855 resultados para Dose-Response Relationship


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The microinjection of carbachol into the medial preoptic area (MPO) of the rat induced natriuresis, kaliuresis and anti-diuresis in a dose-related manner. Atropine blocked all responses to carbachol. Hexamethonium impaired the dose-response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol. Nicotine alone had no effects, but pre-treatment with nicotine enhanced the responses to carbachol. These data show that activity of the muscarinic receptors of the MPO increases renal electrolyte and reduces water excretion. They also suggest that nicotinic receptors have an inhibitory effect on water excretion. Nicotine could act through mechanisms unrelated to nicotinic receptors to enhance the effect of the carbachol. © 1989.

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The effect of a lyophilized mistletoe infusion (LMI) was studied on isolated guinea-pig vas deferens. LMI caused a contraction which was partially blocked by phentolamine but not by atropine. LMI caused a shift to the left of the norepinephrine concentration-effect curve (CEC), an effect which appeared to be blocked by atropine and was absent in animals previously treated with reserpine and α-methyl-para-tyrosine. The increase of the norepinephrine maximal response induced by LMI was not blocked by atropine or pharmacological denervation. LMI caused a shift to the right of the acetylcholine CEC and had no effect on the acetylcholine maximal response. These results suggest that the effects seem to be due mainly to the presence of potassium ion in the LMI; however, the participation of muscarinic agonist(s) of reduced intrinsic activity or some tyramine-like substance could not be ruled out.

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The histamine releasing properties of glucose (mannose)-specific lectins isolated from Brazilian beans was examined. The Canavalia brasiliensis, Dioclea rostrata, and Dioclea virgata lectins induced histamine release in rat peritoneal mast cells similar to concanavalin A. Less potency and efficacy was observed for Canavalia maritima, Dioclea guianensis, and Dioclea violacea while very low activities were seen for the lectins from Dioclea grandiflora, Canavalia bonariensis, and Cratylia floribunda. The histamine releasing effect was quenched by higher doses of D. virgata lectin similar to what was reported for concanavalin A. This effect was abrogated by increasing the concentration of calcium in the incubating medium. As these above proteins have sites that bind calcium, higher doses of the lectins might withdraw the calcium which is essential for the mast cell secretion.

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The effect of thiopentone/halothane anaesthesia on the release of endogenous opioid, adrenocorticotrophin, arginine vasopressin, cortisol and catecholamine was investigated in ponies. The contribution made by halothane itself was studied by maintaining six ponies with a constant 12 per cent end tidal halothane concentration and five with a concentration ranging between 0.8 and 12 per cent. Cardiorespiratory depression was more prolonged in the ponies receiving a constant 1-2 per cent end tidal halothane concentration than in those which received less halothane. Plasma lactate concentration increased and haematocrit decreased during halothane anaesthesia. The concentrations of met-enkephalin, dynorphin and catecholamines did not change and those of β-endorphin, adrenocorticotrophin, arginine vasopressin and cortisol increased during halothane anaesthesia. Halothane appeared to be a major stimulus to pituitary adrenocortical activation because the adrenocortical secretion was proportional to the amount of halothane inhaled. β-endorphin increased proportionally more than adrenocorticotrophin and their plasma concentrations were not correlated, suggesting that they have independent secretion mechanisms.

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The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α 1-adrenergic receptor antagonist) and yohimbine (an α 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α 1-adrenoceptors and that inhibitory effects require α(2A)-adrenoceptors.

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Four trials of identical experimental design were conducted to determine the effects of temperature, dietary Lys level, and dietary Arg:Lys ratios on performance and carcass yield of male broilers. Birds of a commercial strain were grown from 21 to 42 d of age in wire-floored finishing batteries placed in environmental chambers. The chambers were programmed to provide either a constant thermoneutral temperature (21.1 C), a constant cold temperature (15.5 C), or a cycling hot diurnal temperature (25.5 to 33.3 C). Within each environment there was a factorial arrangement of three Lys levels (1.0, 1.1, and 1.2%) with four Arg:Lys ratios (1.1:1, 1.2:1, 1.3:1, and 1.4:1). Environmental temperature significantly influenced virtually every characteristic examined. Hot cyclic temperatures reduced weight gain, feed intake, and breast meat yield, and increased feed conversion, dressing percentage, leg quarter yield, and abdominal fat content. The cold environment promoted increased feed intake and mortality. Ascites and cardiomyopathy were the leading causes of death under cold exposure and thermoneutral conditions, whereas complications arising from heat exposure were the main cause of death under hot cyclic conditions. Levels of Lys affected leg quarter yield and abdominal fat content over all environments but increased breast meat yield only under cold conditions. Increasing Arg: Lys ratios improved feed conversion and dressing percentage and reduced abdominal fat content; it could not be determined whether these responses were consistent with Arg per se or were due to a nonspecific N response. As increasing Lys levels or Arg:Lys ratios did not improve weight gain, increase breast meat yield, or attenuate adverse effects due to heat or cold exposure, it is concluded that the levels of Lys and Arg suggested for 21 to 42 d by the NRC are adequate for birds of this age under the environmental conditions encountered.

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Malnutrition is related to diabetes in tropical countries. In experimental animals, protein deficiency may affect insulin secretion. However, the effect of malnutrition on insulin receptor phosphorylation and further intracellular signaling events is not known. Therefore, we decided to evaluate the rate of insulin secretion and the early molecular steps of insulin action in insulin-sensitive tissues of an animal model of protein deficiency. Pancreatic islets isolated from rats fed a standard (17%) or a low (6%) protein diet were studied for their secretory response to increasing concentrations of glucose in the culture medium. Basal as well as maximal rates of insulin secretion were significantly lower in the islets isolated from rats fed a low protein diet. Moreover, the dose-response curve to glucose was significantly shifted to the right in the islets from malnourished rats compared with islets from control rats. During an oral glucose tolerance test, there were significantly lower circulating concentrations of insulin in the serum of rats fed a low protein diet in spite of no difference in serum glucose concentration between the groups, suggesting an increased peripheral insulin sensitivity. Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate-1 as well as the insulin receptor substrate-1-p85 subunit of phosphatidylinositol 3-kinase association in response to insulin. Values were greater in hind-limb muscle from rats fed a low protein diet compared with controls. No differences were detected in the total amount of protein corresponding to the insulin receptor or insulin receptor substrate-1 between muscle from rats fed the two diets. Therefore, we conclude that a decreased glucose-induced insulin secretion in pancreatic islets from protein-malnourished rats is responsible, at least in part, for an increased phosphorylation of the insulin receptor, insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase. These might represent some of the factors influencing the equilibrium in glucose concentrations observed in animal models of malnutrition and undernourished subjects.

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The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.

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The present study was undertaken to look for the effect of chloroethylclonidine (CEC) on prejunctional alpha-2 autoreceptors of the canine saphenous vein. The effect was tested on tritium overflow evoked by electrical stimulation from tissues preloaded with 0.2 μM 3H- norepinephrine. Yohimbine (3-300 nM) and CEC (1-125 μM) increased and UK- 14,304 reduced the overflow of tritium evoked by 300 pulses (1 Hz). The maximal increase of tritium overflow caused by yohimbine was much higher than that caused by CEC: 3.82 and 1.74 times, respectively. CEC (5 μM) abolished both the inhibition caused by UK-14,304 and the enhancement of tritium overflow caused by yohimbine. However, when CEC was added after yohimbine, it reduced the electrically evoked overflow of tritium, the maximal effect being a reduction of tritium overflow by 35%. Prazosin (1-100 nM) did not change either the inhibitory effect of UK-14,304 or the facilitatory effect of CEC. These results suggest that CEC acts on two different subtypes of prejunctional alpha-2 autoreceptors; on one of them it acts as an antagonist and increases the electrically evoked overflow of tritium (and inhibits both the effect of UK-14,304 and yohimbine); on the other it acts as an agonist and reduces the electrically evoked overflow of tritium. Alternatively, one can admit that CEC is able to inhibit alpha-2 autoreceptors, which causes an increase of the transmitter release, and to activate a nonadrenergic inhibitory receptor thus causing a reduction of the transmitter release.

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To establish safety parameters, we in vitro studied the increase in intrapulpal temperature caused by the use of a cw CO2 laser. A thermistor was implanted in the inner part of the pulpal chamber of 25 human lower third molars to measure the intrapulpal temperature produced by laser powers between 2-10 W and exposure times of 0.5-25.0 s. The Pearson linear correlation factor applied to the measured values showed there is a direct relationship between the independent variable and the applied power. A variance analysis produced the linear regression equation: T=1.10+(0.127)E where T is the temperature and E the energy. The results showed that, with a power of 4 W and maximum exposure time of 2.5 s (10 J) and a power density of 12738.85 W cm-2, there will be no damaging reactions affecting the pulpal tissues.

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Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of α2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.

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In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1.0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n=10). Myocardial histology was analysed in 3 μm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.