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Biomedical subjects

M García

Publications and source records attributed to M García.

At least 127 records · Page 7Linked to original sources
PubMed1999

Effect of Electrolyte on the Surface and Thermodynamic Properties of Amphiphilic Penicillins.

Critical micelle concentrations and surface properties of the penicillins cloxacillin, dicloxacillin, and nafcillin in aqueous solution at 303 K and at electrolyte concentrations over the range 0.0-0.4 mol dm(-3) were determined by surface tension measurements. A mass action model, modified for application to associating systems of low aggregation number, was used to calculate the standard Gibbs energy of micellization of these drugs at each electrolyte concentration. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Influence of Molecular Structure on the Ideality of Mixing in Micelles Formed in Binary Mixtures of Surface-Active Drugs.

The influence of the structure of the hydrophobic group on the ideality of mixing in binary mixtures of surface active molecules has been investigated using combinations of amphiphilic penicillins. Critical concentrations (cc) of the binary mixtures of these anionic surfactants were determined by conductivity measurements as a function of the composition. The nonideality of mixing was evaluated using a regular solution approximation and expressed in terms of the interaction parameter, beta. Mixing in micelles formed in binary mixtures of the structurally similar penicillins cloxacillin, dicloxacillin, and flucloxacillin was ideal (beta = 0). In contrast, the combination of either cloxacillin or dicloxacillin with the penicillin nafcillin produced mixed micelles in which the mixing deviated from ideality (beta = +0.1 to +0.2). The positive values of beta for these systems indicated negative synergism between components of the mixtures that may be a consequence of the marked structural differences between the hydrophobic groups of these drugs. The composition of the mixed micelles was derived from the cc data by application of a theoretical treatment based on excess thermodynamic quantities. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals.

In order to investigate the possibility of whether or not the lymphocytes of patients with Alzheimer's Disease (AD) are in an activated state, blood mononuclear cells from 45 AD patients and 45 healthy age matched controls were immunophenotyped by measuring the expression of CD3, CD4, CD7, CD8, CD25, CD28, CD56 and HLA-DR by flow cytometry. Circulating and in-vitro-produced cytokines were also measured by ELISA tests. CD7 and CD8 were significantly decreased in AD patients (48.3% and 18.2%, respectively) when compared to healthy subjects (63.2% and 28.3%, respectively). A significant increase in the CD4, CD25 and CD28 antigen expression was also observed in the AD group (55.3% 24.8% and 65.1%) with respect to healthy subjects (44.5%, 10.3% and 54.3%). In addition there was a significant difference in the extent of apoptosis in lymphocyte culture, as measured by mean fluorescence intensity (MFI) of Fas antigen (CD95) expression on CD4+ T cells in 6 AD patients (MFI = 36% and 43%, by anti-CD3 and hyperthermia mediated-apoptosis, respectively) with respect to 6 healthy individuals (MFI = 24% and 31%, by anti-CD3 and hyperthermia mediated-apoptosis, respectively), as well as in T-cell proliferation assay. A decline of Fas antigen expression on CD8+ subset was observed in the AD group with both stimuli (19% and 28%) comparing to the control group (29% and 39%). No differences were observed on circulating cytokines and spontaneous in vitro production of proinflammatory interleukin 1beta (IL-1beta), Tumor Necrosis Factor-alpha (TNF-alpha), IL-6 and IL-10 cytokines. Lipopolysaccharide (LPS)-stimulated in vitro production of IL-1beta, TNF-alpha, IL-6 and IL-10 measured by a whole blood culture system was significantly higher in AD patients comparing to controls. Furthermore, the observed differences were more evident at late stages of disease. These findings suggest that immunological tests, based on lymphocyte immunophenotyping combined with pro-inflammatory cytokine determinations and measurement of apoptosis in peripheral blood might represent a useful tool to obtain more insight into the pathogenesis of AD and into the level of immune activation which could characterize the pathological state of lymphocytes from individual AD patients.

ADP-ribosyl Cyclase↗
PubMed1999

[Validation of the Spanish version of the Liebowitz social anxiety scale, social anxiety and distress scale and Sheehan disability inventory for the evaluation of social phobia].

BACKGROUND: Social phobia is an anxiety disorder of increasing interest in clinical psychiatric practice and research. The questionnaires most widely used in the psychometric evaluation of these patients are: Liebowitz Social Anxiety Scale (LSAS), Social Anxiety and Distress Scale (SADS) and Sheehan Disability Inventory (SDI). The objective of this study was to evaluate the validity and reproducibility of the Spanish versions. SUBJECTS AND METHODS: Convergent validity was analysed by correlating patients' scores on the LSAS, SADS and SDI with scores on the Global Activity Evaluation Scale (GAES), the Hamilton Anxiety Scale (HAM-A) and the Visual Analogue Scale (VAS) of the EuroQol. Validity of the internal structure was examined by analysing the correlations between the different sub-escales of the questionnaires. Internal consistency was analysed using Cronbach's alpha and Kuder-Richardson coefficients. Discriminative capability was analysed by comparing LSAS, SADS and SDI scores of patients with social phobia with scores from healthy subjects, and with that obtained on the HAM-A and the EuroQol VAS. Reproducibility was analysed by re-testing patients after 15 days. RESULTS: 57 patients and 57 healthy subjects were recruited in 4 psychiatric centres. The three questionnaires showed an adequate convergent validity with the GAES, the HAM-A and the EuroQol VAS (r = -0.24-0.40 and r = 0.29-0.52). The LSAS and SDI questionnaires showed a homogenous internal structure in terms of correlation between sub-scales (r = -0.61-0.93 for LSAS, and r = -0.04-0.61 for SDI). All the sub-scales of the questionnaires showed an adequate internal consistency (with coefficients between 0.72 and 0.88). The questionnaires discriminated between groups of patients with different levels of symptom severity and self-perceived overall health. They also discriminated between patients with social phobia and healthy subjects (area under the Receiver's Operating Characteristics curves = 0.95-0.99). All sub-scales from the questionnaires showed adequate reproducibility (with intraclass correlation coefficients between 0.63 and 0.88). CONCLUSIONS: The Spanish versions of the LSAS, SADS and SDI questionnaires have shown adequate validity and reproducibility for use in clinical research and the clinical assessment of patients with social phobia in Spain.

Adolescent↗
PubMed1999

A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms.

A randomized blinded clinical trial was performed in 53 patients bitten by Bothrops sp. and Porthidium sp. in Antioquia and Chocó, Colombia, in order to compare the efficacy and safety of two antivenoms made of whole IgG obtained by either ammonium sulphate (monovalent anti-B. atrox) or caprylic acid (polyvalent) fractionation. Additionally, antivenoms were compared by electrophoretic and chromatographic analyses and anticomplementary activity in vitro. With a protocol of 2, 4 and 6 antivenom vials for the treatment of mild, moderate and severe envenomings, respectively, both antivenoms were equally efficient to neutralize the most relevant signs of envenoming and to clear serum venom levels in patients from the first hour and later on. Three patients with severe envenoming and initially treated with less than six vials on admission had persistent or recurrent venom antigenemia within 12-48 h. Monovalent antivenom fractionated by ammonium sulphate precipitation had higher amounts of protein aggregates and nonimmunoglobulin proteins than polyvalent antivenom fractionated by caprylic acid precipitation. Both antivenoms presented anticomplementary activity in vitro, being higher in the monovalent product. In agreement, monovalent antivenom induced a significantly higher incidence of early antivenom reactions (52%) than polyvalent antivenom (25%).

Adolescent↗
PubMed1999

Liposomes as vehicles for the presentation of a synthetic peptide containing an epitope of hepatitis A virus.

Previous work from our group showed that the entrapment of HAV-related synthetic peptides into multilamellar liposomes yielded satisfactory immunoresponses when administered to mice. In the present work we report investigative results for several liposome formulations of a 20-mer peptide related to VP3 capsid protein of HAV. In this sense, the recently introduced surface plasmon resonance technique has been applied to compare the different strategies of association between the synthetic peptide and phospholipid vesicles and to demonstrate that no significant alteration in antigenicity is produced when the peptide sequence is covalently coupled to the surface of small unilamellar vesicles. In addition, conformational data obtained by the circular dichroism technique have shown a decrease in the helical contribution of peptide-once linked to phospholipid; probably this change is due to the restriction introduced at the N-terminus of the sequence when coupled to the derivatized phospholipids at the surface of vesicle bilayers.

Animals↗
PubMed1999

Comparison of the pharmacokinetics of moxidectin (Equest) and ivermectin (Eqvalan) in horses.

A study was undertaken in order to evaluate and compare plasma disposition kinetic parameters of moxidectin and ivermectin after oral administration of their commercially available preparations in horses. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups of five horses. Group I was treated with an oral gel formulation of moxidectin (MXD) at the manufacturers recommended therapeutic dose of 0.4 mg/kg bw. Group II was treated with an oral paste formulation of ivermectin (IVM) at the manufacturers recommended dose of 0.2 mg/kg b.w. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Computerized kinetic analysis was carried out. The parent molecules were detected in plasma between 30 min and either 30 (IVM) or 75 (MXD) days post-treatment. Both drugs showed similar patterns of absorption and no significant difference was found for the time corresponding to peak plasma concentrations or for absorption half-life. Peak plasma concentrations (Cmax) of 70.3+/-10.7 ng/mL (mean +/- SD) were obtained for MXD and 44.0+/-23.1 ng/mL for IVM. Moreover, the values for area under concentration-time curve (AUC) were 363.6+/-66.0 ng x d/mL for the MXD treated group, and 132.7+/-47.3 ng x d/mL for the IVM treated group. The mean plasma residence times (MRT) were 18.4+/-4.4 and 4.8+/-0.6 days for MXD and IVM treated groups, respectively. The results showed a more prolonged residence of MXD in horses as demonstrated by a four-fold longer MRT than for IVM. The longer residence and the higher concentrations found for MXD in comparison to IVM could possibly explain a more prolonged anthelmintic effect. It is concluded that in horses the commercial preparation of MXD presents a pharmacokinetic profile which differs significantly from that found for a commercial preparation of IVM. To some extent these results likely reflect differences in formulation and doses.

Administration, Oral↗
PubMed1999

Effect of insulin-like growth factor I on in vivo intestinal absorption of D-galactose in cirrhotic rats.

Insulin-like growth factor I (IGF-I) bioavailability is reduced in liver cirrhosis, a condition frequently associated with malnutrition. We have analyzed in vivo absorption of D-galactose by jejunal loops in rats with CCl4-induced liver cirrhosis and the influence of IGF-I on intestinal sugar transport in this disease. Two different study protocols were followed. In protocol 1, healthy control rats or cirrhotic rats received saline or IGF-I (2 micrograms . 100 g body wt-1. day-1) for 2 wk. In protocol 2, control and cirrhotic rats received saline or IGF-I as a bolus injection of 1 microgram/100 g body wt followed by continuous infusion of the same dose for 100 min. In vivo D-galactose absorption was reduced in cirrhotic rats compared with healthy controls. IGF-I, as both a chronic (protocol 1) and acute treatment (protocol 2), was able to improve sugar transport in cirrhotic rats but had no effect on sugar absorption in healthy rats. A significant elongation of enterocyte microvilli was observed in cirrhotic animals; this alteration was totally or partially corrected by chronic or acute IGF-I administration. Our results show that in vivo jejunal sugar transport and microvilli structure are altered in liver cirrhosis and that IGF-I, among other effects, may correct these changes by modulating cytoskeletal organization in enterocytes.

Animals↗
PubMed1999

Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Adult↗
PubMed1999

Prolactin stimulates leptin secretion by rat white adipose tissue.

Leptin, the obese (Ob) gene product, is an adipocyte-derived satiety factor that is involved in the regulation of food intake and body weight. Leptin signals nutritional status to several other physiological systems and modulates their function. As PRL is involved in energy and lipid metabolism, this study was undertaken to investigate the role of PRL on in vivo regulation of leptin serum concentration and Ob messenger RNA expression in white adipose tissue in rats. It was found that increased serum PRL levels, obtained by pituitary graft or exogenous injected ovine PRL (oPRL, 5 mg/kg), significantly stimulate serum leptin concentration. A significant increase (P < 0.01) in serum leptin concentration was present in hyperprolactinemic animals (4.7+/-0.4 microg/liter) in comparison to controls (1.2+/-0.1 microg/liter and 1.09+/-0.09 microg/liter of intact sham operated and ovariectomized rats, respectively). Similar results were obtained in oPRL-treated animals where leptin levels were 5.4+/-0.1 microg/liter vs. 1.1+/-0.1 microg/liter and 0.8+/-0.08 microg/liter of intact sham operated rats and ovariectomized, respectively (P < 0.001). This stimulatory effect of PRL on serum leptin levels was significantly reduced by food deprivation (P < 0.01) where serum leptin levels were 12.5+/-0.65 microg/liter in grafted animals vs. 3.2+/-0.36 microg/liter of grafted animals subjected to 48 h of food deprivation. Moreover, in vivo, PRL was able to induce leptin messenger RNA levels in several areas of rat white adipose tissue. The data demonstrate that PRL acts on the adipose tissue increasing leptin synthesis and secretion, suggesting a new role for this lactogenic hormone in the regulation of food intake.

Adipose Tissue↗