Simvastatin improves the healing of infected skin wounds of rats

This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. Methods: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. Results: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm2) than in saline (2120.0 ± 327.1 ìm2). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. Conclusion: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising

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

Sistemas microemulsionados como carreador lipídico para fármacos insolúveis

Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market

Muscle response to the association of statin and physical exercise in rats

Physical exercise and statins, which are recommended for the treatment of dyslipidemia, are independently associated to the occurrence of muscle injury. The objective is analyze the effect of aerobic exercise associated to the use of simvastatin on the morphology of the gastrocnemius muscle. Thirty Wistar rats were divided into six groups, two of which received a standard diet (1 sedentary and 1 exercised) and four (1 sedentary with medication, 1 sedentary without medication, 1 exercised with medication, 1 exercised without medication) received a hypercholesterolemic diet (standard diet with the addition of cholesterol and coconut oil). Simvastatin (20 mg/Kg) was administered five days a week for eight weeks, together with aerobic training on a treadmill (9.75 m/min) for 60 minutes a day. The gastrocnemius muscle was removed, sliced, stained with Hematoxylin-Eosin and submitted to a histochemical reaction to determine mitochondrial activity. The data were analyzed using a paired t-test, analysis of variance and Scheffe's post hoc test (p<0.05). Greater histological alterations were found in the medicated and exercised animals, with a greater frequency of occurrence as well. The histochemical analysis revealed that the medicated groups had fibers with more intensive mitochondrial activity alongside fibers with an absence of reaction. The morphometric analysis revealed no significant differences between groups. It is suggested that simvastatin is a medication that leads to the occurrence of muscle injury and its administration in association with physical activity may exacerbate these injuries. This finding may be related to cellular respiration.

Efeito do exercício físico e estatinas na função muscular em animais com dislipidemia

As estatinas são utilizadas no tratamento das dislipidemias, com grande tolerância; no entanto, vários efeitos colaterais podem surgir, destacando-se miopatia. A prática regular do exercício físico (EF) produz modificações favoráveis no perfil lipídico; entretanto, pode gerar lesões musculares. OBJETIVO: Avaliar o efeito da associação entre exercício físico e estatinas na função muscular, pela análise histológica, em modelo experimental animal com dislipidemia. MÉTODOS: Foram utilizados 80 ratos machos Wistar, distribuídos em oito grupos, incluindo animais submetidos à dieta hipercolesterolêmica (DH), sinvastatina com (G1) e sem (G2) EF; DH e fluvastatina, com (G3) e sem EF (G4); alimentados com ração comercial (RC) na presença (G5) e ausência de (G6) EF; DH submetidos (G7) ou não (G8) a EF. A DH foi administrada por 90 dias, as estatinas e prática de EF em esteira rolante por oito semanas. Os animais foram sacrificados, e o músculo sóleo retirado para análise histológica. Aplicaram-se os testes t de Student pareado e análise multivariada, com nível significante para p < 0,05. RESULTADOS: As principais alterações histológicas encontradas foram fibras de diferentes diâmetros, atróficas, em degeneração, splitting, edema, infiltrado inflamatório. Essas alterações foram observadas em 90% dos animais do grupo G1, 80% do G2, 70% do G3, 30% do G4, 40% do G5 e 30% do G7. Nos grupos G6 e G8 identificaram-se fibras musculares com morfologia preservada. CONCLUSÕES: Na avaliação histológica muscular, a associação entre fluvastatina, sinvastatina e exercício físico acarreta alterações morfológicas com predomínio no uso da sinvastatina, variando de grau leve a grave, no músculo sóleo de ratos, induzidos pelos inibidores da HMG-CoA redutase.

Vicilinas de leguminosas e seus efeitos no metabolismo lipídico de ratos dislipidêmicos

Pós-graduação em Alimentos e Nutrição - FCFAR

Dermatomiosite, neoplasia da mama e Orlistat : que associação?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Caracterização e desfecho clínico nos doentes com insuficiência cardíaca crónica, seguidos numa consulta especializada de ICC

Introdução: A Insuficiência Cardíaca (IC) é uma doença frequente e com considerável aumento de prevalência, já designada como sendo a epidemia do século XXI. Os doentes com IC manifestam uma alta taxa de mortalidade cardiovascular, em que as arritmias ventriculares malignas estão envolvidas. A remodelagem estrutural e elétrica nos portadores de IC levam a alterações eletromecânicas que desencadeiam a dissincronia cardíaca e natural agravamento da doença, provocando o aumento da predisposição para o aparecimento de arritmias e consequentemente aumento do risco de morte súbita. Objetivo: Caracterização dos doentes com IC seguidos na consulta de ICC do Centro Hospital Leiria-Pombal (CHLP) e avaliação da ocorrência dos eventos cardiovasculares. Avaliação dos parâmetros de repolarização ventricular e o seu contributo no aumento da suscetibilidade a arritmias malignas e/ou morte súbita. Métodos: Selecionou-se um grupo de 130 indivíduos inscritos na consulta externa de ICC-Avançada do CHLP, avaliando-se durante uma média de 42,15 meses de follow-up. Caracterizou-se a amostra quanto aos dados clínicos (anamnese clinica, analises e exames complementares de diagnóstico) e parâmetros de repolarização ventricular (QT, QTc, Tpeack-Tend). Os indivíduos em FA forem classificados quanto ao risco trombótico CHADS2 e CHA2DS2VAS. Quanto aos eventos hospitalares agrupou-se a amostra em Com MACE e Sem MACE. Resultados: Verificou-se que 76,2% da amostra é do sexo masculino, com uma média de idades de 65,9 ±14,8, a etiologia da IC mais comum nesta amostra foi a HTA e a isquémica (n=41 e n=39, respetivamente); segundo a classificação de NYHA 64,6% encontra-se em grau II; 43,1% da amostra encontra-se em FA. Dos 84 indivíduos com avaliação da FEVE, 42,7% tinham a FEVE bastante diminuída e 40,4% depressão ligeira/moderada da FEVE. 10,8% dos indivíduos da amostra foi tratado com ressincronização cardíaca. Durante o follow-up foram registadas 1.479 admissões hospitalares, das quais 1.039 são no serviço de urgência e 182 no serviço de cardiologia. 12,3% da amostra faleceu durante a recolha de dados. A mortalidade total foi influenciada, com significado estatístico (p<0,05), pela idade, QTc, Tpeack-end, total de internamentos, admissões no serviço de urgência, creatinina, ureia e pela TFG. As determinantes independentes para a mortalidade foram a dislipidémia e o total de internamentos, sendo que a idade se revelou tendencialmente significativa. As variáveis TFG, HTA, os antecedentes familiares cardíacos e a terapêutica sem sinvastatina revelaram-se marginalmente significativos para a variável MACE. Os indivíduos com IC mais idosos, com maior percentagem de peso, com diabetes e com alterações na creatinina e TFG revelaram relação estatística com a admissão num dos serviços de internamento. A duração do QRS, do QTC, do Tpeack-Tend e a terapêutica sem anticoagulantes revelaram-se marginalmente significativos na necessidade de internamento hospitalar. Em relação aos doentes em FA segundo a classificação em CHa2DS2VASC e CHADS2 verificou-se que 76,8% da amostra e 48,2% (respetivamente) encontrava-se num score acima do 3. Verificou-se um aumento tendencialmente exponencial em relação ao risco de morte com o aumento do score de CHADS2, bem como a relação direta com o aumento da probabilidade de eventos cardiovasculares. Conclusões: Os portadores de IC são um grupo de doentes peculiares; em que a remodelagem estrutura e elétrica proporciona modificações que culminam no aumento da predisposição para o surgimento de arritmias e consequente aumento de risco de morte súbita.

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. Methods: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-a, IL-1b, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. Results: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-a, IL-1b and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. Conclusion: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines

Simvastatin improves the healing of infected skin wounds of rats

This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. Methods: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. Results: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm2) than in saline (2120.0 ± 327.1 ìm2). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. Conclusion: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising

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

Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. Methods: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-a, IL-1b, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. Results: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-a, IL-1b and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. Conclusion: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines

Simvastatin improves the healing of infected skin wounds of rats

This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. Methods: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. Results: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm2) than in saline (2120.0 ± 327.1 ìm2). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. Conclusion: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising

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

Utilização das estatinas e o seu impacto na prevalência das doenças cardiovascular

Introdução: As doenças cardiovasculares são a principal causa de morte em Portugal. Apesar das taxas de óbitos terem vindo progressivamente a descer, são ainda valores preocupantes em termos de saúde pública. Neste particular, o papel da dislipidémia na patogénese das doenças cardiovasculares, está bem documentado. Das várias classes de fármacos utilizadas para reduzir os níveis de colesterol, as Estatinas assumem especial importância na redução das co-morbilidades das doenças cardiovasculares. Assim, o objectivo deste trabalho, consiste em analisar as taxas de prevalência das doenças cardiovasculares e as co-morbilidades associadas ao uso de Estatinas no período de 2000-2013. Métodos: Este estudo é de natureza epidemiológica, de cunho descritivo, tendo a análise retrospectiva incidido sobres os dados das doenças cardiovasculares e os consumos das estatinas em Portugal no período de 2000-2013. Resultados: O número de óbitos por doenças do aparelho circulatório entre 2000 e 2012 apresentou, um decréscimo de 19,8% de óbitos. O número de embalagens de Estatinas dispensadas entre o mesmo período representou um aumento de 489%. A sinvastatina é a substância mais dispensada. Conclusão: O benefício da utilização das Estatinas e o seu impacto nas doenças do aparelho circulatório tem superado, o risco associado. Contudo haverá muito, para ser investigado em relação às reacções adversas das Estatinas.