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M Garcia-Fuentes

Publications and source records attributed to M Garcia-Fuentes.

10 recordsLinked to original sources
PubMed2006

Protection of the peptide glutathione by complex formation with alpha-cyclodextrin: NMR spectroscopic analysis and stability study.

The main objective of this work was to investigate the complexation mechanism of the tripeptide glutathione with alpha-cyclodextrin (alpha-CyD). The final purpose was to explore the possibility of using this complexation approach for preserving the stability of this peptide in all biological environments relevant for oral drug delivery. The complexes between the peptide and alpha-CyD were formed in aqueous solution and the complexation mechanism was investigated using different (1)H NMR experimental approaches. The resulting complexes were also studied with respect to their ability to protect the peptide against proteolytic degradation by the exopeptidase, gamma-glutamyltranspeptidase. The NMR experiment, 1D-saturation transfer NOE difference (STD), evidenced the interaction between alpha-CyD and glutathione. The binding constants, calculated by a titration method, were in the range of 55-70 M(-1) at 25 degrees C and in the range 68-72 M(-1) at 37 degrees C. Moreover, from the 1D-pulse field gradient spin echo-transverse-rotating frame nuclear Overhauser (PFGSE-T ROESY) spectra it was concluded that alpha-CyD binds preferably to the l-glutamate (side chain) moiety of glutathione, leaving the glycine residue exposed to the external medium. This result was consistent with those of the in vitro stability study, which indicated that the degradation of glutathione was markedly reduced to the half in 2h upon inclusion in alpha-CyD. Overall, these results show the possibility of protecting specific peptide groups by their inclusion in CyDs as well as the utility of NMR experiments for the understanding of this stabilization strategy.

Chromatography, High Pressure Liquid↗
PubMed2005

A comparative study of the potential of solid triglyceride nanostructures coated with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery.

We have previously reported the formation and characterization of poly(ethylene glycol) (PEG)-coated and chitosan (CS)-coated lipid nanoparticles. In the present work our goal was to study the interaction of these surface-modified lipid nanoparticles with Caco-2 cells and to evaluate the potential of these nanostructures as oral delivery systems for salmon calcitonin (sCT). The interaction of rhodamine-loaded nanoparticles with the Caco-2 cell monolayers was evaluated quantitatively and qualitatively by confocal laser scanning microscopy and fluorimetry, respectively. The ability of these nanoparticles to reversibly enhance the transport of hydrophilic macromolecules through the monolayers was investigated by measuring the transepithelial electric resistance and the permeability to Texas Red-dextran. Finally, in vivo studies of the response to sCT-loaded nanoparticles were performed in rats. The results showed that the association of rhodamine-loaded nanoparticles to the Caco-2 cell monolayer was independent of the surface coating of the nanoparticles (CS-coated versus PEG-coated nanoparticles). However, while PEG-coated nanoparticles did not affect the permeability of Caco-2 monolayers, CS-coated nanoparticles produced a dose-dependent reduction in the transepithelial electric resistance, simultaneously to an enhanced dextran transport. The results obtained following oral administration of sCT-loaded CS-coated nanoparticles to rats showed a significant and prolonged reduction in the serum calcium levels as compared to those obtained for control (sCT solution). In contrast, the hypocalcemic response of sCT-loaded PEG-coated nanoparticles was not significantly different of that provided by the control (sCT solution). Therefore, these results indicate that the surface composition of the particles is a key factor in the improvement of the efficiency of oral sCT formulations. Moreover, the encouraging results obtained for CS-coated nanoparticles underline their potential as carriers for peptide delivery.

Administration, Oral↗
PubMed2000

Variables affecting BMI evolution at 2 and 5 years after vertical banded gastroplasty.

BACKGROUND: Vertical banded gastroplasty (VBG) has been found to result in significant reduction in body mass index (BMI) during the first postoperative year. We investigated the impact of some intrinsic and extrinsic factors on long-term BMI evolution in morbidly obese patients who underwent VBG, with the aim of establishing a long-term weight-loss prognosis. METHODS: 67 consecutive morbidly obese patients who underwent VBG were followed for 2 years; of these, 34 were followed 3 more years, for a total follow-up of 5 years. BMI was monitored and correlated with demographic (preoperative BMI, obese relatives, age and gender) and lifestyle variables (physical activity, habitual dietary transgression and occupational status). RESULTS: Global BMI fell from 47.5 at the time of the intervention to 32.1 when patients were examined 12 months after surgery. From the second year, an upward trend was observed, and at 5 years, mean BMI was above 35, considered in the high-risk range. Modifiable variables affecting lifestyle have shown significantly favorable effects on BMI evolution. Among intrinsic variables, BMI before surgery and obese parents also affect long-term evolution. CONCLUSION: Different variables should be considered in order to establish a long-term weight-loss prognosis for each patient, thus making it possible to act more specifically on modifiable variables.

Adult↗
PubMed1998

Polymorphism of the platelet glycoprotein IIIa gene in patients with coronary stenosis.

Based on genetic variability, structural differences in the glycoprotein IIb/IIIa platelet receptor for adhesive proteins result in individual differences in the thrombogenicity of platelets. Recent studies suggest a controversial association between a genetic polymorphism of the glycoprotein IIIa gene (PlA2) and the risk of coronary artery disease. In our study, the prevalence of the PlA2 allele in a group of patients undergoing percutaneous coronary revascularization was 37%, a value significantly higher than in controls [13%, odds ratio (OR) = 3.93, 95% CI, 1.84 to 8.53] suggesting a significant association between this polymorphism and documented coronary stenosis, which is strongest among <60 years old patients (OR = 12.30, 95% CI, 2.98 to 70.93). This polymorphism represents an inherited risk factor for severe cardiovascular disease due to coronary occlusion.

Aged↗
PubMed1997

Clinical features and outcome of 95 patients with hypersensitivity vasculitis.

PURPOSE: To evaluate the clinical features and outcome of patients with isolated hypersensitivity vasculitis (HV). PATIENTS AND METHODS: Retrospective study of patients with cutaneous vasculitis followed up at a University Hospital from 1975 to 1994. Patients with vasculitis secondary to collagen vascular diseases, neoplasia, or major infections were excluded. Patients were classified as HV according to the differential criteria proposed by Michel et al (J Rheumatol. 1992;19:721-728). RESULTS: Ninety-five patients were classified as HV. The mean age was 42.7 +/- 21.7 years, with similar disease frequency in both sexes. In 43 patients, the precipitating event was drug therapy, either alone or as a treatment for a coexistent infection, usually an upper respiratory tract infection. The most frequent clinical manifestation was palpable purpura followed by joint symptoms. Systemic involvement was infrequent: 7 patients had nephropathy, manifested almost exclusively by microhematuria, and 5 patients had gastrointestinal symptoms. In 54 subjects the vasculitis did not require treatment; 26 patients were treated with NSAIDs, and 14 required corticosteroids (associated to immunosuppressive agents in 2 of them). After a mean follow-up of 15.5 +/- 28.9 months (median 6), only 2 patients had slight renal impairment, whereas the remaining had a complete recovery. CONCLUSION: Hypersensitivity vasculitis is usually a benign syndrome, often secondary to drugs or infections, or both. Its main clinical manifestations are skin and joint symptoms. The systemic involvement is scarce and its prognosis is excellent.

Adolescent↗
PubMed1983

Increased IgA-producing cells in the blood of patients with active Henoch-Schönlein purpura.

Peripheral blood lymphocytes (PBL) producing IgA, IgM, and IgG, both spontaneously and after pokeweed mitogen stimulation in cell culture, were determined by a protein A hemolytic plaque assay in 20 children with active Henoch-Schönlein purpura (HSP), 42 with inactive disease, 22 normal controls of the same ages, and 18 children with upper respiratory tract infections (URTI). The geometric mean of circulating IgA-producing cells in active HSP (1,016 X divided by 1.55 cells/10(6) PBL) was increased when compared with the group with inactive disease (P less than 0.001), normal controls (P less than 0.001), and children with URTI (542 X divided by 2.03 cells/10(6) PBL, P less than 0.05). The number of circulating IgM-producing cells was slightly increased in active HSP (260 X divided by 2.65 cells/10(6) PBL) and URTI (256 X divided by 3.16 cells/10(6) PBL). Both values were higher than those found in the group with inactive disease (113 X divided by 2.26 cells/10(6) PBL, P less than 0.01). There were no significant differences among the 4 groups in the number of circulating IgG-producing cells. The number of cells producing each type of immunoglobulin after in vitro stimulation with pokeweed mitogen was similar in patients with active HSP, normal controls, and the group with inactive disease. These data demonstrate a selective increase in the number of circulating IgA-producing cells only during disease activity, and add further support to a possible pathogenic role of this immunoglobulin in HSP.

Adolescent↗
PubMed1978

Serum complement components in Henoch-Schönlein purpura.

Serum levels of C1q, C4, C3, C5, factor B, and properdin were measured in patients with Henoch-Schönlein purpura (HSP). In the cases of acute HSP, 9 of 23 (39%) had a low CH50, and 5 of 17 (30%) a low properdin; C1q, C4, and C3 levels were not depressed. In 10 cases with chronic nephritis following HSP, complement components were normal except for 2 with reduced C4 and one with low properdin. These findings confirm that complement activation occurs in HSP; the low serum levels of properdin in the acute group indicate that there is activation of the alternative pathway in these patients.

Acute Disease↗
PubMed1977

Cryoglobulinaemia in Henoch-Schönlein purpura.

Sera from patients with Henoch-Schönlein purpura were examined for cryoglobulinaemia. Thirty patients had acute Henoch-Schönlein purpura, with or without renal diseas; 14 had chronic nephritis after a previous episode of purpura; and 17 were well, without urinary abnormalities, after recovering from Henoch-Schönlen purpura. Raised concentrations of cryoglobulins were present in 14 (47%) of those with acute purpura, nine (64%) of those with chronic nephritis, but none of those who had recovered completely from Henoch-Schönlein purpura. This suggests that acute Henoch-Schönlein purpura and the chronic nephritis that sometimes follows it have an immune-complex pathogenesis. IgA and properdin were found in several cryoglobulins, which suggested that complement had been activated via the alternative pathway, but isolated cryoglobulins capable of splitting C3 in vitro did so via the classical pathway.

Adolescent↗
PubMed1975

Distal renal tubular acidosis in infancy: a bicarbonate wasting state.

Three unrelated infants with apparently distal RTA were investigated. Growth retardation, polyuria, nephrocalcinosis, inappropriately high urinary pH, and marked dependence of bicarbonate excretion on urinary flow were characteristic of the distal or classic form of RTA, but the urinary loss of bicarbonate at normal serum values exceeded that usually found in children or adults with this disorder. Renal tubular function was studied during hypotonic saline diuresis in the three patients and in seven healthy control infants of similar age. Fractional delivery of sodium to the distal nephron was significantly higher in the patients than in control subjects. Sodium transport at the diluting segment was not impaired. The results support the assumption that the bicarbonate wasting was the consequence of an increased delivery of this substance to an already impaired distal nephron and thus further inhibited the distal mechanisms of net acid excretion.

Acidosis, Renal Tubular↗