CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Sintomas musculares relacionados ao uso de estatinas / Statin-associated muscle symptoms

Nas últimas duas décadas, comprovou-se que a terapia com estatinas é o instrumento isolado mais potente para atenuar o risco cardiovascular, e seu uso frequente foi enfatizado como um dos elementos mais importantes para reduzir a mortalidade cardiovascular nos países desenvolvidos. Uma incidência igualmente frequente de sintomas musculares em usuários de estatinas levanta a possibilidade de um nexo de causalidade, que leva a uma entidade patológica conhecida como sintomas musculares associados a estatinas (SMAS). Estudos e ensaios clínicos mecanicistas destinados a estudar os SMAS levaram a uma definição clara da sua história natural e incidência exata. Essa informação é essencial para evitar riscos desnecessários de formas graves de SMAS. Ao mesmo tempo, essa compreensão concreta dos SMAS evita o diagnóstico exagerado e a suspensão desnecessária de uma das mais poderosas estratégias de prevenção atuais. Nesse contexto, este artigo de revisão reuniu todas as informações disponíveis sobre o assunto, que são apresentadas em detalhe neste documento como a base da identificação e tratamento dos SMAS

In the last 2 decades, statin therapy has proved to be the most potent isolated instrument for attenuating cardiovascular risk, and its frequent use has been highlighted as one of the most important elements for reducing cardiovascular mortality in developed countries. An equally frequent incidence of muscle symptoms in statin users raises the possibility of a causal link, leading to a disease entity known as statin-associated muscle symptoms (SAMS). Mechanistic studies and clinical trials designed to the study of SAMS have led to a clear definition of its natural history and accurate incidence. This information is vital for avoiding unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents over-diagnosis and unnecessary suspension of one of the most powerful prevention strategies available today. In this context, this review has gathered all the available information on the issue, which is presented in detail, in this document, as the basis for the identification and management of SAMS

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Estatinas para el síndrome coronario agudo: medicina basada en evidencia sobre la administración temprana con dosis de carga / Stations in acute coronary syndrome: use of an early loading dose

Objetivo: En algunos Servicios de Emergencias de la CCSS, a los pacientes con infarto agudo de miocardio se les administra una dosis alta aunque variables de lovastatina en las primeras horas de evolución de los síndromes coronarios agudos, con la expectativa de lograr efectos pleiotrópicos, un resultado positivo sobre el endotelio y la disminución de mediadores inflamatorios. Analizar la evidencia científica que sustenta el beneficio de esta intervención farmacológica y clarificar la posible dosis oral y el potencial intervalo idóneo. Búsqueda vías electrónicas en sistemas secundarios de información científica y análisis de fuentes primarias, con énfasis en ensayos clínicos aleatorizados que evalúen la eficacia de las estatinas en los eventos coronarios agudos; también de fuentes terciarias , específicamente revisiones sistemáticas y guías de consenso para prácticas clínicas basadas en evidencia y revisiones por instancias evaluadoras de tecnología con reconocimiento internacional. Resultados: Cuatro ensayos clínicos aleatorizados controlados con placebo, no demostraron diferencias significativas ni clínicamente relevantes en la variable primaria combinada: evento cardiaco mayor, muerte, IAM recurrente fatal, AVC fatal u otra causa de muerte cardiovascular, ninguno usó dosis de carga, ni se inició la administración en las 24hs del inicio de la sintomatología. Conclusión: Ante la falta de evidencia que permita proyectar con claridad un papel beneficioso para las estatinas en el manejo inicial del síndrome coronario agudo, esta práctica desequilibra la relación beneficio/riesgo y se aleja de los principios del uso racional de medicamentos y la aplicación del paradigma de la medicina basada en evidencia.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

Elevated yield of Monacolin K in Monascus purpureus by fungal elicitor and mutagenesis of UV and LiCl

In China, Monascus spp., a traditional fungus used in fermentation, is used as a natural food additive. Monascus spp. can produce a secondary metabolite, monacolin K namely, which is proven to be a cholesterol-lowering and hypotensive agent. Hence, recently, many researchers have begun focusing on how to increase the production of monacolin K by Monascus purpureus. In the present study, we investigated the effect of the fungal elicitor and the mutagenesis of UV & LiCl on the amount of monacolin K produced by Monascus purpureus. The fugal elicitor, Sporobolomyces huaxiensis, was isolated from tea leaves and its filtrate was added into the culture filtrate of Monascus purpureus during growth to induct the production of monacolin K. The results showed that the highest amount of monacolin K produced by the liquid fermentation was 446.92 mg/mL, which was produced after the fungal elicitor was added to the culture filtrate of Monascus purpureus on the day 4; this amount was approximately 6 times greater than that of the control culture filtrate, whereas the highest amount of monacolin K produced by the mutated strain was 3 times greater than the control culture after the irradiation of UV light in the presence of 1.0 % LiCl in the medium.

Production of angkak through co-culture of Monascus purpureus and Monascus ruber

Angkak (red mold rice, red yeast rice, Chinese red rice) is a traditional Chinese medicine produced by solid-state fermentation of cooked non-glutinous rice with Monascus species. The secondary metabolite of Monascus species, monacolin K /lovastatin, has been proven to lower blood lipid levels. In this study, a co-culture of Monascus purpureus MTCC 369 and Monascus ruber MTCC 1880 was used for angkak production. Four medium parameters screened by Plackett-Burman design were optimized by response surface methodology for highest lovastatin production in angkak during solid-state fermentation by the co-culture. Maximum lovastatin production of 2.84 mg g-1 was predicted in solid medium containing 20 g rice and 40 ml liquid nutrients medium (malt extract 9.68 g l-1, dextrose 38.90 g l-1, MnSO4.H2O 1.96 g l-1, and MgSO4.7H2O 0.730 g l-1) by point prediction tool of Design Expert 7.1 software (Statease Inc. USA).

Las estatinas afectan la viabilidad de líneas celulares de leucemia y linfoma humanas in vitro / Statins affect the viability of leukemia cell lines in vitro and human lymphoma

Se ha propuesto que las estatinas inducen apoptosis sobre células tumorales. Para probar dicha hipótesis, se analizó el efecto de las estatinas atorvastatina, fluvastatina, lovastatina, mevastatina, pravastatina y simvastatina en el rango de concentraciones de 1 pM hasta 100 µM, sobre la viabilidad de las líneas celulares humanas Jurkat E6.1, Jurkat D1.1 (Linfoma T) , Daudi (Linfoma B), U937 (leucemia monocítica) y HL-60 (leucemia promielomonocítica) in vitro en cultivos de 48 horas, analizados por la técnica de hidrolización del compuesto bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difenilltetrazolio (MTT). Lovastatina y mevastatina son los más potentes inductores de muerte celular independientemente del tipo celular (Ic 50 entre 12 y 50 µM). Para las otras estatinas se observan diferencias en el Ic50 según la línea celular atorvastatina (38,1 y 48,6 µM Jurkats, 55,3 µM Daudi y 100 µM para las otras líneas), pravastatina (25 µM HL-60, 55,6 y 60,7 µM Jurkats y > 100 µM Daudi y U937), simvastatina (25,1 µM Jurkat D1.1, 50,2 µM Jurkat E6.1, 45,2 µM Daudi y 51,3 µM HL-60, y > 100 µM U937) y para fluvastatina en todos los casos > 100 µM. La disminución de la viabilidad celular se revierte completamente cuando las células son incubadas con 10 µM mevalonato. Se concluye que la lovastatina y mevastatina son las más potentes inductoras de muerte seguida por atorvastatina, pravastatina y simvastatina cuyo efecto depende del tipo de línea celular y la fluvastatina no tiene efectos importantes en la viabilidad de las líneas celulares estudiadas

Statins have been proposed to induce apoptosis of tumor cells. In order to test this hypothesis, the effect of atorvastatin, fluvastatin, lovastatin, mevastatin, pravastatin, simvastatin on cell viability was assessed by in vitro culture for 48 hr, at concentrations ranging from 1 pM to 100 µM on human cell lines Jurkat E6.1, Jurkat D1.1 (T cell lymphoma), Daudi (B cell lymphoma), U937 (monocitic leukemia) and HL-60 (pro mielomonocitic leukemia) and analyzed the oxidation of (3-(4.5-Dimethylthiazol-2-yl)-2.5- diphenyltetrazolium bromide (MTT). Lovastatin and mevastatin are the most potent inductors of cell death independently of the cell type (Ic 50 between 12 and 50 µM). Differences in the Ic50 are observed depending on the cell line: atorvastatina (38.1 and 48.6 µM Jurkats, 55.3 µM Daudi y 100 µM for the others lines), pravastatin (25 µM HL-60, 55.6 y 60.7 µM Jurkats and > 100 µM Daudi and U937), simvastatin (25.1 µM Jurkat D1.1, 50.2 µM Jurkat E6.1, 45.2 µM Daudi and 51,3 µM HL-60, and > 100 µM U937) and for fluvastatin > 100 µM in all cases. The decrease in cell viability is reverted completely when the cells were incubated with 10 µM mevalonate. It is concluded that lovastatin and mevastatin are the most potent inductors of cell death followed by atorvastatin, pravastatin and simvastatin whose effect depends upon the cell type and fluvastatin does not have any important effects on cell viability on the cell lines studied

Response surface methodology for optimization of production of lovastatin by solid state fermentation

Lovastatin, an inhibitor of HMG-CoA reductase, was produced by solid state fermentation (SSF) using a strain of Aspergillus terreus UV 1718. Different solid substrates and various combinations thereof were evaluated for lovastatin production. Wheat bran supported the maximum production (1458 ± 46 µg g-1 DFM) of lovastatin. Response surface methodology (RSM) was applied to optimize the medium constituents. A 2(4) full-factorial central composite design (CCD) was chosen to explain the combined effects of the four medium constituents, viz. moisture content, particle size of the substrate, di-potassium hydrogen phosphate and trace ion solution concentration. Maximum lovastatin production of 2969 µg g-1 DFM was predicted by the quadratic model which was verified experimentally to be 3004 ± 25 µg g-1 DFM. Further RSM optimized medium supplemented with mycological, peptone supported highest yield of 3723.4±49 µg g-1 DFM. Yield of lovastatin increased 2.6 fold as with compared to un-optimized media.

The effects of lovastatin on conventional medical treatment of lower urinary tract symptoms with finasteride

OBJECTIVE: To explore whether or not statins have any impact on the progression of components of benign prostatic hyperplasia (lower urinary tract symptoms severity, prostate volume and serum prostate specific antigen (PSA) when combined with other agents inhibiting growth of prostate cells. MATERIALS AND METHODS: This was a preliminary, clinical study. Eligible patients were aged > 50 yrs, with International Prostate Symptom Score (IPSS) between 9 and 19, total prostate volume (TPV) > 40 mL, and serum PSA > 1.5 ng/mL. Patients were divided in two groups: those with and those without lipidemia. After selection, eligible BPH patients with lipidemia (n = 18) were prescribed lovastatin 80 mg daily and finasteride 5 mg daily, while eligible patients without lipidemia (n = 15) were prescribed only finasteride 5 mg daily. IPSS, TPV and serum PSA were evaluated at end point (4 months). RESULTS: There was no difference between the two groups on the primary end point of mean change from baseline in IPSS (p = 0.69), TPV (p = 0.90) and PSA (p = 0.16) after 4 months of treatment. CONCLUSIONS: Short-term lovastatin treatment does not seem to have any effect on IPSS, TPV and PSA in men with prostatic enlargement due to presumed BPH.

Oxamniquine, praziquantel and lovastatin association in the experimental Schistosomiasis mansoni

The activity of lovastatin associated with oxamniquine or praziquantel against schistosomiasis mansoni was evaluated in mice infected with Schistosoma mansoni. Forty days after infection, mice were treated with lovastatin, 400 mg/kg for five consecutive days by oral route, and on the last day of this sequence with 50 mg/kg oxamniquine or with 200 mg/kg praziquantel, both by oral route, single dose. Fifteen days later, the animals were perfused in parallel with an untreated control group. Studies were carried out in vitro, using lovastatin in culture medium containing S. mansoni worms proceeding from experimentally infected mice. In the in vivo trials, the association of lovastatin with oxamniquine or praziquantel did not show any additive action, but there were oogram changes when lovastatin was associated with oxamniquine. In vitro lovastatin was able to interrupt the maturation of S. mansoni eggs, which remained at the 1st or 2nd stages, depending on the dose used. The total number of morphologically dead eggs found in culture of worms exposed to 2 µg/ml or 4 µg/ml concentrations of lovastatin was significantly higher than the number of viable eggs. Using the probe Hoescht 33258 it was observed that 70 percent of the eggs considered morphologically viable in the treated groups (against 16 percent in the control group) were labeled, indicating that the majority of the viable eggs had membrane permeability increased due to lovastatin action.

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

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

Efeitos de bifosfonatos e estatinas na reparação de fraturas em tíbias de ratas com osteoporose induzidacom dexametasona / Effects of bisphosphonates and statins on tibial bone healing in rats with osteoporosis induced by dexamethasone treatment

A osteoporose é uma doença caracterizada por diminuição da massa óssea, com consequente aumento da incidência de fraturas, necessitando de métodos preventivos e de tratamentos eficazes. Alguns estudos demonstram que não somente a osteoporose, mas fármacos como alendronato, promovem a não consolidação de fraturas, presumivelmente pelo desequilíbrio de atividade osteoblástica e osteoclástica ocasionadas por esse fármaco. O presente estudo teve como objetivo verificar, comparativamente, os efeitos de alendronato de sódio, risedronato sódico, atorvastatina cálcica e lovastatina na reparação de fraturas em ratas osteoporóticas induzidas com dexametasona. Os efeitos desses fármacos foram analisados pelos marcadores bioquímicos cálcio, fósforo, albumina, proteínas totais, fosfatase alcalina e exame histomorfométrico de densidade trabecular óssea. Além disso, foi realizada morfometria através das medidas de comprimento, espessura, diâmetro do calo ósseo e densidade das tíbias dos animais. Os resultados bioquímicos não apresentaram diferenças significativas. Através damorfometria e histomorfometria foi possível constatara indução da osteoporose com o glicocorticóide, assim como a melhoria na densidade óssea, densidade trabecular óssea e diâmetro do calo ósseo em todos os grupos tratados. Estas técnicas mostraram que a recuperação óssea foi equiparável ao do grupo normal, o que demonstra que os fármacos usados são eficazes em animais osteoporóticos submetidos à fratura, ressaltando que os melhores efeitos foram obtidos como alendronato.

Hipotiroidismo y miopatia por atorvastatina: reporte de un caso / Hypothyroidism and myopathy by atorvastatin: report of a case

Se presenta un caso de un hombre de 56 años con dislipidemia e hipotiroidismo, quien desarrolló una miopatía inflamatoria asociada al uso de atorvastatina. Siete meses después de iniciado el tratamiento el paciente presentó debilidad e hipotrofia muscular progresiva, dolor tarácico y elevación sérica de los niveles de creatinquinasa total. El cuadro clínico revirtió en su totalidad después de suspender el tratamiento con lovastatina. Se revisa la literatura más reciente sobre estatinas y miopatía y se presenta su diagnóstico diferencial.

Disminución de homocisteína plasmática con vitaminas B6, B12 y ácido fólico. Su efecto en la concentración de los lípidos en pacientes con hiperlipoproteinemia secundaria tipo IV, con y sin tratamiento con Lovastatina / Lowering plasma homocysteine with vitamins B6, B12 and folic acid. Effect on lipids concentration in patients with secondary hyperlipoproteinemia type IV, with and without Lovastatina treatment

Se disminuyó la concentración de homocisteina plasmática mediante el uso oral de vitaminas B6 (300 mg/día), B12 (250μg/dνa) y ácido fólico (10 mg/día), y se estudió su efecto en los lípidos de pacientes con hiperlipoproteinemia secundaria tipo IV, durante 120 días, en 30 pacientes, de 45 a 70 años de edad, con infarto al miocardio. Se dividieron en grupo A (n=15) sin tratamiento con Lovastatina y grupo B (n=15) con el hipolipemiante. La homocisteina basal fue de 17,4±1,0 μmol/L y 16,7±1,0 µmol/L para los grupos A y B respectivamente, disminuyendo un 24% al final del tiempo experimental, en ambos grupos. El colesterol total se redujo por debajo de 220 mg/dl, mientras que los triglicéridos disminuyeron 25,4 mg/dl y 27,0 mg/dl en los grupos A y B respectivamente, por cada µmol/L de homocisteina catabolizada. Las lipoproteínas de baja densidad (LDL) y de muy baja densidad (VLDL) disminuyeron significativamente (p<0,005), mientras que las de alta densidad (HDL) se incrementaron en 1,0 mg/dl para el grupo A y 1,15 mg/dl para el grupo B, por cada μmol/L de homocisteina metabolizada, disminuyendo el riesgo coronario en un 28,5% grupo A y 35,9% grupo B. Se concluye que estas vitaminas disminuyen la concentración de homocisteína plasmática, promoviendo la disminución de la concentración de lípidos y lipoproteínas en este tipo de pacientes; mientras que la Lovastatina no reduce la concentración plasmática del aminoácido; pero si ejerce un efecto sinérgico con las vitaminas en la disminución de la concentración de los lípidos, en el grupo B.

The concentration of plasma homocysteine was diminished by the oral use of vitamins B6 (300 mg/day), B12 (250μg/day) and folic acid (10 mg/day), and the effect was studied in the lipids of patient with hiperlipoproteinemia secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with myocardial heart attack. They were divided in group A (n=15) without treatment with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine concentration was 17,4±1,0 µmol/L and 16,7±1,0 µmol/L for the groups A and B respectively, diminishing 24% at the end of the experimental time, in both groups. Total cholesterol decreased below 220 mg/dl, while the triglycerides diminished 25,4 mg/dl and 27,0 mg/dl in groups A and B respectively, by each µmol/L of homocysteine catabolissed. Low density lipoproteins (LDL) and very low density (VLDL) diminished significantly (p<0,005), while the high-density (HDL) increased 1,0 mg/dl in group A and 1,15 mg/dl in group B, for each μmol/L of homocysteine metabolized, lowering the coronary risk factor in 28,5% group A and 35,9% group B. We concluded that these vitamins decreased plasma homocysteine concentration, promoting the lowering of lipids and lipoprotein concentratation in this type of patients; while Lovastatin doesn't reduce homocysteine, but it had a synergic effect with the vitamins, dincreasing the lipid concentration, in group B.

Fármacos hipolipemiantes / Antilipemic agents

En el presente artículo se describen los diferentes fármacos hipolipemiantes. Se especifican sus modos de acción, sus efectos adversos y las precauciones y advertencias de cada uno de ellos

Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results

OBJETIVO: Capacidade da lovastatina em prevenir a perda de neurônios hipocampais após o status epilepticus (SE) induzido pela pilocarpina. MÉTODO: Ratos adultos Wistar foram divididos em 4 grupos: (A) ratos controles que não receberam pilocarpina nem lovastatina (n=5); (B) ratos controles que receberam somente lovastatina (n=5); (C) ratos que receberam somente pilocarpina (n=5); (D) ratos que receberam pilocarpina e lovastatina (n=5). Após a administração de pilocarpina (350mg/kg, i.p.), somente ratos que evoluíram para o status epilepticus foram incluídos em nosso estudo. A atividade epiléptica foi interrompida com uma injeção de diazepam (10 mg/kg, i.p.) após 4h do início do SE. Os ratos tratados com lovastatina receberam duas doses de 20mg/kg via esofágica, imediatamente e 24 h após a indução do SE. Sete dias após o SE induzido pela pilocarpina, todos os animais foram perfundidos e seus cérebros processados para análise histológica através do método de Nissl. RESULTADOS: A contagem celular da formação hipocampal mostrou uma significante perda celular nos animais que receberam pilocarpina e apresentaram SE (CA1= 26,8 ± 13,67; CA3= 38,1 ± 7,2; hilus= 43,8 ± 3,95) quando comparados com animais pertencentes ao grupo controle (Grupo A: CA1= 53,2 ± 9,63; CA3= 63,5 ± 13,35; hilus= 59,08 ± 10,24; Grupo B: CA1= 74,3 ± 8,16; CA3= 70,1 ± 3,83; hilus= 70,6 ± 5,10). O número de células neuronais na região CA1 do hipocampo de ratos que apresentaram SE e receberam lovastatina (44,4 ± 17,88) foi estatisticamente maior quando comparado com animais que somente apresentaram SE. CONCLUSÃO: A lovastatina exerce papel neuroprotetor na atenuação do dano cerebral após o SE.

Tratamento hipolipemiante em situações especiais: pós-transplante e/ou terapia imunossupressora / Hypolipidemic treatment under special conditions: posttransplant and/or immunosupressive therapy

Existem dados limitados sobre o uso concomitante de agentes hipolipemiantes e drogas imunosupressoras. As melhores evidências provêm do uso de estatinas e ciclosporina. Em termos farmacodinâmicos, estas duas drogas têm substratos diferentes. No tocante a farmacocinética, as estatinas não modificam as concentrações plasmáticas de ciclosporina. Entretanto, quando combinada a qualquer estatina, um controle rigoroso dos níveis de ciclosporina é recomendado, levando-se em conta o seu estreito intervalo terapêutico. Ciclosporina afeta a área sob a curva de muitas estatinas, pela inibição do CYP450 3A4, aumentando a exposição sistêmica dessas drogas. Pravastatina se apresenta como o composto de maior segurança, uma vez que é glucuronidado. A área sob a curva para as outras estatinas (sinvastatina, lovastatina, atorvastatina, cerivastatina e rosuvastatina) pode aumentar em graus variáveis de acordo com o seu sítio de metabolização, extração hepática pelo OATP-transportador, secreção biliar, excreção renal, e extrusão da droga pelo sistema MDR.

Miopatía por estatinas / Myopathy for statins

Se presenta el caso de un hombre de 34 años con dislipidemia, quien desarrolló una miopatía inflamatoria asociada al uso de lovastatina. Siete meses después de iniciado el tratamiento el paciente presentó debilidad e hipotrofia muscular progresiva, dolor torácico y elevación sérica de los niveles de creatínquinasa total. El cuadro clínico revirtió en su totalidad después de suspender el tratamiento con lovastatina. Se revisa la literatura más reciente sobre estatínas y miopatía y se presenta su diagnóstico diferencial