RESUMO
OBJECTIVE: To observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor on the healing of experimental gastric ulcer in rats and explore its mechanisms in light of gastric acid secretion. METHODS: Gastric ulcers were induced in rats by an application of acetic acid to the serosal surface of the anterior gastric body. The effects of selective COX-2 inhibitor, celecoxib, on the healing of gastric ulcer, the total acidity of gastric juice, the expressions of H+, K+-ATPase mRNA and protein, and the ultrastructure of the parietal cell were observed in comparison with the effects of normal saline. RESULTS: Nine days after ulcer induction, the ulcer area was 11.9-/+3.1 mm square and 19.7-/+3.8 mm square in rats with normal saline and celecoxib treatments, respectively (P<0.01). The total acidity of gastric juice and the expressions of H+, K+-ATPase mRNA and protein in celecoxib group were significantly higher than that in normal saline group at both 6 and 9 days after ulcer induction, but no significant difference was found between the two groups in the amount of secretary canaliculus and microvillus. CONCLUSION: Selective COX-2 inhibitor can significantly delay the healing of experimental gastric ulcer in rats, the mechanism of which might be associated with enhanced digestive action of gastric acid on the new granulation tissue at the ulcer base as a result of celecoxib-stimulated gastric acid secretion of the parietal cells.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ácido Gástrico/metabolismo , Pirazóis/farmacologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Sulfonamidas/farmacologia , Animais , Celecoxib , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , ATPase Trocadora de Hidrogênio-Potássio/genética , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Microvilosidades/efeitos dos fármacos , Microvilosidades/patologia , Células Parietais Gástricas/efeitos dos fármacos , Células Parietais Gástricas/ultraestrutura , Pirazóis/uso terapêutico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/patologia , Sulfonamidas/uso terapêuticoRESUMO
Structural and thermodynamic features of the sheets formed by beta-peptides have been studied by quantum mechanics calculations using peptide models. Calculations using dipeptide models indicate that the intrinsic hydrogen bond strength is great for both parallel and antiparallel sheets and that it is little affected by proper substituents. Heterochiral-beta(2,3)-peptides have much stronger sheet-forming propensity than other types of peptides because their favored backbone conformation is ideal for sheet formation. A planar or ideally pleated strand has a curved geometry, which is unfavorable for the formation of sheets. Thus, sheets have to adopt twisted geometries. There is a large cooperativity in the formation of the hydrogen bond network in the sheets of beta-peptides in the perpendicular direction due to long-range electrostatic attractions because all carbonyl groups are roughly in the same direction, in contrast to the situation in beta-sheets of alpha-peptides.
Assuntos
Peptídeos/química , Dipeptídeos/química , Ligação de Hidrogênio , Modelos Moleculares , Oligopeptídeos/química , Conformação ProteicaRESUMO
OBJECTIVE: To study the effect of exogenous antioxidant vitamins on antioxidant capacity and lipid peroxide status in patients with bone marrow transplantation. METHODS: Nineteen bone marrow transplantation (BMT) recipients were randomly divided into experimental group (n=10), who received Vit C (300 mg/d) and Vit E (600 mg/d) consecutively 15 d before the initiation of pretreatment of BMT, and the control group (n=9), who received the same treatment only without prior vitamin administration. The levels of ferric-reducing ability of plasma (FRAP), plasma malondialdehyde (MDA), the activity of glutathione peroxidase (GSH-Px) in the blood and the red blood cell superoxide dismutase (RBC-SOD) were measured in both groups before and after the operation. RESULTS: The levels of FRAP, GSH-Px and RBC-SOD are approximately within the normal range in the experimental group, but below the normal levels in the control group, showing significant differences between the two groups before and after BMT. After BMT, MDA levels in the experimental group soon dropped to normal range, but which in the control group, in contrast,always retained its high levels in the control group in spite of the operation. CONCLUSION: Exogenous supplementation of antioxidant vitamins before BMT may improve the antioxidant capacity and reduce lipid peroxidation in patients with BMT, effectively alleviating their peroxide stress induced by high-dose chemo/radiotherapy.