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.

Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level / 浙江大学学报·医学版

To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels.One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed.Serum uric acid levels were decreased after treatment in both groups (all<0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level (<0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group (<0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups (>0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels (<0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid (<0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI (=1.01, 95%:1.01-1.11,<0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) (<0.01).High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

Preoperative predictive factors for intensive care unit admission after pulmonary resection / Fatores preditivos pré-operatórios de internação em unidade de terapia intensiva após ressecção pulmonar

Objective: To determine whether the use of a set of preoperative variables can predict the need for postoperative ICU admission. Methods: This was a prospective observational cohort study of 120 patients undergoing elective pulmonary resection between July of 2009 and April of 2012. Prediction of ICU admission was based on the presence of one or more of the following preoperative characteristics: predicted pneumonectomy; severe/very severe COPD; severe restrictive lung disease; FEV1 or DLCO predicted to be < 40% postoperatively; SpO2 on room air at rest < 90%; need for cardiac monitoring as a precautionary measure; or American Society of Anesthesiologists physical status ≥ 3. The gold standard for mandatory admission to the ICU was based on the presence of one or more of the following postoperative characteristics: maintenance of mechanical ventilation or reintubation; acute respiratory failure or need for noninvasive ventilation; hemodynamic instability or shock; intraoperative or immediate postoperative complications (clinical or surgical); or a recommendation by the anesthesiologist or surgeon to continue treatment in the ICU. Results: Among the 120 patients evaluated, 24 (20.0%) were predicted to require ICU admission, and ICU admission was considered mandatory in 16 (66.6%) of those 24. In contrast, among the 96 patients for whom ICU admission was not predicted, it was required in 14 (14.5%). The use of the criteria for predicting ICU admission showed good accuracy (81.6%), sensitivity of 53.3%, specificity of 91%, positive predictive value of 66.6%, and negative predictive value of 85.4%. Conclusions: The use of preoperative criteria for predicting the need for ICU admission after elective pulmonary resection is feasible and can reduce the number of patients staying in the ICU only for monitoring. .

Objetivo: Avaliar se a utilização de um conjunto de variáveis pré-operatórias é capaz de antever a necessidade de internação em UTI no pós-operatório. Métodos: Estudo de coorte observacional prospectivo, com 120 pacientes submetidos à ressecção pulmonar eletiva entre julho de 2009 e abril de 2012. A previsão de indicação de internação em UTI indicação foi baseada na presença de uma ou mais das seguintes condições pré-operatórias: previsão de pneumonectomia; DPOC grave/muito grave; doença restritiva grave; VEF1 ou DLCO previstos para o pós-operatório < 40% do previsto; SpO2 em repouso e ar ambiente < 90%; necessidade de monitorização cardíaca profilática; classificação da American Society of Anesthesiologists ≥ 3. O padrão ouro para internação justificada em UTI foi baseado na presença de uma ou mais das seguintes condições pós-operatórias: manutenção de ventilação mecânica ou reintubação; insuficiência respiratória aguda ou necessidade de ventilação não invasiva; instabilidade hemodinâmica ou choque; intercorrências intraoperatórias ou no pós-operatório imediato (cirúrgicas ou clínicas); indicação do anestesiologista ou cirurgião para a manutenção de tratamento na UTI. Resultados: Dos 120 pacientes avaliados, houve previsão de necessidade de internação em UTI em 24 (20,0%), sendo essa considerada justificada em 16 deles (66,6%) desses 24, ao passo que dos 96 pacientes sem previsão de necessidade de internação em UTI, essa foi necessária em 14 (14,5%). A utilização dos critérios preditivos para a internação em UTI mostrou boa acurácia (81,6%), sensibilidade de 53,3%, especificidade de 91%, valor preditivo positivo de 66,6% e valor preditivo negativo de 85,4%. Conclusões: A utilização de critérios pré-operatórios para a indicação de internação em UTI após ressecção pulmonar eletiva é factível e é capaz de reduzir o número de pacientes que aí permanecem apenas para vigilância. .

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. .

Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury

OBJECTIVES: Prevention of the development of paraplegia during the repair of the damage caused by descending thoracic and thoracoabdominal aneurysms remains an important issue. Therefore, we investigated the protective effect of atorvastatin on ischemia-induced spinal cord injury in a rabbit model. METHOD: Thirty-two rabbits were divided into the following four equally sized groups: group I (control), group II (ischemia-reperfusion), group III (atorvastatin treatment) and group IV (atorvastatin withdrawal). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation. Seventy-two hours postoperatively, the motor function of the lower limbs of each animal was evaluated according to the Tarlov score. Spinal cord and blood samples were obtained for histopathological and biochemical analyses. RESULTS: All of the rabbits in group II exhibited severe neurological deficits. Atorvastatin treatment (groups III and IV) significantly reduced the level of motor dysfunction. No significant differences were observed between the motor function scores of groups III and IV at the evaluated time points. Light microscopic examination of spinal cord tissue samples obtained at the 72nd hour of reperfusion indicated greater tissue preservation in groups III and IV than in group II. CONCLUSION: This study demonstrates the considerable neuroprotective effect of atorvastatin on the neurological, biochemical and histopathological status of rabbits with ischemia-induced spinal cord injury. Moreover, the acute withdrawal of atorvastatin therapy following the induction of spinal cord ischemia did not increase the neuronal damage in this rabbit model. .

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System / Efetividade de Estatinas em Dose Alta, Moderada e Baixa na Prevenção de Eventos Vasculares no SUS

Background: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. Objective: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective. Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied. Results: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. Conclusions: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil. .

Fundamento: Estatinas tem eficácia comprovada na redução de eventos cardiovasculares, mas o impacto financeiro de seu uso disseminado pode ser substancial. Objetivo: Conduzir análise de custo-efetividade de três esquemas de doses de estatinas na perspectiva do SUS. Métodos: Foi desenvolvido modelo de Markov para avaliar a razão de custo-efetividade incremental (RCEI) de regimes de dose baixa, intermediária e alta, em prevenção secundária e quatro cenários de prevenção primária (risco em 10 anos de 5%, 10%, 15% e 20%). Regimes com redução de LDL abaixo de 30% (ex: sinvastatina 10mg) foram considerados dose baixa; entre 30-40% (atorvastatina 10mg, sinvastatina 40mg), dose intermediária; e acima de 40% (atorvastatina 20-80 mg, rosuvastatina 20 mg), dose alta. Dados de efetividade foram obtidos de revisão sistemática com aproximadamente 136.000 pacientes. Dados nacionais foram usados para estimar utilidades e custos (expressos em dólares internacionais - Int$). Um limiar de disposição a pagar (LDP) igual ao produto interno bruto per capita nacional (aproximadamente Int$11.770) foi utilizado. Resultados: A dose baixa foi dominada por extensão nos cenários de prevenção primária. Nos cinco cenários, a RCEI da dose intermediária ficou abaixo de Int$10.000 por QALY. A RCEI de dose alta ficou acima de Int$27.000 por QALY em todos os cenários. Nas curvas de aceitabilidade de custo-efetividade, dose intermediária teve probabilidade de ser custo-efetiva acima de 50% com RCEIs entre Int$9.000-20.000 por QALY em todos os cenários. Conclusões: Considerando um LDP razoável, uso de estatinas em doses intermediárias é economicamente atrativo, e deveria ser intervenção prioritária na redução de eventos cardiovasculares no Brasil. .

Hepatotoxicity of combined therapy of atorvastatin with platelet P2Y[12]-ADP receptor antagonist in coronary heart disease treated patients

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in coronary disease and percutaneous coronary stenting. It appears to be a safe drug with few occurrences of liver side-effects that usually resolved after drug withdrawal. The goal of this study was to investigate whether the co-administration of atorvastatin could aggravate the hepatic - toxicity of clopidogrel. Eighty patients with coronary disease were included in this study. All patients received a dose of 75 mg/day of clopidogrel. Forty patients group A with recent treatment [< 3 months] of clopidogrel; other forty patients group B with [> 1 year] treatment of clopidogrel. Liver function tests were measured and studied at baseline [clopidogrel without atorvastatin] and at 2, 4, 6 weeks of clopidogrel with atorvastatin [40 mg/day] afterwards. Liver function tests with co-therapy showed high significant elevation in mean serum total alkaline phosphatase [P<0.001], significant decrease [P< 0.05] in mean serum gamma-glutamyl transferase ,significant elevation [P< 0.05] in mean serum direct bilirubin and insignificant elevation [P>0.05] in mean serum total bilirubin, whereas the results appeared within normal range in mean serum levels of alanine aminotransferase, aspartate aminotransferase ,glutamate dehydrogenase -1,and total protein. Combination of atorvastatin and clopidogrel may induce hepatic injury cholestatic type resulting from abnormal bile flow caused by either drugs or its metabolites

Pteridic acid hydrate and pteridic acid C produced by StreStreptomyces pseudoverticillus YN17707 induce cell cycle arrest / 中国天然药物

The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on tsFT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate (1) and pteridic acid C (2), which arrested the tsFT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L(-1), respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.

Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese patients / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Statins are still underused for the prevention of cardiovascular disease (CVD) in China. Hence, we conducted a systemic review on the pharmacology, clinical efficacy, and adverse events of atorvastatin, as well as on patient adherence.</p><p><b>DATA SOURCES</b>We conducted a systemic search in PubMed with the following keywords: "atorvastatin" (Supplementary concept) or "atorvastatin" (All field) and ("China" [AD] or "China" [all field] or "Chinese" [All field]).</p><p><b>STUDY SELECTION</b>Clinical or basic research articles on atorvastatin were included.</p><p><b>RESULTS</b>Atorvastatin is a reversible and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decreasing the de novo cholesterol synthesis. The pharmacokinetics of atorvastatin among Chinese is similar to those in Caucasians, and several gene polymorphisms have proved to be associated with the metabolism of atorvastatin in the Chinese population. Several international multiple-center randomized control trials have demonstrated the benefit of atorvastatin for primary and secondary prevention of CVD. None of them, however, included the Chinese, and current evidence in the population is still inadequate, due to the small sample size, low study quality, short study duration, and the use of surrogate endpoints instead of clinical endpoints. The overall incidence of adverse events observed with atorvastatin did not increase in the 10-80 mg dose range, and was similar to that observed with placebo and in patients treated with other statins, which makes atorvastatin well-tolerated in the Chinese population. Moreover, high patient adherence was observed in clinical studies.</p><p><b>CONCLUSIONS</b>Based on the current available evidence, there is no significant difference between Chinese and non-Chinese population in term of pharmacology and clinical efficacy/safety. High-quality evidence is still needed to support the use of atorvastatin in high-risk Chinese population.</p>

Effect of intensive pretreatment with atorvastatin calcium on outcomes of percutaneous coronary intervention in elderly patients with coronary heart disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of different loading doses of atorvastatin calcium on the outcomes of percutaneous coronary intervention (PCI) in elderly patients with coronary heart disease (CHD).</p><p><b>METHODS</b>A total of 120 CHD patients aged over 80 years were randomly assigned into 3 equal groups to receive intensive pretreatment with statin at the doses of 20, 40, or 60 mg prior to PCI performed within 48 to 72 h after admission. The changes of postoperative cardiac biochemical markers including creatine kinase isoenzyme (CKMB), troponin I (cTNI) and high-sensitivity c-reactive protein (hs-CRP) were observed and the incidence of major adverse cardiac events (MACE, including cardiac death, myocardial infarction, and target vessel revascularization) were recorded within 30 days after PCI.</p><p><b>RESULTS</b>Thirty-four patients in 20 mg statin group, 40 in 40 mg statin group, and 38 in 60 mg statin group completed this study. In all the 3 groups, hs-CRP level significantly increased at 12 and 24 h after PCI compared with the preoperative levels (P<0.05). The patients in 60 mg statin group showed significantly lower levels of CKMB, cTNI, and hs-CRP at 24 h after PCI than those in 20 mg statin group (P<0.05), and had also a significantly lower incidence of total MACE within 30 days after PCI (2.6% vs 26.5%, P=0.003) resulting primarily from significantly reduced myocardial infarction associated with PCI (2.6% vs 20.6%, P=0.016). The adverse drug reactions were comparable among the 3 groups (P>0.05).</p><p><b>CONCLUSIONS</b>Intensive pretreatment with 60 mg/day atorvastatin calcium can significantly reduce myocardial infarction related to PCI with good safety in elderly patients with CHD.</p>

Ganoderic acid A suppresses proliferation and invasion and induces apoptosis in human osteosarcoma cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of ganoderic acid A (GA-A) on the biological behaviors of human osteosarcoma cells in vitro.</p><p><b>METHODS</b>MG63 and HOS cells were treated with 0.1, 0.25, and 0.5 mmol/L GA-A, and the changes in cell proliferation, apoptosis and migration were evaluated using MTT assay, flow cytometry, and Transwell assay, respectively. The expressions of STAT3, p38, and NF-κB1 in the cells were analyzed by Western blotting.</p><p><b>RESULTS</b>GA-A effectively inhibited the proliferation of human osteosarcoma HOS and MG-63 cells in a dose-dependent manner, and induced obvious cell apoptosis in both cells. Treatment with 0.5 mmol/L GA-A also resulted in significant inhibition of the invasion of both cells. The results of Western blotting showed that GA-A down-regulated the expression level of phosphorylated STAT3 and increased the phosphorylation level of p38 and NF-κB1 expression in both cells.</p><p><b>CONCLUSION</b>GA-A can induce proliferation inhibition, apoptosis and suppression of invasion in human osteosarcoma HOS and MG-63 cells.</p>

La combinación de atorvastatina y meloxicam inhibe la neuroinflamación y atenúa el daño celular en la isquemia cerebral experimental por embolia arterial / Atorvastatin-meloxicam association inhibits neuroinflammation and attenuates the cellular damage in cerebral ischemia by arterial embolism.

Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.

Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .

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.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.

Atorvastatin in the management of tinnitus with hyperlipidemias

To determine the role of atorvastatin in management of tinnitus in patients with hyperlipidemia. Quasi-experimental study. ENT Department, Combined Military Hospital, Rawalpindi, from July 2011 to August 2012. Ninety eight patients of tinnitus with sensorineural hearing loss having hyperlipidemia were included in the study. Their pre-therapy serum cholesterols were measured, and tinnitus scores were recorded on a 'Tinnitus handicap questionnaire'. They were administered tablet atorvastatin 40 mg once daily with low fat diet for 8 months. After 8 months of therapy, patients were purposefully divided into responsive and unresponsive group depending on serum cholesterol levels. Post therapy serum cholesterol levels and tinnitus scores were also recorded after 8 months and compared with pre-therapy records. Serum cholesterol came to within normal limits in 51 [52%] patients [responsive group], while it remained high in 47 [48%] patients [unresponsive group]. Improvement in tinnitus score in the responsive group was seen in 36 [70.5%] patients and in 2 [4.2%] patients of the unresponsive group. Improvement in tinnitus scores was compared in the two groups using Fisher's exact test and were found to be statistically better in the responsive group [p < 0.001]. Tinnitus, in patients having hyperlipidemia, can be successfully dealt with by treating hyperlipidemia with lipid lowering agent atorvastatin

Efficacy of statins in dyslipidemia: a non interventional comparative study in a tertiary care hospital, Ajman, UAE

The reduction of serum total cholesterol and LDL-cholesterol levels varies with different statins. The objective of the present study was to compare the efficacy of Simvastatin, Atorvastatin and Rosuvastatin in the treatment of newly diagnosed dyslipidemia. A prospective, non-interventional 12-week study was conducted after approval from the Ethics Committee. A total of 70 patients with newly diagnosed dyslipidemia receiving 20mg of Simvastatin, Atorvastatin or Rosuvastatin were included. The primary efficacy measure was reduction of lipid levels from the initial baseline values at the end of 12 weeks with the respective Statins. Data was analyzed using descriptive statistics, Paired -t test, and analysis of variance [ANOVA]. Of total 70 patients, 14 patients received Simvastatin; 40 patients received Atorvastatin and 16 patients received Rosuvastatin. Demographic and baseline clinical characteristics were similar between the three groups. Significant reduction in lipid levels [total cholesterol, and LDL] was seen within the three treatment groups [p<0.01]. However, statistically significant difference in the reduction lipid levels was not observed between the three groups. We found no significant difference in the reduction of lipid levels between Simvastatin, Atorvastatin or Rosuvastatin patients with newly diagnosed dyslipidemia

Atorvastatin attenuates involvement of RhoA/Rho-kinase pathway and NF-κB activation in hypoxic pulmonary hypertensive rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxic pulmonary hypertension (HPH) contributes to the pathogenesis of cardiopulmonary diseases. Several lines of evidence indicate that the Rho A/Rho-kinase pathway play an important role in the progress of pulmonary hypertension. Stains have been shown exert numerous biological effects that are independent of their cholesterol-lowering property. We hypothesized that the Rho A/Rho-kinase pathway is involved in the pathogenesis of HPH, and that atorvastatin would attenuate involvement of the Rho A/Rho-kinase pathway in a HPH rat model.</p><p><b>METHODS</b>Thirty-two Wistar rats were randomly divided into four groups: control group, hypoxic group, atovastatin group, and normal saline group. The control group was kept in a normoxia environment. The other groups were exposed to hypoxia for three weeks. Atovastatin was administered daily via a gastric gavage in the atovastatin group. We measured the mean pulmonary arterial pressure (mPAP), the ratio of the right ventricular weight to the sum of the weights of the left heart ventricle and septum (RV/(LV+S)), arteriole wall thickness/vascular external diameter (WT%), vascular area/total vascular area (WA%), expression of RhoA and phos-MYPT-1 protein in lung tissue, and NF-κB activation in pulmonary vascular smooth muscle cells.</p><p><b>RESULTS</b>Compared with the control group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were increased in the hypoxic and normal saline groups (P < 0.05). Compared with the hypoxic group, mPAP, RV/(LV+S), WT%, WA%, NF-κB activation, expression of RhoA, and phos-MYPT-1 were decreased in the atovastatin group (P < 0.05). Correlations between phos-MPTY-1 and mPAP, WA%, WT%, and NF-κB activation were all positive.</p><p><b>CONCLUSIONS</b>The Rho A/Rho-kinase pathway plays an important role in the development of HPH. Atorvastatin reversed HPH by inhibiting the activity of Rho A/Rho-kinase and NF-κB.</p>

Atorvastatin induces autophagy of mesenchymal stem cells under hypoxia and serum deprivation conditions by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The survival ratio of implanted mesenchymal stem cells (MSCs) in the infarcted myocardium is low. Autophagy is a complex "self-eating" process and can be utilized for cell survival. We have found that atorvastatin (ATV) can effectively activate autophagy to enhance MSCs survival during hypoxia and serum deprivation (H/SD). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway is a non-canonical autophagy pathway. We hypothesized that the MEK/ERK pathway mediated ATV-induced autophagy of MSCs under H/SD.</p><p><b>METHODS</b>MSCs were pretreated with ATV (0.01-10 µmol/L) under H/SD for three hours. For inhibitor studies, the cells were pre-incubated with the MEK1/2 inhibitor U0126. Cell autophagy was assessed by acidic vesicular organelles (AVO)-positive cells using flow cytometry, autophagy related protein using Western blotting and autophagosome using transmission electron microscopy.</p><p><b>RESULTS</b>Autophagy was elevated in the H/SD group compared with the normal group. ATV further enhanced the autophagic activity as well as the phosphorylation of ERK1/2 evidenced by more AVO-positive cells ((8.63 ± 0.63)% vs. (5.77 ± 0.44)%, P < 0.05), higher LC3-II/LC3-I ratio (4.36 ± 0.31 vs. 2.52 ± 0.18, P < 0.05) and more autophagosomes. And treatment with U0126 downregulated the phosphorylation of ERK1/2 and attenuated ATV-induced autophagy.</p><p><b>CONCLUSION</b>The MEK/ERK pathway participates in ATV-induced autophagy in MSCs under H/SD, and modulation of the pathway could be a novel strategy to improve MSCs survival.</p>

Atorvastatin inhibits macrophage-derived foam cell formation by suppressing the activation of PPARγ and NF-κB pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate whether atorvastatin inhibits oxidized low-density lipoproteins (Ox-LDL)-stimulated foam cell formation from THP-1 macrophages by regulating the activation of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor-κB (NF-κB). Methods THP-1 macrophages were pretreated with 10, 20, or 40 µmol/L atorvastatin for 2 h, and after washing with PBS twice, the cells were incubated with 60 µg/ml of Ox-LDL for 48 h. The quantity of intracellular lipid of the cells was detected with Oil red O staining and enzymatic fluorometric method. The expression of the scavenger receptors of CD36 and SRA were analyzed with Western blotting. We also examined the effect of atorvastatin on adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and the activation of PPARγ and p-iκB, and further assessed the capacity of the macrophages to bind to Dil-oxLDL.</p><p><b>RESULTS</b>Atorvastatin potently inhibited ox-LDL-induced macrophage-derived foam cell formation, down-regulated the expression of CD36 and SRA, and up-regulated the expression of ABCA1. Atorvastatin markedly suppressed the activation of PPARγ and p-iκB in ox-LDL-stimulated THP-1 macrophages (P<0.05) and significantly decreased the Dil-oxLDL-binding capacity of the macrophages (P<0.05).</p><p><b>CONCLUSION</b>Atorvastatin as an effective anti-atherosclerosis agent can suppress the activation of PPARγ and p-iκB to reduce lipid accumulation in macrophages.</p>