RESUMEN
Since neurotoxicity of aluminium (Al) resembles the progressive neurodegeneration observed in Alzheimer Disease (AD), Al administration in several ways has been used to produce AD model. Intraperitoneal (ip) low dose (4.2 mg/ kg) Al injection in rats for long periods is the preferred method by some researchers. In this paper, the efficiency of this method for producing an AD model was evaluated. In this study, we looked at the neuropathology of Al and the characteristic lesions of AD by histological and immunohistochemical techniques and determined oxidative stress markers in the brains of Al-treated and control rats. We also made electrophysiological recordings at the hippocampus and evaluated possible behavioural changes by Morris water maze test. However, no pathologic changes occurred in the animals except for an impairment in long-term potentiation (LTP) in the hippocampus (e.g. the LTPs of population spike (PS) amplitude at 15 min post-tetanus were measured as 217±27% in Al-treated rats and as 240±42% in sham-treated rats, of baseline PS amplitude). According to the findings of the present study, low dose of ip Al in rats is not sufficient to produce a good AD model. Higher doses (≥10 mg/kg) should be used.
Asunto(s)
Aluminio , Enfermedad de Alzheimer/inducido químicamente , Aluminio/administración & dosificación , Aluminio/metabolismo , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Fenómenos Electrofisiológicos/efectos de los fármacos , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Femenino , Hipocampo/efectos de los fármacos , Inmunohistoquímica , Inyecciones Intraperitoneales , Potenciación a Largo Plazo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Xantina Oxidasa/metabolismoAsunto(s)
Antipsicóticos/efectos adversos , Síndrome de Dificultad Respiratoria/inducido químicamente , Insuficiencia Respiratoria/inducido químicamente , Risperidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Adulto , Antiparkinsonianos/uso terapéutico , Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Clorpromazina/uso terapéutico , Quimioterapia Combinada/efectos adversos , Distonía/inducido químicamente , Resultado Fatal , Haloperidol/uso terapéutico , Humanos , Laringe/efectos de los fármacos , Masculino , Olanzapina , Risperidona/uso terapéuticoRESUMEN
The effects of warming on the response to various contractile agents of calf cardiac vein were studied using 2.5-mm long cylindrical segments. Concentration-response curves for carbachol (10(-9)-3 x 10(-4) m), 5-hydroxytryptamine (5-HT; 10(-8)-3 x 10(-3)), potassium chloride (KCl; 10(-4)-5 x 10(-2) m) and calcium chloride (CaCl2; 10(-4)-10(-2)) were isometrically recorded at 37 and 41 degrees C (warming). During warming the sensitivity, but not the maximal response, of carbachol 5-HT, KCl, and CaCl2 was significantly higher than at 37 degrees C. Warming to 41 degrees C after treatment with NG-nitro-L arginine methyl esther (10(-5) m) did not modify the effect of warming. These results suggest that nitric oxide seems to have no role in the warming-induced responses in calf cardiac vein.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Calefacción , Óxido Nítrico/fisiología , Vasoconstrictores/farmacología , Animales , Cloruro de Calcio/administración & dosificación , Cloruro de Calcio/farmacología , Carbacol/administración & dosificación , Carbacol/farmacología , Bovinos , Vasos Coronarios/fisiología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Cloruro de Potasio/administración & dosificación , Cloruro de Potasio/farmacología , Serotonina/administración & dosificación , Serotonina/farmacología , Vasoconstrictores/administración & dosificación , VenasRESUMEN
The role of K+ ions on the vasoconstrictions induced by carbachol during cooling (28 degrees C) in the endothelium of a denuded calf coronary artery and cardiac vein (noncutaneous vessel) was studied. Carbachol (10(-9) - 3 x 10(-4) M) induced concentration-dependent contractions at both 37 degrees C and 28 degrees C. The sensitivity, but not the maximal response, of carbachol (10(-9) -3 x 10(-4) M) was significantly lower at 28 degrees C than at 37 degrees C. Cooling to 28 degrees C after treatment with tetraethylammonium (TEA, 10(-3) M) or ouabain (10(-5) M), after incubation in K+-free medium increased the sensitivity to carbachol in both preparations. The results suggest a role for K+ ions in the cooling-induced changes of noncutaneous vessels.
Asunto(s)
Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Frío , Potasio/fisiología , Vasoconstricción/efectos de los fármacos , Animales , Bovinos , Vasos Coronarios/anatomía & histología , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/fisiología , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Ouabaína/farmacología , Bloqueadores de los Canales de Potasio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Tetraetilamonio/farmacología , Vasoconstricción/fisiologíaRESUMEN
Increases in extracellular potassium (K+) concentration (up to 20 mM) cause dilation in some blood vessels. This may be particularly important in myocardial ischemia because in this condition K+ is released from ischemic cells. In this study, we investigated mechanisms of effect of increased K+ concentration on the tone of isolated bovine coronary artery. Bovine coronary arteries were isolated and mounted in organ baths for isometric tension recording. After an equilibration period, arteries were contracted with serotonin (1 microM). When serotonin contraction reached a steady-state, K+ concentration of organ baths was increased from physiological levels to 10 mM, 14 mM, 18 mM or 22 mM in four groups of the arteries. After a washout period, this procedure was repeated in presence of ouabain, a blocker of Na+ /K+ ATPase or a K+ channel blocker (tetraethylammonium, 4-aminopyridine, glibenclamide or barium). Increasing K+ concentration of the organ baths to 10 mM, 14 mM and 18 mM caused dilation in the arteries. Ouabain abolished the dilation and barium (a blocker of inward rectifier K + channels) inhibited the dilation significantly.According to our results there is K+ -induced dilation in bovine coronary artery and it involves activation of both Na+ /K+ ATPase and inward rectifier K+ channels.
Asunto(s)
Vasos Coronarios/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Potasio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Vasodilatación , Animales , Bario/metabolismo , Bovinos , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Bloqueadores de los Canales de Potasio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Vasoconstrictores/farmacologíaRESUMEN
In the present study, the effects of magnesium sulfate on tissue lactate and malondialdehyde (MDA) levels after cerebral ischemia in rabbits were studied. The rabbits were divided equally into three groups. Group 1 (n = 8) was the sham-operated control group, in group 2 (n = 8) only cerebral ischemia was induced by clamping bilaterally the common carotid arteries for 60 min, and in group 3 (n = 8) magnesium sulfate was administered at a dose of 100 mg/kg i.v. within 5 min after opening the clamps. In group 1 EEG recordings were obtained immediately and 60 and 120 min after craniectomy. In groups 2 and 3 EEG recordings were obtained immediately after craniectomy but before clamping and 60 min after clamping. One hour after opening the clamps and taking EEG recordings, brain cortices were resected, and the concentrations of lactate and MDA were determined using spectrophotometric/enzymatic and thiobarbituric acid methods, respectively. In all groups, there were significant differences between MDA and lactate levels (p < 0.05). There were no significant differences in lactate levels between groups 2 and 3 (p > 0.05), and also the preischemic EEG grades were the same in all groups. Preischemic and postischemic EEG values were significantly different (p < 0.05), and there were also significant differences between postischemic EEG grades in groups 2 and 3 (p < 0.05). There was a correlation between postischemic EEG grades and MDA and lactate levels. These results demonstrate that cerebral ischemia-reperfusion injury leads to an increase in brain tissue lactate and MDA levels, that magnesium sulfate suppresses the increase of MDA and lactate concentrations, and that magnesium sulfate treatment improves the EEG changes. The EEG grades correlated well with MDA and lactate levels.