ABSTRACT
The 5-HT(4) receptor agonists, and gastrointestinal (GI) prokinetic agents, cisapride and tegaserod, lack selectivity for the 5-HT(4) receptor. Cisapride is a potent human ether-à-go-go-related gene (hERG) potassium channel inhibitor while cisapride and tegaserod have significant affinity for 5-HT(1) and 5-HT(2) receptor subtypes. Marketing of both compounds was discontinued due to cardiovascular concerns (cardiac arrhythmias with cisapride and ischemic events with tegaserod). The reported association of tegaserod with ischemia has been postulated to involve coronary artery constriction or augmentation of platelet aggregation. This in vitro study investigated the effects of two of the new generation of highly selective 5-HT(4) receptor agonists, velusetrag and TD-8954, on canine, porcine and human coronary artery tone, human platelet aggregation and hERG potassium channel conductance. No significant off-target actions of velusetrag or TD-8954 were identified in these, and prior, studies. While cisapride inhibited potently the hERG channel currents, tegaserod failed to affect platelet aggregation, and had only a small contractile effect on the canine coronary artery at high concentrations. Tegaserod inhibited the 5-HT-induced contractile response in the porcine coronary artery. New generation 5-HT(4) receptor agonists hold promise for the treatment of patients suffering from GI motility disorders with a reduced cardiovascular risk.
Subject(s)
Azabicyclo Compounds/pharmacology , Benzimidazoles/pharmacology , Cisapride/pharmacology , Indoles/pharmacology , Piperidines/pharmacology , Serotonin 5-HT4 Receptor Agonists/pharmacology , Adult , Animals , CHO Cells , Coronary Vessels/drug effects , Coronary Vessels/metabolism , Cricetinae , Cricetulus , Dogs , Ether-A-Go-Go Potassium Channels/drug effects , Ether-A-Go-Go Potassium Channels/metabolism , Female , Humans , In Vitro Techniques , Male , Middle Aged , Platelet Aggregation/drug effects , SwineABSTRACT
Oribius species are small flightless weevils endemic to the island of New Guinea and far northern Cape York, Australia. The adults feed externally on leaves, developing fruit and green bark, but their impact as pests and general host use patterns are poorly known. Working in Eastern Highlands Province, Papua New Guinea, we carried out structured host use surveys, farmer surveys, shade-house growth trials and on-farm and on-station impact trials to: (i) estimate the host range of the local Oribius species; (ii) understand adult daily activity patterns; (iii) elucidate feeding habits of the soil dwelling larvae; and (iv) quantify the impacts of adult feeding damage. Oribius inimicus and O. destructor accounted for nearly all the Oribius species encountered locally, of these two O. inimicus was the most abundant. Weevils were collected from 31 of 33 plants surveyed in the Aiyura Valley, and a combination of farmer interviews and literature records provided evidence for the beetles being pestiferous on 43 crops currently or previously grown in the Highlands. Adult weevils had a distinct diurnal pattern of being in the upper plant canopy early in the morning and, to a lesser extent, again late in the afternoon. For the remainder of the day, beetles resided within the canopy, or possibly off the plant. Movement of adults between plants appeared frequent. Pot trials confirmed the larvae are root feeders. Quantified impact studies showed that the weevils are damaging to a range of vegetable and orchard crops (broccoli, capsicum, celery, French bean, Irish potato, lettuce, orange and strawberry), causing average yield losses of around 30-40%, but up to 100% on citrus. Oribius weevils pose a significant and, apparently, growing problem for Highland's agriculture.
Subject(s)
Crops, Agricultural/parasitology , Host-Parasite Interactions/physiology , Weevils/physiology , Animals , Behavior, Animal/physiology , Circadian Rhythm/physiology , Feeding Behavior/physiology , Larva , Papua New GuineaABSTRACT
La hidrogenación biológica de los rumiantes o la industrial producen isomerización de los ácidos grasos que componen la grasa, pudiéndose formar isómeros trans. Se ha postulado que una dieta alta de estos isómeros puede ser un riesgo para la salud, aunque no se conocen con certeza las consecuencias de su ingesta. Existen numerosos estudios epidemiológicos que asocian el consumo de ácidos grasos trans con riesgos como: aumento del colesterol LDL y disminución del HDL, aumento del riesgo de enfermedad coronaria, aumento del la Lp(a), aumento de la probabilidad de padecer cáncer de mama y de colon, la interferencia en el metabolismo de los ácidos grasos esenciales y también se cree que pueden comprometer el desarrollo fetal e infantil. En varios países se ha disminuído el consumo de isómeros trans mediante la reducción del contenido de los mismos en margarinas (una de las principales fuentes de trans) pero no así en productos alimenticios industriales. La ingesta estimada de AG trans para EE.UU. es de 5,3 - 8,1 g/día y en Europa de 1,4 - 5,4 g/día. Hasta nuestro conocimiento, en la Argentina todavía no hay datos de ingesta de AG trans como así tampoco información sobre el contenido de éstos en los alimentos. En este trabajo se incluyen los resultados de análisis realizados en algunos alimentos potenciales fuentes de AG trans y datos sobre su contenido en leche materna como reflejo de su consumo. Los valores más altos fueron hallados en las margarinas (19 a 9,5 g por ciento), mientras que papas fritas de "fast food" contenían 6,5 g por ciento y algunos panificados con 0,1 a 3,6 g por ciento. En la leche materna se halló que un 2,5 g por ciento del total de ácidos grasos se hallaban en forma de isómeros trans (AU)
Subject(s)
Humans , Animals , Pregnancy , Infant, Newborn , Fatty Acids/adverse effects , Dietary Fats/adverse effects , Fatty Acids/analysis , Plant Oils/analysis , Milk, Human , Dietary Fats/analysis , Coronary Disease/diet therapy , Child Development , Hydrogenation , Isomerism , Table of Food Composition , Fetal Development , Breast Neoplasms/chemically induced , Colonic Neoplasms/chemically induced , Margarine/analysis , Margarine/adverse effectsABSTRACT
Heparin-induced thrombocytopenia is an increasingly common side effect associated with heparin usage. In the more severe manifestation of the syndrome, patients can develop thrombosis; a 10% mortality is associated with heparin induced thrombocytopenia. To date, the therapeutic options for patients with heparin-induced thrombocytopenia are limited. Glycoprotein IIb/IIIa inhibitors have been shown to block platelet aggregation induced by a wide variety of agonists. The ability of antibody and synthetic small molecule inhibitors of glycoprotein IIb/IIIa to block in vitro activation and aggregation of platelets in response to heparin-induced thrombocytopenia positive serum/heparin was examined using flow cytometry, platelet aggregometry, and luminescence aggregometry. Abciximab, YM 337, and SR 121566A were each found to inhibit platelet microparticle formation and P-selectin expression in whole blood, in response to heparin-induced thrombocytopenia positive serum/heparin. In a platelet rich plasma system, the platelet aggregation response was inhibited by all three agents. The IC50 for inhibition of heparin-induced thrombocytopenia positive serum/heparin induced platelet aggregation by SR 121566A was 18 nM, a concentration which was 4 to 8 fold lower than that observed for collagen and arachidonic acid induced aggregation. Adenosine triphosphate release from activated platelets, as measured by luminescence aggregometry, was concentration-dependently inhibited by SR 121566A. These results suggest that glycoprotein Ilb/IIIa inhibitors may be beneficial in the management of heparin-induced thrombocytopenia and warrant further investigation.
Subject(s)
Blood Platelets/physiology , Blood Proteins/pharmacology , Heparin/adverse effects , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Thrombocytopenia/blood , Benzylamines , Drug Interactions , Humans , Immunoglobulin Fab Fragments/immunology , Immunoglobulin Fab Fragments/pharmacology , Piperidines , Platelet Glycoprotein GPIIb-IIIa Complex/immunology , Thiazoles , Thrombocytopenia/chemically inducedABSTRACT
Referente a la intoxicación crónica por arsénico en Argentina, cuya fuente principal son las aguas subterráneas ya que ciertas áreas endémicas sobrepasan las concentraciones máximas aceptadas. Presenta la fisiopatología de la intóxicación y cuatro casos clínicos
Subject(s)
Argentina , Arsenic , ToxicologyABSTRACT
Referente a la intoxicación crónica por arsénico en Argentina, cuya fuente principal son las aguas subterráneas ya que ciertas áreas endémicas sobrepasan las concentraciones máximas aceptadas. Presenta la fisiopatología de la intóxicación y cuatro casos clínicos
