Abstract Rock materials are often subjected to cyclic loads during construction. A full understanding of the deformation behavior of rock under cyclic loads is of great significance in engineering. In this study, by using the endochronic constitutive model proposed by Valanis, the reinforcement function form and constitutive parameters of the endochronic model are improved. An endochronic plasticity constitutive program for rock based on the finite element method is used to study the mechanical properties of rock under different cyclic loading conditions (of maximum loading stress, amplitude, and confining pressure), and through the use of red sandstone, marble, and basalt, experimental and simulation results are compared to verify the model. The results show that the theory can better simulate the hysteresis loop width and cumulative plastic strain of rock under cyclic loading and, under different loading conditions, the numerical simulation results are consistent with the actual rock experimental law. Therefore, the endochronic plasticity constitutive model in this study can be applied to investigate the influence of cyclic loading on the dynamic deformation behavior of rock.

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

INTRODUÇÃO: Atorvastatina 80 mg é recomendada a pacientes portadores de doença coronária para redução de eventos cardiovasculares, havendo controvérsia sobre as interações farmacocinéticas entre doses elevadas das estatinas e uso concomitante de clopidogrel, por compartilharem a mesma via de biotransformação. Este estudo avaliou os efeitos da terapia combinada atorvastatina/clopidogrel na farmacocinética da estatina e função plaquetária em pacientes com doença coronária estável, sob uso crônico e efetivo de estatina MÉTODO: Os pacientes foram admitidos quatro vezes para internação (V1 a V4) em leito-dia. Sete dias (D) antes da primeira internação a estatina em uso foi suspensa. A seguir, receberam atorvastatina 80 mg (D1 a D22) e clopidogrel 75 mg/dia (D8 a D29). Em todas as V foram obtidas amostras de sangue em jejum para dosagens lipídicas, avaliação da função plaquetária (técnica da placa e cone) e quantificação dos níveis plasmáticos de atorvastatina (cromatografia líquida e espectrometria de massa) RESULTADOS: A suspensão por uma semana da estatina modificou o perfil lipídico (P < 0,05 vs. basal), ocorrendo rápida melhora de todas as frações lipídicas após atorvastatina 80 mg (P < 0,005; V1 > V2, V3 e V4). A adesão plaquetária foi menor com clopidogrel isolado (P = 0,003; V4 < V1, V2 e V3), enquanto para a agregação houve menor valor com tratamento combinado atorvastatina/clopidogrel ou clopidogrel isolado comparado aos demais períodos (P < 0,0001; V3 e V4 < V1 e V2). O clopidogrel não modificou as concentrações de atorvastatina CONCLUSÃO: Atorvastatina em alta dose não afetou as respostas plaquetárias ao clopidogrel; entretanto, curto período de suspensão da estatina piorou o perfil lipídico e a função plaquetária.

BACKGROUND: Atorvastatin 80 mg is recommended in patients with coronary artery disease to reduce cardiovascular events, however, there is controversy regarding the pharmacokinetic interactions between high doses of statins and the concomitant use of clopidogrel, since they share the same biotransformation pathway. This study evaluated the effects of the atorvastatin/clopidogrel combination therapy on the pharmacokinetics of statins and on platelet function of patients with stable coronary artery disease receiving chronic statins METHOD: Patients were admitted four times (V1 to V4) to a day-clinic. Statin was discontinued seven days (D) before the first admission. Patients then received atorvastatin 80 mg (D1 to D22) and clopidogrel 75 mg/day (D8 to D29). Fasting blood samples were obtained at all time points for lipid measurements, platelet function tests (cone and plate technique), and quantification of atorvastatin plasma levels (liquid chromatography and mass spectrometry) RESULTS: The discontinuation of statins for one week changed the lipid profile (P < 0.05 vs. baseline), with an early improvement of all lipid parameters after the administration of atorvastatin 80 mg (P < 0.005; V1 > V2, V3 and V4). Platelet adhesion was lower with clopidogrel alone (P = 0.003; V4 < V1, V2 and V3), whereas platelet aggregation values were lower following the atorvastatin/clopidogrel combination therapy or clopidogrel alone when compared to the other time points (P < 0.0001; V3 and V4 < V1 and V2). The use of clopidogrel did not affect atorvastatin serum levels CONCLUSION: High-dose atorvastatin did not affect platelet responses to clopidogrel, however the short-term statin discontinuation worsened the lipid profile and platelet function.

Reações de biocatálise foram realizadas em microplacas (200 µL) visando a utilização de substratos fluorogênicos (100 µmol L-1) para prospecção rápida de epóxido hidrolases (EHs) e Baeyer-Villiger monoxigenases (BVMOs) em microrganismos (células inteiras). Um protocolo final foi alcançado para EHs, com a detecção de 3 novas fontes enzimáticas (Agrobacterium tumefaciens, Pichia stipitis, Trichosporom cutaneum). O ensaio fluorogênico para BVMO não ocorreu como esperado. A abordagem de algumas variáveis envolvidas (aeração; pH) proporcionou a detecção inédita da atividade enzimática de BVM em T. cutaneum.

Biocatalysis reactions were performed on microtiter plates (200 µL) aiming at the utilization of fluorogenic substrates (100 µmol L-1) for rapid whole cell screening for epoxide hydrolases (EHs) and Baeyer-Villiger monoxygenases (BVMOs). A final protocol was achieved for EHs, with 3 new enzymatic sources being detected (Agrobacterium tumefaciens, Pichia stipitis, Trichosporom cutaneum). The fluorogenic assay for BVMO did not work as expected. However, an approach to possible variables involved (aeration; pH) provided the first detection of a BVMO activity in T. cutaneum.

OBJETIVOS: Avaliar o 1,5-anidroglucitol (AG) plasmático em pacientes com (DM) e sem (não-DM) diabetes numa população chinesa, e compará-lo à frutosamina, hemoglobina glicada (HbA1c) e glicemia de jejum (GJ). MÉTODOS: Estudo caso-controle sobre a significância do AG conduzido em centro médico no sul de Taiwan com 356 pacientes selecionados (300 não-DM e 56 DM2). Os níveis de AG, frutosamina, HbA1c e GJ foram avaliados no 2º. dia de admissão, e apenas aqueles com resultados normais (exceto GJ) foram incluídos. Esses marcadores foram examinados apenas uma vez nos não-DM, enquanto os DM foram amostrados sequencialmente por 3 meses. RESULTADOS: As concentrações de AG foram mais baixas nos DM do que nos não-DM (4,02±2,96 vs 26,68±11,33µg/ml, P<0,001), e mais baixas nas mulheres do que nos homens não-DM (22,90±9,51 vs 29,45±11,7µg/ml, P<0,05). Houve boa correlação entre AG e GJ. AG plasmático apresentou correlação inversa com a GJ, frutosamina e HbA1c nos pacientes com DM, e mostrou-se tão eficaz quanto outros marcadores na detecção de mudança de curto prazo no controle glicêmico. Os níveis de AG nos pacientes DM não foram diferentes quanto ao tabagismo, hipertensão e complicações micro e macrovasculares. CONCLUSÕES: O emprego clínico do AG plasmático é recomendado em pacientes com DM de longa duração para detecção e monitoração da condição glicêmica a curto prazo.

PURPOSES: To estimate plasma 1,5-anhydroglucitol (AG) in diabetic (DM) and non-DM patients in a Chinese population, and to compare it with fructosamine, glycosylated hemoglobin (HbA1c), and fasting glucose (FG) levels. METHODS: Case-control study on the significance of AG conducted in a medical center of southern Taiwan, including 356 inpatients (300 non-DM and 56 type 2 DM). Plasma AG, fructosamine, HbA1c and FG were measured on the second day of admission and only those with normal values (except glucose) were enrolled. Glycemic markers of the non-DM patients were examined only once whereas DM patients were sequentially sampled over 3 months. RESULTS: Mean plasma AG levels were lower in DM than in non-DM patients (4.02±2.96 vs 26.68±11.33µg/ml, P<0.001), and lower in non-DM females than males (22.90±9.51 vs 29.45±11.7µg/ml, P<0.05). AG showed a good correlation with FG. Mean plasma AG were inversely correlated with FG, fructosamine and HbA1c in DM patients and worked as well as other glycemic markers in detecting short-term changes in glycemic control. AG levels of DM patients demonstrated no difference with or without smoking, hypertension, micro- and macro-vascular complications. CONCLUSIONS: We recommend clinical application of plasma AG in long-standing DM patients for short-term detection and monitoring glycemic condition.