RESUMEN
Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). Therefore, there is an urgent need for therapeutic strategies capable of returning cancer survivors back to their previous quality of life. The present study investigated whether resveratrol (RSV) or curcumin (CUR) administration could affect mnemonic function and brain morphological changes following DOX administration in rats. Male Wistar rats were divided into 4 groups: DOX group (2.5 mg/kg/week for 4 weeks, i.p., plus distilled water for 28 days, oral gavage - OG), DOX + RSV group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus RSV, 10 mg/kg/day for 28 days, OG), DOX + CUR group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus CUR, 100 mg/kg/day for 28 days, OG) and control (CTR) group (0.9% saline solution weekly for 4 weeks, i.p., plus distilled water for 28 days, OG). Behavioral analyses (open field - OF - and the novel object recognition test - NORT) were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry for GFAP (glial fibrillary acidic protein) expression in astrocytes and Iba1 (ionized calcium-binding adaptor molecule 1) expression in microglia. DOX-injected rats presented short-term and long-term memory impairments as seen in the NORT at 3 and 24 h after habituation and increased GFAP and Iba1 expression, respectively, in astrocytes and microglia of the frontal cortex, hypothalamus and hippocampus. Such cognitive deficits were prevented by CUR at both periods and by RSV at 24 h. DOX-induced astrogliosis and microgliosis were avoided by RSV and CUR. No signs of demyelination or neuronal loss were found in any group. Thus, CUR and RSV prevented memory loss, astrogliosis and microgliosis induced by DOX monotherapy.
Asunto(s)
Disfunción Cognitiva , Curcumina , Animales , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Curcumina/farmacología , Curcumina/uso terapéutico , Doxorrubicina/toxicidad , Masculino , Calidad de Vida , Ratas , Ratas Wistar , ResveratrolRESUMEN
One hundred thirteen patients undergoing cardiopulmonary bypass were randomly assigned to receive either bovine or porcine heparin. Heparin was infused at 4.5 mg/kg during bypass and administered at the lesser of 70 units/kg or 5000 units/dose at 12-hour intervals postoperatively. Platelet counts decreased to 45% of preoperative levels during the first 3 days postoperatively (porcine, 44 +/- 13%, n = 50; bovine, 46 +/- 15%), but returned to preoperative levels by the seventh postoperative day. The average blood loss in the porcine heparin group significantly exceeded that of the bovine heparin group (porcine, 1350.7 +/- 727.8 ml; bovine, 1059.6 +/- 381.0 ml; p less than .01). Consequently, the platelet transfusion requirement was greater in the porcine heparin group (porcine, 1.7 +/- 3.9 units; bovine, 0.5 +/- 1.7 units; p less than .05); however, blood and blood component (with the exception of platelets) administration was not significantly different between the two groups. The four patients taking anticoagulants or antiinflammatory agents in the porcine group required a mean of 8.5 units of red blood cells (RBC) plus supplemental platelets. The seven such patients in the bovine group received a mean of 3.0 units of RBC and no platelets. Thus, the use of porcine heparin resulted in a generalized increase in postoperative bleeding with increased management problems in patients undergoing cardiopulmonary bypass.
Asunto(s)
Puente Cardiopulmonar , Hemorragia/inducido químicamente , Heparina/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Trombocitopenia/inducido químicamente , Animales , Transfusión Sanguínea , Bovinos , Femenino , Humanos , Masculino , Recuento de Plaquetas/efectos de los fármacos , Transfusión de Plaquetas , Estudios Prospectivos , Especificidad de la Especie , PorcinosRESUMEN
Two hundred seven consecutive patients were randomized into four groups based on left ventricular end-diastolic pressure and subsequently into groups receiving crystalloid cardioplegia or blood cardioplegia. Hemodynamic data and enzymatic evidence of myocardial ischemia were examined postoperatively. We found slight but significant improvement in the blood cardioplegia group regarding left ventricular stroke work index. Similarly, the levels of creatine kinase and serum glutamic oxaloacetic transaminase were slightly but significantly better with blood cardioplegia. We believe that the technique of blood cardioplegia offers a slight but statistically significant advantage.
Asunto(s)
Paro Cardíaco Inducido/métodos , Compuestos de Potasio , Anciano , Aspartato Aminotransferasas/sangre , Sangre , Gasto Cardíaco/efectos de los fármacos , Ensayos Clínicos como Asunto , Frío , Puente de Arteria Coronaria , Creatina Quinasa/sangre , Femenino , Hemodinámica , Humanos , Isoenzimas/sangre , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Miocardio/enzimología , Potasio/uso terapéutico , Distribución Aleatoria , Volumen Sistólico/efectos de los fármacos , Factores de TiempoRESUMEN
A significant amount of red blood cells were conserved with use of the Cell Saver in cardiac surgery patients and in some orthopedic and vascular surgery patients. No major complications have been associated with its use in our cases. Our results are similar to those of others who have reported on the use of this device. In the cardiac surgery patients we observed significant serum protein losses which had to be replaced. We recommend the use of intraoperative albumin to help maintain adequate urinary output and hemodynamic stability.
Asunto(s)
Transfusión de Sangre Autóloga/instrumentación , Procedimientos Quirúrgicos Cardíacos , Ortopedia , Procedimientos Quirúrgicos Vasculares , Proteínas Sanguíneas , Transfusión de Sangre Autóloga/efectos adversos , Prótesis de Cadera , HumanosRESUMEN
The effects of a blood borne vasoconstrictor on prostaglandin synthesis by microsomal enzyme preparations from rat aorta, heart and stomach fundus were determined. The principle product formed from arachidonate by these preparations in the absence of added vasoactive factor was prostaglandin I2 (as measured by recovery of 6-keto-prostaglandin F1 alpha). Addition of vasoactive factor stimulated overall prostaglandin synthesis and also reduced the ratio of 6-keto-prostaglandin synthesis F1 alpha to other products. No correlation was found between factor induced increases in overall synthesis and changes in this ratio. However, the factor produced a ratio which was specific for each tissue. The further the initial ratio of preparation was from its tissue specific level, the greater the effect of the factor. Blood free tissues continued considerable factor activity. Hence the variations in ratios in the absence of exogenous factor could be due to the presence of endogenous factor contaminating the preparations. Indomethacin not only inhibited overall prostaglandin synthesis but also decreased the ratio of 6-keto-prostaglandin F1 alpha to other products. Both these effects of indomethacin were counteracted by addition of exogenous factor. These results provide evidence that, in addition to their effects on the cyclooxygenase reaction, the factor and indomethacin interact a the second site; one involved in the change in ratio 6-keto-prostaglandin F1 alpha to other products.
Asunto(s)
Ácidos Araquidónicos/metabolismo , Epoprostenol/metabolismo , Prostaglandinas/metabolismo , Vasoconstrictores/farmacología , Adulto , Animales , Aorta/metabolismo , Fundus Gástrico/metabolismo , Humanos , Indometacina/farmacología , Masculino , Microsomas/metabolismo , Miocardio/metabolismo , Conejos , RatasRESUMEN
The effects of a coronary vasoconstrictor, obtained from human blood plasma, on aggregation and arachidonate metabolism by human platelets was determined. At low concentrations, the vasoactive factor stimulated formation of prostaglandins, thromboxane B2, and 12-L-hydroxyeicosatetraenoic acid in both intact platelets and in platelet microsomal enzyme preparations. As factor concentration was increased, thromboxane B2 formation decreased, but production of the other products continued to rise. Low concentrations of factor initiated platelet aggregation, whereas high concentrations prevented arachidonate-induced aggregation. Low levels of factor could induce aggregation via stimulation of thromboxane A2 production. Increases in formation of 12-L-hydroperoxyeicosatetraenoic acid at high factor concentrations could inhibit formation of thromboxane A2 and thus prevent aggregation.
Asunto(s)
Plaquetas/enzimología , Vasos Coronarios/fisiología , Lipooxigenasa/sangre , Vasoconstrictores/sangre , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Adulto , Ácidos Araquidónicos/metabolismo , Plaquetas/efectos de los fármacos , Humanos , Indometacina/farmacología , Microsomas/enzimología , Agregación Plaquetaria/efectos de los fármacos , Prostaglandinas E/metabolismo , Prostaglandinas F/metabolismo , Tromboxano B2/metabolismoAsunto(s)
Microsomas/metabolismo , Prostaglandinas/biosíntesis , Vasoconstrictores/farmacología , Animales , Ácidos Araquidónicos/farmacología , Aspirina/farmacología , Depresión Química , Sinergismo Farmacológico , Epinefrina/farmacología , Hemina/farmacología , Indometacina/farmacología , Médula Renal/metabolismo , Masculino , Prostaglandinas D/biosíntesis , Prostaglandinas E/biosíntesis , Prostaglandinas F/biosíntesis , Conejos , Estimulación Química , Triptófano/farmacología , Vasoconstrictores/sangreAsunto(s)
Fenómenos Fisiológicos Sanguíneos , Vasos Coronarios , Microsomas/metabolismo , Prostaglandinas/biosíntesis , Vasoconstricción , Animales , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Técnicas In Vitro , Riñón/metabolismo , Riñón/ultraestructura , Masculino , Microsomas/efectos de los fármacos , Miocardio/metabolismo , Miocardio/ultraestructura , Conejos , Estimulación Química , Vasoconstricción/efectos de los fármacosRESUMEN
Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.