Biomedical subjects

W Jimenez

Publications and source records attributed to W Jimenez.

11 recordsLinked to original sources

PubMed1997

Lack of renal effects of fish oil administration in patients with advanced cirrhosis and impaired glomerular filtration.

The treatment of renal failure in cirrhotic patients with ascites remains unsatisfactory. Recent studies have shown that the dietary supplementation with fish oil improves the renal function of normal subjects, as well as that of patients with renal failure of different etiologies. We have investigated the renal effects of a daily supplementation for 1 month of 12 g fish oil (27% C20:5 n-3 eicosapentanoic acid [EPA], and 23% C22:6 n-3 docosahexanoic acid [DHA]) in a prospective study of cirrhotic patients with ascites, nine with normal renal function (group 1) and eight with renal failure (glomerular filtration rate [GFR] < 60 mL/min, group 2). Compliance with the dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentration of EPA (from 1.5 +/- 0.7% to 3.7 +/- 0.8%, P = .024, in group 1; and from 0.53 +/- 0.3% to 2.9 +/- 0.8%, P = .03, in group 2) and of DHA (from 2.1 +/- 0.4% to 3.4 +/- 0.3%, P = .008, in group 1; and from 1.45 +/- 0.5% to 3.8 +/- 0.4%, P = .05, in group 2). At the end of the study, in patients from group 1, the glomerular filtration rate increased by 19% (from 94 +/- 8 to 113 +/- 13 mL/min, P = .039), and the urine flow increased by 39% (from 0.85 +/- 0.14 to 1.12 +/- 0.2 mL/min, P = .039), while no changes occurred in the renal function of patients from group 2. No changes were observed in the urinary excretion of prostaglandin (PG) E2 or of 6-keto prostaglandin-1-alpha (6-K-PGF1-alpha) nor in plasma renin activity (PRA) or the plasma concentration of aldosterone (PA) or antidiuretic hormone (ADH) in both groups. As far as undesirable effects of fish oils were considered, the mean arterial pressure (MAP) decreased in both groups (group 1: from 88.6 +/- 2 to 85.3 +/- 2 mm Hg, P = .015; group 2: from 88.2 +/- 3 to 82.8 +/- 3 mm Hg, P = .05), and bleeding time displayed a significant increase when patients were considered collectively (from 744 +/- 89 to 872 +/- 106 seconds, P = .0068). In conclusion, the administration of fish oil for 1 month was unable to improve renal function in cirrhotic patients with ascites and renal failure. The occurrence of undesirable effects, such as the reduction of arterial pressure and the prolongation of bleeding time, argues against the use of fish oils in these patients.

Ascites↗

PubMed1997

Impairment of renal function during moderate physical exercise in cirrhotic patients with ascites: relationship with the activity of neurohormonal systems.

Moderate physical exercise does not affect glomerular filtration rate (GFR) and renal excretory function in normal subjects. This study is aimed at assessing the effects of moderate physical exercise on renal function in 21 nonazotemic cirrhotic patients with ascites. Arterial pressure, heart rate, and renal function were assessed in the patients after 2 hours in the supine position and during 30 minutes of moderate cycloergometric exercise in the sitting position. The activity of the renin-aldosterone and sympathetic nervous systems and the plasma levels of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were determined at the end of each period. Physical exercise induced a marked reduction in GFR (75 +/- 10 to 49 +/- 6 mL/min), free-water clearance (6.1 +/- 1 to 3.4 +/- 1 mL/min), and sodium excretion (7.8 +/- 2 to 4.3 +/- 1 microEq/min) in 10 patients (Group I). In the remaining 11 cases (Group II) there were no changes in these parameters. Renal perfusion significantly decreased in both groups although the reduction was greater in Group I (-34.7% +/- 4.6% vs. -7.5% +/- 3.1%, P < .001). Physical exercise was associated with a significant and comparable increase in arterial pressure, heart rate, and plasma levels of renin, aldosterone, and norepinephrine (NE) in the two groups of patients. The ANP concentration did not change. Patients from Groups I and II differed significantly (P < .05) only in plasma renin activity (PRA) and NE concentration, which were higher in Group I patients both in the supine rest (renin: 4.7 +/- 1.6 vs. 1.4 +/- 0.5 ng/mL x h; NE: 576 +/- 115 vs. 288 +/- 42 pg/ mL) and during exercise (renin: 7.1 +/- 1.8 vs. 2.6 +/- 1 ng/ mL x h; NE: 925 +/- 135 vs. 630 +/- 90 pg/mL). In conclusion, moderate physical exercise has no detrimental effects on renal function in cirrhotic patients with ascites with no or mild activation of the renin-aldosterone and sympathetic nervous systems. However, moderate physical exercise causes a marked impairment in the renal function of patients with ascites with marked stimulation of these vasoconstrictor systems.

Ascites↗

PubMed1995

Reversible decrease of surface beta 2-adrenoceptor number and response in lymphocytes of patients with pheochromocytoma.

To study the effect of chronic exposure to elevated plasma catecholamines on surface beta 2-adrenoceptor density, we measured these receptors in the lymphocytes of 9 patients with pheochromocytoma as well as in 27 healthy control subjects. Binding experiments were performed on intact lymphocytes using the hydrophilic ligand [3H]-CGP12177. Lymphocyte beta 2-adrenergic response was also measured in three patients. beta 2-adrenoceptor density (p < 0.01), and isoproterenol-stimulated increase in cAMP were reduced in patients with pheochromocytoma. Both parameters normalized (p < 0.05) when patients were reevaluated 4 weeks after tumor removal, coinciding with normalization of plasma epinephrine (r = -0.95, p < 0.01) and to log of plasma norepinephrine (r = -0.58, p < 0.05) in patients. We conclude that chronic catecholamine excess induces a decrease of lymphocyte beta 2-adrenoceptor surface number and response that is reversible upon normalization of plasma catecholamine levels. This regulation is mainly dependent on plasma levels of the hormone epinephrine, but norepinephrine may also play a regulatory role at supraphysiological levels.

Adrenal Gland Neoplasms↗

PubMed1994

15-Hydroxyeicosatetraenoic acid inhibits neutrophil migration across cytokine-activated endothelium.

15-hydroxyeicosatetraenoic acid (15-HETE) is an eicosanoid, formed by the actions of 15-lipoxygenase, epoxygenases, and cyclooxygenases on arachidonic acid, whose tissue levels are often elevated during inflammation. The present study demonstrates that 15(S)-HETE is a potent inhibitor of polymorphonuclear neutrophil (PMN) migration across cytokine-activated endothelium in vitro. 15(S)-HETE is rapidly esterified into PMN phospholipids, and we report that 15-(S)-HETE-remodeled PMN displayed blunted adhesion to, and migration across, human endothelial cells that had been activated with either interleukin-1 beta or tumor necrosis factor-alpha Several lines of evidence suggested that 15(S)-HETE inhibited PMN transmigration by attenuating PMN responsiveness to endothelial cell-derived platelet-activating factor (PAF). The inhibitory action of 15(S)-HETE on transmigration was not restricted by the profile of adhesion molecules expressed by cytokine-activated endothelium. Interleukin-1 beta and tumor necrosis factor-alpha induce PAF production by endothelium, and PMN migration across cytokine-activated endothelium was inhibited by a PAF receptor antagonist. PMN migration across endothelium in response to exogenous PAF was dramatically inhibited following exposure of PMN to 15(S)-HETE. Furthermore, 15(S)-HETE-remodeled PMN displayed impaired cytoskeletal and adhesion responses when stimulated by exogenous PAF, two pivotal events in PMN migration across activated endothelium. 15(S)-HETE seemed to attenuate PMN responsiveness to PAF by inhibiting membrane-associated signal transduction events. In keeping with this interpretation, remodeling of PMN phospholipids with 15(S)-HETE was associated with a sixfold reduction in the affinity of specific high-affinity PAF receptors for their ligand and impaired PAF-triggered IP3 generation. In contrast, PMN adhesion responses stimulated by calcium ionophore or activators of protein kinase C remained intact. These results provide further evidence that 15(S)-HETE may be an important endogenous inhibitor of PMN-endothelial cell interaction that serves to limit or reverse neutrophil-mediated inflammation in vivo.

Cell Adhesion↗

PubMed1992

Neutrophils, monocytes, and lymphocytes bind to cytokine-activated kidney glomerular endothelial cells through L-selectin (LAM-1) in vitro.

The role of L-selectin (LAM-1) as a regulator of leukocyte adhesion to kidney microvascular glomerular endothelial cells was assessed in vitro by using L-selectin-directed mAb and an L-selectin cDNA-transfected cell line. The initial attachment of neutrophils, monocytes, and lymphocytes to TNF-activated bovine glomerular endothelial cells was significantly inhibited by the anti-LAM1-3 mAb. Under static conditions, anti-LAM1-3 mAb inhibited neutrophil adhesion by 15 +/- 5%, whereas the anti-LAM1-10 mAb, directed against a functionally silent epitope of L-selectin, was without effect. The binding of a CD18 mAb inhibited adhesion by 47 +/- 6%. In contrast, when the assays were carried out under nonstatic conditions or at 4 degrees C, the anti-LAM1-3 mAb generated significantly greater inhibition (approximately 60%). CD18-dependent adhesion was minimal (approximately 10%) under these conditions. TNF-activated glomerular endothelial cells also supported adhesion of a mouse pre-B cell line transfected with L-selectin cDNA, but not wild-type cells. This process was also inhibited by the anti-LAM1-3 mAb. Leukocyte adhesion to unstimulated endothelial cells was independent of L-selectin, but, after TNF stimulation, L-selectin-mediated adhesion was observed at 4 h, with maximal induction persisting for 24 to 48 h. Leukocyte adhesion was not observed if glomerular endothelial cells were exposed to TNF in the presence of RNA or protein synthesis inhibitors. Leukocyte attachment to TNF-activated glomerular endothelial cells was also partially inhibited by treatment of the cells with mannose-6-phosphate or phosphomannan monoester, a soluble complex carbohydrate, or by prior treatment of glomerular endothelial cells with neuraminidase, suggesting that the glomerular endothelial cell ligand shares functional characteristics with those expressed by lymph node and large vessel endothelial cells. These data suggest that TNF activation induced the biosynthesis and surface expression of a ligand(s) for L-selectin on glomerular endothelial cells, which supports neutrophil, monocyte, and lymphocyte attachment under nonstatic conditions.

Antigens, CD↗

PubMed1992

Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury.

Infiltration of glomerular mesangium by monocytes/macrophages is a prominent pathologic finding in many forms of glomerulonephritis (GN). While the mechanism(s) by which infiltration occurs is incompletely understood, monocyte adhesion to glomerular endothelial cells, provoked by inflammatory mediators, appears to be an important early step. In the present study, we assessed the influence of chemotactic peptides (C5a) and lipids (LTB4 and PAF) on adhesion of human monocytes and mesangial cells, to determine if mesangial cells (glomerular pericytes with smooth muscle properties) represent potential targets for adhesion of chemoattractant-activated monocytes following their diapedesis from the intravascular space. C5a and LTB4 provoked rapid (onset less than 1 min) monocyte-mesangial cell adhesion at nanomolar concentrations via actions with monocytes, while PAF was less potent in this regard. Monoclonal antibodies (mAb) were used to define the monocyte and mesangial cell adhesion molecules involved in these interactions. C5a- and LTB4-induced monocyte adhesion was inhibited (approximately 54%) by mAb against the common beta CD18 subunit of CD11/CD18 leukocyte integrins, while mAb against monocyte L-selectin was without effect. MAb against unique CD11 subunits were used to determine the relative contributions of different CD11/CD18 integrins. In this regard, adhesion was inhibited by mAb against CD11b (approximately 41%), and CD11c (approximately 23%), but not CD11a. MAb against mesangial cell ICAM-1 afforded approximately 27% reduction in adhesion, while mAb against VCAM-1, E-selectin, and P-selectin were without effect. GM-CSF, a cytokine generated by monocytes and mesangial cells, also provoked CD11/CD18-dependent adhesion, and primed monocytes to the actions of chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1991

Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction.

To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction.

Adult↗

PubMed1991

Effects of endothelin on renal haemodynamics and segmental sodium handling in conscious rats.

The effects of endothelin (100 and 600 pmol/kg) on renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion (UNa V) and segmental sodium handling were investigated in conscious rats. Low-dose endothelin decreased renal plasma flow by 26% without affecting glomerular filtration rate and sodium excretion. High-dose endothelin reduced renal plasma flow, glomerular filtration rate, sodium excretion and lithium clearance by 57, 45, 38 and 52%, respectively. The fall in sodium excretion was not due to a direct effect of endothelin on tubular sodium transport since sodium excretion corrected by glomerular filtration rate and fractional proximal and distal sodium reabsorption did not change throughout the study. These results indicate that the impairment in renal perfusion is responsible for the antinatriuretic effect of endothelin in conscious rats.

Animals↗

PubMed1991

Large-volume paracentesis and intravenous saline: effects on the renin-angiotensin system.

Fourteen cirrhotic patients with tense ascites were treated with total paracentesis and intravenous isotonic saline infusion. Standard liver and kidney function tests, plasma renin activity and aldosterone concentration were measured before, at 48 hrs and at 7 days after total paracentesis. The volume of ascites removed was 7.7 +/- 5.6 l (mean +/- S.E.M.). None of the treated patients had clinical complications or significant alterations in liver or kidney function test results. Paracentesis and intravenous isotonic saline infusion were not associated with significant changes in mean plasma renin activity or plasma aldosterone concentration. These results suggest that this therapeutic procedure could be a safe and cost-effective alternative treatment of tense ascites in patients with cirrhosis.

Aged↗

PubMed1989

Effects of atrial natriuretic peptide on urinary kallikrein excretion and renal function in rats.

We investigated whether the renal kallikrein-kinin system is involved in the renal effects of atrial natriuretic peptide (ANP) by measuring the glomerular filtration rate (GFR), urine volume (UV) and urinary excretion of sodium (UNaV) and kallikrein (UkkV) in 4 groups of 10 anesthetized rats before and during (two 10 min periods) the i.v. infusion of Ringer solution (control group) or different doses of ANP (0.25, 0.5 and 1 microgram, respectively). The administration of ANP was associated with a marked and significant increase in UV, UNaV, UkkV and GFR. The diuretic and natriuretic responses to ANP were dose-related, while the changes in GFR and UkkV were short-lived and not related to the dose of ANP. There was no relationship between UV or UNaV and UkkV after ANP administration. In contrast, UkkV correlated closely with GFR (r = 0.675, P less than 0.001). These data do not support the hypothesis that the kallikrein-kinin system contributes to the diuretic and natriuretic effects of ANP, but it might be involved in the renal hemodynamic action of this peptide.

Animals↗

PubMedDate not supplied

Measurement of fibrosis in needle liver biopsies: evaluation of a colorimetric method.

Collagen content was measured in 38 needle liver biopsies (8 steatosis, 8 chronic hepatitis, 7 fibrosis and 15 cirrhosis) by a new colorimetric method based on the selective capacity of Sirius red and Fast green to bind to collagen and noncollagenous proteins, respectively. The values were compared with those obtained after determination of the degree of fibrosis by morphometry in the same tissue. In biopsies with cirrhosis and fibrosis, there was a higher amount of collagen than in biopsies with chronic hepatitis and steatosis. Furthermore, there was a highly significant direct correlation between the collagen content measured colorimetrically and the degree of fibrosis determined morphometrically (r = 0.77, p less than 0.001), suggesting that this new colorimetric method is useful in measuring the degree of fibrosis in needle liver biopsies.

Biopsy, Needle↗