Effect of oleic, lauric and myristic acids on phenylephrine-induced contractions of isolated rat vas deferens.

-004, a lipid extract of Roystonea regia fruits that contains oleic, lauric and myristic acids as major components inhibits α1-adrenoreceptors-mediated contractile responses in isolated rat vas deferens and prostate trips; no study has demonstrated a similar effect for oleic, lauric or myristic acids individually. Therefore, the effects of D-004 (250 g/ml), oleic (100 g/ml), lauric (50 g/ml) or myristic (25 g/mL) acids and their combined effects on phenylephrine (PHE: 10-7- 10-4 mol/L) induced contractions has been studied. No treatment changed the basal tone of the preparations, but all inhibited PHE-induced contractions. D-004 produced the highest inhibition, followed by lauric acid, which was more effective than myristic and oleic acids against PHE-induced contractions of control group. D-004 and the mixture of the three acids produced similar inhibitions.

Cierre espontáneo de la comunicación interventricular muscular aislada y la perimembranosa con aneurisma del septum / It closes spontaneous of the isolated muscular interventricular communication and the perimembranosa with aneurism of the septum

Introducción y objetivo: La comunicación interventricular (CIV) es la cardiopatía congénita más frecuente en todas las edades. El presente estudio se realizó con el fin de conocer el procentaje de CIVs musculares aisladas y perimembranosas con aneurisma del septum que se cierran espontáneamente y en cuánto tiempo lo hacen. Métodos: De febrero 2003 a diciembre 2005 se recolectaron 75 casos de neonatos diagnosticados con CIV muscular aislada y 10 con CIV perimembranosa aislada y con formación de aneurisma, quienes fueron seguidos por un período de al menos 30 meses. Se usó como método de diagnóstico la ecocardiografía bidimensional y el mapeo con Doppler color. Resultados: Al año de seguimiento, el 68 por ciento de las CIV musculares se cerró espontáneamente y 90 por ciento a los 2 años. Solo un 10 por ciento de las CIV perimembranosas con aneurisma del septum se cerraron a los 2 años de seguimiento. El tamaño de las comunicaciones varió de 1,5 a 6 mm en ambos grupos. Conclusión: Las CIV musculares cierran espontáneamente en el 90 por ciento de los casos a los 2 años de edad, no así las perimembranosas en que lo hacen solo en un 10 por ciento de los casos.

Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia

Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane wax, with cholesterol-lowering effects demonstrable in experimental models and in patients with type II hypercholesterolemia. The protective effects of policosanol on atherosclerotic lesions experimentally induced by lipofundin in rabbits and rats and spontaneously developed in stumptail monkeys have been described. The present study was conducted to determine whether policosanol administered orally to rabbits with exogenous hypercholesterolemia also protects against the development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to 2 kg were randomly divided into three experimental groups which received 25 or 200 mg/kg policosanol (N = 7) orally for 60 days with acacia gum as vehicle or acacia gum alone (control group, N = 9). All animals received a cholesterol-rich diet (0.5 percent) during the entire period. Control animals developed marked hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima thickness was significantly less (32.5 +/- 7 and 25.4 +/- 4 µm) in hypercholesterolemic rabbits treated with policosanol than in controls (57.6 +/- 9 µm). In most policosanol-treated animals, atherosclerotic lesions were not present, and in others, thickness of fatty streaks had less foam cell layers than in controls. We conclude that policosanol has a protective effect on the atherosclerotic lesions occurring in this experimental model.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46 percent) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40 percent) and brain (28-44 percent) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans

Effect of policosanol on cerebral ischemia in Mongolian gerbils

Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders

Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20 percent, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme

Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts

Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity

Estudio del efecto sobre lípidos y lipoproteínas séricos y de la tolerancia al tratamiento oral con dosis crecientes de policosanol en monos macaca arctoides / Study of effect of oral treatment with increased dosis of policosanol on serum an lipoproteins macaca arctoides mankeys

En diferentes modelos experimentales se ha demostrado que el Policosanol reduce los niveles séricos de colesterol. En el presente trabajo se investiga el efecto del tratamiento oral con dosis sucesivas crecientes de Policosanol sobre los lípidos y las lipoproteínas séricos de monos de la especie Macaca arctoides, así como la tolerancia a este tratamiento. Dosis de 50, 150, 300, 400 y 500 mg/kg de Policosanol se administraron a 4 animales adultos por períodos de 10 días. Los valores séricos de los lípidos y lipoproteínas se determinaron antes de iniciar el tratamiento, al finalizar la administración de cada dosis y a los 15, 30 y 45 días del período de lavado. De igual forma se cuantificaron los parametros de hematología y bioquímica sanguínea investigados. Además, se controló sistemáticamente el estado físico de los animales, su peso corporal, así como su repertorio conductual para determinar si el tratamiento afectaba alguno de los parámetros conductuales habituales de esta especie o si aparecía algún signo de fármaco toxicidad. Mediante la décima de Freidman se compararon los valores de los diferentes períodos de tratamiento con los niveles basales, así como los del período de lavado con la última etapa de tratamiento. Los resultados sugieren que la administración oral de dosis sucesivamente crecientes de Policosanol producen un rápido y notable decremento de las cifras de colesterol y LDL-C en monos de la especie Macaca arctoides y que el tratamiento es bien tolerado por esta especie a dosis tan elavadas como 500 mg/kg de peso corporal

Efectos del tratamiento con ateromixol (PPG) (5 mg) en pacientes con hiperlipoproteinemia tipo II / Effects of treatment with ateromixol (PPG) (5 mg) in patient with type II hypercholesterolaemia

Se presentan los resultados de un ensayo clínico doble ciego vs. placebo realizado en 2 hospitales de Ciudad de la Habana (Cuba), en el cual se investigó la eficacia y tolerancia de dosis únicas diarias de 5 mg deateromixol (PPG) en pacientes hipercolesterolémicos tipo II. Los niveles basales de los lípidos y lipoproteínas se definieron al culminar un período inicial de dieta hipocolesterolémica. El tratamiento redujo significativamente las cifras de colesterol (10.85%), LDL-C (16.08%), los índices LDL-C/HDL-C (18.95%) y colesterol/HDL-C (14.80%) e incremento modesto estadísticamente significativa las HDL-C (8.84%), mientras que los triglicéridos y las VLDL-C descendieron no significativamente. En el grupo placebo no se produjeron variaciones significativas de los parámetros referidos. Tampoco se registraron afectaciones de la frecuencia cardíaca, presión arterial, ni de los parámetros bioquímicos y hematológicos investigados atribuibles al tratamiento. El PPG fue muy bien tolerado. De 164 pacientes incluidos en el ensayo, 151 (92.07%) culminaron el tratamiento, no produciéndose bajas por reacciones adversas. Las experiencias adversas fueron leves y transitorias y su comparación entre grupos no reveló diferencias significativas. Los resultados demuestran la eficacia del PPG (5 mg), así como su excelente tolerancia, hechos que justifican su utilidad en el tratamiento de la hiperlipoproteinemia tipo II

Justicia pectoralis no previne las convulciones inducidas por PTZ y PTX / Justicia pectoralis in not prevention of the comvulsions induced by PTZ and PTX

Se evaluan los efectos de extractos acuosos de Justicia pectoralis sobre las convulsiones inducidas por pentilentetrazol y picrotoxina en ratones. Se realizaron curvas dosis-efectos de estos agentes convulsivantes en ausencia y presencia de una decocción de la planta verde, de un liofilizado hidrosoluble de la planta seca y de un psicofármaco de referencia, diazepam. Se demostró que los extractos de Justicia pectoralis no protegen contra las convulsiones inducidas por los agentes convulsivantes a diferencia del diazepam. Los resultados indican que el posible efecto sedante de Justicia pectoralis no está relacionado con el mecanismo de acción de los ansiolíticos del tipo de las benzodiazepinas

Posee Justicia pectoralis las características farmacológicas de los neurolépticos clásicos? / Posee Justicia pectoralis the pharmacological characteristics of classic neuroleptics?

Se estudian los efectos producidos por extractos acuosos de Justicia pectoralis sobre la estereotipia inducida por apomorfina en ratas y sobre los enlaces totales del spiperone-3H en sinaptosomas striatales de ratas. Pretratamientos con inyecciones intraperitoneales de extractos acuosos de la planta verde y seca, así como de soluciones del linfilizado del extracto de tilo seco (LT) no antagonizaron la estereotipia apomorfínica en ratas. De igual modo, la incubación de las preparaciones sinaptosomales con soluciones de LT (1-500 microng/mL) no produjo desplazamiento del spiperone-3H de receptores dopaminérgicos striatales. Los resultados indican que Justicia pectoralis no presenta las características antidopaminérgicas de los neurolépticos típicos

Efecto de Justicia pectoralis sobre la conducta exploratoria en ratones / Efect of Justicia pectoralis about of exploratory behaviour in mice

Se estudió el efecto de extractos acuosos de Justicia pectoralis sobre la conducta exploratoria en ratones. Se encontró que las decocciones de la planta (verde y seca) y el liofilizado de la planta seca inhibieron la conducta exploratoria de forma dependiente de la dosis. Este efecto fue similar al de varios psicofármacos de referencia. Estos resultados sugieren la presencia en Justicia pectoralis de compuestos neuroactivos con propiedades sedantes