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

The present study was performed to determine quantitative and qualitative effects of hypoxia on murine erythron. CF1 mice were submitted to hypobaric hypoxia (HH) along 18 days. The proliferative response to recombinant human erythropoietin (rHuEPO: 0-250 mU/ml) was analyzed by DNA assays from bone marrow and spleen cells at different times. Bone marrow proliferative response showed a slight increment under stress but remained over control by the end of the experience. Splenic erythroid proliferative response was observed at a maximum rate on day 6 of HH (26 fold) and returned near to control values after day 10. The assessment of erythropoietic maturative pattern was performed by 59Fe uptake assays. Total nuclear cell counts increased in both tissues (1.5 times in marrow and 5 times in spleen) under hypoxia. In addition, percentages of different lineages (erythroid, myeloid and lymphoid) were scored. Total erythroid marrow cell counts increased in a narrowly degree and persisted above basal counts after day 18. Meanwhile, splenic red cells rose to 30 times over control on day 6 and failed sharply near control values from day 12 of HH. Splenic red cells contribution was approximately 60% of total production between 6-8 days. By the end of the assay bone marrow took back erythroid command (90%). These findings indicate correlation between the time course as well as quantitative and qualitative parameters in the patterns of proliferation and maturation. Moreover, the erythron response to hypoxia, seemed to be related to microenvironmental regulations rather than to hormonal variances.

In order to investigate the implications of oxidative disturbances in the hemolysis associated with the Hemolytic Uremic Syndrome (HUS), basal levels of lipid peroxidation products, the response to t-butyl hydroperoxide induced damage and membrane fluidity were assayed by the technique of electron spin resonance in erythrocytes spin labeled with 5-Doxyl stearic acid obtained from eight children with HUS, during the 1st, 2nd, 4th and 12th weeks after diagnosis. During the acute phase of the disease, red blood cells (RBC) showed increased initial lipid peroxidation products, a higher susceptibility to oxidative insult and a lower membrane fluidity. All parameters reached control values the 12th week after diagnosis. The results suggest that in the acute phase of HUS, RBCs are exposed to an oxidative imbalance that could contribute to hemolysis directly through oxidative damage and/or by decreasing membrane fluidity.

Cardiovascular responses to several agents should be modified by glucocorticoid administration in the rat. We investigate the response to adrenergic agonists such as phenylephrine, noradrenaline, clonidine and isoproterenol and ganglionic blocking agent such as hexamethonium in conscious rats treated during 7 days with dexamethasone. Wistar rats were treated with either Dex (150 micrograms daily x 7 days, p.o.) or water. Mean arterial pressure were calculated from the intraarterial recordings of blood pressure. No differences in basal mean arterial pressure were seen between dexamethasone and control groups of rats. Phenylephrine and noradrenaline showed a pressor effect in control rats that was reduced by dexamethasone treatment. Clonidine showed similar pressor effect in both groups of rats but ten minutes after drug administration, a light hypotension was seen in dexamethasone rats. Isoproterenol and hexamethonium showed a similar hypotensive effect on control and dexamethasone rats. In conclusion, dexamethasone treatment should reduce the pressor responses to phenylephrine and noradrenaline. Moreover, the alpha adrenergic agonist clonidine showed a hypotensive effect in dexamethasone treated rats, although the response of isoproterenol and hexamethonium remains unchanged.

The medullary raphe nuclei are involved in central autonomic regulation. In all species investigated, electrical stimulation of the raphe nuclei causes cardiovascular responses, although, these changes vary between species. The present study was designed to investigate the participation of these nuclei in cardiovascular regulation in the guinea pig. We studied the effects on arterial blood pressure (BP) and heart rate (HR) of electrical stimulation (isolated cathodal square wave pulses for 10 s at 100 Hz, 40-100 microA and 1-ms pulse duration) within the medullary raphe nuclei in urethane-anesthetized (1.2 g/kg, i.p.) guinea pigs (400-600 g, either sex). Electrical stimulation of the same sites was performed on a group of paralyzed (Flaxedil, 1 mg/kg, i.v.) and artificially ventilated animals. Stimulation sites were histologically defined and maps of the stimuli were obtained for the effect of electrical stimulation on arterial blood pressure. In another series of experiments L-glutamate (0.2 M) was microinjected (75 to 150 nl) into the nucleus raphe obscurus. Electrical stimulation of the raphe nuclei produced predominantly pressor responses (delta = +15 to +100 mmHg; 43% of the stimulated sites). Hypotension (delta = -10 to -25 mmHg, 24% of the stimulated sites), biphasic responses (2%) or no change in BP (31%) were evoked from fewer stimulation sites. Pressor responses were also predominant in paralyzed animals (delta = +15 to +95 mmHg; 47% of the stimulated sites), and after microinjection of L-glutamate into the raphe obscurus (A = +20 to +45 mmHg). The present results demonstrate that in the guinea pig the stimulation of these nuclei evokes mainly pressor responses. These responses are similar to those obtained in the rat and hamster but opposite to those observed in the cat and rabbit.

Efficient superinfection of H9HTLVIIIB cell line (persistently infected with HIVHXB2 strain) with HIVMN strain is reported. The superinfecting viral DNA was found in the chromosomic and extrachromosomic fractions at early stages, but at 48 hours post superinfection, it remained mainly unintegrated. Interestingly, superinfected cells only produced HIVHXB2 in the supernatant and no increase of viral yield of this persistent virus was observed. Remarkably, virions of both strains. HIVHXB2 and HIVMN, were recovered after cocultivating superinfected cells with MT2 cell line. In the extrachromosomic fractions of seven different superinfected subclons of H9HTLVIIIB, viral DNA of the superinfecting HIVMN strain predominated while in the chromosomic fraction, the proportion of superinfecting viral DNA differed. The study of the presence of different integrated and unintegrated genomes in a single cell could be crucial in the understanding of HIV biology.

The present work describes and analyzes the results of a randomized clinical trial on adolescents (age 18.2 +/- 0.6) carried out in order to evaluate the effects of a twice daily mouthrinse application containing xylitol, sorbitol, sacarine, ciclamate, aspartame, chlorhexidine, hexetidine or NaF for 14 days on amylase, peroxidase, thiocyanate, hypothiocyanite, secretory IgA and total proteins in whole saliva. No significative changes were observed in health and bucodental parameters nor in flow salivary rate, protein, secretory Ig A, or thiocyanate levels as a consequence of the mouthrinses application. On the other hand, NaF treatment (0.02%, 0.05% or 0.1%) did cause an increase in salivary peroxidase and hypothiocyanite, being the former increase higher than the second one. Peroxidase increase was proportional to the mouthrinse dose (r = 0.78; p < 0.01), but not to the hypothiocyanite increase (r = 0.407; p = 0.12). Since the adolescents' health condition was the adequate, it is suggested that the peroxidase increase was due to a higher enzyme synthesis and/or secretion by the parotid and/or submaxillar glands. It is concluded that the increases in salivary peroxidase and hypothiocyanite caused by the NaF treatment favour the host, as they potentiate one of the mechanisms that modulate dental plaque composition, preventing in such a way the colonization by cariogenic pathogens.

Mice of 18 and 20 g were injected intradermally with 0.1 ml of serial dilution of venom in saline solution 0.9 buffered pH 7.2. Groups of 4 animal were formed, they were sacrificed 2 hours after inoculation. Skin of every mouse was put out, and the haemorrhagic area was measured Bothrops alternatus, Bothrops jararaca, Bothrops jararacussu and bothrops neuwiedii venoms were used. Crotalus durissus terrificus did not show any haemorrhagic activity.

Biosynthetic processes related to the production of an insect hexamerin, very high density lipoprotein (VHDL), have been examined in the fat body of fifth-instar nymph and adult Triatoma infestans. Fat bodies were incubated in vitro with [3H]leucine and the incubation media were precipitated using a specific antiserum. The SDS-polyacrylamide gel electrophoresis followed by blotting on nitrocellulose showed that both larval and adult fat body secreted the VHDL subunit. Moreover, the radiolabel recovered in this subunit is indicative of the de novo synthesis. When the incubation medium was subjected to density gradient ultracentrifugation, a radiolabeled fraction was found at density 1.27 g/ml, value identical to the hemolymph circulating VHDL, indicating that the secreted apoprotein is combined with lipids. The SDS-polyacrylamide gel electrophoresis and immunoblotting of this fraction corroborated the presence of the VHDL-apoprotein. These results demonstrate that the fat body of T. infestans is able to synthesize the protein subunit which is associated to lipids as a lipoprotein particle that is released into the medium as VHDL.

Simultaneous recordings of action potential and isometric tension of right papillary muscles were performed. After regular stimulation at 1 Hz, pauses of 10 min were allowed. In the first beat after rest, we measured action potential duration at the 90% of the repolarization (APD90), maximal twitch tension (T), time to peak of contraction (TTP), and rate of development of tension (+dT/dt) and relaxation (-dT/dt). Values were normalized against pre-rest ones. No significative changes were observed after rest at 35 degrees C. After rest at 25 degrees C APD90 and TTP were prolonged but T was reduced. Post-rest +dT/dt were slower, dT/dt did not show significative changes. Nifedipine 10 microM prevented post-rest APD90 lengthening, and produced a further reduction of mechanical response. Substitution of external Na+ by Li+ shortened APD90, increased T of either regular or post-rest beats and led to calcium overload signs. When pause were allowed during Na+ substitution, calcium overload signs were attenuated. We conclude that the combination of rest and room temperature diminished [Ca++]i mainly by Na+/Ca++ mechanism. The reduction of [Ca++]i in turn could delay the inactivation of iCa. As a consequence, longer APs were obtained, accompanied by weaker and slower mechanical responses. Changes in TTP and + dT/dt could suggest that post-rest contractions in room temperature, are dependent of extracellular Ca++ rather than a deplected RS.

With the purpose of studying the effectivity of an intratumoral single dose of chromic [32P] phosphate (Phosphocol) for the treatment of solid tumors, studies of bioelimination, biodistribution and therapeutic action were carried out in rats with experimental induced tumors. The results show that the percentage of total elimination is equal to 29.76 +/- 9.60% with a higher percentage in faeces 23.28 +/- 8.81% than in urine 6.48 +/- 2.11%. Biodistribution studies show that, 51.61 +/- 5.82% of the injected activity is found in the tumor while in organs with reticuloendothelial cells, the percentage of activity was 13.09 +/- 5.15% in liver and 2.88 +/- 1.23% in lung. On the other hand, when therapeutic action was evaluated, we found that the percentage of tumor regression (P.T.R) was 61.0% for the injected tumors. It is important to point out that 4 of the treated animals show bioelimination patterns in which the elimination rises suddenly at some time of the study. These results demonstrate that the use of this kind of colloids is not to be recommended for the treatment of solid tumors with moderated degree of vascularization, since its mobilization from the injection point may result in the consequent irradiation of different organs that are not under treatment.