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Biomedical subjects

F López

Publications and source records attributed to F López.

At least 127 records · Page 7Linked to original sources

Interaction of low density lipoproteins with arterial proteoglycans. The role of charge and sialic acid content.

The interaction of low density lipoproteins (LDL) with chondroitin sulfate-rich arterial proteoglycans appears to be initiated by coulombic interactions that lead to insoluble complexes. Once formed, large LDL aggregates are held together by non-polar associations. The irreversible formation of LDL proteoglycans aggregates was evaluated for different LDL preparations by definition of an avidity coefficient (Ar) using a Langmuir isotherm. LDL from different subjects, when tested against the same lipoprotein-complexing proteoglycan (LCP), gave Ar values ranging from 1-9 X 10(6) L/M. High avidity values were associated to lipoproteins with apparent isoelectric points above 6.5. These lipoproteins show low sialic acids content. The content of N-acetyl and N-acetyl,O-acetyl sialic acid was found inversely correlated with the avidity coefficient for the arterial LCP. Reductions of 42% on the LDL sialic acid content, by neuraminidase treatment, induced a 10-fold increment in their avidity for the lipoprotein complexing proteoglycan. The results indicate that at low ionic strength and physiological Ca2+-concentration and pH, the surface charge of LDL is an important modulator of the interaction with the arterial proteoglycan. Sialic acid, perhaps because of its exposure at the LDL surface, plays a determinant role in the in vitro association of LDL with the polyanionic proteoglycans. It is possible that in the intima-media the sialic residues of LDL and its balance of surface charges will control part of the interactions with the proteoglycans of the extracellular matrix.

Arteries↗

Effect of low oral doses of disopyramide and amiodarone on ventricular and atrial arrhythmias of chagasic patients with advanced myocardial damage.

Low-dose (7 mg/kg per day) disopyramide administration to arrhythmic chagasic patients decreased the frequency of ventricular extrasystoles in 4 of 17 patients (24%) and suppressed most complex ventricular arrhythmias in 12 of 15 patients (80%). This assessment was made from 72-h continuous Holter monitoring recorded during the course of this double blind, placebo-controlled randomized crossover study. Seven patients (41%) complained of anticholinergic side effects, but no contractile or conduction system depression was seen. Amiodarone (200 mg) given on a single blind, placebo-controlled basis to 9 of these patients reduced the frequency of ventricular extrasystoles in 6 of 9 patients (67%) and suppressed complex ventricular ectopy in 6 of 7 patients (85%). One patient was unable to tolerate this drug (11%). Both drugs seemed less effective in controlling supraventricular arrhythmias, although disopyramide eliminated paroxysms of supraventricular tachycardia in 9 of 13 (69%) and amiodarone in all 6 patients with this arrhythmia. Amiodarone appears to be a better antiarrhythmic drug for chagasic patients, due to its greater effectiveness and lower incidence of side effects.

Administration, Oral↗

Effects of pimozide and domperidone administration on prolactin levels in neonatally estrogenized female rats.

The effects of two dopaminergic blockers, pimozide and domperidone, on the prolactin secretion were investigated in adult female rats treated neonatally with estrogens (100 micrograms of estradiol benzoate s.c. on day 1). These rats showed hyperprolactinemia (556 micrograms/l vs 57.7 in oil-injected) and treatment with pimozide or domperidone failed to increase prolactin levels in the adult age. These results suggest that the hyperprolactinemia in neonatally estrogenized female rats is produced by loss of the dopaminergic inhibition on prolactin secretion, so that the pharmacological blockade of dopaminergic receptors is uneffective. The dopamine levels in hypothalamus were similar in control and estrogenized females suggesting that failure in dopaminergic inhibition is due to a decrease in dopamine secretion to portal vessels.

Animals↗

Involvement of prolactin in the onset of puberty in female rats.

Pimozide (1 mg/kg per day), bromocriptine (1 mg/kg per day) or domperidone (0.1 mg/kg per day) administered daily to rats from day 21 did not change the age at which vaginal opening occurred, nor did they affect the body weight at that age. Therefore the evolution of prolactin levels was different in these three groups. The pimozide-treated group showed high prolactin levels measured on day 23, at vaginal opening and at first oestrus. In the bromocriptine-treated group, levels were undetectable on the day of vaginal opening. Chronic treatment with domperidone failed to increase prolactin levels on day 23 and at vaginal opening. Nevertheless, large increases were observed after a single injection of domperidone at both 21 and 30 days of age. A significant increase in LH observed on day 23 in the pimozide-treated group was the only effect on gonadotrophin levels which was detected. Ovarian weights were unaffected by the treatments, whereas adrenal weight was increased in the bromocriptine-treated group and decreased in the pimozide- and domperidone-treated groups. Female rats grafted on day 21 with one additional pituitary gland from adult (90 days) or young (21 days) donors showed a similar advancement in the time of vaginal opening, although the animals bearing an adult pituitary gland showed higher prolactin levels than those observed in animals grafted with young pituitary glands. This study suggested that the onset of puberty is not closely linked with the evolution of prolactin levels and that the hormone itself is not indispensible for the process.

Adrenal Glands↗

Effects of stress and stress-therapy on plasma beta-endorphin-like immunoreactivity.

Beta-Endorphin-like immunoreactivity (B-ELI) was determined in the plasma of ten patients in presurgical stress conditions and after administration of dehydrobenzperidol (DHB, n = 3) and DHB plus fentanyl (Innovar, n = 7). Human B-ELI was determined by radioimmunoassay. The B-ELI was extracted from plasma with ODS-silica columns. B-ELI plasma levels increased significantly (P less than 0.02) during stress (7,7 +/- 1.2 fmol/ml and 23.3 +/- 4.1 fmol/ml for the control and stress, respectively). After administration of DHB plus fentanyl, a significant decrease (p less than 0.05) of B-ELI plasma levels was observed as compared with the presurgical stress conditions (10.1 +/- 0.8 fmol/ml and 21.1 +/- 5.2 fmol/ml, respectively), whereas no significant difference was observed (p greater than 0.05) in B-ELI plasma levels obtained in the DHB group compared with presurgical stress conditions (10.4 +/- 5.0 fmol/ml, and 28.3 +/- 7.1 fmol/ml, respectively). These results suggest a direct correlation between the emotional stressful situation of presurgery and increase in B-ELI plasma levels. The findings obtained with administration of DHB plus fentanyl seem to lend support to the hypothesis that this premedication is a good stress therapy.

Adolescent↗

Relation between body weight, growth rate, chronological age and puberty in male and female rats.

Body weight, growth rate, chronological age and puberty in female and male rats from litters of 8 and 12 offsprings/mother have been studied. Age and body weight at the moment of vaginal opening (VO) and balanopreputial separation (BPS) were analyzed. Results show that animals reared in smaller groups grew faster than others. After weaning there was an increase in growth rate. VO and BPS occurred at the same age in groups with different growth rates and different body weights. In conclusion this work evidences that external signs of sexual maturation are not linked to a "critical weight" or to a "growth rate".

Aging↗

Partial structure of the active moiety of a lipoprotein complexing proteoglycan from human aorta.

Proteoglycans and glycosaminoglycans of the intima-media extracellular matrix have been stated to play a role in lipoprotein deposition associated with atherogenesis. It is therefore important to characterize the active lipoprotein-complexing moiety of these macromolecular aggregates. We have isolated a soluble proteoglycan aggregate of approximately 5 X 10(6) molecular weight after homogenization of human aortic intima-media in an isosmotic sucrose solution, sequential differential centrifugation, dialysis, exclusion chromatography and preparative electrophoresis. This proteoglycan aggregate, labelled lipoprotein-complexing proteoglycan (LCP), has been previously shown to form specific complexes with low density lipoproteins, either isolated or in sera. Density gradient centrifugation in dissociative conditions of the LCP, cellulose acetate acetate electrophoresis of the subfractions, chondroitinases treatment and high performance liquid chromatography of the unsaturated disaccharides indicated that the glycosaminoglycan moiety was composed of 56% chondroitin-6-SO4, 26% hyaluronate and/or undersulfated chondroitin and 17% chondroitin-4-SO4. In pore-gradient polyacrylamide gel electrophoresis, the hyaluronate monomer appeared to have a molecular weight of 250000 while that of the chondroitin sulfates ranged between 50000 and 70000 after extensive treatment with protease. The fractions enriched in the chondroitin sulfate monomers were the most reactive towards LDL and their reactivity was abolished by chondroitinase AC indicating that the lipoprotein-complexing capacity of the LCP aggregate is associated to these molecules.

Aorta↗

[Effect of constant illumination on the response to castration in rats].

The effects of constant light from birth on compensatory ovarian or testicular hypertrophy and gonadotropins levels after gonadectomy have been studied. Ovarian hypertrophy was not affected by constant light either in young or adult rats. The degree of testicular hypertrophy increased in young males submitted to constant light without changes in FSH levels after hemicastration. FSH and LH levels after gonadectomy were similar in young and adult females, while those levels were higher for adult males than for young ones. Constant light increases LH and FSH postcastration levels in young males without effects in the other groups.

Animals↗

ApoLDL: evidence for an aggregating system of heterogeneous subunits.

The protein moieties of low density lipoprotein (LDL) (d 1.019-1.063 g/ml) and subfractions: I (d 1.018-1.023 g/ml), II (d 1.023-1.028 g/ml), III (d 1.028-1.034 g/ml), and IV (d 1.034-1.052 g/ml) were obtained by a mild delipidation procedure involving attachment of LDL to an ionic-exchange column and a gradient of the non-ionic detergent Brij-36T (J. Lipid Res. 1979. 20: 631.). The apoLDL, eluted in the presence of 6 M urea, 0.1% SDS, or 4 M guanidine-HCl and analyzed by pore-gradient polyacrylamide gel electrophoresis and high performance gel exclusion chromatography, appeared to be made up of several polypeptide components with molecular weights between 250,000 and 14,000. The complex pattern was observed in the apoprotein of LDL subfractions I to IV; however the distribution of the most prominent components was different for each density range. These results, those from immunoelectrophoresis, N-terminal analysis, and measurements of tetramethylurea-soluble apoproteins discounted the possibility that the presence of bands with molecular weights below 250,000 could be caused by contamination with VLDL or HDL or nonspecific proteolysis. Delipidation of subfractions I to IV with organic solvents produced, on the other hand, simple patterns of highly aggregated apoLDL subfractions, where most of the protein had molecular weights above 250,000. The more disaggregated apoLDL preparations were those obtained from LDL rapidly isolated by single-spin centrifugation in KBr gradients, from fresh plasma immediately mixed with EDTA, phenylmethyl sulfonylfluoride, and chloramphenicol. ApoLDL fractionated by single-pore polyacrylamide gel electrophoresis appeared to be a system of heterogeneous antigens unevenly distributed on the different polypeptide components. These results, and those obtained by peptide maps of tryptic hydrolyzates from the major constituents, suggest that apoLDL is made of several polypeptides of different lengths with similar repetitive sequences but with some dissimilar segments specific for the major protein constituent of LDL. These polypeptides show a high tendency to form multiple aggregates with size distribution dependent on the preparation history.-Socorro, L., F. López, A. López, and G. Camejo. ApoLDL: evidence for an aggregating system of heterogeneous subunits.

Apolipoproteins↗

Characterization and properties of a lipoprotein-complexing proteoglycan from human aorta.

The preparation of a proteoglycan (PG) from human aortic intima-media is described. The PG was obtained from intima-media homogenates by differential centrifugation, exclusion chromatography and preparative agarose electrophoresis. Crude or purified preparations of the proteoglycan are capable of forming specific insoluble complexes with LDL, purified or in serum. This product has been labelled lipoprotein-complexing proteoglycan (LCP-3). On agarose and cellulose acetate electrophoresis LCP-3 appears as a single band. However, its glycosaminoglycan (GAG) moiety shows a composition and chromatographic behaviour compatible with hybrid or mixed chains of chondroitin-6-so4, dermatan sulfate and heparin and/or heparan sulfate. The specificity of LCP-3 for LDL disappears when it is treated with testicular hyaluronidase or proteolytic enzymes. Ionic strength, pH, Ca++ and Mg++ modulate the amount of LDL insolubilized. The amino acid composition of the protein from LCP-3 is that of a basic protein(s), perhaps bound covalently through xylose--serine residues to the GAG's. The estimated molecular weight of LCP-3 is 1 to 5 x 10(6) daltons. The presence of LCP-3 to intima-media and its specificity for interacting with LDL at conditions near to physiological ones are suggestive of the role that this type of structure may play in the association of the atherogenic lipoproteins with components of the arterial intima-media.

Aorta↗

Factors modulating the interaction of LDL with an arterial lipoprotein complexing proteoglycan: the effect of HDL.

The presence of a lipoprotein complexing proteoglycan (LCP) in extracts of human arterial intima/media that forms specific complexes with low density lipoproteins (LDL) has suggested that it may play a role in the interaction of LDL with the arterial wall and the atherogenic process. The formation of insoluble LDL-LCP complexes by incubation of serum with arterial extracts appears directly related to the concentration of LDL and inversely to the content of high density lipoproteins (HDL), indicating that HDL may inhibit the interaction between LDL and LCP. This inhibition is clearly visible by addition of HDL to LCP containing extracts before their incubation with LDL. This effect is also shown by apoHDL but not by lipoprotein-free plasma. It is suggested that the HDL/LDL ratio of the plasma crossing the endothelial barrier may be an important modulator of the net accumulation of LDL in the intima/media and of its contribution to atherogenesis.

Adult↗