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

We previously reported that aqueous extract of Larrea divaricata Cav. had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. To determine the probable mechanism of the inhibitory action of the extract upon cell growth, the participation of intracellular signals involved in the inhibition of cell proliferation, namely the activation of adenylate cyclase system was studied. The production of cyclic 3', 5 adenosine monophosphate (cAMP) in presence and absence of extract was analized. The extract increased the cAMP levels, but neither the cAMP production nor the inhibitory effect of the extract on proliferation were blocked by a beta adrenergic receptor antagonist (propranolol) or by histaminergic receptor antagonists (cimetidine and mepyramine). So, we concluded that the antiproliferative activity of the extract of BW 5147 cells would be mediated by an increase in cAMP intracellular levels no related to the activation of the membrane receptors here studied. In parallel, the extract was administered to a pregnant rat with a spontaneous mammarian carcinoma and "in vivo" antitumoral activity was found.

A method was devised to determine the nature of the mechanism of the increase in renal (Na(+)+K+)-ATPase in rats fed dilute ethanol for ten weeks. Antiserum to (Na(+)+K+)-ATPase obtained from rabbits was added to microsomal fractions of kidney and the activities of (Na(+)+K+)-ATPase and Mg2+ ATPase were determined. The addition of antiserum resulted in a same pattern of dose-related inhibition of (Na(+)+K+)-ATPase activity in control and ethanol-fed rats, whereas Mg(2+)-ATPase was not affected by the antiserum. These results suggest that the mechanism of ethanol-induced enhancement of renal (Na(+)+K+)-ATPase activity could be explained through an increase in the number of catalytic units.

The effects of estrogen (E), progesterone (P) and estrogen plus progesterone (E+P) treatment on Ca-induced contraction in the KCL-depolarized uterine muscle, and the influences on the Ca2+ antagonism induced by reserpine and verapamil "in vitro" were studied. Uterine muscles from rats in estrus were taken as controls. Uteri from spayed untreated rats showed the same sensitivity to Ca2+ as those from estrus rats, but castration decreased maximal contractile tension to Ca2+ and Ca2+ threshold. P treatment failed to modified the effects of castration on the responses to Ca2+. E or E+P treatments decreased the sensitivity to Ca2+ but only E+P increased slope values and maximal contractile tension. E and E+P increased the potency of verapamil Ca2+ antagonism but none of the treatments modified reserpine direct inhibitory effects. The results obtained suggest that alterations on uterine contractility by hormone treatment are the result of complex interactions between both genomic effects on the contractile process as well as non-genomic direct actions of the hormones on Ca2+ membrane permeability.

Animal lectins are classified on the basis of structural and functional studies in two types: the C-type, characterized by their dependence on calcium ions and the S-type which are not calcium-dependent, but thiol-dependent. In this late one, a group has been extensively studied as the S-Lac type. They are extracted with saline buffers added with lactose in presence of thiol agents, and constitute a family of structurally related protein which contain a series of conserved amino acids. They specifically bind to complementary glicoconjugates, and their biosynthesis and localization are developmentally regulated. Their role could be related to several biological activities in different organs.

Bothrops alternatus venom was inoculated in gastrocnemius muscle of mice between 18 and 20g. The dose was 50 micrograms in 0.1 ml in ClNa 0.85% solution. Groups of 5 animals were sacrified between 3, 6 and 12 hours after inoculation. Hystopathology was performed with muscle and different organs fixed with Bouin. The venom reproduced a local inflammatory reaction. Histopathology observations of muscle revealed myolytic and coagulative necrosis. There and six hours after inoculation, hepatocellular degeneration and tumefaction in area of central veins was observed. In kidneys there were cortical congestion and hydropic tumefaction of proximal and distal tubules. There were no anormality in heart, lung and brain.

The distribution, density and histochemical subtype of mast cells (mucosal and connective tissue) were studied in the ileum, trachea and skin of rats treated with IFN alpha (70.000 IU/kg) treated rats. Light and electron microscopic procedures were utilized. The total number of mucosal mast cells in the sections of ileum and trachea were markedly increased in the IFN-alpha treated group (ileum: 31.9 +/- 2.2 cells/villuscrypt unit; trachea: 10,355 +/- 264 cells/mm3). However, the number of connective tissue mast cells did not show any significant change in the skin between IFN-alpha treated (1,472 +/- 125 cells/mm3) and saline-treated (1,757 +/- 264 cells/mm3) groups. We conclude that mast cell proliferation does exist in the rat ileum and trachea but no in the skin response to IFN-alpha. We suggest that this model provides a powerful tool to study differential effects of IFN-alpha on mast cell subtypes and to identify their role in the immunoregulatory and inflammatory reactions.

Myonecrotic and oedema-inducing activities of Bothrops jararaca of Argentina were studied. For oedema-inducing activity 0.05 ml of different solutions of venom in 0.9% NaCl were injected in mice. The dose of 0.86 micrograms/20 g mouse induced an oedema of 30% respect the other member in one hour. The myonecrotic effects were studied injecting mice gastrocnemius muscle with 70 micrograms of venom in 0.1 ml of 0.9% NaCl, which were sacrificed in different time. The inoculation area was obtained for hystophatological process. Animal sacrificed 30 minutes after the inoculation showed oedema, hemorrhage and inflammatory infiltrate. Those sacrificed in one and three hours after the inoculation also had got necrosis.

Thymus development and function are under the influence of hormones secreted by the gonads and pituitary. On the other hand, thymus is crucial for the development of reproductive capacities in female and male rats and we have shown that a factor derived from the prepubertal rat thymus has antigonadotropic effect in ovarian and testis cells in vitro. In the present paper we show that the rat thymic factor which modulates gonadotropin action in the gonads is an heparin-binding factor. This capacity was also used as a useful tool to obtain this activity from semipure extracts. An acetone extract was prepared from 15 day old male rats and subjected to molecular filtration chromatography. The activity, of those fractions was investigated in a testis cells bioassay, by measuring testosterone secretion under basal and hCG-stimulation. Active fraction were processed in an heparin-Sepharose affinity column. We found that fractions that eluted with 0.6 and 2M NaCl/10mM Tris had biological specific activity. The electrophoretic procedure showed that the apparent molecular weight of the Heparin Sephadex binding factor is 60 kDa. Since this factor was obtained from a protein peak that eluted in the volume of carbonic anhidrase a dimerization process could be involved. Present results show that the rat thymus has an heparin-binding factor that interacts with hCG in testis cells. This factor could play an interesting role in the mutual influence between thymus and gonads.

The difficulty of a reliable diagnosis of pancreatic diseases by scintiscanning, is mainly derived from the lack of adequate radiopharmaceuticals. With this purpose 125I-L-3 Iodo-a-Methyl Tyrosine (125I-IMT) has been studied, which has also been used for the diagnosis of different kind of brain tumors. The purpose of this work is the development of a quick and easy method for the synthesis and purification of the 125I-IMT in order to be used in a Nuclear Medicine Service. The L-alpha-Methyl Tyrosine was labeled with 125I using I-/I03 and afterwards purified by an anionic exchange resin. The labeling yield obtained was (96.0 +/- 0.5)% when the incubation time was 15 minutes. No significant statistical differences were observed when the incubation time was extended to 1 hour. Biodistribution studies in mice show that the percentage of activity concentration in pancreas is (34.24 +/- 14.03)% at 15 minutes post injection, remaining constant for 30 minutes. The pancreas/liver ratio 15 minutes after the injection of the labeled product was (12.22 +/- 3.59) and it remained constant for 45 minutes more. These results show that 125I-IMT can be used as a diagnostic agent for pancreatic diseases. Since 123I was not available at the moment, this new methodology was developed with 125I.

The efficacy and tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle, rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post- and menstrual periods; possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptoms. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24, 24/24 and only 2 out of the 24 patients, respectively. Concomitant symptoms consisted in headache (12), mastalgia (14) and discomfort (12). Results were obtained by averaging the data from the treatment periods with each drug. Menstrual pain was reduced from 2.9 +/- 0.7 to 1.9 +/- 0.7 with P administration and to 0.66 +/- 0.4 with the administration of LC, a highly significant difference between treatments (p < 0.0001). Premenstrual pain was reduced nonsignificantly from 0.79% to 0.58% with P administration and significantly to 0.29% with administration of LC (p < 0.001). Intramenstrual pain affecting all patients at baseline was reduced significantly by 9% with P and also significantly by 50% with LC (p < 0.001). No differences were encountered in concomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p < 0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.