Effect of ophiopogonin D in resisting vascular endothelial cell apoptosis induced by AngⅡthrough up-regulating CYP2J2/EETs / 中国中药杂志

This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH). The cell apoptosis was assayed by flow cytometry. According to the results, different doses of Ang Ⅱ had no significant effect on cell survival; treatment with Ang Ⅱ at 1×10⁻⁶ mol·L⁻¹ could increase the release of LDH (<0.001). The phosphorylation of JNK and c-Jun could be inhibited by the pre-treatment with SP600125, 11,12-EET and OP-D. Pre-treatment with OP-D could significantly reduce the release of LDH induced by Ang Ⅱ stimulation, decrease the expression of caspase-3, and diminish the apoptosis of cells. The protective effect of OP-D was suppressed, when being pretreated with PPOH. The experimental results showed that the apoptosis of HUVECs induced by Ang Ⅱ may be associated with JNK/c-Jun signaling pathway. OP-D-mediated CYP2J2 expression increased 11,12-EET levels, and could remarkably resist Ang Ⅱ-induced injury and apoptosis of cells, which is associated with the maintenance of endothelium homeostasis.

The relationship of CYP2C19 gene polymorphism with clopidogrel responsiveness and the level of EETs in patients with acute coronary syndrome / 实用医学杂志

Objective To assess the relationship of CYP2C19 gene polymorphism with clopidogrel respon-siveness and the level of EETs in patients with ACS. Methods A total of 123 patients with ACS receiving aspirin combined with clopidogrel dual antiplatelet were enrolled. According to the results of CYP2C19 genotype,patients were divided into three groups:fast metabolic type ,medium metabolic type ,and slow metabolism type. The concentration of EETs and PAIR were compared between three groups. Logistic analysis was used to analyze the risk factors of LCR. Results There were differences statistically in level of EETs and PAIR among the three groups(P<0.05). Logistic analysis showed that the slow metabolism of CYP2C19 gene and lower EETs level were risk factors for LCR. The area under the ROC curve was 0.893(P < 0.05)by EETs level to predict the CYP2C19 genotype. Conclusion The slow metabolism of CYP2C19 gene was an independent risk factor for LCR,while the increase of plasma EETs level was a protective factor.

Perfil das amostras do sistema nervoso central de bovinos com síndrome neurológica e diagnóstico da raiva bovina no serviço de defesa sanitária de Minas Gerais, 2003-2010 / Profile of central nervous system samples from cattle with neurological syndrome and diagnosis of bovine rabies by the service of sanitary defense of Minas Gerais, 2003-2010

As enfermidades do sistema nervoso central (SNC) são frequentemente relatadas em bovinos no Brasil. Apesar de Minas Gerais ter o segundo maior rebanho bovino do país, há escassez de informações referentes às doenças neurológicas que acometem esses animais. O Laboratório de Saúde Animal do Instituto Mineiro de Agropecuária (LSA/IMA) é o responsável pelo diagnóstico das enfermidades neurológicas dos animais de produção no Estado, com ênfase para a raiva e as encefalopatias espongiformes transmissíveis. Foi realizado um estudo retrospectivo dos dados referentes às amostras de SNC de bovinos com síndrome neurológica avaliadas pelo LSA/IMA de janeiro/2003 a junho/2010, com o objetivo de determinar o perfil das amostras encaminhadas para análise no serviço de defesa sanitária animal, com ênfase no diagnóstico da raiva bovina. Foram consideradas características do animal (sexo, idade, raça e tipo de morte) e da amostra (método de conservação e responsável pela coleta), sendo nas positivas para raiva, avaliada sua composição, assim como as alterações histopatológicas encontradas. Os dados relacionados à frequência de positividade nas diferentes categorias foram submetidos à análise pelo Teste Exato de Fisher. Durante o período avaliado, foram analisadas 3.731 amostras de bovinos com doença neurológica, havendo predomínio de fêmeas e mestiços, o que reflete a composição do rebanho do Estado. O método de conservação foi o principal problema encontrado, sendo apenas 25,89% das amostras encaminhadas em gelo e formol a 10%. Verificou-se uma diminuição gradativa no envio de material para análise. Quanto a raiva bovina diagnosticada no Estado, foram avaliadas 3.703 amostras pela imunofluorescência direta (IFD) e prova biológica (PB), com 41,58% de positividade, sendo dessas 282 submetidas a histopatologia. A frequência de positividade foi influenciada pela raça, idade e tipo de morte do animal. A composição da amostra alterou significativamente o resultado das análises, havendo maior frequência de positividade naquelas compostas por três ou mais fragmentos de SNC, tanto na IFD/PB, quanto na histopatologia. O bulbo, fragmento de eleição para o diagnóstico da EEB, tem sido erroneamente enviado refrigerado e não em formol a 10%. Cerebelo, tálamo, tronco encefálico e medula apresentaram maior frequência de corpúsculos de Negri que cérebro e gânglio trigeminal. O infiltrado inflamatório não supurado foi menos frequente no cérebro, que nos demais fragmentos avaliados. Conclui-se que as amostras de bovinos com síndrome neurológica enviadas ao serviço de defesa sanitária animal de Minas Gerais apresentam características distintas, sendo o método de conservação o principal problema encontrado. Além disso, a raiva bovina diagnosticada na população estudada é influenciada pelas características do animal e da amostra, sendo indicado o envio de diferentes fragmentos do SNC para análise, conservados adequadamente, o que contribui para um diagnóstico mais preciso.(AU)

Diseases of the central nervous system (CNS) are often reported in cattle in Brazil. Although the State of Minas Gerais has the second largest cattle herd in the country, there is little information from this state concerning neurological diseases that affect cattle. The Laboratório de Saúde Animal of the Instituto Mineiro de Agropecuária (LSA/IMA) is in charge of the diagnosis of neurological diseases of livestock in the State, with emphasis on rabies and transmissible spongiform encephalopathies. A retrospective study was conducted on data from cattle with neurologic diseases evaluated by the LSA/IMA from January/2003 to June/2010, aiming to determine the profile of CNS samples sent for analysis, with emphasis on the diagnosis of bovine rabies. Issues related to the animal (sex, age, breed and type of death) as well as to the sample (method of conservation, person in charge the collection, and region of the CNS sampled) were evaluated. Data on frequency of rabies positive samples were analyzed by Fisher's exact test. During the period studied, 3,731 samples from cattle with neurological signs were analyzed, with a predominance of females and crossbred cattle. The method of preservation was the main problem encountered with only 25.89% of samples sent both refrigerated and fixed in 10% formaldehyde. There was a gradual decrease in submission of samples during the course of this study. All 3,703 samples were evaluated by direct fluorescent antibody test (DFA) and biological test (BT) for rabies, 41.58% being positivity for rabies, and 282 of those samples being subjected to histopathology examination. The frequency of positivity was influenced by breed, age, and type of death. Composition of the sample significantly influenced the results, with higher frequency of positivity in samples containing three or more CNS fragments by DFA, BT, or histopathology. The medulla, which is the fragment of choice for diagnosis of BSE, has often been mistakenly submitted under refrigeration, but not in 10% formalin. Cerebellum, thalamus, brain stem, and spinal cord had higher frequency of Negri bodies than the cerebral cortex and trigeminal ganglia. The nonsuppurative inflammatory infiltrate was less frequent in the cerebral cortex than in other CNS fragments. In conclusion, CNS samples from cattle with neurological syndrome sent to the animal health protection service of Minas Gerais are heterogeneous, and the preservation method was the major problem hindering and adequate diagnosis. In addition, diagnosis of rabies was influenced by parameters of the animal as well as the CNS sample. Submission of properly preserved fragments from various segments of the CNS contributes to a more accurate diagnosis of rabies in cattle.(AU)

Distribution of CYP2J3 in rats of gene transfection through vena dorsalis penis / 基础医学与临床

Objective To detect CYP2J3 gene expression and contents of 11,12-EET in heart,liver,lung,kidney and aorta thoracalis after CYP2J3 gene transfection.Methods The rat transgenic model was developed by injecting plasmid through vena dorsalis penis.The animals were divided into control group、 pcDNA3.1 transgenic group and pcDNA3.1-CYP2J3 transgenic group.The expression of CYP2J3 mRNA was detected by RT-PCR and content of 11,12-EET was examined by the HPLC at 14 days and 28 days after injection.Results Twenty eight days after injection,both expression of CYP2J3 mRNA and the content of 11,12-EET were significantly increased as compared with that of control and pcDNA3.1 transgenic group(P

Advances in the research on homo sapiens cytochrome P450 2J2 / 中国药理学通报

For many years, researches on Cytochrome P450 had been focused on their roles in exogenous drugs and poisons metabolism. In fact, Cytochrome P450 also showed significant importance in conversion of endogenous materials, such as steroids, cholesterol, hormones, fatty acid and vitamins. Among such Cytochrome P450 enzymes, CYP2J2 mainly metabolizing arachidonic acids into epoxyeicosatrienoic acids, was detected recently in human beings. The association of CYP2J2 with diseases attracts many researchers great interests. This article briefly summarized those researches of homo sapiens CYP2J2 on its distribution, physical significance, coding gene and mutants of gene as well.