PubMed Health⌕ Search

Biomedical subjects

J A Gonzalez-Correa

Publications and source records attributed to J A Gonzalez-Correa.

9 recordsLinked to original sources
PubMed1997

Pharmacological characterization and distribution of muscarinic receptors in human placental syncytiotrophoblast brush-border and basal plasma membranes.

Based on the existence of choline acetyltransferase and acetylcholine in human placenta, we have investigated the presence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta. Radioligand binding assay, using [3H]N-methyl-scopolamine as tracer, showed the existence of acetylcholine muscarinic receptors in brush-border (Kd 0.28 +/- 0.04 nM; Bmax 9.4 +/- 1.6 fmol/mg protein) and basal plasma membranes (Kd 0.24 +/- 0.05 nM; Bmax 34.3 +/- 6.3 fmol/mg protein). In order to perform a pharmacological characterization of these receptors, competition binding experiments were carried out using the muscarinic receptor antagonists pirenzepine, (11(2-diethyl-amino)methyl)-1-piperidinylacetyl-5-11-dihydro-6H-py rido(14) benzodiazepine (AF-DX 116), himbacine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), dicyclomine and hexahydro-sila-difenidol (HHSD). The results obtained showed that the muscarinic receptors in brush-border and basal plasma membranes belong to different subtypes. In brush-border membranes, the receptor found match in terms of affinity for the antagonists with the muscarinic M1 receptor subtype (Ki pirenzepine, 13.6 +/- 8.2 nM; Ki AF-DX 116, 1680 +/- 271 nM; Ki himbacine, 212 +/- 6.5 nM; Ki 4-DAMP. 1.5 +/- 0.4 nM; Ki dicyclomine, 5.1 +/- 0.8 nM; Ki HHSD, 34.3 +/- 7.3 nM), whereas the receptor in basal plasma membrane seems to be of the muscarinic M2 receptor subtype (Ki pirenzepine, 202 +/- 48 nM; Ki AF-DX 116, 124 +/- 60 nM; Ki himbacine, 20.6 +/- 4.8 nM; Ki 4-DAMP, 4.5 +/- 1.2 nM; Ki dicyclomine, 54.6 +/- 22 nM; Ki HHSD, 89.2 +/- 15.8 nM). The results obtained show the existence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta with a different distribution pattern in terms of number of receptors and distribution of different subtypes. The functional significance of these findings is as yet unknown, but these receptors probably mediate different functions as they belong to different subtypes and are coupled to different second messengers.

Binding, Competitive↗
PubMed1997

Effects of S-adenosyl-L-methionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats.

We used an animal model of extrahepatic biliary obstruction of 7 days' duration to study the production of thiobarbituric acid reactive substances (TBARS), total glutathione (TG), reduced glutathione (GSH), and oxidized glutathione (GSSG), and the enzymatic activities of GSH-peroxidase, GSSG-reductase, and GSH-transferase. Four groups of six rats each were treated with saline, drug solvent, S-adenosyl-L-methionine (SAM) 5 mg/kg/d, subcutaneously, or SAM 10 mg/kg/d, subcutaneously. Extrahepatic biliary obstruction increased TBARS. SAM had the dose-dependent effects of inhibiting TBARS production and increasing TG content, mainly as a result of the increase in GSH. The activity of GSH-peroxidase and GSH-transferase was also significantly increased. In renal tissue these effects were statistically significant only in animals given the higher dose of SAM. In liver we found a reduction in biochemical values indicative of liver damage. We conclude that effect of SAM on hepatorenal function is strongly influenced by the drug's ability to reestablish equilibrium after oxidative tissue stress.

Animals↗
PubMed1997

Effect of S-adenosyl methionine on muscarinic receptors in young rats.

In the present study we have investigated the effect of a chronic administration of S-Adenosyl Methionine (SAM) on muscarinic receptor subtypes in young rat forebrain, cerebellum, heart and lacrimal gland. Saturation binding experiments were performed using 3H-N-methylscopolamine (3H-NMS) to label the total population of muscarinic receptors in plasma membranes from forebrain, cerebellum, heart and lacrimal gland. 3H-Pirenzepine (3H-Pz) was used to label the M1 subtype in plasma membranes from forebrain. The results obtained in cerebellum, heart and lacrimal gland show no changes in the affinity (Kd) nor in the number of receptors (Bmax) of the treated versus control groups. Saturation experiments in forebrain show an increase in the number of receptors of the treated versus control groups when using 3H-NMS (Bmax 2117 +/- 63 versus 1643 +/- 104 fmol/mg protein) without changes in the affinity. Saturation experiments with 3H-Pz, show an increase in the number of M1 receptors in the treated group with no changes in the affinity (Bmax 421 +/- 16 versus 225 +/- 19 fmol/mg protein). From our results, we conclude that SAM increase the number of receptors in forebrain and this increase is mainly due to changes in the number of M1 receptor subtypes.

Animals↗
PubMed1996

Inhibition of ferrous-induced lipid peroxidation by dipyridamole, RA-642 and mopidamol in human lung tissue.

1. The in vitro production of ferrous-induced lipid peroxidation was 5.71 times higher in rat lung tissue than in human lung membranes. 2. The pyrimido-pyrimidine derivative RA-642 shows a more potent inhibition of ferrous-induced lipid peroxidation than dipyridamole; mopidamol had no effect. All the compounds showed higher anti-peroxidative effect in rat than in human lung tissue.

Adult↗
PubMed1995

Aminoglycoside-associated nephrotoxicity in extrahepatic obstructive jaundice.

Experimental data demonstrate that biliary obstruction increases renal sensitivity to gentamicin. In the present study the incidence of and risk factors for aminoglycoside nephrotoxicity were prospectively studied in patients with extrahepatic obstructive jaundice. Two hundred and thirty-seven hospitalized adult patients were classified into three groups. Group I consisted of 84 patients with extrahepatic obstructive jaundice, who received aminoglycoside (gentamicin or tobramycin). Group II consisted of 81 patients with extrahepatic obstructive jaundice, who received either antibiotics other than aminoglycoside or no antimicrobial therapy. Group III consisted of 72 noncholestatic patients receiving aminoglycosides for different disorders. Nephrotoxicity developed in 27 patients (32%) in group I vs 9 patients (11%) in group II and 4 patients (5.6%) in group III (p < 0.00001). In group I, a comparison of patients with and without nephrotoxicity revealed significantly higher values in the former for mean serum bilirubin concentration, initial steady-state trough aminoglycoside concentration and estimated half-life. Stepwise multivariate analysis with nephrotoxicity status as the dependent variable determined that the most significant variable for predicting nephrotoxicity was serum total bilirubin level. In extrahepatic cholestasis a high serum bilirubin level is a distinct factor predisposing to aminoglycoside nephrotoxicity.

Aged↗
PubMed1994

Endogenous digoxin-like substance in liver failure.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin. We therefore studied the sensitivity of EMIT Convenience Pack Digoxin immunoassay to interference by DLIS in patients with liver failure. Serum digoxin was measured in cirrhotic patients with moderate to severe liver failure (Child-Pugh B or C grade), patients with mild liver disease (chronic hepatitis) and matched control patients without liver disease. Excluded were patients taking or who had ever received any cardiac glycoside in the past. Blood samples were obtained by venipuncture and assayed in duplicate. Twenty-two out of 30 cirrhotic patients (73%) showed false-positive results, vs. one of 6 patients (16.7%) with mild liver disease, and 1 of 10 (10%) controls. The serum DLIS level was negatively correlated with prothrombin activity (r = -0.55, p < 0.00011). Digoxin levels must be interpreted carefully in patients with moderate to severe liver failure.

Chronic Disease↗
PubMed1993

Short-term effect of various doses of cyclosporin A on plasma lipoproteins and its distribution in blood: an experimental study.

Hyperlipidaemia commonly develops in both transplant recipients and experimental animals receiving cyclosporin A (CsA). However, the threshold of CsA induced-changes on lipoproteins and the role of parenteral vehicle (cremophor) has not been defined. Male Wistar rats were classified into five groups of six animals each and received CsA in cremophor vehicle at doses of 5, 10 or 20 mg kg-1 d-1, s.c., vehicle alone or saline for 7 d. Blood was obtained 24 h after the last dose and plasma was analysed. Plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein subfractions (HDL-2, HDL-3) were isolated by sequential ultracentrifugation and their content of cholesterol, triglyceride and phospholipid was determined. Whole blood and trough plasma CsA levels were measured by monoclonal radioimmunoassay. Plasma lipids did not differ significantly among the five groups. At a dose of 20 mg kg-1 d-1 of CsA VLDL cholesterol rose significantly (P < 0.05). Administration of either CsA or cremophor vehicle increased HDL-2 phospholipids (P < 0.05) and decreased HDL-3 cholesterol. There was not a linear relationship between whole blood and plasma CsA levels and increasing CsA doses. Short-term treatment with low doses of CsA have little influence on lipid profile in the rat. Changes on lipoprotein composition can be attributed mainly to cremophor vehicle, conceivably due to its ethanol content.

Animals↗
PubMed1989

Enhanced gentamicin nephrotoxicity after experimental biliary obstruction in rats.

To explore whether bile duct ligation increased the risk for gentamicin nephrotoxicity, male Wistar rats were subjected to bile duct ligation or sham surgery and given either gentamicin 20 mg/kg or saline twice daily intraperitoneally for 8 days. Bile duct ligated and gentamicin injected rats elicited a decline in renal function and tubular cell necrosis after 8 days of treatment whereas equal dosage regimen in sham operated rats exhibited no evidence of renal dysfunction. In addition, though serum and kidney gentamicin levels were higher in bile duct ligated rats (1.84 +/- 0.11 micrograms/ml versus 0.20 +/- 0.03 microgram/ml, and 1453 +/- 164 micrograms/g versus 698 +/- 138 micrograms/g of cortex, respectively, P less than 0.05). The data indicate that complete biliary obstruction enhances renal sensitivity to gentamicin.

Animals↗