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Biomedical subjects

J Gálvez

Publications and source records attributed to J Gálvez.

At least 19 recordsLinked to original sources
PubMed2004

New hypoglycaemic agents selected by molecular topology.

New compounds showing hypoglycaemic activity have been designed through a computer aided method based on quantitative structure-activity relationship (QSAR) and molecular connectivity. After calculation of topological indices for a set of 89 compounds including active and inactive with regards to hypoglycaemic action, linear discriminant analysis was performed so that a useful model to predict such an activity was achieved. Later on, the discriminant model was applied on a huge database so that fourteen compounds were selected as potential new hypoglycaemics. From them, just five were finally selected for experimental test on expected hypoglycaemic activity. Among the selected compounds, l-arabitol, Acid blue 161, 1,4-butanediol diglycidil ether and Acid red 151 stand out, which are comparable in potency to standard drugs such as tolbutamide. Acid blue has a glycaemia profile similar to that of tolbutamide but does not lead to a severe hypoglycaemic condition, while the profile of the other agents is near normality.

Drug Design↗
PubMed2004

Definition of a novel atomic index for QSAR: the refractotopological state.

PURPOSE: In this work, a novel descriptor of atoms in molecules is introduced. The Refractotopological State Index for atoms (R-state,R), rectifies the atomic refractivity values reported by Crippen et al with the atomic refractivity values of the topological environment of each skeletal atom in the molecule. METHOD: The R-state (R(i)), for atom i is an hybrid index that is defined as the intrinsic refractivity value of the atom i (AR(i)) plus a perturbation term Delta AR(i) in the non-hydrogen depleted graph. RESULTS: The variations of the R values in different molecules are showed. QSAR examples previously reported by other authors are given for benzimidazole inhibition of Lee strain flu virus and receptor binding affinity of beta-carbolines. CONCLUSIONS: The index does not only describe the representation of the atomic dispersive forces related to the molar refractivity but also the influence of bounded and unbounded atoms as a measure of the distance-effect of the other groups in the molecule. The R-state index has proved a good performance, either alone or combined with the electro topological (E)-state index. This implies that in those cases this representation of dispersive forces between the molecule and the active site is a valid approach to the biological problem

Benzimidazoles↗
PubMed2004

Structural invariants for the prediction of relative toxicities of polychloro dibenzo-p-dioxins and dibenzofurans.

Multivariate models are reported that can predict the relative toxicity of compounds with severe environmental impact, namely polychloro dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Multiple linear regression analysis (MLR) and partial least square projections of latent variables (PLS) show the usefulness of graph-theoretical descriptors, mainly topological charge indices (TCIs), in these series. The general trends of the group are correctly reproduced and better results are presented than have previously been published. In general, the more toxic compounds exhibit more symmetric molecular structures.

Animals↗
PubMed2003

Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity.

A topological virtual screening (tvs) test is presented, which is capable of identifying new drug leaders with anticonvulsant activity. Molecular structures of both anticonvulsant-active and non active compounds, extracted from the Merck Index database, were represented using topological indexes. By means of the application of a linear discriminant analysis to both sets of structures, a topological anticonvulsant model (tam) was obtained, which defines a connectivity function. On the basis of this model, 41 new structures with anticonvulsant activity have been identified by a topological virtual screening.

Anticonvulsants↗
PubMed2003

Intestinal anti-inflammatory activity of dietary fiber (Plantago ovata seeds) in HLA-B27 transgenic rats.

BACKGROUND & AIMS: Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis. METHODS: HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells. RESULTS: Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production. CONCLUSIONS: Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.

Animals↗
PubMed2003

[HIV related Foix-Chavany-Marie syndrome].

Automatic-voluntary motor dissociation of the face and lower cranial nerves of brainstem is the hallmark of Foix-Chavany-Marie syndrome (biopercular syndrome). It is commonly caused by ischemic strokes. We present a biopercular syndrome associated with HIV. A 41 year old female who presents a progressive automatic- voluntary motor dissociation of face and lower cranial nerves with later involvement of limbs. She was immunodepressed as a result of HIV. MRI showed bilateral lesions in opercular areas and ventrolateral thalamic nucleus, likely as a result of retrograde neuronal degeneration. Automatic-voluntary dissociation occur after biopercular lesions with sparing of motor pathway proceeding from the cingulate cortex.

Adult↗
PubMed2002

Use of molecular topology for the prediction of physico-chemical, pharmacokinetic and toxicological properties of a group of antihistaminic drugs.

We used molecular connectivity to search mathematical models for predicting physico-chemical (e.g. the partition coefficient, P), pharmacokinetic (e.g. the time of maximum plasma level, and toxicological properties (lethal dose, LD) for a group of antihistaminic drugs. The results obtained clearly reveal the high efficiency of molecular topology for the prediction of these properties. Randomization and cross-validation by use of leave-one-out tests were also performed in order to assess the stability and the prediction ability of the connectivity functions selected.

Histamine H1 Antagonists↗
PubMed2002

Effect of quercitrin on the early stages of hapten induced colonic inflammation in the rat.

Quercitrin is a flavonoid with antiinflammatory activity in experimental colitis, associated with an antioxidative action and amelioration of water absorption in vivo. However, its mechanism of action is unclear. This study focuses on the effect of quercitrin (1 and 5 mg/kg) in the early stages (24 h) of trinitrobenzene sulfonic acid colitis. Treatment with the flavonoid prevented the increase in colonic malondialdehyde and inhibited nitric oxide synthase and alkaline phosphatase activity but had no significant effects on observable damage. No effect on neutrophil infiltration (myeloperoxidase) was observed. On the other hand, quercitrin exerted complex effects on colonic hydroelectrolytic transport, showing a slight potentiation of water absorption in vivo (5 mg/kg) as well as a normalization of carbachol stimulated electrogenic ionic transport in the proximal colon in vitro (5 mg/kg). It is concluded that the beneficial effects of quercitrin on trinitrobenzene sulfonic acid chronic colitis arise from an early downregulation of the inflammatory cascade that is associated with amelioration of the disturbances in hydroelectrolytic transport.

Alkaline Phosphatase↗
PubMed2002

Disturbances of colonic ion secretion in inflammation: role of the enteric nervous system and cAMP.

We used the trinitrobenzenesulphonic acid (TNBS) rat model of experimental colitis to study the alterations in electrogenic ion transport in the inflamed distal colon. The distal colon exhibited decreased basal transport and reduced short-circuit current responses to carbachol and isobutylmethylxanthine (IBMX). The concentration/response curve for IBMX was also shifted to the right. Ion substitution experiments indicated that electrogenic transport was attributable chiefly to Cl(-) secretion. The mucosal layer of the inflamed distal colon (devoid of the submucosa) exhibited normal maximal responses to carbachol and IBMX, although the concentration/response curve for the latter was again shifted to the right. Tetrodotoxin markedly increased the response of the normal distal colon to both secretagogues and nullified the inhibition of the response to carbachol, but not that to IBMX, in the inflamed colon. The response of the mucosal preparation to 8-bromoadenosine 3',5'-cyclic monophosphate was similar in the normal and inflamed intestine, while the G protein activator NaF had a greater effect in the latter. The expression of the cystic fibrosis transmembrane conductance regulator (CFTR), as assessed by Northern blotting, was unchanged. cAMP levels in isolated colonocytes were markedly reduced by inflammation. We conclude that colonic inflammation produces disturbances of the enteric nervous system resulting in defective mucosal cAMP production and inhibition of ionic secretion.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Delayed examination of synovial fluid by ordinary and polarised light microscopy to detect and identify crystals.

OBJECTIVE: To determine the reliability of a delay in the microscopic examination of synovial fluid (SF) to detect and identify crystals. METHODS: Ninety one SF samples were examined, 31 with monosodium urate (MSU) crystals, 30 with crystals of calcium pyrophosphate dihydrate (CPPD), and 30 containing no crystals. The specimens were stored with EDTA, sodium heparin, and without anticoagulant at 4 degrees C before examination at 24 and 72 hours with ordinary and polarised light microscopy. Another aliquot of the same samples was stored in a plastic container without anticoagulant at -80 degrees C and examined after two months. RESULTS: When the samples stored at 4 degrees C were re-examined after 24 hours, intracellular crystals of MSU were seen in 90/93 (97%) cases where they had been identified previously and 89/93 (96%) cases after 72 hours. Similarly, CPPD crystals were identified in 90/90 (100%) and 87/90 (97%) cases after 24 and 72 hours. Examination of the samples stored at -80 degrees C showed intracellular MSU crystals in 25/31 (81%) of cases and CPPD crystals in 25/30 (83%). No crystals were seen in any sample which had previously been diagnosed as crystal-free. CONCLUSIONS: Deferred microscopic examination of refrigerated or deep frozen SF provides a strong probability of detecting MSU or CPPD crystals if these are present initially.

Calcium Pyrophosphate↗
PubMed2001

Optimization of a mathematical topological pattern for the prediction of antihistaminic activity.

Molecular topology was used to develop a mathematical model capable of classifying compounds according to antihistaminic activity. The equations used for this purpose were derived using multilinear regression and linear discriminant analysis. The topological pattern of activity obtained allows the reliable prediction of antihistaminic activity in drugs frequently used for other therapeutic purposes. Based on the results, the proposed pattern is seemingly only valid for drugs that interact with histamine through competitive inhibition with H1 receptors.

Histamine H1 Antagonists↗
PubMed2001

Dietary vitamin E supplementation protects the rat large intestine from experimental inflammation.

Vitamin E, the most potent antioxidant in the lipid phase, was tested for antiinflammatory activity in trinitrobenzenesulfonic acid-induced rat colitis. Rats were fed a nonpurified diet (saline and control groups) or a vitamin E supplemented diet (treated group, 300 mg/kg nonpurified diet). Vitamin E supplementation, which resulted in increased colonic vitamin E levels, reduced colonic weight and damage score, prevented lipid peroxidation and diarrhea, reduced interleukin-1 beta levels and preserved glutathione reductase activity and total glutathione levels. However, it did not modify myeloperoxidase levels, which are indicative of neutrophil infiltration in the inflamed colon. Vitamin E protects the rat colon from oxidative stress associated with inflammation.

Animals↗
PubMed2001

Intestinal anti-inflammatory activity of morin on chronic experimental colitis in the rat.

BACKGROUND: Morin, a bioflavonoid with antioxidant properties, shows intestinal anti-inflammatory activity in the acute phase of the trinitrobenzenesulphonic acid model of rat colitis. AIM: To assess the anti-inflammatory activity of morin in the chronic stages of trinitrobenzenesulphonic acid-induced rat colitis. METHODS: Rats were rendered colitic by a single colonic instillation of 30 mg of the hapten trinitrobenzenesulphonic acid dissolved in 0.25 mL of 50% ethanol. A group of colitic animals was given morin orally at doses of 25 mg/kg daily. Animals were sacrificed every week for 4 weeks. Colonic damage was evaluated macroscopically and microscopically. Different biochemical markers of colonic inflammation were also assayed, including myeloperoxidase activity, leukotriene B4 and interleukin-1beta synthesis, glutathione and malonyldialdehyde levels and nitric oxide synthase activity. RESULTS: The administration of morin facilitated tissue recovery during the 4 weeks following colonic insult with trinitrobenzenesulphonic acid, as demonstrated macroscopically and microscopically, as well as biochemically by a reduction in myeloperoxidase activity. The intestinal anti-inflammatory effect of morin was accompanied by a significant reduction in colonic leukotriene B4 and interleukin-1beta levels, improvement in colonic oxidative stress and inhibition of colonic nitric oxide synthase activity. CONCLUSIONS: Morin exerts a beneficial anti-inflammatory effect in the chronic phase of trinitrobenzenesulphonic acid-induced rat colitis through the down-regulation of some of the mediators involved in the intestinal inflammatory response, including free radicals, cytokines, leukotriene B4 and nitric oxide.

Administration, Oral↗
PubMed2001

Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis.

The intestinal anti-inflammatory activity of several doses of silymarin was tested in the acute stage of the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. The results obtained show that oral pre-treatment with 50 mg/kg of silymarin significantly attenuated macroscopic colonic damage as well as reduced colonic myeloperoxidase activity compared to non-treated colitic animals. The beneficial effect was accompanied by an improvement in the colonic oxidative status, which was altered in colonic inflammation, by preventing glutathione depletion and reducing malonyldialdehyde production. This suggests that the well known antioxidant properties of silymarin can participate in its intestinal anti-inflammatory activity. In addition, a preservation in the colonic absorptive function was also observed, and this effect can also account for the colonic protective effect observed in this model of acute colitis.

Animals↗
PubMed2001

Search of a topological pattern to evaluate toxicity of heterogeneous compounds.

Molecular connectivity has been applied to the search of mathematical models able to predict the carcinogenic and teratogenic activity of a wide group of structurally heterogeneous compounds. Through the linear discriminant analysis and the diagrams of distribution of pharmacological activity, the classification criteria that minimizes the percentage of error are established. The easiness and speed of the calculation of the descriptors used in this work make the models developed useful in data bases containing a huge number of compounds.

Databases, Factual↗
PubMed2000

Indices of differences of path lengths: novel topological descriptors derived from electronic interferences in graphs.

Novel topological descriptors, namely indices of differences of path lengths (DPs), are deduced from the physical model of wave interferences. Two electrons, moving through a circuit graph within a diffraction experiment, interfere in a given vertex of the graph. It is demonstrated that the overall sum of the inverse of the squares of the differences of topological distances between all pairs of vertices of the graph is a measure of the mean global kinetic energy of the electrons which are able to produce a constructive interference. New topological indices, namely indices of differences of path lengths are thus introduced as derived from such a diffraction pattern. These indices, according to the above expressed, should be a measure of the electron mobility within the molecule. As a consequence, a good prediction is to be expected for properties related to such mobility, such as resonance energy in aromatic hydrocarbons. Our results confirm that in fact, the resonance energies are well predicted by this means. Moreover, the new indices demonstrate to be very useful in the evaluation of biological properties such as antibacterial activities of a wide set of heterogeneous compounds.

Electrons↗
PubMed2000

Intestinal anti-inflammatory activity of UR-12746, a novel 5-ASA conjugate, on acute and chronic experimental colitis in the rat.

The present study was undertaken to investigate the intestinal anti-inflammatory effects of UR-12746 on the acute and chronic stages of a trinitrobenzene sulphonic acid (TNBS) experimental model of inflammatory bowel disease (IBD) in the rat. UR-12746 is a novel, locally-acting compound which combines, through an azo bond, 5-aminosalicylic (5-ASA) and UR-12715, a potent platelet activating factor (PAF)-antagonist. UR-12746 oral pretreatment of colitic rats (50 and 100 mg kg(-1)) reduced acute colonic damage when evaluated 2 days after colonic insult. Postreatment for 4 weeks with UR-12746 (50 and 100 mg kg(-1)) resulted in a faster recovery of the damaged colonic mucosa, which was macroscopically significant from the third week. The intestinal anti-inflammatory effect of UR-12746 was associated with a decrease in leukocyte infiltration in the colonic mucosa, which was evidenced both biochemically, by a reduction in myeloperoxidase activity, and histologically, by a lower leukocyte count after morphometric analysis. This effect was higher than that seen with sulphasalazine, when assayed at the same doses and in the same experimental conditions. Several mechanisms can be involved in the beneficial effects showed by UR-12746: inhibition of leukotriene B(4) synthesis in the inflamed colon, improvement of the altered colonic oxidative status, and reduction of colonic interleukin-1beta production. The results suggest that the intestinal anti-inflammatory activity of UR-12746 can be attributed to the additive effects exerted by 5-ASA and UR-12715, the PAF antagonist compound, that are released in the colonic lumen after reduction of the azo bond by the intestinal bacteria.

Acute Disease↗