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

Previous studies on the effect of the oral administration of bacterial immunomodulators (1M-104 and RN-301) during the protein free diet period, have shown an increase on B and T cell gut repopulation, accompanied by IgA antibody production. The usefulness of oral administration of the immunomodulator thymomodulin (TmB) during the protein refeeding period was investigated. TmB allowed the recovery of a normal repopulation of gut lamina propria with IgA B and CD5 T cells and decreases to control values the number of activated intraepithelial lymphocytes (CD25+ T cell subset). Therefore, the oral administration of TmB may be useful as a therapeutic agent as it seems to improve the repopulation of intestinal villi with immunocompetent cells. Also, it seems to regulate the immunosurveillance at the epithelium level as it increases the CD5+ T cells but decreases the activated ones.

Hexachlorobenzene (HCB) is a widespread environmental pollutant. Chronic exposure of laboratory animals to HCB triggers porphyria, induction of liver microsomal enzymes, low levels of T4 reproductive dysfunction's, liver and thyroid tumors. Previous findings from our laboratory have shown that HCB increased the activity of the liver thyroid-responsive enzymes: malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) without any change in the mytochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD). In this study we have demonstrated that HCB treatment increased ME mRNA. We also have investigated if HCB affected: a) the thyroid hormone receptor (TR) concentration and binding affinity for its ligands, b) specifically the ME gene expression, or other thyroid hormone responsive enzymes were affected as well, c) Protein/DNA complex formed on the thyroid responsive element (TRE). Livers from female Wistar rats intoxicated with HCB (100 mg/100 g b.w.), for 9 and 15 days, were analyzed. Northern blot hybridization analysis, have demonstrated that ME mRNA levels increased 4 times and 2 times after 9 and 15 days intoxication respectively, without any alterations in the mRNA levels of other thyroid hormone responsive enzymes such as glyceraldheyde 3- phosphate dehydrogenase, phosphoenolpyruvatecarboxikinase and alpha-GPD. These results suggest that HCB affects specifically, ME gene expression. Hepatic T3 and T4 levels evaluated by RIA were not affected by HCB. Scatchard analyses showed that TR affinity and number of sites were not altered after 9 and 15 days of HCB treatment (control, Ka: 1.9 nM, Bmax 3.9 f/mol 100 micrograms DNA: HCD 9 days Ka: 2.1 nM, Bmax 4.5 fmol/100 micrograms DNA: HCB 15 days Ka 1.9 nM. Bmax 5.1 fmol/100 micrograms DNA intoxication, neither at 9 nor at 15 days. Electrophoresis mobility shift assay showed that HCB did not modify nuclear protein extract affinity for the TREs sequence. Our results suggest that TR itself was not directly involved in the induction of ME gene expression by HCB. Nevertheless TR could interact with other transcription factors in the overexpression of ME gene.

The environmental effect on growth and sexual dimorphism is mediated by endocrinological dysfunctions. It was shown that malnutrition acts on the hypotalamus-pituitary-glandular axis. An experiment was made in Wistar rats to determine the effect of some gonadic hormones on the functional components of the skull to which sex dimorphism was alterated by a postnatal undernutrition. The effects of these hormones in restoring sexual cranial dimorphism was tested. Four treatments were applied: control, with food intake ad-libitum; undernutrition (50% of the control food intake); undernutrition plus periodic injections of testosterone and estradiol to males and females, respectively and sham-operated animals, which were injected with oil vehicle only. A radiological longitudinal study was performed between 20 and 80 days of postnatal age. The length width and height of the neural and facial components were measured on each radiograph. Data were processed by ANOVA and Mann-Whitney statistical tests were performed by means of the SYSTAT 7.0 statistical package. Results showed that gonadic hormones restored the sexual cranial dimorphism by stimulating (testosterone) or suppressing (estradiol) the growth of the cranial components.

To explain the cytotoxicity of excessive free radical production in the liver of rats, the lipoperoxidation in subcellular structures and some antioxidants systems were evaluated. We measured Cu-Zn superoxide dismutase (Cu-Zn-SOD) activity, reduced glutathione (GSH) levels and lipid peroxidation in homogenates and subcellular fractions of hepatocytes. Female Wistar rats were given a 0,2 per cent solution of CUSO4 in water, to induce the Cu toxicity. Serum copper levels and acid phosphatase (AP) activity were determined at frequent intervals. Six treated rats were euthanased to the twelfth week of begun the assay. During the sixteenth week, at time of the increase of serum AP activity the others treated rats also were killed. We found high liver Cu content and evidence of lipid peroxidation. In whole homogenate, mitochondrial and microsomal fractions, the thiobarbituric acid reacting substances were increased. This was correlated with an increase in the Cu-Zn-SOD activity and with decrease of the GSH levels. It could be argued that high copper status might have increased the Cu-Zn-SOD activity and induced lowest levels of GSH. Additionally, lipid peroxidation was induced by Cu-overload.

Chagas' disease is an important cause of heart disfunction in Latin America. Previous works from our laboratory reproducing experimental Chagas' disease in mice, demonstrated that the affinity and density of cardiac beta-adrenergic receptors were altered during the acute, indeterminate and chronic phase in Albino Swiss mice inoculated with Trypanosoma cruzi. Keeping in mind that Propranolol is a beta-blocking agent that binds in the same receptors' site, which we have described as altered along T. cruzi infection. The present study was performed to determine if a beta-blocker treatment could prevent cardiac beta-receptors' disorders provoked by T. cruzi infection. Two different doses of Propranolol (9 and 40 mg/kg/day) were injected in the mice during 3 days; then they were infected with 7 x 10(4) parasites/mouse and propranolol was continued daily for one week. The results showed that the concentrations of propranolol used did not protect the beta-receptors' sites by administration of each doses.

Viral load (HIV-RNA copies per milliliter of plasma) has good correlation to prognosis considering progression to AIDS. The evaluation of commercial kits to measure viral load has become a need to find the most specific, sensitive and reproducible procedure to follow up HIV-infected patients. Hereby, a comparative analysis was done by using three different assays available in Argentina for quantitation of HIV-RNA in plasma. A plasma panel: 20 from HIV-1 infected individuals (9 asymptomatic and 11 symptomatic) and 9 from HIV-1 seronegative individuals was studied. Samples were run by Amplicor HIV-1 Monitor (Roche Diagnostic System, USA) Quantiplex HIV-1 RNA 2.0 Assay (Chiron Corporation, USA) and NASBA HIV-1 RNA QT (Organon Teknika, Holland). RNA was extracted from 0.2 ml of plasma for Amplicor, 0.1 ml and 1 ml of plasma for NASBA and, duplicates of 1 ml of plasma was centrifuged and pellet was used for bDNA assay no RNA extraction step. For a given specimen, a log difference of < 0.5 between assays was considered as concordant result. All seronegative samples were bellow the detection limit for all assays (Amplicor 200 c/ml, NASBA 400 c/ml and Quantiplex (bDNA) 500 c/ml). Two samples from asymptomatic patients were not detectable by NASBA (Sensitivity: 90%) Sensitivity was increased to 100% by using 1 ml of plasma. All samples were detectable by the other assays (sensitivity: 100%). For NASBA-bDNA, 74% samples were concordant, 35% for Amplicor-bDNA and 53% for NASBA-Amplicor. By using 1 ml of plasma from asymptomatic patients, concordance was 65% for NASBA-bDNA and 60% for NASBA Amplicor. Comparing samples from asymptomatic patients, only 22% was concordant in both cases. Reproducibility of NASBA was low (33% with differences lower than 0.5 Log) when 0.1 and 1 ml were used. Due to the levels of concordance of these results, it would be suggested to use always the same technique to follow up HIV-1 infection. The reproducibility of the assays should be tested by every laboratory and for every technician in charge of the assay in order to have confidence in the results specially to follow up HIV-infected patients or to monitor anti-viral therapies.

Embryo development depends on maternal and embryonic factors that may regulate genetic programs in early development. Effects of growth factors on proliferation, differentiation and morphogenesis along embryogenesis have been documented. However, studies have not established the role of growth factors in the preimplantational period. The purpose of this study was to investigate the possible effects of growth factors and embryo density on mouse preimplantation development in vitro. Two- and eight-cell CF-1 embryos were cultured individually or in groups of ten in HTF medium, alone or with EGF, TGF-beta 1 and IGF-I. Cleavage rate varied greatly with growth factors and increased significantly when eight-cell embryos were cultured in groups. On the other hand, when two-cell embryos were cultured in groups, the cleavage rate was slower than that obtained when embryos were individually cultured. The differentiation rate increased significantly in two-cell embryos cultured in groups (p < 0.05). EGF, TGF-beta 1 and IGF-I increased differentiation rates significantly in two-cell embryos individually cultured for 68 hours. The combination of EGF and TGF-beta 1 increased the differentiation rates significantly. The other combinations were not effective in modifying this parameter. Hatching rates increased in embryos cultured in groups (p < 0.05). TGF-beta 1 decreased this parameter significantly in two- or eight-cell embryos cultured in groups (p < 0.05). The data described in this report suggest that preimplantational mouse embryos produce some factor or factors that enhance its development, specially the differentiation and hatching rates. However, a functional role for polypeptide growth factors during preimplantational development has to be determined.

This paper reports the occurrence of bilateral hemianopia in a 16 year old male who was having unusual seizures accompanied by severe migrainous headaches and loss of vision while watching a television programme and while playing with the computer. Electrophysiological tests not only confirmed his photo and pattern sensitivity, but also showed that he had bitemporal hemianopia. Hence, his basic EEG showed a great deal of abnormality including generalised spike and wave activity which was more marked in the temporal regions. The patient showed classical occipital spikes on exposure to 25 and 50 Hz of intermittent photic stimulation. Pattern sensitivity test evoked photo paroxysmal response within the range of 2-4.5 cycles per degree (cpd). The visual evoked response to binocular flash stimulation produced N2 at 74 ms, P2 at 112-118 ms and N3 at 168 ms. P2 amplitude was 15-17 uV. Monocular right stimulation produced N2 at 72 ms, P2 at 122-124 ms. Monocular left stimulation produced N2 at 82 ms, P2 at 120-124 ms of 14 uV and N3 at 178 ms. Pattern reversal stimulation produced some abnormality. Poor phase reversals were mainly seen to the left occiput with right eye stimulation and poor phase reversals to the right occiput with left eye stimulation. The pattern responses were of normal latency but showed a marked hemispheric asymmetry. The reduction of the response in the left hemisphere with right eye stimulation and the reduction in the right hemisphere with left eye stimulation would suggest the presence of bitemporal field deficit.

To evaluate the risk factors involved in antituberculosis treatment-induced hepatotoxicity. In a retrospective study we analyzed the rate of drug-induced hepatotoxicity in a sample of 456 patients. Patients received a combination of drugs including isoniazid, rifampin, pirazinamide and streptomycin or ethambutol. The association among hepatotoxicity and several risk factors (age, sex, alcoholism and HIV infection) was studied by univariate methods, stratified analysis and the multiple logistic regression model. Signs of liver injury were found in 9.86% of the treated patients. In the logistic model, the adjusted odds ratios (OR) and significance were found as follows: a) for alcoholism, OR = 17.31 (95% CI: 6.35-47.16), p < 0.001; b) for HIV infection, OR = 3.23 (95% CI: 1.47-7.11), p = 0.003 and c) for female sex, OR = 2.44 (95% CI: 1.22-4.86), p = 0.011. Age was not significantly associated with hepatotoxicity. Alcoholism, HIV infection and female sex were associated with an increased risk of hepatotoxicity in this study.

Forskolin-stimulated adenylate cyclase activity, measured in the hypothalamus and cerebral cortex differs in male and female rats. The gonadal steroid treatment performed induced changes in the studied adenylate cyclase activity probably in relation to the sex of the animals. The stimulated-forskolin adenylate cyclase activity in the hypothalamus from orchidectomized males showed more sensitivity than ovariectomized females. Finally, in male rats, the effects of castration on the hypothalamic enzymatic activity were partially restored by the administration of testosterone dipropionate. On the other hand, estradiol decreased the forskolin-adenylate cyclase activity in the female hypothalamus and cerebral cortex. The results show that the forskolin-stimulated adenylate cyclase activity may be related with the sex and/or the gonadal state of experimental animals.