Acta physiologica, pharmacologica et therapeutica latinoamericana : organo de la Asociacion Latinoamericana de Ciencias Fisiologicas y [de] la Asociacion Latinoamericana de Farmacologia最新文献

It was decided to made a pharmacological study of the cholinergic participation in the sinoaortic denervation experimental model by analyzing the cardiovascular effects of several muscarinic agonists and the anticholinesterase neostigmine administered either by intravenous via or by the intracerebroventricular via. The activity of the enzyme acetylcholinesterase was also evaluated in diverse structures of the central nervous system after the intracerebral administration of neostigmine. Sinoaortic denervation increases the pressor response to the i.c.v. administration of the agonist bethanechol and of the anticholinesterase neostigmine but it diminishes the bradycardic effect. However it would not alter the cardiovascular responses to the i.v. injection of the agonist oxotremorine and to the i c v. administration of the agonist McNeil-A-343. After the i c v. administration of neostigmine, the enzymatic activity oscillated among 24%-30% in hypothalamic structures and among 42%-52% in the remaining tissues, without differences between the rats with sham operation and those with sinoaortic denervation. The results suggest that M, muscarinic receptor subtype would not be involved in the cardiovascular effects of the central cholinergic stimulation On the other hand, it would support the idea of an involvement of muscarinic receptors in the observed changes. Because the used route of administration of neostigmine, a greater degree of inhibition of the hypothalamic acetylcholinesterase is observed, suggesting then that the hypothalamic structures could be involved in the cardiovascular effects induced by the intracerebral administration of the anticholinesterase.

This work includes results on chronotropic, inotropic and lusitropic changes induced by capsaicin on isolated rat atria. As regards spontaneous frequency, it was stimulated from 10(-9) M up to 7 x 10(-7) M of capsaicin. A simultaneous depression in developed force (F) showed a significant correlation with this positive chronotropic effect up to 7 x 10(-8) M of capsaicin, which is the result of the negative staircase phenomenon in the rat heart. The correlation was lost at 2 and 7 x 10(-7) M of capsaicin since in spite of the sustained increase in atrial rate the decrease in F was reversed and then depressed again at 2 and 7 x 10(-6) M of capsaicin without changes in frequency. A concentration of capsaicin that overcome the negative staircase phenomenon, 5 x 10(-7) M, was tested as unique dose resulting in stimulation of the chronotropic, inotropic and lusitropic states of the atria. Percentual differences with respect to control values were maximal after 1-3 minutes for frequency (10 +/- 3%), F (29 +/- 4%), maximal velocity of force development (+F = 50 +/- 12%) (in all cases +F and -F bold indicates +F and -F, respectively), and maximal velocity of relaxation (-F = 64 +/- 13%); a positive lusitropic effect was significant after 8-10 minutes (+F/-F = 17 +/- 7%). Capsaicin did not affect the rat atria in the presence of 10(-6) M of ruthenium red, a blocker of capsaicin activation of sensory nerves, indicating that the stimulatory effects were entirely mediated by the release of neurotransmitters and that this concentration of capsaicin was not deleterous "per se". Capsaicin elicited similar inotropic responses in electrically driven isolated atria (+F = 41 +/- 9%) but the positive lusitropic effect was lost suggesting that capsaicin-induced increases in -F are limited at a frequency higher than the spontaneous frequency (11 +/- 6 vs. 32 +/- 4%, respectively). 10(-6) M of CGRP8-37, an antagonist of CGRP1 receptors, suppress the stimulatory effects of capsaicin on atrial contraction. In summary, atrial rate as compared to atrial contraction is more sensitive to the neurotransmitter released by capsaicin, which results in mechanical effects expressing the negative staircase phenomenon in the rat at low concentrations of capsaicin. The positive chronotropic, inotropic and lusitropic responses elicited by capsaicin are mediated by the release of neurotransmitters from sensory fibbers and no deletereous effects of capsaicin "per se" became evident when the release of neuropeptides was prevented. Atrial contraction was depressed at higher capsaicin concentrations than the one showing stimulatory effects. Stimulation of atrial contractility is mediated by activation of CGRP receptors.

Here we demonstrate that T. cruzi antigen molecule SAPA (shed acute phase antigen) with neuraminidase-trans sialidase activity triggers down-regulation of T lymphocyte proliferation by interacting with T lymphocyte muscarinic acetylcholine receptors (mAChR). SAPA attachment to mAChR from Lyt 2.2+ T cells resulted in synthesis of cyclic GMP (cGMP) and secretion of PGE2, an immunoregulator effector substance. These T suppressor cell signals were blunted by atropine and by indomethacin. Cell sorter analysis showed that the interaction of SAPA with purified T cells, affected the ratio of L3T4+/Lyt 2.2+ T cells increasing the percentage of Lyt 2.2+ T cells, effect that was inhibited by the mAChR antagonist, atropine. The interaction between SAPA and mAChR from Lyt 2.2+ T cells may result, therefore, in the down-regulation of the host immune response as consequence of T suppressor/cytotoxic cells activation and PGE2 release as they were observed. These results support the theory of an immunosuppressive state that contribute to the chronic course of Chagas' disease.

Albendazole (ABZ) is an anthelmintic benzimidazole drug widely used in human and veterinary medicine. ABZ has binding affinity to both mammalian and helminth parasite tubulin. In the current work, we have performed in vitro assays and in vivo experiments in which rats were given ABZ orally to better characterize the action of the drug on the polymerization of rat brain microtubules and on the detyrosination/tyrosination cycle that occurs on the COOH-terminal end of alpha-tubulin. The results showed that ABZ inhibits brain microtubule polymerization in vitro, and significantly delayed microtubule assembly in vivo. The tyrosination reaction cycle was not affected in vitro; however, in rats to which the drug was administered orally, the levels of in vitro tyrosination were reduced when compared to the controls with mock treatment. These results suggest that this apparent inhibition would be due to a decrease in the amount of substrate caused by the depolymerizing effect of ABZ and the subsequent tyrosination in the intact brain with endogenous tyrosine. In conclusion, ABZ strongly affects tubulin dynamics both in vivo and in vitro. The outcome of these experiments is a contribution to the understanding of the molecular mechanisms involved in the antimicrotubular action of benzimidazole compounds.

Fluorescence anisotropy determinations were performed on hypotonically lysed red blood cells from 12 healthy, free living, premenopausal and 10 postmenopausal women fed a self-selected diet. Fatty acid composition of phospholipids and cholesterol esters, lipid/lipid and lipid/protein ratios were also determined in erythrocyte ghosts along the menstrual cycle or during hormonal replacement therapy. The postmenopausal women were treated with transdermal 17-beta estradiol (approx, delivery rate of 50 micrograms/day) for a 5-week period and with a combination of percutaneous administration of estradiol and orally administered medroxyprogesterone acetate (5 mg/day) for 5 weeks more. Premenopausal women were studied in the mid-follicular and mid-luteal phases of their menstrual cycles. Membrane fluidity in cells from the luteal phase was greater than that observed in the follicular phase. After estradiol treatment, postmenopausal women exhibited a significant raise in the fluorescence anisotropy. The association with progesterone prevented the estrogen-induced increase of the anisotropy values. Estrogen administration also produced an increment in the relative content of cholesterol and membrane proteins that was reverted by progesterone addition. Changes induced by estradiol treatment in the fatty acid pattern of phospholipids and cholesterol esters were characterized by an increment in the monoenoic/saturated fatty acid ratio and linoleic relative content, with a concomitant decrease in the proportion of arachidonic and docosatetraenoic acids. These results suggest that the modification of the desaturase activities may be involved in a mechanism by which these hormonal-induced changes take place. The present study demonstrated that human erythrocyte fluidity is under hormonal control subjected through changes in the proportion and quality of the membrane lipids.

Here we described a critical analysis of the neonatological procedure of early cord clamping, meaning this, within 40 seconds after birth. Fifty three cases are here analysed, in which this practice was not performed, but instead a late umbilical cord clamping was done after birth or after the cord had stopped beating. Variations in hematocrito values within 24 to 36 hours after birth were studied. A transitory polycithemia, with a maximum peak 12 hours post-delivery was observed. These values returned to normal levels between 24 and 36 hours after birth. K vitamin was not administered to any of the newborns. No pathology appeared related to this transitory polycithemia. In can be concluded that the late umbilical cord clamping represents no risk to the new-born and that the pathological phenomena described under these circumstances may be attributed to the increase in K vitamin dependent coagulation factors that are induced by the routinary administration of phitonadione to all normal newborns.

The purpose of this study was to analyze the effect of fluoxetine upon human T lymphocyte proliferation, and to assess the early signals elicited after T cell triggering and cAMP formation. Blood samples from normal human volunteers were drawn from venipuncture and T cells were cultured in the presence or absence of Concanavalin A (Con A) and fluoxetine. Protein Kinase C (PKC) levels and cyclic adenosine monophosphate (cAMP) formation were also measured. Fluoxetine exerted dual effect, depending on the degree of lymphocyte activation: at mitogenic concentrations of Con A (2 micrograms/ml), we observed an inhibitory effect on cellular proliferation. This inhibitory effect involves PKC degradation and cAMP formation. On the other hand, when submitogenic Con A concentrations (1 microgram/ml) were used, fluoxetine stimulated the cellular response and increased PKC translocation. The participation of extracellular calcium mobilization could be involved in these mechanisms. According to our results, fluoxetine seems to modulate calcium influx which, in turn, would influence PKC translocation, thus modulating the immune response through a mechanism that could be involving cAMP participation.

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome.

Velocity of erosion on human teeth exposed to a carbonated beverage as a function of time and temperature has been studied in vitro, as well as the effect of the experimental formation of a acquired pellicle and the influence of the inclusion of either F or saliva on the dissolving capacity of beverage. During the first stage of exposition, erosion as a function of time showed a biphasic curve, being the rate low during the first 10 minutes time; thereafter, velocity increased and remained stable until the 60 minute incubation period finished. At the second stage, demineralization followed a monophasic curve, displaying a stable rate until the end of it. At the initial stage, molar ratio Ca/P was much less than that corresponding to hydroxyapatite (approximately 1.67); however, as exposition to erosive beverage was prolonged, the former ratio reached values compatible with this mineral species. F or saliva incorporation together with the experimental formation of the acquired pellicle significatively reduced beverage demineralizing capacity (p < 0.0001). This finding introduces the possibility of attenuating such erosive capacity of carbonated beverages by including not excessively toxic fluoride quantities.

Reductions in the hemoglobin (Hb) mass are followed by increases in the level of plasma erythropoietin (EPO) concentrations which are directly proportional to the level of the hormone required to bring the hemoglobin values back to normalcy. Hypoplastic anemias (AHC) on the other hand, are accompanied by significantly larger increases in the erythropoietin concentration. In this study we have measured the relationship between the severity of the anemia and the levels of erythropoietin elimination in the urine patients (EpoU) under treatment with cytostatic drugs. Simultaneously other parameters used as indicators of bone marrow activity were determined. These observations suggest that the levels of erythropoietin depends not only by the tissue oxygen availability but by others factors related to the marrow cellularity.