Pharmacological effects of two cytolysins isolated from the sea anemone Stichodactyla helianthus.

Sticholysins I and II (St I/II) are cytolysins purifi ed from the sea anemone Stichodactyla helianthus. In this study, we show their pharmacological action on guinea-pig and snail models in native and pH-denatured conditions in order to correlate the pharmacological fi ndings with the pore-forming activity of both isoforms. In guinea-pig erythrocytes (N = 3), St II possessed higher haemolytic activity in comparison with St I and this activity was lost at an alkaline pH. In molluscan central neurons (N = 30), they irreversibly decreased the amplitude of the cholinergic response; St I (EC 50 0.6 μmolL–1) was more potent than St II (EC 50 >6.6 μmolL–1) and they both increased the duration of the action potential; these effects were absent at an alkaline pH. In guinea-pig isolated atrium (N = 25), both increased the amplitude of the contraction force, but St II was more potent than St I (EC 50 0.03 μmolL–1 and 0.3 μmolL–1, respectively) and this effect persisted at an alkaline pH. In summary, both cytolysins have neuroactive and cardioactive properties. The main mechanism in molluscan neurons seems to be associated with the cytolytic activity of these molecules, whereas in guinea-pig atrium, the existence of an additional pharmacological mechanism might be contributing to the observed effect.

Terapéutica psiquiátrica integral / Comprehensive psychiatric therapy

El manual pretende contribuir a la actualización de los recursos biológicos, psicológicos y sociales apoprtados hasta hoy para el tratamiento de las afecciones psiquiátricas mayores y menores.

Enfermedad hemolítica perinatal por dos aloanticuerpos: presentación de un caso / Alloantibody linked perinatal hemolytic disease: case report

La etiopatogenia de la enfermedad hemolítica del recién nacido está basada en la incompatibilidad de grupo sanguíneo entre la madre y el recién nacido. Los neonatos con enfermedad hemolítica por incompatibilidad ABO usualmente tienen madres de grupo O porque la IgG anti-A y anti-B puede atravesar la placenta y sensibilizar los eritrocitos neonatales. Otros anticuerpos además de los ABO han sido reportados como causa de enfermedad hemolítica del recién nacido, ejemplo: anti-D, anti-C, anti-K, anti-Jk, anti-Fy, anti-S, etc. Presentamos el caso de una mujer de 33 años de edad, que en el segundo trimestre de su segunda gestación presentó una hemorragia que motivó la transfusión de una unidad de concentrado de eritrocitos. No se reportó reacción transfusional. El producto de dicha gestación fue un neonato masculino de 2,5 Kg de peso y apgar 6-8 que presentó íctero a las 24 horas después del parto. El fenotipaje ABO de los eritrocitos maternos y del neonato arrojó que la madre era de grupo O y el neonato de grupo B. La prueba de Coombs directa fue positiva 2+ en el neonato y la prueba de Coombs indirecta resultó positiva 3+ en la madre. Dos aloanticuerpos fueron detectados en el suero materno como causa del íctero neonatal, un anti-A y un anti-Jk b. Los eritrocitos maternos fueron fenotipados como Jk b negativos. El tratamiento con fototerapia al neonato se inició a las 40 horas de edad y se prolongó hasta los 10 días de nacido. Una transfusión simple de concentrado de eritrocitos fenotipados fue administrada al neonato a los 8 días de edad.

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

Síndrome diarreico de evolución prolongada en el lactante e intolerancia transitoria a la glucosa: uso de alimentación enteral con una fórmula con glucosa / Diarrhoeal syndrome with long evolution in infants and transient glucose malabsorption: use of enteral feeding with a glucosed formula

45 niños con el diagnóstico de intolerancia transitoria a la glucosa hecho sobre la base de persistencia de deposiciones líquida en forma prolongada y exámenes de pH y Fehling de heces alterados en dos oportunidades después de 48 horas de estar recibiendo exclusivamente una fórmula con glucosa como único hidrato de carbono, fueron alimentados con gastroclisis de esa misma fórmula en goteo permanente durante 24 horas y por (x ñ EE) 9,2 ñ 1,2 días. Se concluye que el procedimiento es útil por los seguientes hechos: 1) Representa un paso previo a la nutrición parenteral total al mismo tiempo que permite usar la vía enteral. 2) Es capaz de evitar que los enfermos tengan que recibir por vía enteral mezclas elementales complejas que alargan el retorno a la normalidad, una vez controlada la diarrea. 3) Permite el uso de una fórmula equilibrada y preparada industrialmente lo que evita la manipulación a nivel local. 4) Da buen resultado en el 58% de los casos. 5) En caso de fracasar y si la fórmula se usa por un período corto no desnutre al niño dejándolo en condiciones semejantes a las que tenían previamente al uso del procedimiento

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