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

With the purpose of studying the effect of diphenylhydantoin (DPH) administration on the growth of the functional components of the rat skull, male Wistar rats weighing 61.6 +/- 0.6g were assigned to 1 out of 4 different groups. One of them received saline and was taken as normal control. The others were injected once daily with 25, 50 or 100 mg/kg of b.w. of DPH i.p. for 20 days. Another group of rats was put under a restricted diet (RD) (20% of normal intake) for the same time for evaluation of the cranial dimensions. On day 21 the rats were killed by ether overdose and fifteen cranial dimensions were evaluated as previously described employing Pucciarelli's method. The body weight gain of DPH injected rats was up to 20.7% lower independently of drug dose. The rats of the RD group showed a similar reduction. The amount of food consumed by DPH rats was 16% lower than that consumed by controls independently of drug doses. The concentration of alkaline phosphatase and hemoglobin in rats treated with 50 or 100 mg/kg b.w. of DPH was lower than in controls and RD-animals. However, urea and total calcium in plasma were unchanged in DPH-treated rats as compared to controls. Mean appetite quotient, efficiency of protein and energy utilization did not appear to change in response to the treatment with DPH or maintained under a restricted diet. The cranial dimensions of rats, injected with 25 mg/kg b.w. of DPH were not statistically different from those of the control and RD-groups. When the dose of DPH injected was 50 mg/kg b.w. the neurocranial width and height and the spachnocranial length were significantly lower than controls and RD-values. Moreover, all the dimensions corresponding to neurocranium and splachnocranium (width, height and length) of the rats injected with 100 mg/kg b.w. of DPH were significantly lower than those of control and RD-groups. The disharmonius growth of the skull do not appear to be dependent on suboptimal energy intake, efficiency of protein, energy utilization renal failure and anemia.

In the present work we have measured the guanylate cyclase activity in soluble fractions from several tissues relevant to the visual response under different illumination conditions. Guanylate cyclase was sensitive to changes of light/dark periods in incubated extract obtained from soluble fractions of retina, optic nerve and optic chiasm. The changes in soluble guanylate cyclase activity found, about 100 fold between dark and light periods in those tissues, indicate a key role for this enzyme. The results showed that light inhibit strongly the soluble retinal guanylate cyclase activity; while it increases the activity of this enzyme in the optic nerve. A generalized photoinhibited response of soluble guanylate cyclase was observed in all studied tissues in prolonged dark adapted animals. The effect of Na+ 1 and 10 mM, and free Ca++ 28 eta M and 2.8 microM on the guanylate cyclase activity was performed in the studied tissues. The enzymatic activity appeared to be inversely related in the retina and optic nerve with regard to the ion exposure, which may involve different ionic control mechanisms. All indicate an active role for the soluble guanylate cyclase in the phototransduction process not only in retina, also in other tissues relevant in the visual response.

We studied the production of interleukin-1 (IL-1) by peripheral blood monocytes (Mo) from twelve normal subjects (NS) and eight and nine untreated lung and colorectal cancer patients (CP), respectively. No significant changes of extracellular IL-1 biological activity was observed between CP and NS by thymocyte proliferation assay. This result was independent that the cells were treated or not with lipopolisaccharide from E. coli (LPS, 10 micrograms/ml). Moreover, CP present normal amount of antigenic IL-1 beta in LPS treated Mo culture supernatants by enzyme-linked immunosorbent assay (ELISA). The biological activity of IL-1 released was not significant modified after indomethacin (Indo, 10(-6)M) and LPS + Indo treatments. Furthermore, patients showed a low percentage of LPS activated Mo with intracytoplasmatic IL-1 (alpha + beta) compared to normal values. These results were obtained by immuno-alkaline phosphatase staining using monoclonal antibody anti IL-1 (alpha + beta). In conclusion, CP had a reduced number of Mo with intracytoplasmatic IL-1 (alpha + beta) and the difference observed may depend on degradation or in the rate of synthesis of this cytokine.

The effects of chronic diazepam (D) treatment and exercise training on total body mass (TBM), microsomal protein yield (MPY), calcium uptake by fragmented sarcoplasmic reticulum (SR), muscle fibre cross-sectional area, and both PFK and SDH activities were investigated in the tibialis anterior (TA), soleus (Sol), and plantaris (Plt) muscles of 50 male albino Sprague-Dawley rats. Rats were assigned randomly to control (C), sprint-trained (S), or endurance-trained (E) groups. Training was of 12 weeks duration. One-half of each group received daily intraperitoneally D doses of 5 mg kg-1 of TBM. Exercise reduced TBM (p < 0.05); increased the relative BM of the TA (E = 2.02 +/- 0.02, p < 0.01) and Plt (E = 1.15 +/- 0.02, p < 0.01; S = 1.13 +/- 0.03, p < 0.01), as well as the Ca++ uptake of the Sol SR (C = 0.08 +/- 0.02, E = 0.16 +/- 01, p < 0.05). MPY was elevated in S-Sol (C = 1.12 +/- 0.6, S = 1.52 +/- 0.1, p < 0.01). D elevated Sol MPY as well as TA PFK. S-trained animals had lower mean fibre areas than the E-trained (D-treated and untreated) animals. The elevated relative masses of TA and Plt are explained by a decreased TBM with exercise. The increased Ca++ uptake of the Sol indicates that E enhances this function, and the increased MPY probably implies an increased SR. The D could be responsible for the D-elevated Sol MPY as well as the TA PFK. El D did not reduce neuromuscular activity to a level adversely affecting oxidative enzyme activity, but in the case of PFK activity in the TA muscle, such a reduction was evident.

Erythropoietin (EPO) is a glycoprotein which appears as the primary regulator of erythropoiesis under either normal or most of the pathologic conditions. In the rat with experimentally-reduced erythropoiesis, daily administration of 1.3 IRP units can restore the function and maintain steady-state conditions of red cell formation. This important information for the programming of both physiologic and pharmacologic studies is lacking for the mouse, in spite of the fact that most of the experiments performed on the regulation of erythropoiesis have been conducted in this species. In the present study, designed to determine EPO requirement for maintenance of steady-state erythropoiesis in the adult mouse under standard laboratory conditions, adult females of the CF#1 strain were exposed to hypobaria (18 h/day) during a 3-week period for induction of polycythemia (P). At the end of the hypoxic period. P mice were maintained at sea level conditions, as were normocythemic (N) mice during the entire experimental period. P mice were daily injected with 0, 0.5, 1.0, 1.5, or 2.0 IRP units of rHu-EPO during the 4-day period that followed the hypoxic one. The rate of erythropoiesis in N and P mice were measured by RBC-59Fe uptake. The plasma 59Fe half-clearance time was also measured in other groups of N and P mice similarly treated. One-way ANOVA showed that the only non-significant difference (P > 0.05) between N and EPO-injected P mice was established for the 1.0 unit dose group. It is thus suggested that approximately 1.0 unit of EPO should be synthesized daily in an adult mice to maintain a normal rate of erythropoiesis.

Two groups of patients were studied, both in accordance with ACR criteria. First group (41 cases) suffering R.A. Second group (36 cases) suffering O.A. In both pathologies MMPs, ICAM and VCAM from synovial fluid and plasma were studied. Measurements were made with ELISA-sandwich in a Metrolab spectrophotometer at 410 nm for MMPs, and 491 nm for ICAM and VCAM. As control, samples of patients with noninflammatory muscle skeletal disorders or traumatic arthritis and healthy witness were used. Synovial concentration of MMPs in R.A. was 1402 +/- 76 ng/ml, a higher significant value (p < 0.0001) compared with osteoarthritis: 353 +/- 23 ng/ml. In the witness plasma, MMPs were not detected. Plasmatic and synovial levels of the adhesion molecules present different values in both pathologies and between them. Synovial ICAM level in R.A. (280 +/- 9.8 ng/ml) is significantly higher than in O.A. (163 +/- 10 ng/ml) (p < 0.001), but lower than the plasmatic ones (370 +/- 35 ng/ml) (p < 0.001). All these values are significantly higher than the normal plasma (121 +/- 6.5 ng/ml) (p < 0.01, p < 0.005, and p < 0.0001, respectively) VCAM increase regarding basal values (140 +/- 5.6 ng/ml) (p < 0.001) and in a similar proportion for both pathologies (R.A.: 186 +/- 9.3 ng/ml and O.A.: 207 +/- 14.3 ng/ml). Their plasmatic levels were higher (270 +/- 45 and 320 +/- 38 ng/ml) (p < 0.001) but without significative difference between them. There is correlation among MMPs, ICAM and VCAM variations. The variability can be explained by concomitance several evolutive steps. Each pathology shows a different grade of cellularity, inverted predominance in the relation TIMPs/ collagenase and different generator mechanisms of MMPs. Our findings reinforce the importance as diagnostic guide of adhesion molecules dosage, and possible therapeutic use of MMPs inhibitors and ICAM or VCAM antagonists en R.A. and related pathologies.

beta-adrenergic agonists are able to increase erythropoiesis in the polycythemic mouse model by possibly increasing erythropoietin secretion. Since a great deal of evidence indicates that the actions of thyroid hormones and catecholamines are intimately interrelated, the present study was designed to estimate the erythropoietic response to isoproterenol, a very well-known beta-adrenergic agonist, in hypothyroid mice. Adult male CF-1 mice, maintained on a standard rodent chow and water (euthyroid) or 0.1% propylthiouracil (PTU) solution (hypothyroid) ad libitum during 37 days. Plasma T4 concentration was 1.75 +/- 0.25 micrograms/ml in euthyroid and < 1.0 microgram/ml in hypothyroid mice at this time. Mice were transfused with 1.0 ml of packed homologous red cells and the erythropoietic effect of graded doses (50, 500 and 5000 micrograms/kg) were tested by the RBC-59Fe incorporation method. No statistically significant differences (unpaired t test) were found between euthyroid and hypothyroid mice. Hypothyroidism, therefore, does not affect beta-adrenergic agonist-induced erythropoietin secretion in the present experimental conditions.

The aim of the present study was to investigate the effects of methylene blue, a guanylyl cyclase inhibitor, on the development of intrinsic contractile responses of the guinea pig tracheal smooth muscle. Paired tracheal chains were mounted for isotonic contractions under 500 mg of tension in Krebs-Henseleit solution. The intrinsic contractile tone modulated carbachol-induced contractions and was inhibited by indomethacin, suggesting the involvement of cyclooxygenase products on this tone. Methylene blue (5 x 10(-5)M) irreversibly inhibited the intrinsic contractile responses. Considering that methylene blue prevents any endogenous production of cGMP, it would be expected to enhance the contractions. However, since methylene blue has effects over nitric oxide synthase and nitric oxide itself, we suggest that guanylyl cyclase activation is not important for the development of the intrinsic tone.

As several side effects of neuroleptics would be related to their interactions with several neurotransmitter receptors (R) haloperidol action on muscarinic cholinergic (mACh) R on frontal cerebral cortex preparations was analyzed. Here we show that haloperidol was able to inhibit in a concentration dependent manner the binding of specific mAChR radiolabeled antagonist on cerebral cortex membranes. This effect would be related to its interaction on mAChR of the M1 subtype as haloperidol blocked the stimulation of phosphoinositides (PIs) turnover induced by low concentrations of carbachol similarly as the M1 antagonist pirenzepine. However at high carbachol concentrations haloperidol triggered a potentiating stimulation of PIs hydrolysis that was only blocked by the alpha 1 adrenergic antagonist prazosin indicating an alpha 1 agonistic action of haloperidol on these Rs. These multireceptor actions of haloperidol found "in vitro" would strengthen its association with "in vivo" neuroleptic-induced side effects.