Effects of simvastatin in abdominal sepsis in rats

Statins are widely recognized as hypolipemic drugs, but some studies have observed anti-inflammatory and immunomodulatory effects, known as pleiotropic. The aims of this work was to study possible anti-inflammatory effects of simvastatin in abdominal sepsis. Serum pro-inflammatory cytokines and leukocytes count were determined in an experimental model of abdominal sepsis, using cecal ligation and puncture (CLP) in rats. Methods: Twenty eigth Wistar rats weighing 285±12g were randomly divided in: CLP/Sinvastatin rats (n=7), treated with 10 mg/Kg of oral simvastatin 18 and 2 hs berofe CLP; CLP/Saline group rats (n=7), treated with oral saline; group Sham/Simvastatin (n=7), treated with simvastatin, and group Sham/Saline (n=7), treated with saline. Serum TNF-α, IL-1β and IL-6 by ELISA and total leukocytes, neutrophils, lymphocytes, and eosinophils were determined 24 hs after CLP. ANOVA and Tukey test were used considering significant p<0.05. Results: It was demonstrated that serum TNF-α, IL-1β and IL-6 were respectively 364,8±42pg/mL; 46,3±18pg/mL and 28,4±13pg/mL in CLP/Sinvastatin rats, significantly lower (p<0.05) than in group CLP/Saline (778,5±86pg/ml; 176,9±46pg/ ml; 133,6±21 pg/ml, respectively). The same results were observed in total leukocytes and neutrophils counts. Conclusion: These results clearly demonstrate that simvastatin is an effective agent that reduces cytokines levels and leukocyte count in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA reductase inhibitors like simvastatin have important anti-inflammatory effects in abdominal sepsis in rats

Pleiotropic effects of statins may improve outcomes in atherosclerotic renovascular disease

BACKGROUNDAtherosclerotic renovascular disease (ARD) coexists with arterial obstructive disease in the coronary, cerebral, and peripheral arteries that may remain underdiagnosed and untreated.METHODSThis retrospective study compares overall survival and renal survival (i.e., time to doubling of serum creatinine or end-stage renal disease (ESRD)) over an 11-year period in 104 ARD patients of whom 68 received statin therapy (group S) because of elevated lipid levels and 36 had no statin (group NS) because of normal lipid profile at entry.RESULTSAtherosclerosis in another vascular bed was documented in 84%. Lipid profiles at end point were virtually identical in both the groups Group S had mean survival 123 months (confidence interval (CI) 113-134) with four deaths, and mean renal survival 122 months (CI 113-131). Group NS had mean survival 33 months (CI 23-42) with 13 deaths, and mean renal survival 27 months (CI 17-37).CONCLUSIONSStatin therapy was associated with lesser rate of progression of renal insufficiency (with 7.4% of S patients reaching renal end points vs. 38.9% of NS patients) and lower overall mortality (5.9% in S vs. 36.1% in NS patients), P < 0.001 for both. Although both groups received what was deemed optimal therapy, they did have other differences that may have affected the outcomes (a limitation addressed by Cox multiple regression analysis). These results suggest the need for prospective randomized controlled studies in ARD patients in order to explore potential benefits of statins that may not be attributable solely to lipid lowering.

Caracterização do tratamento medicamentoso com estatinas em unidade básica de saúde

Study Model: Retrospective study. Study Objective: To characterize statin treatment management due to lipid alterations and side effects throughout statin treatment in basic healthcare unit. Methods: Medical reports of women from a basic healthcare unit were analyzed, obtaining: disease presence, regular medication prescription, statin type and dosage, biochemical exams results, musculoskeletal complaints, and statin use cessation, going back the information until the medical consultation of first prescription. Results: Prescribed statins were Simvastatin and Atorvastatin at low doses (10-20 mg). Dose (48,4%) and/or type (25,4%) alterations occurred for lipid profile adequacy. Lipid levels were reduced without creatine kinase elevation. Treatment withdrawn (30,6%) was mainly due to their own decision (74%), which was strongly associated with records of musculoskeletal complaints (Odds Ratio: 6,40[1,53-26,78]). Conclusion: Statin treatment was effective in reducing serum lipid levels and self-reported pain was underestimated, characterizing the major limiting factor for treatment adherence.

Simvastatin treatment increases nitrite levels in obese women: Modulation by T-786C polymorphism of eNOS

Objective and Subjects: Evidence indicates an impairment of nitric oxide (NO) in obesity. Statins present pleiotropic effects independently of cholesterol-lowering, including increasing of eNOS expression and antioxidant effects. We evaluated the effects of simvastatin treatment at 45 days on circulating nitrite (NO marker) and TBARS-MDA levels in obese women without comorbidities (hypertension, diabetes and dyslipidemia). Moreover, we verified whether obese women carrying the C variant of T-786C polymorphism located in eNOS may have increased levels of nitrite after treatment compared to TT genotype. Results: After simvastatin treatment, while the plasma nitrite levels increased 42% (P = 0.0008), the TBARS-MDA levels reduced 58% (P = 0.0069). We observed increased levels of nitrite in both groups of genotypes (TT vs. TC + CC); however, rise in C-allele carriers was 60% comparing with 44% in TT. Conclusion: Our results demonstrated a restoration of nitrite levels in obese women treated with simvastatin, which is modulated by T-786C polymorphism. © 2013 Elsevier Inc. All rights reserved.

Estudo das respostas bioquímica e muscular da administração de estatina e sua descontinuidade associadas à atividade física em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Assessment of the damage caused by flood rains and landslides in association with hurricane Michelle, october 2001: implications for economic, social and environmental development

Preface This study was prepared for the Government of Jamaica following the significant physical damage and economic losses that the country sustained as a result of flood rains associated with the development of Hurricane Michelle. The Planning Institute of Jamaica (PIOJ) submitted a request for assistance in undertaking a social, environmental and economic impact assessment to the Economic Commission for Latin America and the Caribbean (ECLAC) on 14 November 2001. ECLAC responded with haste and modified its work plan to accommodate the request. A request for training in the use of the ECLAC Methodology to be delivered to personnel in Jamaica was deferred until the first quarter of 2002, as it was impossible to mount such an initiative at such short notice. This appraisal considers the consequences of the three instances of heavy rainfall that brought on the severe flooding and loss of property and livelihoods. The study was prepared by three members of the ECLAC Natural Disaster Damage Assessment Team over a period of one week in order to comply with the request that it be presented to the Prime Minister on 3 December 2001. The team has endeavoured to complete a workload that would take two weeks with a team of 15 members working assiduously with data already prepared in preliminary form by the national emergency stakeholders. There is need for training in disaster assessment as evidenced by the data collected by the Jamaican officials engaged in the exercise. Their efforts in the future will be more focused and productive after they have received training in the use of the ECLAC Methodology. This study undertakes a sectoral analysis leading to an overall assessment of the damage. It appraises the macroeconomic and social effects and proposes some guidelines for action including mitigating actions subsequent to the devastation caused by the weather system. The team is grateful for the efforts of the Office of Disaster Preparedness and Emergency Management (ODPEM), the associated government ministries and agencies, the Statistical Institute of Jamaica (STATIN), the Planning Institute of Jamaica and the Inter American Development Bank (IDB) for assistance rendered to the team. Indeed, it is the recommendation of the team that STATIN is poised to play a pivotal role in any disaster damage assessment and should be taken on board in that regard. The direct and indirect damages have been assessed in accordance with the methodology developed by ECLAC (1). The results presented are based on the mission's estimates. The study incorporates the information made available to the team and evidence collected in interviews and visits to affected locations. It is estimated that the magnitude of the losses exceeds the country's capacity to address reparations and mitigation without serious dislocation of its development trajectory. The government may wish to approach the international community for assistance in this regard. This appraisal is therefore designed to provide the government and the international community with guidelines for setting national and regional priorities in rehabilitation and reconstruction or resettlement programmes. A purely economic conception of the problem would be limited. A more integrated approach would have a human face and consider the alleviation of human suffering in the affected areas while attending to the economic and fiscal fallout of the disaster. Questions of improved physical planning, watershed management, early warning, emergency response and structural preparedness for evacuation and sheltering the vulnerable population are seen as important considerations for the post disaster phase. Special attention and priority should be placed on including sustainability and increased governance criteria in making social and productive investments, and on allocating resources to the reinforcing and retrofitting of vulnerable infrastructure, basic lifelines and services as part of the reconstruction and rehabilitation strategy. The Jamaican society and government face the opportunity of undertaking action with the benefit of revised paradigms, embarking on institutional, legal and structural reforms to reduce economic, social and environmental vulnerability. The history of flood devastation in the very areas of Portland and St. Mary shows a recurrence of flooding. Accounts of flooding from the earliest recorded accounts pertaining to 1837 are available. Recurrences in 1937, 1940, 1943 and 2001 indicate an ever-present probability of recurrence of similar events. The Government may wish to consider the probable consequences of a part of its population living in flood plains and address its position vis-à­¶is land use and the probability of yet another recurrence of flood rains. (1) ECLAC/IDNDR, Manual for estimating the Socio-Economic Effects of Natural Disasters, May,1999.

An assessment of the economic impact of climate change on the health sector In Jamaica

Climate change is a naturally occurring phenomenon in which the earth‘s climate goes through cycles of warming and cooling; these changes usually take place incrementally over millennia. Over the past century, there has been an anomalous increase in global temperature, giving rise to accelerated climate change. It is widely accepted that greenhouse gas emissions from human activities such as industries have contributed significantly to the increase in global temperatures. The existence and survival of all living organisms is predicated on the ability of the environment in which they live not only to provide conditions for their basic needs but also conditions suitable for growth and reproduction. Unabated climate change threatens the existence of biophysical and ecological systems on a planetary scale. The present study aims to examine the economic impact of climate change on health in Jamaica over the period 2011-2050. To this end, three disease conditions with known climate sensitivity and importance to Jamaican public health were modelled. These were: dengue fever, leptospirosis and gastroenteritis in children under age 5. Historical prevalence data on these diseases were obtained from the Ministry of Health Jamaica, the Caribbean Epidemiology Centre, the Climate Studies Group Mona, University of the West Indies Mona campus, and the Meteorological Service of Jamaica. Data obtained spanned a twelve-year period of 1995-2007. Monthly data were obtained for dengue and gastroenteritis, while for leptospirosis, the annual number of cases for 1995-2005 was utilized. The two SRES emission scenarios chosen were A2 and B2 using the European Centre Hamburg Model (ECHAM) global climate model to predict climate variables for these scenarios. A business as usual (BAU) scenario was developed using historical disease data for the period 2000-2009 (dengue fever and gastroenteritis) and 1995-2005 (leptospirosis) as the reference decades for the respective diseases. The BAU scenario examined the occurrence of the diseases in the absence of climate change. It assumed that the disease trend would remain unchanged over the projected period and the number of cases of disease for each decade would be the same as the reference decade. The model used in the present study utilized predictive empirical statistical modelling to extrapolate the climate/disease relationship in time, to estimate the number of climate change-related cases under future climate change scenarios. The study used a Poisson regression model that considered seasonality and lag effects to determine the best-fit model in relation to the diseases under consideration. Zhang and others (2008), in their review of climate change and the transmission of vector-borne diseases, found that: ―Besides climatic variables, few of them have included other factors that can affect the transmission of vector-borne disease….‖ (Zhang 2008) Water, sanitation and health expenditure are key determinants of health. In the draft of the second communication to IPCC, Jamaica noted the vulnerability of public health to climate change, including sanitation and access to water (MSJ/UNDP, 2009). Sanitation, which in its broadest context includes the removal of waste (excreta, solid, or other hazardous waste), is a predictor of vector-borne diseases (e.g. dengue fever), diarrhoeal diseases (such as gastroenteritis) and zoonoses (such as leptospirosis). In conceptualizing the model, an attempt was made to include non-climate predictors of these climate-sensitive diseases. The importance of sanitation and water access to the control of dengue, gastroenteritis and leptospirosis were included in the Poisson regression model. The Poisson regression model obtained was then used to predict the number of disease cases into the future (2011-2050) for each emission scenario. After projecting the number of cases, the cost associated with each scenario was calculated using four cost components. 1. Treatment cost morbidity estimate. The treatment cost for the number of cases was calculated using reference values found in the literature for each condition. The figures were derived from studies of the cost of treatment and represent ambulatory and non-fatal hospitalized care for dengue fever and gastroenteritis. Due to the paucity of published literature on the health care cost associated with leptospirosis, only the cost of diagnosis and antibiotic therapy were included in the calculation. 2. Mortality estimates. Mortality estimates are recorded as case fatality rates. Where local data were available, these were utilized. Where these were unavailable, appropriate reference values from the literature were used. 3. Productivity loss. Productivity loss was calculated using a human capital approach, by multiplying the expected number of productive days lost by the caregiver and/or the infected person, by GDP per capita per day (US$ 14) at 2008 GDP using 2008 US$ exchange rates. 4. No-option cost. The no-option cost refers to adaptation strategies for the control of dengue fever which are ongoing and already a part of the core functions of the Vector Control Division of the Ministry of Health, Jamaica. An estimated US$ 2.1 million is utilized each year in conducting activities to prevent the post-hurricane spread of vector borne diseases and diarrhoea. The cost includes public education, fogging, laboratory support, larvicidal activities and surveillance. This no-option cost was converted to per capita estimates, using population estimates for Jamaica up to 2050 obtained from the Statistical Institute of Jamaica (STATIN, 2006) and the assumption of one expected major hurricane per decade. During the decade 2000-2009, Jamaica had an average inflation of 10.4% (CIA Fact book, last updated May 2011). This average decadal inflation rate was applied to the no-option cost, which was inflated by 10% for each successive decade to adjust for changes in inflation over time.

Jamaica: Report of the macro socio-economic effects of the events in western Kingston area 22 May- 7 June 2010

.--I. Background.--II. The affected population.--III. Sectoral analysis of damage and loss.--IV. The macro socio economic effect of the event.--V. Conclusions and recommendations

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose: To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS).Methods: This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05) in PATIENTS.Results: BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26-3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15-9.40, p<0.001).Conclusions: After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.

Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Simvastatin Does Not Reduce Chemokine Production in Obesity Without Comorbidities

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The effect of simvastatin treatment on bone repair of femoral fracture in animal model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prática supervisionada de exercícios físicos durante o tratamento regular com estatinas de pacientes da atenção básica: caracterização, aderência e delimitação das respostas musculares

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of simvastatin on passive strain-induced skeletal muscle injury in rats

Introduction: HMG-CoA reductase inhibitors are the most frequently prescribed drugs for treatment of lipid imbalance, but they have side effects, such as myopathy. Our aim was to assess the effect of simvastatin on the inflammatory process induced by skeletal muscle injury. Methods: Rats were divided into experimental groups [control group, simvastatin (20 mg/kg) group, group treated with simvastatin (20 mg/kg) and subjected to injury, and group subjected to injury only]. Histological analysis and analyses of creatine kinase activity and C-reactive protein were performed. Results: Animals treated with simvastatin exhibited significantly greater morphological and structural skeletal muscle damage in comparison to the control group and injured animals without treatment. Conclusions: Although simvastatin has a small anti-inflammatory effect in the early stage after a muscle strain injury, the overall picture is negative, as simvastatin increases the extent of damage to muscle morphology. Further studies are needed. Muscle Nerve 46: 908-913, 2012

Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

Background: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. Objective: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10 mg/simvastatin 20 mg (E10/S20) with simvastatin 80 mg (S80). Methods and results: CAD patients (n = 83, 63 +/- 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 +/- 13% vs. 28 +/- 30%, p = 0.46), apo-B (18 +/- 17% vs. 22 +/- 15%, p = 0.22) and oxidized LDL (15 +/- 33% vs. 18 +/- 47%, p = 0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 +/- 43% vs. 8 +/- 33%, p = 0.02). Conclusions: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4x less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80. (C) 2011 Elsevier Ireland Ltd. All rights reserved.