII) levels in children with cyanotic and acyanotic congenital heart defects (CHDs) are not well characterized. FXIII activity (determined by Berichrom assay), prothrombin index, activated partial thromboplastin time, and fibrinogen were measured before open heart surgery with CPB and 5 days postoperatively for children older than 3 years with acyanotic (n = 30) and cyanotic (n = 30) CHDs. The preoperative FXIII levels did not differ significantly among the children of the compared groups. The cyanotic patients showed a significantly longer duration of CPB (111.4 ± 45.8 vs 71.5 ± 33.6 min; p = 0.026) and aortic cross-clamp (68.0 ± 27.1 vs 45.4 ± 31.4 min; p = 0.034). The drop in FXIII levels after termination of CPB was more profound for the children with cyanotic CHDs (87.1 ± 13.4 to 49.1 ± 13.2 vs 81.5 ± 12.6 to 58.6 ± 11.1 %, respectively; p = 0.018). The cyanotc patients also were restored to their baseline FXIII levels later than the children with acyanotic CHDs (at 48 vs 24 h). The post-CPB dynamics of the majority of the other coagulation parameters in the compared groups of patients were similar. The cyanotic patients experienced significantly greater postoperative blood loss than the acyanotic patients (12.6 ± 4.9 vs 5.0 ± 2.1 mL/kg; p < 0.001) and were transfused with larger volumes of red blood cells (10.4 ± 6.5 vs 4.2 ± 2.5 mL/kg; p = 0.007). The decrease in FXIII levels after CPB is more profound and lasts longer in children with cyanotic CHDs than in acyanotic patients. The rational strategy of postoperative FXIII replacement therapy for these categories of patients needs to be determined.

Coagulação Sanguínea/fisiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Cianose/sangue , Fator XIII/metabolismo , Cardiopatias Congênitas/cirurgia , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Cianose/etiologia , Cianose/cirurgia , Feminino , Seguimentos , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/complicações , Humanos , Masculino , Período Pós-Operatório , Prognóstico , Estudos Prospectivos
Appl Microbiol Biotechnol ; 89(6): 1929-38, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21069315


4-Hydroxyisoleucine (HIL) found in fenugreek seeds has insulinotropic and anti-obesity effects and is expected to be a novel orally active drug for insulin-independent diabetes. Here, we show that the newly isolated strain Bacillus thuringiensis 2e2 and the closely related strain B. thuringiensis ATCC 35646 operate a novel metabolic pathway for L-isoleucine (L-Ile) via HIL and 2-amino-3-methyl-4-ketopentanoic acid (AMKP). The HIL synthesis was catalyzed stereoselectively by an α-ketoglutaric acid-dependent dioxygenase and to be useful for efficient production of a naturally occurring HIL isomer, (2S,3R,4S)-HIL. The (2S,3R,4S)-HIL was oxidized to (2S,3R)-AMKP by a NAD(+)-dependent dehydrogenase. The metabolic pathway functions as an effective bypass pathway that compensates for the incomplete tricarboxylic acid (TCA) cycle in Bacillus species and also explains how AMKP, a vitamin B(12) antimetabolite with antibiotic activity, is synthesized. These novel findings pave a new way for the commercial production of HIL and also for AMKP.

Bacillus thuringiensis/metabolismo , Vias Biossintéticas/genética , Isoleucina/análogos & derivados , Isoleucina/biossíntese , Bacillus thuringiensis/genética , Coenzimas/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Cetoácidos/metabolismo , NAD/metabolismo , Oxirredução , Oxirredutases/metabolismo , Ácidos Pentanoicos/metabolismo