Ganoderic acid A protects lens epithelial cells from UVB irradiation and delays lens opacity / 中国天然药物

A contributory role of oxidative stress and protection by antioxidant nutrients have been suspected in cataract formation. Ganoderic acid A (GAA), an effective lanostane triterpene, is widely reported as an antioxidant. The aim of this study is to investigate the potential effects of GAA on cataract formation. After lens epithelial cells (LECs) were exposed to UVB radiation for different periods, cell viability, apoptosis-related protein levels, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were monitored. We found that cell viability, the Bcl-2/Bax ratio and SOD activity were increased, while Cleaved caspase-3 levels and MDA activity were decreased compared with those in UVB-impaired LECs after GAA treated. Furthermore, GAA activated PI3K/AKT in UVB-impaired LECs and effectively delayed the occurrence of lens opacity in vitro. In conclusion, these findings demonstrated that GAA exhibited protective functions in SRA01/04 cells and rat lenses against UVB-evoked impairment through elevating cell viability and antioxidant activity, inhibiting cell apoptosis, activating the PI3K/AKT pathway and delaying lens opacity.

Evaluation of Nosocomial Infection Control Programs in health services / Avaliação dos Programas de Controle de Infecção Hospitalar em serviços de saúde / Evaluación de los Programas de Control de Infección Hospitalaria en servicios de salud

OBJECTIVES: to evaluate the Nosocomial Infection Control Programs in hospital institutions regarding structure and process indicators. METHOD: this is a descriptive, exploratory and quantitative study conducted in 2013. The study population comprised 13 Nosocomial Infection Control Programs of health services in a Brazilian city of the state of São Paulo. Public domain instruments available in the Manual of Evaluation Indicators of Nosocomial Infection Control Practices were used. RESULTS: The indicators with the highest average compliance were "Evaluation of the Structure of the Nosocomial Infection Control Programs" (75%) and "Evaluation of the Epidemiological Surveillance System of Nosocomial Infection" (82%) and those with the lowest mean compliance scores were "Evaluation of Operational Guidelines" (58.97%) and "Evaluation of Activities of Control and Prevention of Nosocomial Infection" (60.29%). CONCLUSION: The use of indicators identified that, despite having produced knowledge about prevention and control of nosocomial infections, there is still a large gap between the practice and the recommendations. .

OBJETIVOS: avaliar os Programas de Controle de Infecção Hospitalar nas instituições hospitalares, quanto aos indicadores de estrutura e processo. MÉTODO: trata-se de um estudo descritivo, exploratório e quantitativo, realizado em 2013. A população foi composta por 13 Programas de Controle de Infecção Hospitalar de serviços de saúde, de uma cidade brasileira do interior paulista. Foram utilizados instrumentos de domínio público, disponibilizados no Manual de Indicadores de Avaliação de Práticas de Controle de Infecção Hospitalar. RESULTADOS: os indicadores com maior média de conformidade foram "Avaliação da Estrutura dos Programas de Controle de Infecção Hospitalar" (75%) e "Avaliação do Sistema de Vigilância Epidemiológica de Infecção Hospitalar" (82%) e os com menores médias foram "Avaliação das Diretrizes Operacionais" (58,97%) e "Avaliação das Atividades de Controle e Prevenção de Infecção Hospitalar" (60,29%). CONCLUSÃO: o uso de indicadores identificou que, apesar do conhecimento produzido sobre ações de prevenção e controle de infecções hospitalares, ainda existe um grande hiato entre prática e recomendações. .

OBJETIVOS: evaluar los Programas de Control de Infección Hospitalaria en las instituciones hospitalarias respecto a los indicadores de estructura y proceso. MÉTODO: se trata de un estudio descriptivo, exploratorio y cuantitativo, desarrollado en 2013. La población fue compuesta por 13 Programas de Control de Infección Hospitalaria de servicios de salud de una ciudad brasileña del interior paulista. Fueron utilizados instrumentos de dominio público, disponibles en el Manual de Indicadores de Evaluación de Prácticas de Control de Infección Hospitalaria. RESULTADOS: los indicadores con mayor promedio de conformidad fueron "Evaluación de la Estructura de los Programas de Control de Infección Hospitalaria" (75%) y "Evaluación del Sistema de Vigilancia Epidemiológica de Infección Hospitalaria" (82%) y aquellos con menores promedios "Evaluación de las Directivas Operacionales" (58,97%) y "Evaluación de las Actividades de Control y Prevención de Infección Hospitalaria" (60,29%). CONCLUSIÓN: el uso de indicadores posibilitó identificar que, a pesar del conocimiento producido sobre acciones de prevención y control de infecciones hospitalarias, todavía existe un gran hiato entre la práctica y las recomendaciones. .

Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort / Papel do Dimorfismo Sexual na Eficácia e Segurança da Terapia com Sinvastatina ou Atorvastatina em uma Coorte no Sul do Brasil

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations. .

Fundamento: A dislipidemia é o principal fator de risco para doenças cardiovasculares e as estatinas são efetivas no controle do perfil lipídico. Diferenças sexuais na farmacocinética e farmacodinâmica contribuem para a variação interindividual na eficácia e toxicidade de fármacos. Objetivo: Avaliar a existência de dimorfismo sexual na eficácia e segurança do tratamento com sinvastatina/atorvastatina. Métodos: 495 sujeitos (331 mulheres e 164 homens) tiveram seus níveis lipídicos mensurados antes e após 6±3 meses de tratamento com sinvastatina/atorvastatina para avaliação dos perfis de eficácia e segurança. Resultados: As mulheres apresentaram maiores níveis basais de colesterol total, LDL-C e HDL-C quando comparadas aos homens (p < 0,0001). Após o tratamento, mulheres tiveram uma maior redução dos níveis de colesterol total e de LDL-C que homens. Após ajuste para covariáveis, foi observado que os níveis basais de colesterol total e de LDL-C são responsáveis por cerca de 30% da eficácia (p < 0,001), independentemente do sexo. Mialgia (com ou sem alteração de creatina fosfoquinase - CPK) ocorreu mais frequentemente em mulheres (25,9%) (p = 0,002), enquanto o aumento isolado de CPK e alterações de função hepática foram mais frequentemente observados em homens (17,9%) (p = 0,017). Conclusões: Nossos resultados demonstram que os níveis basais de colesterol total e LDL-C são os maiores preditores da eficácia do tratamento, independente do sexo. Adicionalmente, sugerimos que existe dimorfismo sexual na segurança do tratamento com sinvastatina/atorvastatina. O efeito das diferenças sexuais em receptores, proteínas transportadoras e rotas de expressão gênica devem ser avaliados ...

Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia / La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.

Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg) y carboximetilcelulosa (placebo) administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata , disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.

Effect of Vanillin on lipid profile in a model of hyperlipidemia, a preliminary study.

To evaluate the effect of vanillin on the lipid profile of high fat diet induced hyperlipidemia in rats, the hyperlipidemia was induced by feeding cholesterol-rich high fat diet for 45 days in wistar rats of either sex. The reduction in the triglycerides and VLDL-C was significant at 200 & 400 mg/kg dose of vanillin compared to atorvastatin group. Reduction in total cholesterol was significant at 200 and 400 mg/kg doses compared to hyperlipidemic control. The results demonstrate that vanillin at a dose of 200 and 400 mg/kg body weight lowers the serum triglyceride, VLDL-C and total cholesterol level significantly in high fat diet induced hyperlipidemic rats. However there was no significant effect on the lipid profile at 100 mg/kg dose. There were no statistically significant changes in the HDL-C and LDL-C levels at any of the given doses.

Efeitos da atorvastatina e do polimorfismo T-786C do gene eNOS sobre parâmetros do metabolismo lipídico plasmático / Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters

FUNDAMENTO: A atividade do óxido nítrico sintase endotelial (eNOS) pode ser modulada pelo colesterol da lipoproteína de alta densidade (HDL-C), estatinas ou polimorfismos, como o T-786C de eNOS. OBJETIVO: Este estudo teve como objetivo avaliar se o polimorfismo T-786C está associado a alterações nos efeitos da atorvastatina no perfil lipídico, nas concentrações de metabólitos de óxido nítrico (NO) e da proteína C reativa de alta sensibilidade (PCR-as). MÉTODOS: Trinta voluntários do sexo masculino, assintomáticos, com idade entre 18-56 anos foram genotipados e classificados de acordo com a ausência (TT, n = 15) ou presença (CC, n = 15) do polimorfismo. Eles foram selecionados aleatoriamente para a utilização de placebo e atorvastatina (10 mg/dia por 14 dias). Após cada tratamento foram medidos lípides, lipoproteínas, frações HDL2 e HDL3, atividade da proteína de transferência de colesteril éster (CETP), metabólitos de NO e PCR-as. RESULTADOS: As comparações entre genótipos após a administração de placebo mostraram aumento da atividade da CETP polimorfismo-dependente (TT, 12 ± 7; CC, 22 ± 12, p < 0,05). As análises da interação entre os tratamentos indicaram que a atorvastatina tem efeito sobre colesterol, LDL, nitrito e razões lípides/proteínas (HDL2 e HDL3) (p < 0,001) em ambos os genótipos. É interessante notar as interações genótipo/droga sobre a CETP (p < 0,07) e a lipoproteína (a) [Lp(a)] (p < 0,056), levando a uma diminuição limítrofe da CETP, embora sem afetar a Lp(a). A PRC-as não mostrou alterações. CONCLUSÃO: Os resultados sugerem que o tratamento com estatinas pode ser relevante para a prevenção primária da aterosclerose em pacientes com o polimorfismo T-786C do eNOS, considerando os efeitos no metabolismo lipídico.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. OBJECTIVE: This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). METHODS: Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. RESULTS: The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. CONCLUSION: These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.

Effect of atorvastatin, with or without ezetimibe, on serum lipid profile and ALT in hyperlipidemic patients

Hyperlipidaemia is raised serum levels of one or more of total cholesterol, low-density lipoprotein and triglycerides. Many drugs have been used for the treatment of this disorder. This work compares the effects of atorvastatin with or without ezetimibe on lipid profile, atherogenic index and serum alanine aminotransferase. This study covers 90 subjects, 60 untreated hyperlipidemic patients, and 30 healthy subjects. Patients were divided into 2 groups, the first group included 30 patients treated with atorvastatin 20 mg/day alone, the second group included 30 patients treated with a combination of 2 drugs [atorvastatin 10 mg plus ezetimibe 10 mg] taken daily at night. Serum lipid profile, atherogenic index and serum alanine amniotransferase were measured after 12 hours fasting for the patients in 3 intervals: before, and after 8 weeks and 16 weeks of treatment. After therapy for both groups of patients, as compared to the levels before treatment, has shown that serum total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol were significantly reduced while high density lipoprotein cholesterol was significantly increased. Serum alanine aminotransferase increased by both groups of treatment with no significant difference between the two modes of treatment which has the same findings in comparison to the control group. Combination of atorvastatin 10 mg and ezetimibe 10 mg daily, is more effective than atorvastatin 20 mg taken alone

Ausência de interação clopidogrel-estatina em pacientes submetidos a implante de "stent" coronário / Lack of clopidogrel-statin interaction in patients undergoing coronary stent implantation / Ausencia de interacción clopidogrel-estatina en pacientes sometidos a implante de "Stent" coronario

FUNDAMENTO: Alguns estudos têm sugerido redução da atividade do clopidogrel sobre a ativação e adesão plaquetárias em pacientes em uso de estatinas. OBJETIVO: Avaliar se a ativação e agregação plaquetárias diminuem com clopidogrel, e se ocorre redução da ação do clopidogrel quando associado à atorvastatina ou à sinvastatina. MÉTODOS: Estudo prospectivo que incluiu 68 pacientes com angina estável em uso prévio de sinvastatina, atorvastatina, ou nenhuma estatina (grupo controle), com indicação prévia eletiva de realização de intervenção coronária percutânea. Foi analisada a ativação plaquetária através do número de plaquetas, níveis de P-selectina e glucoproteína IIb/IIIa (com e sem estímulo de ADP) através de citometria de fluxo. Os resultados foram analisados antes e após a intervenção coronária percutânea e da administração de clopidogrel. RESULTADOS: Observamos redução da atividade plaquetária com uso de clopidogrel. Além disso, não houve diferenças entre as variáveis analisadas que comprovassem redução da atividade do clopidogrel quando associado à estatinas. Observou-se níveis de p-selectina (pré-angioplastia: 14,23±7,52 x 11,45±8,83 x 7,65±7,09; pós angioplastia: 21,49±23,82 x 4,37±2,71 x 4,82±4,47, ρ<0,01) e glicoproteína IIb/IIIa (pré-angioplastia: 98,97±0,43 x 98,79±1,25 x 99,21±0,40; pós angioplastia: 99,37±0,29 x 98,50±1,47 x 98,92±0,88, ρ=0,52), respectivamente nos grupos controle, atorvastatina e sinvastatina. CONCLUSÃO: Concluímos que a ativação plaquetária diminui com a administração de clopidogrel, e que o clopidogrel não tem seu efeito antiplaquetário reduzido na presença de sinvastatina ou atorvastatina.

BACKGROUND: Some studies have suggested reduced activity of clopidogrel on platelet activation and adherence in patients using statins. OBJECTIVE: To assess whether platelet activation and aggregation decrease with clopidogrel, and whether there is a reduction of the action of clopidogrel when associated with atorvastatin or simvastatin. METHODS: This prospective study included 68 patients with stable angina with previous use of simvastatin, atorvastatin, or no statin (control group), with previous elective indication of percutaneous coronary intervention (PCI). Platelet activation was analyzed by means of platelet count, levels of P-selectin and glycoprotein IIb/IIIa (with and without ADP stimulation) by flow cytometry. The findings were analyzed before and after percutaneous coronary intervention and the administration of clopidogrel. RESULTS: We observed reduction in platelet activity with use of clopidogrel. Furthermore, no differences were found between the variables analyzed to prove reduced activity of clopidogrel when combined with statins. We observed levels of p-selectin (pre-angioplasty: 14.23 ± 7.52 x 8.83 x 11.45 ± 7.65 ± 7.09; after angioplasty: 21.49 ± 23.82 x 4 37 ± 2.71 x 4.82 ± 4.47, ρ < 0.01) and glycoprotein IIb/IIIa (pre-angioplasty: 98.97 ± 0.43 ± 1.25 x 98.79 x 99.21 ± 0.40 after angioplasty: 99.37 ± 0.29 ± 1.47 x 98.50 x 98.92 ± 0.88, ρ = 0.52), respectively, in the control, atorvastatin and simvastatin groups. CONCLUSION: We concluded that platelet activation decreases with administration of clopidogrel, and clopidogrel has no antiplatelet effect reduced in the presence of simvastatin or atorvastatin.

FUNDAMENTO: Algunos estudios han sugerido reducción de la actividad del clopidogrel sobre la activación y adhesión plaquetarias en pacientes en uso de estatinas. OBJETIVO: Evaluar si la activación y agregación plaquetarias disminuyen con clopidogrel, y si ocurre reducción de la acción del clopidogrel cuando está asociado a la atorvastatina o a la sinvastatina. MÉTODOS: Estudio prospectivo que incluyó 68 pacientes con angina estable en uso previo de sinvastatina, atorvastatina, o ninguna estatina (grupo control), con indicación previa electiva de realización de intervención coronaria percutánea. Fue analizada la activación plaquetaria a través del número de plaquetas, niveles de P-selectina y glucoproteína IIb/IIIa (con y sin estímulo de ADP) a través de citometría de flujo. Los resultados fueron analizados antes y después de la intervención coronaria percutánea y de la administración de clopidogrel. RESULTADOS: Observamos reducción de la actividad plaquetaria con uso de clopidogrel. Además de eso, no hubo diferencias entre las variables analizadas que comprobasen reducción de la actividad del clopidogrel cuando está asociado a las estatinas. Se observaron niveles de p-selectina (pre-angioplastia: 14,23±7,52 x 11,45±8,83 x 7,65±7,09; post angioplastia: 21,49±23,82 x 4,37±2,71 x 4,82±4,47, ρ<0,01) y glicoproteína IIb/IIIa (pre-angioplastia: 98,97±0,43 x 98,79±1,25 x 99,21±0,40; post angioplastia: 99,37±0,29 x 98,50±1,47 x 98,92±0,88, ρ=0,52), respectivamente en los grupos control, atorvastatina y sinvastatina. CONCLUSIÓN: Concluimos que la activación plaquetaria disminuye con la administración de clopidogrel, y que el clopidogrel no tiene su efecto antiplaquetario reducido en la presencia de sinvastatina o atorvastatina.

Antihyperlipidaemic activity of a poly herbal drug [Muym], in egg yolk induced hyperlipidaemic rats: a comparison with atorvastatin

The Purpose of this research study was to examine the lipid lowering activity of a traditionally used poly herbal product "Mufarreh Yaqooti Motadil [MUYM], in Egg yolk induced hyperlipidaemic rats. The product is being manufactured by Hamdard Laboratories [waqf] Pakistan for the last thirty years and has shown significant therapeutic effects. During our study the product was found to have protective effects against hyperlipidemia in Human dose. The activity was performed by the help of Biochemical Investigation, using Spectrophotometric method. The results were justified by the presence of scientific data during the retrospective literature search of the Product's Ingredients. A comparative study with the Allopathic Medicine used for Antihyperlipidemic activity was also performed. Significant effect of Herbal Drug on LDL and HDL and Triglyceride levels were observed which was statistically comparable with that of Atorvastatin

El tratamiento con atorvastatina reduce la actividad de xantina-oxidasa unida al endotelio en pacientes con insuficiencia cardíaca crónica: ¿un posible nuevo efecto pleiotrópico? / Treatment with atorvastatin reduces the activity of xanthine oxydase bound to endothelium in patients with chronic heart failure

El aumento en la actividad de la xantina-oxidasa unida al endotelio (XOec) puedeparticipar como un importante mediador de la disfunción endotelial en la insuficiencia cardíaca crónica (IC). Las estatinas son capaces de reducir el estrés oxidativo y restaurar la disfunción endotelial a través de mecanismos independientes de la reducción del colesterol. Sin embargo, el efecto de estos fármacos en la actividad de XOec es completamente desconocido. Nosotros estudiamos la hipótesis que atorvastatina durante 8 semanas reduce la actividad de XOec de manera independiente de los cambios en el colesterol. Metodología: Un total de 25 pacientes con IC (Fracción de eyección < 40 por ciento y Clase funcional NYHA II-III) recibieron placebo por 4 semanas, seguido por 8 semanas de atorvastatina 20 mg por día. Muestras desangre fueron recolectadas basalmente, 4 semanas y 12 semanas. La actividad de XOec y los niveles de ácido úrico fueron medidos por espectrofotometría.Resultados: El tratamiento con atorvastatina, pero no el placebo, redujo la actividad de ecXO (p<0.01), los niveles de ácido úrico (p<0.05), colesterol total (p<0.01), LDL-colesterol (p<0.01) y triglicéridos (p<0.05) sin cambios en los niveles de HDL-colesterol y creatinina. Además, no se encontraron correlaciones estadísticas entre la fracción de cambio de XOec y las fracciones de cambio de parámetros lipídicos. Conclusión: El efecto beneficioso a corto plazo de la atorvastatina en relación a la mejoría de la función endotelial demostrado en estudios previos, estaría asociado a una disminución en la actividad de XOec de una manera independiente a los cambios en el colesterol, lo que sugiere la presencia de un nuevo efecto pleiotrópico de las estatinas.

An increased activity of endothelium bound xanthine oxydase (XOeb) may play an important role as a mediator of endothelial dysfunction in chronic heart failure (CHF). Statins reduce oxydative stress and improve endothelial dysfunction through mechanisms unrelated to cholesterol lowering. However, the effect of statins on XOeb activity is unknown. We hypothesized that atorvastatin administered for 6 weeks would reduce XOeb independently of changes in serum cholesterol levels. Methods: 25 patients with CHF (NYHA class II or III with ejection fraction <40 percent received placebo for 4 weeks followed by atorvastatin, 20mg per day, for 8 weeks. Blood samples were obtained before statin administration and 4 and 12 weeks later. Spectrophotometry was used to determine XOeb and uric aced levels. Results: Atorvastatin, but not placebo, reduced XOeb activity (p<0.01), and uric acid (p<0.05), total cholesterol (p<0.01), LDL-cholesterol (p<0.01) and triglyceride levels (p<0.05). No changes were observed inHDL and creatinine levels. There was no correlation between XOeb changes and changes in the other lipid parameters. Conclusion: The known improvement in endothelial dysfuncion related to statin use previously reported is associated to a decrease in XOec activity independently of changes in cholesterol levels, suggesting a new pleiotropic effect of statins.

Efectos pleiotrópicos de las estatinas: [revisión] / Pleiotropic effects of statins: [review]

Results of numerous epidemiologic studies indicate that elevated serum cholesterol, especially the LDL fraction, is a major cause of coronary heart disease (CHD). Epidemiologic and angiographic evidence from primary and secondary prevention studies involving several HMG-CoA reducíase inhibitors (statins) indicate that decreasing elevated serum cholesterol concentration (specifically LDL-cholesterol) can reduce the incidence of CHD and/or progression of atherosclerosis and results in a decrease in associated morbidity and mortality. It has been estimated that each 1 percent reduction in LDL-cholesterol concentration may result in a 1 percent decrease in the incidence of CHD. Furthermore, an analysis of pooled data from primary and secondary prevention studies found that treatment with a statin for a median duration of 5.4 years was associated with a 31 percent and 21 percent reduction in the risk of major coronary events and total mortality, respectively. This paper deals with the pharmacology of statins, specially with the pleiotropic effects ofthese drugs.

Effects of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure in rats / 华中科技大学学报（医学）（英德文版）

The effect of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure (SBP) of rats induced by warfarin was studied. Thirty healthy and adult rats were randomly divided into Warfarin group (n=10), Atorvastatin group (n=10) and normal control group (n=10). Caudal arterial pressure of rats was measured once a week, and 4 weeks later, aorta was obtained. Elastic fiber, collagen fiber and calcium accumulation in tunica media of cells were measured by Von Kossa staining. The results showed that warfarin treatment led to elevation of systolic blood pressure and aortic medial calcification. The chronic treatment also increased collagen, but decreased elastin in the aorta. However, the atorvastatin treatment had adverse effects. It was concluded that treatment with atorvastatin presented evidence of blood pressure lowing and calcification reducing. These data demonstrate that atorvastatin protected aortic media from warfarin-induced calcification and elevation of systolic blood pressure.

[Assessment of osteoinduction by statins in rat]

To date, studies about the systemic effects of statins on bone tissue have led to different resuts. The aim of this study was to assess the osteoinductivity by statins when injected intramuscularly or subcutaneously in rats. In this experimental study, 68 injections of Simvastatin, Lovastatin, Atorvastatin in polyethyleneglycole with 1mg/ml and polyethyleneglycole 300 were injected either S.C in rat`s backs or I.M into their hand and foot. After 6 weeks, the rats were killed and samples of the injection areas were provided and were studied under a microscope. In two of the samples, few bony areas were seen which were a mixture of lamellar and woven bone. Around these areas' an osteoblastic rim was visible. In another sample, a chondral area with an active mesanchimal connective tissue which was in a differentiation state to become cartilage, was seen. Finding of this study and the gradual differentiation of muscular tissue to bony stem tissue in around samples, confirms the probable osteoinductivity effect of theses compound. To confirm further we propose that this effect should be investigated on stem cell cultures, in vitro

Hypolipidemic effect of methanolic extract of Dolichos biflorus Linn. in high fat diet fed rats.

High fat diet fed rats showed significant increased levels of plasma and tissue total cholesterol, triglycerides, free fatty acids, phospholipids, plasma LDL cholesterol and decreased level of plasma HDL cholesterol. Methanolic extract of D. biflorus administration to high fat diet fed rats showed near to normal levels of the above lipids in plasma and tissues. Higher dose of the extract (400 mg/kg body weight) showed comparable results with standard drug atorvastatin. It is concluded that the methanolic extract of D. biflorus possesses hypolipidemic activity in high fat diet fed rats.

Efeitos da atorvastatina, fluvastatina, pravastatina e simvastatina sobre a função endotelial, a peroxidação lipídica e a aterosclerose aórtica em coelhos hipercolesterolêmicos / Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits

OBJETIVO: Comparar os efeitos da atorvastatina, fluvastatina, pravastatina e simvastatina sobre a função endotelial, a aterosclerose aórtica e o teor de malonodialdeído (MDA) nas LDL nativas, oxidadas e na parede arterial de coelhos hipercolesterolêmicos, depois que as doses destas estatinas foram ajustadas para reduzir o colesterol total plasmático a valores similares. MÉTODOS: Coelhos machos, foram separados em grupos de 10 animais (n=10), chamados hipercolesterolêmico (controle), atorvastatina, fluvastatina, pravastatina e normal. A exceção do grupo normal, os animais foram alimentados com ração padrão acrescida de colesterol a 0,5 por cento e óleo de coco a 2 por cento durante 45 dias. As drogas foram administradas a partir do 15° dia do início do experimento e no 30° dia, as doses foram ajustadas, através do controle do colesterol plasmático, para obter valores semelhantes em cada grupo. Ao final do experimento foi dosado o colesterol plasmático e as lipoproteinas e retirado um segmento de aorta torácica para estudo da função endotelial, da peroxidação lipídica e exame histológico para medida da aterosclerose aórtica. RESULTADOS: As estatinas reduziram significantemente o colesterol total plasmático, as LDL-colesterol e a aterosclerose aórtica. O teor de MDA também foi significantemente reduzido nas LDL nativas e oxidadas, assim como na parede arterial. O relaxamento-dependente do endotélio foi significantemente maior no grupo tratado em comparação ao hipercolesterolêmico. CONCLUSÃO: As estatinas, em doses ajustadas, tiveram efeito significante e similar em reduzir a peroxidação lipídica nas LDL e na parede arterial, na regressão da aterosclerose aórtica e na reversão da disfunção endotelial.