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Biomedical subjects

J Sabater

Publications and source records attributed to J Sabater.

At least 19 recordsLinked to original sources
PubMed1996

Urinary calcium excretion in treated and untreated essential hypertension.

A high prevalence of hypercalciuria has been reported in patients with essential hypertension. Nevertheless, the clinical and therapeutic implications of this finding have scarcely been studied. This study was designed to determine the prevalence of hypercalciuria in an unselected population with essential hypertension and to analyze the relationship between the urinary calcium and the clinical and therapeutic status of these patients. This article presents a prospective study of 112 patients with essential hypertension and 49 healthy normotensive control subjects. Urinary excretion rates of calcium, sodium, chloride, potassium, urinary calcium/creatinine index, the fractional excretion of sodium, potassium and uric acid, the creatinine clearance and serum values of creatinine, urea, uric acid, electrolytes, total proteins, parathormone (intact molecule), plasma renin activity, aldosterone, glucose, and insulin (fasting and after an oral glucose load) were performed in every patient and control subject. Untreated hypertensive patients had a higher prevalence of hypercalciuria (35% had a urinary calcium/creatinine ratio > 0.20 versus 20% of treated hypertensives and 2% of control subjects; P < 0.001). Patients on thiazide or beta-blocker monotherapy had lower urinary excretion rates of calcium and urate than patients on calcium-antagonist monotherapy or untreated patients. Urinary calcium, sodium, and urate correlated positively both in treated and untreated essential hypertension patients. Patients with the higher urinary calcium levels also had higher excretion rates of sodium and urate, higher creatinine clearance rates, and lower serum creatinine and serum uric acid levels. It was concluded that hypercalciuria is a frequent finding of untreated essential hypertension. The association of high urinary calcium levels with high urinary urate excretion rates in the same patient may predispose to development of lithiasis in patients with essential hypertension. Antihypertensive drugs have a variable effect on calciuria-uricosuria, which may constitute an additional criterion in the selection and individualization of therapy. Thiazides and beta-blockers can decrease calciuria and uricosuria and, therefore, the lithogenic risk in these patients.

Adrenergic beta-Antagonists↗
PubMed1995

Impairment of tubular secretion of urate in renal transplant patients on cyclosporine.

The prevalence of hyperuricemia was investigated in 214 kidney allograft recipients, 81 were on azathioprine and steroids and 133 on cyclosprine (CyA) and low-dose steroids or on triple therapy. All had stable renal function, serum creatinine < 2.5 mg/dl, and a follow-up between 12 and 120 months. At the time of the study, blood and urine samples were obtained to perform tests of renal function. The renal handling of urate was evaluated by a combined pyrazinamide and probenecid test in 35 selected patients (12 normouricemic on azathioprine, 9 normouricemic on CyA and 14 hyperuricemic on CyA). The prevalence of hyperuricemia was higher in the group of patients on CyA (19.7 vs. 66.9%, p < 0.001), as well as the concentration of serum urate (6.1 +/- 1.9 vs. 7.6 +/- 1.7, p < 0.001), and serum creatinine (1.2 +/- 0.3 vs. 1.4 +/- 0.4, p < 0.001). In patients on CyA, multivariate analysis showed that the most important predictive variables of hyperuricemia were: serum creatinine, FEurate, diuretic use and CyA blood levels (r = 0.73, p < 0.0001). Thirteen patients on CyA (9.9%) had at least one episode of gouty arthritis. Those patients were older than the hyperuricemic patients without gout (45.7 +/- 6.7 vs. 37.1 +/- 13.5 years, p < 0.01), had worse renal function (serum creatinine 1.9 +/- 0.4 vs. 1.5 +/- 0.4 mg/dl, p < 0.01), and higher prevalence of hypertension (100 vs. 63.1%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Insulin inhibits liver expression of the CCAAT/enhancer-binding protein beta.

The CCAAT/enhancer-binding protein beta (C/EBP beta) is a transcription factor that is abundant in the liver. The concentration of C/EBP beta mRNA in the liver of mice and rats fed a high-carbohydrate diet, which causes a rise in blood insulin levels, was lower (80 and 65%, respectively) than that detected in animals fed a standard diet. Similarly, the expression of the human insulin gene in the liver of transgenic mice led to a decrease in the concentration of C/EBP beta mRNA. However, no change was detected in the mRNA levels of C/EBP alpha or cAMP regulatory element-binding protein transcription factors in the livers of these mice. Furthermore, the expression of the C/EBP beta gene increased in the liver of diabetic rats and decreased in the liver of diabetic animals treated with vanadate, an insulin mimetic agent. In addition, a decrease in C/EBP beta protein was observed in liver nuclei from mice after insulin injections, in mice fed a high-carbohydrate diet, and in transgenic mice expressing the insulin gene in the liver. These results suggest that insulin might control gene expression in vivo, at least in part, by a mechanism involving a decrease in the transcription factor C/EBP beta.

Animals↗
PubMed1994

Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations.

Transgenic mice expressing the P-enolpyruvate carboxykinase (PEPCK)/human insulin chimeric gene have been obtained as a model to study the feasibility of gene therapy for diabetes. These transgenic animals were healthy and normoglycemic and expressed human insulin in a physiologically regulated manner, mainly in the liver. Streptozotocin-treated transgenic mice had high levels of human insulin immunoreactivity in serum and showed a significant decrease (up to 40%) in glycemia compared with streptozotocin-treated control mice. The expression of genes involved in liver glucose metabolism, such as glucokinase, pyruvate kinase, and PEPCK, which is markedly altered by diabetes, was significantly recovered in transgenic mice treated with streptozotocin. In addition, the activity of both glucokinase and glycogen synthase, and the content of glucose 6-phosphate and glycogen, were normal in the liver, even when transgenic animals were treated with diabetogenic doses of streptozotocin. These results constitute an indication in vivo that diabetes gene therapy is possible, by means of the production of insulin in extrapancreatic tissues.

Animals↗
PubMed1994

Overexpression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in transgenic mice causes hepatic hyperketogenesis.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) is a key enzyme in the ketone body pathway. To determine its role in the regulation of liver ketogenesis, transgenic mice expressing a P-enolpyruvate carboxykinase/HMG-CoA synthase chimeric gene have been obtained. An increase in the concentration of mitochondrial HMG-CoA synthase mRNA was detected in these mice, which was associated with a 3-fold increase in HMG-CoA synthase activity in liver mitochondrial extracts. Transgenic mice were normoglycemic and had normal levels of plasma triglycerides and lower free fatty acids. However, the plasma concentration of ketone bodies was about three times higher in transgenic mice than in control animals. Hepatocytes in primary culture from transgenic mice expressed the chimeric gene in a regulated manner and showed a 3-fold increase in beta-hydroxybutyrate and acetoacetate concentrations in the medium. This animal model thus shows that the overexpression of mitochondrial HMG-CoA synthase causes ketone body overproduction, suggesting that this enzyme may be a regulatory step in liver ketogenesis.

3-Hydroxybutyric Acid↗
PubMed1993

Urinary acidification response to furosemide administration in patients on low-dose cyclosporine therapy.

The response of urinary acidification parameters and electrolytes to furosemide administration was prospectively studied in 9 psoriatic patients treated with a low-dose cyclosporine A schedule (initial dose: 5 mg/kg body weight) before beginning cyclosporine A, after 3 months on cyclosporine A and 1 month after cyclosporine A withdrawal. The test was also performed in 29 psoriatic patients after 3 months on 5 mg/kg body weight cyclosporine A treatment. There were no significant differences between before and after cyclosporine A treatment regarding furosemide-induced changes in urinary volume, sodium or potassium excretion. Contrarily, the post-furosemide urinary pH decrease and ammonium and titrable acid increase were significantly lower in cyclosporine-A-treated patients. Five of the 29 studied patients showed abnormal furosemide tests (17%). These patients had lower total serum CO2, urea and creatinine but similar serum potassium and fractional potassium excretion. We conclude that some patients treated with low-dose cyclosporine A therapy develop an abnormal tubular distal response to furosemide administration, suggesting an alteration in the H(+)-ATPase pump or a voltage-dependent mechanism.

Adult↗
PubMed1993

Pharmacokinetic study of 4'-acetamidophenyl-2-(5'-p-toluyl-1'-methylpyrrole)acetate in the rat.

A pharmacokinetic study has been performed on a new non-steroidal anti-inflammatory drug, AU-8001 (4'-acetamidophenyl-2-(5'-p-toluyl-1'-methylpyrrole)acetate, CAS 82239-77-8) in the rat, following intravenous (10 mg/kg) and oral (50 mg/kg) administrations. The new molecule constitutes a prodrug of paracetamol and tolmetin. Compartmental and non-compartmental treatment of experimental data lead to the same conclusions. After intravenous administration, the rapid hydrolysis of the ester function of the molecule causes a short transit of the prodrug in the organism and the rapid attainment of maximum plasmatic levels of metabolites. After oral administration, the prodrug shows flip-flop behaviour in which the absorption constant rate is the limiting factor and is responsible for the slow bioconversion of the substance. The bioavailability of the prodrug is incomplete and, according to the urinary excretion data, a fraction of the dose reaches the blood stream in the form of metabolites. AU-8001, however, in spite of its limited bioavailability, is a model prodrug which could be used to prolong the activity of the original drugs.

Acetaminophen↗
PubMed1992

Hemodynamic changes in the dog connected to a dialysis circuit: influence of the body temperature.

Eighteen sessions in 9 mongrel dogs were carried out to know the hemodynamic effects produced by body temperature variation, when blood passes through a dialysis circuit with a Cuprophan dialyzer, without dialysate contact. The decrease of 2 degrees C in body temperature caused a decrease in heart rate and cardiac index (-8.6 and -17.6%, respectively) without significant changes in blood pressure. The increase of 2 degrees C in body temperature increased the heart rate, the cardiac index and the first derivative of ventricular pressure (+14.8, +17.3 and +27.8%, respectively) with a decrease of 13.6% in the systemic vascular resistance. Blood pressure did not change significantly. We conclude that the dog maintains the hemodynamic stability by two different mechanisms: when body temperature rises, by increasing the cardiac index; when body temperature decreases, by increasing the systemic vascular resistance.

Animals↗
PubMed1992

Pharmacokinetic study of tolmetin in the rat.

The pharmacokinetics of tolmetin (CAS 26171-23-3) was studied in male Wistar rats after intravenous and oral administration of 32.95 mg/kg. After intravenous administration of the drug, it was shown that the most probable model was the two-compartment-open model with Michaelis-Menten elimination. After oral administration, the drug was absorbed rapidly (K01 = 0.1304 min-1). The bioavailability was 96.94% and the drug was mostly excreted as 1-methyl-5-(4-carboxybenzoyl)-1H-pyrrole-2-acetic acid, while the excretion of the unchanged drug was 6.12%.

Administration, Oral↗
PubMed1991

Nonenzymatic glycosylation of hemoglobin and total plasmatic proteins in end-stage renal disease.

In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A1 (HbA1) and the A1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 nondiabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA1 levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.

Adult↗
PubMed1991

Reduction of oral bioavailability of paracetamol by tolmetin in rat.

The pharmacokinetics of paracetamol alone and coadministered with tolmetin were studied in male Wistar rats. Open pharmacokinetic model of one and two compartments were fitted to experimental average plasma levels of paracetamol. Simultaneously fittings (intravenous and oral curves showed significant statistical differences for bioavailability estimated parameters (AUCev, F and K01). Also significant statistical differences were found for alfa, beta, K21 and Vd(ss) estimated parameters. Oral paracetamol bioavailability reduction (24%) was observed by coadministration of tolmetin in the rat. Since AUCiv and plasma clearance of paracetamol remained unchanged after intravenous coadministration, may be suggested that absorption process seems responsible of paracetamol bioavailability reduction.

Acetaminophen↗
PubMed1990

Epidemiology of symptomatic hypotension in hemodialysis: is cool dialysate beneficial for all patients?

A prospective study on hypotension in hemodialysis was performed in 60 nondiabetic patients at two different dialysate temperatures during 12 months. A 37 degrees C bath (3,723 sessions) was used and after the first 6 months the temperature was changed to 35 degrees C (4,019 sessions). The prevalence of symptomatic hypotension was 15.3% and it was closely correlated with the presence of other symptoms. The most affected populations were women, patients over 55 years of age, patients with low body surface area and patients with a cardiovascular disease. A slight but significant decrease of symptomatic hypotension was seen by using a 35 degrees C dialysate (16.4 vs. 14.3%, p less than 0.01). In patients with frequent hypotension (in up to 30% of sessions), cool dialysate significantly reduced the incidence of the symptom (44.2 vs. 34.1%, p less than 0.001). These results were obtained in spite of a greater interdialysis weight gain at low temperature (2 +/- 0.6 vs. 1.9 +/- 0.7 kg, p less than 0.001). We consider that low-temperature dialysis is a simple, useful and economic procedure, especially for highly symptomatic patients. The association of cooling dialysate with higher sodium concentration, bicarbonate and special membranes could reduce dialysis symptoms dramatically.

Cold Temperature↗