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Biomedical subjects

M E Hidalgo

Publications and source records attributed to M E Hidalgo.

16 recordsLinked to original sources

A numerical identifiability test for state-space models--application to optimal experimental design.

This paper describes a mathematical tool for identifiability analysis, easily applicable to high order non-linear systems modelled in state-space and implementable in simulators with a time-discrete approach. This procedure also permits a rigorous analysis of the expected estimation errors (average and maximum) in calibration experiments. The methodology is based on the recursive numerical evaluation of the information matrix during the simulation of a calibration experiment and in the setting-up of a group of information parameters based on geometric interpretations of this matrix. As an example of the utility of the proposed test, the paper presents its application to an optimal experimental design of ASM Model No. 1 calibration, in order to estimate the maximum specific growth rate microH and the concentration of heterotrophic biomass XBH.

Biodegradation, Environmental↗

Photoprotector capacity of lichen metabolites assessed through the inhibition of the 8-methoxypsoralen photobinding to protein.

Lichens produce a diversity of phenolic compounds, some of which efficiently absorb ultraviolet radiation, 8-Methoxypsoralen (8-MOP), commonly used in the treatment of psoriasis, binds irreversibly to proteins in the presence of ultraviolet radiation by a mechanism that is not well established. In this paper we demonstrate the photoprotector capacity of three phenolic compounds-pannarin, 1'chloropannarin and atranorin-through the inhibition of 8-MOP-human serum albumin (HSA) photobinding. The method measures the UV-filtering capacity of lichen compounds by means of a double-tube compartment (thus, solubility and interaction with the reaction medium is avoided). Photobinding was determined by measuring the radioactivity of mixtures containing 8-(methyl-3H) MOP and HSA irradiated at 360 and 310 nm in the presence of increasing concentrations of lichen phenolics. Pannarin, l'-chloropannarin and atranorin at a concentration of 10 mM and irradiated at 360 nm, inhibited photobinding to HSA by 40.4%, 31.7% and 20.1% respectively. Pannarin (10 mM) irradiated at 310 nm inhibited the photobinding by 35.2%. The participation of singlet oxygen and hydroxyl radicals was demonstrated in the photoreaction process.

Benzoxepins↗

Molecular characterization of the Entamoeba histolytica enolase gene and modelling of the predicted protein.

Entamoeba histolytica obtains its energy mainly from glucose fermentation. Enzymes involved in this pathway could be potential targets for antiparasite drugs. Here we report the molecular characterization of the E. histolytica enolase gene (Ehenl-I), which in a single copy is located on the 1.6 Mb chromosome. It is transcribed into a 1.4 kb mRNA which starts 13 nucleotides upstream of the ATG start codon. The sequence TATAAG, at -31, interacted with nuclear proteins suggesting that it has a TATA box function. Protein modelling allowed us to identify a putative specific region that differs from human enolase and could be a good target for the design of novel drugs against E. histolytica.

Amino Acid Sequence↗

Activity of compounds isolated from Chilean lichens against experimental cutaneous leishmaniasis.

Three secondary metabolites isolated from Chilean lichens, (+) usnic acid, pannarine and 1'-chloropannarine, were tested against promastigotes forms of three strains of Leishmania ssp. Pannarine and 1'-chloropannarine exhibited in vitro activity at 50 micrograms/ml and (+) usnic acid at 25 micrograms/ml. BALB/c mice infected with Leishmania amazonensis were treated 4 weeks post-infection with (+) usnic acid by subcutaneous or oral routes for 15 days at 25 mg/kg or by five intralesional injections at interval of 4 days at 25 mg/kg of body weight. The reference drug, N-methylglucamine antimonate (Glucantime), was administered by subcutaneous injections (regimens of 28 mg of pentavalent antimony) for 15 days. The subcutaneous and oral treatments with (+) usnic did not produce any effect, but by intralesional administration we observed a significant effect that reduced by 43.34% the weight lesions and by 72.28% the parasites loads in infected footpads.

Animals↗

Antioxidant activity of depsides and depsidones.

The antioxidant activity of lichenic metabolites, depsides and depsidones, was assessed by their effects as inhibitors of rat brain homogenate auto-oxidation and beta-carotene oxidation. The results obtained in both systems indicate that lichenic metabolites afford a moderate protection in the microM concentration range. The largest effect was measured employing 1'-chloropannarin in the brain homogenate auto-oxidation, where a 66% protection was afforded at 1.7 microM. This protection is very similar to that elicited by addition of the reference antioxidant propylgallate (70% protection at 1.3 microM).

Animals↗

Photohemolytic activity of lichen metabolites.

Irradiation of pannarin 1'-chloropannarin and antranorin with 366 nm light leads to significant hemolysis in a red cell suspension. However, their mechanism of action is different. Hemolysis induced by pannarin and 1'chloropannarin increases in the presence of oxygen, whereas hemolysis induced by atranorin is higher in nitrogen-purged solutions. The effect of free radical scavengers, and the lack of effect of D2O in the medium, suggest that the hemolysis induced by pannarin and 1'chloropannarin is not mediated by (1)O2. Both the hemolytic and photohemolytic activities of the depsidones, particularly 1'-chloropannarin, increase when the temperature increases from 21 to 37 degrees C.

Adult↗

New 4-alkyl-1,4-dihydropyridines: evaluation of photostability and phototoxic potential.

The photostability and phototoxic potential of two new 4-alkyl-1,4-dihydropyridines (PCA-4230 and PCA-4248) were investigated. When these 4-alkyl-1,4-dihydropyridines were irradiated with a multilamp photoreactor (band centred at 350 nm), both exhibited a slow photodegradation showing first-order kinetics. The photodegradation rate constants were 0.37 h-1 for PCA-4248 and 0.39 h-1 for PCA-4230 in oxygenated conditions. The photodecomposition was slower for both drugs in the absence of oxygen. In order to evaluate the phototoxicity induced by these drugs, red blood cells and Hep-2 (human laringo carcinoma cell line) were irradiated using a minisolarium, which emits UVA radiation (350-390 nm). The results showed that PCA-4248 and PCA-4230 did not exhibit a phototoxic effect in the two models tested.

Carcinoma, Squamous Cell↗

Phototoxic potential of quinolones.

The photohaemolytic potentials of the quinolones oxolinic acid, pipemidic acid, rosoxacin, norfloxacin, ciprofloxacin and M-193324 (synthesis intermediary) were evaluated and compared with the photohaemolysis induced by nalidixic acid. Quinolones with a piperazine group in position 7 (pipemidic acid, norfloxacin and ciprofloxacin) did not induce photohaemolysis. However, oxolinic acid, rosoxacin and M-193324 produced a concentration- and oxygen-dependent photohaemolysis. Ascorbic acid, histidine and thiourea inhibited the photohaemolysis induced by oxolinic acid, rosoxacin and M-193324, suggesting a photodynamic mechanism similar to that found with nalidixic acid. In addition, deuterium oxide increased the photohaemolysis induced by photohaemolytic quinolones, indicating that this process is mediated by singlet oxygen.

Ascorbic Acid↗

Entamoeba histolytica: correlation of the cytopathic effect of virulent trophozoites with secretion of a cysteine proteinase.

Work from several laboratories suggests a correlation between expression of cysteine proteinase activity and the cytopathic effect of virulent HM1 strain Entamoeba histolytica trophozoites on cultured cell monolayers. Consistent with this relationship, we find that L-6 trophozoites, mutants cloned from the HM1 parent strain, are deficient in both proteinase expression and cytopathic effect. Three other clones, with proteinase expression equal to or greater than that of the HM1 strain, express the cytopathic effect. Furthermore, a nontoxic specific proteinase inhibitor, Z-phenylalanyl-alanyl-CH2F, inhibits the cytopathic effect of live trophozoites in a dose-dependent manner. These results support the hypothesis that expression and release of the cysteine proteinase is an important factor in producing the cytopathic effect, presumably by its degradation of cell anchoring proteins.

Animals↗

Varicocele-associated decrease in antioxidant defenses.

Varicocele is associated with an oxidative stress condition. We have measured the antioxidant defenses of varicocele patients both at the local (seminal plasma) and systemic (blood plasma) levels. The antioxidant defenses, as evaluated by the total reactive antioxidant potential parameter, decrease both in the seminal (controls 676+/-128; patients = 386+/-186) and blood (controls = 519+/-63; patients = 268+/-110) plasma of varicocele patients. Compared with controls, patients with both normal spermiograms and spermiograms altered in motility or morphology demonstrated lower values. The results obtained suggest that varicocele-associated oxidative stress is evidenced both at the local and systemic levels. This conclusion is supported by results showing that urinary spontaneous chemiluminescence is also significantly increased in the patients.

Adolescent↗