RESUMO
The authors describe a case of severe glaucoma in the only seeing eye of a patient with venous circulation disturbance resulting from a chronic anal fissure complicated with progressive anal stenosis, severe sphincter spasm, and pain syndrome. The article presents the results of multiple clinical ophthalmological tests and instrumental examinations performed before and after surgical intervention that evidence the importance of venous circulation disturbances for glaucoma development.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Fissura Anal/complicações , Glaucoma de Ângulo Aberto , Hipertensão Intra-Abdominal/complicações , Adulto , Doença Crônica , Constipação Intestinal/etiologia , Constipação Intestinal/fisiopatologia , Feminino , Fissura Anal/diagnóstico , Fissura Anal/fisiopatologia , Fissura Anal/cirurgia , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/etiologia , Glaucoma de Ângulo Aberto/terapia , Humanos , Período Pós-Operatório , Resultado do TratamentoRESUMO
Comparison of amino acid sequences of NAD+-dependent formate dehydrogenases (FDH, EC 1.2.1.2) from different sources and analysis of structures of holo-forms of FDH from bacterium Pseudomonas sp. 101 (PseFDH) and soya Glycine max (SoyFDH) as well as of structure of apo-form of FDH from yeast Candida boidinii (CboFDH) revealed the presence on the surface of protein globule of hydrophobic Phe residue in structurally equivalent position (SEP). The residue is placed in the coenzyme-binding domain and protects bound NAD+ from solvent. The effects of amino acid changes of the SEP on catalytic properties and thermal stability of PseFDH, SoyFDH, and CboFDH were compared. The strongest effect was observed for SoyFDH. All eight amino acid replacements resulted in increase in thermal stability, and in seven cases, increase in catalytic constant was achieved. Thermal stability of SoyFDH after mutations Phe290Asp and Phe290Glu increased 66- and 55-fold, respectively. KM values of the enzyme for substrate and coenzyme in different cases slightly increased or decreased. In case of one CboFDH, the mutein catalytic constant increased and thermal stability did not changed. In case of the second CboFDH mutant, results were the opposite. In one PseFDH mutant, amino acid change did not influence the catalytic constant, but in three others, the parameter was reduced. Two PseFDH mutants had higher and two mutants lower thermal stability in comparison with initial enzyme. Analysis of results of SEP mutagenesis in FDHs from bacterium, yeast, and plant shows that protein structure plays a key role for effect of the same amino acid changes in equivalent position in protein globule of formate dehydrogenases from different sources.
Assuntos
Biocatálise , Formiato Desidrogenases/metabolismo , Fenilalanina , Sequência de Aminoácidos , Bactérias/enzimologia , Estabilidade Enzimática , Eucariotos/enzimologia , Formiato Desidrogenases/genética , Temperatura Alta , Cinética , Modelos Moleculares , Mutação , NAD/metabolismo , Estrutura Terciária de ProteínaRESUMO
RATIONALE: Targeted temperature management (TTM) improves survival with good neurological outcome after out-of-hospital cardiac arrest (OHCA), but is delivered inconsistently and often with delay. OBJECTIVE: To determine if prehospital cooling by paramedics leads to higher rates of 'successful TTM', defined as achieving a target temperature of 32-34°C within 6h of hospital arrival. METHODS: Pragmatic RCT comparing prehospital cooling (surface ice packs, cold saline infusion, wristband reminders) initiated 5min after return of spontaneous circulation (ROSC) versus usual resuscitation and transport. The primary outcome was rate of 'successful TTM'; secondary outcomes were rates of applying TTM in hospital, survival with good neurological outcome, pulmonary edema in emergency department, and re-arrest during transport. RESULTS: 585 patients were randomized to receive prehospital cooling (n=279) or control (n=306). Prehospital cooling did not increase rates of 'successful TTM' (30% vs 25%; RR, 1.17; 95% confidence interval [CI] 0.91-1.52; p=0.22), but increased rates of applying TTM in hospital (68% vs 56%; RR, 1.21; 95%CI 1.07-1.37; p=0.003). Survival with good neurological outcome (29% vs 26%; RR, 1.13, 95%CI 0.87-1.47; p=0.37) was similar. Prehospital cooling was not associated with re-arrest during transport (7.5% vs 8.2%; RR, 0.94; 95%CI 0.54-1.63; p=0.83) but was associated with decreased incidence of pulmonary edema in emergency department (12% vs 18%; RR, 0.66; 95%CI 0.44-0.99; p=0.04). CONCLUSIONS: Prehospital cooling initiated 5min after ROSC did not increase rates of achieving a target temperature of 32-34°C within 6h of hospital arrival but was safe and increased application of TTM in hospital.