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Biomedical subjects

E Sanz

Publications and source records attributed to E Sanz.

At least 73 records · Page 4Linked to original sources
PubMed1990

Intravascular and interstitial fluid dynamics in rats treated with minoxidil.

Edema is a major complication of vasodilatory therapy. However, the pathophysiologic mechanisms leading to the formation of vasodilator-mediated edema are insufficiently understood. The present study therefore examined the effect of the chronic administration of the potent arteriolar vasodilator, minoxidil (Mx), on extracellular fluid dynamics in rats. Extracellular volume (ECV), plasma volume (PV), interstitial fluid volume (IV), arterial pressure (AP), and interstitial fluid pressure (IP) were measured in rats treated for 10 days with Mx (1.5 mg/kg/day) and in control animals. In addition to a decreased AP, Mx-treated animals had diminished water and sodium excretion. ECV, PV, and IV and plasma renin concentration (PRC) were also increased in the Mx-treated rats. IP, which was subatmospheric in control rats (-2.6 +/- 0.04 mm Hg), was near zero in Mx-treated animals (-0.2 +/- 0.02 mm Hg, p less than 0.05). Saline ECV expansion (20 min, Ringer infusion, 3% body weight) or rat albumin injection (300 mg/2 ml) induced similar changes in the volume of the extracellular fluid compartments in both groups. However, changes in IP were blunted in Mx-treated rats. These results, therefore, show that Mx-treated rats have changes in interstitial fluid dynamics prior to any macroscopic evidence of edema accumulation. These alterations in the extracellular compartment dynamics may be a consequence of the sustained arteriolar vasodilation induced by Mx.

Aldosterone↗
PubMed1990

Diuretic effect and diuretic efficiency after intravenous dosage of frusemide.

1. Frusemide was given intravenously at a dose of 5 mg kg-1 to five healthy volunteers and the diuresis was assessed by frequent spontaneous voiding over 5 h. Urinary volume and contents of sodium, chloride, potassium and frusemide were measured. 2. Diuretic response was evaluated using the sigmoid Emax model and non linear regression of diuresis vs frusemide excretion rate. The time courses of diuresis (pharmacological effect) and diuretic efficiency were constructed from the fitted parameters of the sigmoid Emax model. 3. The frusemide excretion rate associated with maximum efficiency was found, as predicted theoretically, to be less than the excretion rate associated with 50% of maximum effect in four of the five subjects in whom the slope factor was less than 2. 4. The effect over time is dependent both on the instantaneous drug effect but also on its pharmacokinetic properties and mode of administration. An intravenous bolus is the least efficient mode of administration while a controlled input producing a frusemide excretion at maximum efficiency should yield up to a 2.3 times higher diuretic response.

Adult↗
PubMed1990

OX48, a monoclonal antibody against a 70,000 MW rat activation antigen expressed by T cells bearing the high-affinity interleukin-2 receptor.

The monoclonal antibody (mAb) OX48 recognizes a 70,000 MW cell-surface protein present in a small percentage of activated rat T cells and in CD8+ rat x BW5147 interleukin-2 (IL-2)-dependent T-cell hybridomas, but not in resting spleen cells or in IL-2-independent T-cell hybrids. OX48 antibody added simultaneously with concanavalin A (Con A) to resting spleen cells inhibits the cell proliferation and reduces the IL-2 production. However, addition of IL-2 does not restore the mitogenic response. Growth of rat blast T cells or IL-2-dependent hybrids is not affected by the OX48 antibody. There is a close correlation between the expression of high-affinity IL-2 receptors (IL-2R) and the OX48 antigen in T-cell hybridomas. In spite of this striking correlation, OX48 mAb does not inhibit the binding of 125I-IL-2 to the IL-2-dependent hybrids, and is unable to immunoprecipitate any of the proteins chemically cross-linked to 125I-IL-2. Therefore, the OX48 molecule represents a new rat activation antigen, undefined in other species, and probably involved in the early steps of T-cell activation.

Animals↗
PubMed1989

IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors.

IL-2-independent CD8+ rat x BW5147 T cell hybridomas are highly sensitive to treatment with 10(-6) M dexamethasone. This glucocorticoid analog induces a rapid DNA fragmentation with a pattern similar to that observed during glucocorticoid-induced killing of mouse thymocytes, which suggests the activation of a similar specific endonuclease. Among these hybrids, we select variants expressing low affinity IL-2R, as measured by IL-2 binding assay and by the cell surface expression of the IL-2Rp55 Ag (rat CD25 recognized by OX-39 mAb). These OX-39+ IL-2 independent hybrids (named V type) are protected from the toxic action of dexamethasone by IL-2. The addition of IL-2 to V type cells induces the expression of a low number of high affinity IL-2R, which is strongly potentiated by the simultaneous addition of dexamethasone. Furthermore, dexamethasone is strongly synergistic with IL-2 in the induction of mRNA p55/IL-2R, which could be observed 6 h after the treatment. These data suggest that the utilization of the IL-2-R signaling pathway may induce an effective protection against glucocorticoid toxicity in mature T cells. Finally, we proved that the upregulation of IL-2R by IL-2 is strongly potentiated by glucocorticoids, which implies a new role for these agents in the immune system.

Animals↗
PubMed1989

Loss of interleukin 2 dependence in cloned interleukin 2-dependent rat T lymphocyte x BW5147 hybridomas is not associated with segregation of a specific pair of rat chromosomes.

A fusion between the mouse AKR thymoma BW5147 and a culture of homogeneously OX8+ (CD8) rat T lymphoblasts yield interleukin (IL) 2-dependent T cell hybridomas when selected in HAT medium supplemented with IL 2-containing supernatants of concanvalin A-activated cells and dexamethasone. IL 2-independent variants can be selected from cloned IL2-dependent hybrids in the absence of conditioned medium. Karyotype analysis was used to test a previously proposed hypothesis according to which IL2-independent variants arise through loss of a specific cytotoxic T lymphocyte (rat) chromosome carrying a gene responsible for IL2 dependence. Comparison of karyotypes of several independently derived hybrids with those of their IL 2-independent variants showed that the hybrids contain at least one homologue of all rat chromosomes, and that no pair of rat chromosomes is consistently absent in the IL 2-independent variants.

Animals↗
PubMed1989

Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype.

Single oral 10 mg doses of diazepam and demethyldiazepam were given on different occasions to 16 healthy subjects. The subjects included four poor hydroxylators of debrisoquin and three poor hydroxylators of mephenytoin. There was a correlation between the total plasma clearance of diazepam and demethyldiazepam (rs = 0.83; p less than 0.01). There was no relationship between benzodiazepine disposition and debrisoquin hydroxylation. Poor hydroxylators of mephenytoin had less than half the plasma clearance of both diazepam (p = 0.0008) and demethyldiazepam (p = 0.0001) compared with extensive hydroxylators of mephenytoin. The plasma half-lives were longer in poor hydroxylators than they were in extensive hydroxylators of mephenytoin for both diazepam (88.3 +/- SD 17.2 and 40.8 +/- 14.0 hours; p = 0.0002) and demethyldiazepam (127.8 +/- 23.0 and 59.0 +/- 16.8 hours; p = 0.0001). There was no significant difference in volume of distribution of the benzodiazepines between the phenotypes. This study shows that the metabolism of both diazepam (mainly demethylation) and demethyldiazepam (mainly hydroxylation) is related to the mephenytoin, but not to the debrisoquin, hydroxylation phenotype.

Adult↗
PubMed1989

Growth requirements of T cell hybridomas obtained by the fusion between a mouse cytolytic T cell line and the rat tumor C58NTD.

T23 are hybrids derived from the fusion between an IL-2-dependent mouse cell line, C10 and the rat lymphoma C58NTD. Supernatants from exponentially growing T23 cells induce the growth of CTLL2, and IL-2-dependent cell line, suggesting that these hybrids secrete interleukin 2. Addition of recombinant IL-2 to slowly growing T23 cells increases the rate of growth. Using an 125I IL-2 binding assay, a low number of cell surface IL-2 receptors were detected. T23 hybrids contain mouse but not rat IL-2 receptor genes as revealed by Southern blot analysis. These receptors are functional because the growth of exponentially growing hybrids is inhibited by an anti-mouse IL-2 receptor antibody. These data suggest an autocrine-like mechanism as responsible for the growth of these T cell hybridomas.

Animals↗
PubMed1989

Diazepam treatment does not influence the debrisoquine or mephenytoin hydroxylation phenotyping tests.

Debrisoquine and S-mephenytoin hydroxylation phenotyping tests were performed in 9 patients before and during treatment with diazepam at a daily dose of 10 or 15 mg. There was no change in either the debrisoquine/4-hydroxydebrisoquine ratio or the ratio of S/R mephenytoin in urine. The hydroxylation of these two test drugs is apparently not inhibited by administration of therapeutic doses of diazepam.

Adult↗
PubMed1989

Interstitial dynamics in rats with early stage experimental cirrhosis of the liver.

Pathogenesis of edema in cirrhosis of the liver is still incompletely understood. The present study was designed to examine interstitial fluid dynamics in cirrhotic, non-ascitic rats, measuring interstitial fluid pressure by means of a subcutaneous plastic capsule in basal conditions during extracellular fluid volume expansion with Ringer solution and during albumin infusion. Urine flow and sodium excretion and plasma and interstitial fluid volumes were simultaneously measured. Cirrhotic rats exhibited reduced urine flow and sodium excretion, both in basal conditions and in response to expansion maneuvers. Plasma and interstitial fluid volumes were higher in cirrhotic than in control animals. Remarkable alterations were present in capsular pressures in cirrhotic rats. In the control rats, basal capsular pressure values were negative, and they increased after Ringer infusion and markedly decreased with albumin infusion. In contrast, in cirrhotic rats, basal capsular pressures were in the positive range and they remained nearly constant during ringer infusion and albumin administration. These results suggest that in cirrhotic rats there are significant alterations in systemic interstitial dynamics, even before ascites formation. Altered systemic capillary dynamics may therefore be important early changes that precede and thus contribute to the formation of edema in cirrhosis.

Animals↗
PubMed1989

[Compliance of antibiotic treatment in primary health care. Value of the personalized prescription].

A controlled clinical study was carried out in order to evaluate the efficacy of a personalized prescription as a measure to improve the fulfillment of a short course antibiotic treatment. 180 patients completed the study (96 in the active group and 88 in the control group) finding no differences in selected variables between the two groups. Evaluation of treatment fulfillment was performed with an interview and counting the pills, finding with this method that 57.94% of the patients fulfilled the treatment. Except for a higher incidence of adverse side effects in the control group (p less than 0.05) no other significant differences were found between the two groups. The interview showed a 37% sensibility and a 97% specificity, which was specially usefull in the detection of nonfulfillers. The correlation coefficient between both groups was 0.66 (p less than 0.001). Our results suggest that the personalized prescription does not improve the patient compliance achieved by a good verbal information in the short course antibiotic treatment.

Adult↗
PubMed1988

Effect of intrarenal infusion of synthetic PAF-acether in dogs.

The effect of intrarenal infusion of PAF-acether was studied in dogs. PAF-acether infusions caused a dose-dependent decrease in glomerular filtration rate, renal blood flow and urinary flow and electrolyte excretion, without significant changes in mean arterial pressures. In addition, the higher doses used caused also increases in packed cell volume, and decreases in plasma proteins and leukocyte and platelet count, whereas the lower doses did not elicit those changes. These data suggest that PAF-acether causes an impairment in renal function which is in part mediated by vasoactive substances released from platelets and leukocytes.

Animals↗
PubMed1987

Adverse drug reactions in paediatric outpatients.

In accordance with guidelines for a multicentre trial, the incidence and features of adverse drug reactions in a sample of 1327 children attending outpatient consultations have been determined. The incidence was of 0.75% (0.34% - 1.58% with p less than 0.05). The reactions were slight in character and predominantly affected very young female patients. Antibiotics were involved in almost a half of cases, and polypharmacy was used in all of them.

Amoxicillin↗
PubMed1986

Effects of the platelet-activating factor antagonist BN 52021 on the hemodynamics of rats with experimental cirrhosis of the liver.

Previous studies from this laboratory have shown that rats with experimental cirrhosis of the liver induced by the combined administration of oral phenobarbital and inhaled carbon tetrachloride show an hyperdynamic status with enhanced cardiac output (CO), and decreased mean arterial pressure (MAP) and peripheral vascular resistance (PVR). Cirrhotic rats also showed an increased vascular permeability. All these phenomena are similar to some of the known effects of the systemic infusion of low doses of synthetic platelet-activating factor into the systemic circulation of normal rats. The measurement of the levels of platelet-activating factor in samples of blood demonstrated significantly higher levels in cirrhotic (2.65 +/- 0.39; n = 10) than in control rats (1.50 +/- 0.57 ng/ml; n = 10; p less than 0.05). The hemodynamic changes induced by the intravenous injection of the platelet-activating factor receptor antagonist BN 52021 (5 mg/kg body weight) have been measured in 10 control and 10 cirrhotic male Wistar rats, using a radioactive microsphere technique. BN 52021 induced no significant hemodynamic changes in control animals. However, in cirrhotic animals it induced a significant decrease in CO with increase in PVR. MAP increased slightly but not significantly. From these data it can be deduced that platelet-activating factor plays a role in the hemodynamic derangement shown by cirrhotic rats and that these derangement can be reversed by BN 52021, a highly selective antagonist of the platelet-activating factor receptor.

Animals↗
PubMed1986

Systemic and regional haemodynamic effects of a synthetic atrial natriuretic peptide in conscious rats.

The effect of the intravenous injection of synthetic atrial natriuretic peptide (ANP, 2 micrograms) on systemic haemodynamics and blood flow to several organs has been studied in conscious rats by the radioactive microsphere technique. ANP induced a 540% increase in sodium excretion and a 310% increase in urine flow. Mean arterial pressure decreased by 21 mmHg and the peripheral resistances decreased by 26%, without significant changes in cardiac output. Renal blood flow increased by 37.7% and small intestine and portal blood flow increased by 39% and by 28% respectively. No other alterations in organ blood flows were observed. From these data it can be concluded that atrial natriuretic peptide shows acute vascular relaxant properties, which seem to be specific for renal and mesenteric territories.

Animals↗
PubMed1985

[Mediastinal tumors in children].

Forty patients with primary mediastinal masses, treated at the Children's Hospital "La Fe" between 1971-1983, were review. Malignant neoplasms were the most common pathology in this series (23 cases), followed by benign lesions (10 cases), congenital malformations (five cases) and inflammatory diseases (two cases). Complementary explorations for the preoperative evaluation of theses masses is discussed. Surgical removal was carried out on all tumors. Mortality caused by performing biopsy on lymphomas was high. Two of the five congenital malformations were removed. The other three did not receive any therapy. All patients having benign tumors are alive except one who had a cardiac teratoma diagnosed at necropsy. Eleven of the patients with malignant neoplasms are alive, with a median follow-up time two years and nine months.

Child↗