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Biomedical subjects

C J Bentzel

Publications and source records attributed to C J Bentzel.

At least 37 records · Page 2Linked to original sources
PubMed1986

Reduction of proteinuria by indomethacin in patients with nephrotic syndrome.

Immediate and longer-term (five-day) effects of indomethacin on proteinuria and renal function were examined in a group of nephrotic subjects with glomerular filtration rates (GFR) that ranged from near normal to moderately impaired. The modifying role of the patients' sodium/volume (S/V) status on renal prostaglandin inhibition was systematically evaluated by renal clearance and balance studies. After patients were S/V-depleted for five days, indomethacin (75 mg/d) decreased protein excretion by 45%. The decrement in proteinuria was greater than 2 times greater than the fall in creatinine clearance and was unrelated to baseline clearance. In acute clearance studies, 75 mg indomethacin administered orally immediately reduced protein excretion, effective renal plasma flow (CPAH), GFR (C inulin), Na, K, and free water excretion. Indomethacin responsiveness (reduced proteinuria) correlated with the change in PGE2 excretion. The effect of indomethacin on protein excretion and renal hemodynamics was apparent, but blunted, when dietary Na intake was increased to 200 mEq/d. Mean BP increased during indomethacin therapy only when patients were S/V-expanded.

Dinoprostone↗
PubMed1985

Protamine reversibly decreases paracellular cation permeability in Necturus gallbladder.

Protamine, a naturally occurring arginine-rich polycationic protein (pI 9.7 to 12), was tested in Necturus gallbladder using a transepithelial AC-impedance technique. Protamine sulfate or hydrochloride (100 micrograms/ml = 20 microM), dissolved in the mucosal bath, increased transepithelial resistance by 89% without affecting the resistance of subepithelial layers. At the same time, transepithelial voltage (psi ms) turned from slightly mucosa-positive values to mucosa-negative values of approximately +1 to -5 mV. The effect of protamine on transepithelial resistance was minimal at concentrations below 5 micrograms/ml but a maximum response was achieved between 10 and 20 micrograms/ml. Resistance started to increase within 1 min and was maximal after 10 min. These effects were not inhibited by serosal ouabain (5 X 10(-4) M) but could be readily reversed by mucosal heparin. The sequence of protamine effect and heparin reversal could be repeated several times in the same gallbladder. Mucosal heparin, a strong negatively charged mucopolysaccharide, or serosal protamine were without effect. Mucosal protamine reversibly decreased the partial ionic conductance of K and Na by a factor of 3, but did not affect Cl conductance. Net water transport from mucosa to serosa was reversibly increased by 60% by protamine. We conclude that protamine reversibly decreases the conductance of the cation-selective pathway through the tight junction. Although this effect is similar to that reported for 2,4,6-triamino-pyrimidinium (TAP), the mechanism of action may differ. We propose that protamine binds to the apical cell membrane and induces a series of intracellular events which leads to a conformational alteration of the tight junction structure resulting in decreased cationic permeability.

Animals↗
PubMed1985

Peritoneal permeability in the rat: modulation by microfilament-active agents.

A model of peritoneal dialysis in the rat was used to determine the effects of cytochalasins on ultrastructure and peritoneal permeability to molecules of varying molecular weight. The permeability to urea, inulin, and plasma albumin were determined after intraperitoneal administration of cytochalasin B (2 to 10 X 10(-6) M) and cytochalasins D and E (2 X 10(-6) M). Cytochalasin B (20 X 10(-6) M) increased the permeability to inulin, urea, and albumin by 30, 60, and 150%, respectively. These effects were, to a large degree, reversible. Cytochalasins D and E produced greater increments in permeability for all molecules; this increase was only partially reversible. Ultrastructure analysis by scanning electron microscopy revealed extensive development of membrane protuberances (zeiotic knobs) on mesothelial cells exposed to cytochalasin B. A return to a normal apical cell surface was apparent although incomplete at 24 hr. Tight junctions were not grossly altered and major changes in intramembranous junctional strands were not observed. The major effect of cytochalasins on the cell surface may be responsible for the increased permeability to urea, predominately a transcellular probe. Inulin, which follows a paracellular route, was less affected. Altered protein permeability may be due to the action of cytochalasin on the exposed capillary endothelium in subdiaphragmatic areas where the mesothelium is discontinuous.

Animals↗
PubMed1983

Structural alterations in rat kidney proximal tubules perfused with fresh autologous serum.

Two min of intraluminal perfusion of the rat proximal tubules with autologous serum induced marked ultrastructural alterations including extensive cytoplasmic vesiculation due to swelling of rough endoplasmic reticulum cisternae and occasional extrusion of nuclei and cytoplasm into the lumen. Within 4 min pronounced vesiculation of mitochondria was observed. These findings are consistent with the notion that serum-induced inhibition of proximal tubular fluid absorption is due to cell lysis, presumably mediated by complement activation.

Animals↗
PubMed1983

Ca2+ regulation of tight-junction permeability and structure in Necturus gallbladder.

To explore the role of Ca2+ in tight-junction permeability, the Necturus gallbladder was exposed to varying Ca2+ concentrations and to the Ca2+ ionophore A23187 added to the mucosal side (1.9 X 10(-6) to 6.8 X 10(-5) M). Electrophysiological parameters measured in an Ussing-type chamber were correlated with tight-junction morphology revealed by freeze-fracture electron microscopy. In Ca2+-free bathing media, transepithelial resistance decreases and tight-junctional ultrastructure is fragmented. In 1.8 mM Ca2+ media, A23187 induces an initial drop in transepithelial resistance, followed by an increase in transepithelial resistance to a value 20% above base line. At peak response to A23187, NaCl diffusion potentials decrease. Freeze-fracture replicas reveal that the number of junctional strands increase pari passu with junctional depth. Both physiological and morphological changes were partially reversible. The initial decrease in transepithelial resistance coincided with a persistent hyperpolarization of the mucosal cell membrane potential difference and a decrease in the mucosal-to-serosal cell membrane resistance ratio. Thus A23187 alters both the transcellular and paracellular pathway, resulting in opposing effects on transepithelial resistance.

Animals↗
PubMed1983

Induction of epithelial tight junctions by a light chain protein isolated from a patient with Fanconi's syndrome.

Tight junctions have not been described in the adult human glomerulus. In a 22-year-old patient with kappa light chain proteinuria, tight junctions were observed between glomerular epithelial cell foot processes (kidney biopsy). The light chain isolated from urine proved to have a relatively high isoelectric point. When the light chain was exposed in vitro to the mucosal surface of a 'leaky' epithelium, the Necturus gallbladder, transepithelial resistance and potential difference increased in a concentration-dependent, reversible manner and NaCl dilution potentials decreased, consistent with a reduction in tight-junctional ionic permeability. Gallbladders fixed in situ and freeze-fractured during peak electrophysiological responses revealed an increase in tight-junctional depth. This report indicates that certain light chains, possibly by virtue of a positive charge, may induce changes in epithelial tight junction structure and/or permeability.

Adult↗
PubMed1982

Angiotensin-induced sodium excretion patterns in cirrhosis: role of renal prostaglandins.

Changes in renal hemodynamics and sodium excretion induced by an angiotensin II (AII) infusion were correlated with urinary prostaglandin E2 (PGE2) excretion in 15 patients with cirrhosis and ascites. All induced natriuretic responses in 47% and antinatriuretic responses in 53% of the patients. Natriuresis was accompanied by an increase; antinatriuresis by a decrease in PGE2 excretion. Although there was no change in GFR (CIn), renal blood flow (CPAH) decreased. Patients were clinically indistinguishable. Antinatriuretic responders tended, however, to have higher baseline PGE2 excretion rates, were more sensitive to effects of prostaglandin blockade, and were less sensitive to the pressor effect of AII. Following partial inhibition of renal prostaglandin synthesis by indomethacin, AII-induced natriuretic responses were accentuated. GFR, RBF, and urine flow rate markedly decreased in both groups. There was no difference in pressor sensitivity to AII following prostaglandin synthesis blockade. We conclude that in patients with hepatic cirrhosis, the sodium excretion pattern induced by an exogenous AII challenge may depend on the prior state of intrarenal prostaglandin activity. Our findings also support the hypothesis that renal hemodynamic parameters in patients with cirrhosis and ascites are crucially dependent on renal prostaglandins.

Angiotensin II↗
PubMed1982

Effect of protamine on the permeability and structure of rat peritoneum.

The effect of protamine, a polycationic protein, on the mesothelial permeability and ultrastructure was evaluated in a rat model of peritoneal dialysis. The peritoneal permeability to urea and inulin were measured after the intraperitoneal instillation of protamine sulfate in varying concentrations. A functional correlation was made with the ultrastructure of omentum. Protamine concentrations between 5 and 30 micrograms/ml decreased the permeability to inulin without significantly altering that of urea. At concentrations from 30 to 75 micrograms/ml, protamine increased permeability to urea by 50% and to inulin by 20%. Mesothelial cells revealed a loss of microvilli and minor degrees of disorganization of submembranous, cytoplasmic microfilaments without significant changes in the intramembranous structure of occluding junctions. Effects were partially reversible. At a concentration of 100 micrograms/ml, there was an irreversible doubling in permeability to inulin without a comparable effect on permeability to urea associated with the disruption of occluding junctions in focal areas. This complex response to protamine suggests at least two transperitoneal diffusion pathways, transcellular and paracellular. The mesothelial cell occluding junctions may be a diffusion barrier in the latter pathway.

Animals↗
PubMed1982

Hypertension in the elderly.

Successful control of blood pressure through drug therapy can reduce morbidity and mortality in the elderly population. However, age-related factors also make this group prone to adverse side effects. A cautious approach is therefore recommended in the effort to achieve ideal control of blood pressure.

Adrenergic beta-Antagonists↗
PubMed1980

Cytoplasmic regulation of tight-junction permeability: effect of plant cytokinins.

The significance of the "leaky" tight junction might be understood better if cells of the epithelial monolayer possessed mechanisms to regulate molecular flow through the junction. To test this possibility, Necturus gallbladder, a representative leaky epithelium, was studied before, during, and after mucosal exposure to plant cytokinins and two other microfilament-active drugs, cytochalasin B and phalloidin. Concomitant with morphological changes in microfilaments, cytokinins induced rapid reversible increases in transepithelial resistance and potential difference (PD) and decreases in NaCl dilution potentials, with no change in the ratio of relative cell membrane resistances. Cytochalasin B (0.2-1.2 microM) and phalloidin (0.6-12.7 microM) caused similar changes in transepithelial resistance and PD. When the intramembranous structure of tight junctions was studied by freeze fracture, peak cytokinin-induced increments in transepithelial resistance were associated with more disorder in the strand meshwork resulting in a small increase in tight junction depth, but there was no evidence of de novo strand assembly. These studies suggest that permeability of the tight junction of Necturus gallbladder is subject to rapid reversible modulation, possibly under cytoskeletal control.

Animals↗
PubMed1978

Permeability changes in Necturus proximal tubule during volume expansion.

The permeability of Necturus proximal tubule to hydrophilic nonelectrolytes of varying molecular size was studied under control conditions and during isotonic expansion of the animal's extracellular volume. Transepithelial permeability was measured in perfused tubular segments under conditions of zero net water flux. During volume expansion, tubular permeability to urea increased slightly, whereas mannitol decreased slightly and permeability to sucrose was significantly decreased. Volume expansion had a greater effect on osmotic flow parameters; the NaCl reflection coefficient decreased from 0.64 to 0.47 (summer animals) and from 0.41 to 0.27 (winter animals). Osmotic water flux and hydraulic conductivity increased but only in the lumen-to-capillary direction. Reflection coefficients of nonelectrolytes measured at the apical surface were reduced during volume expansion for probing molecules greater than 3 A in radius and were unchanged for smaller molecules, less than 3 A, suggesting two pore populations. We propose that an increase in tight-junction permeability can account for modification of osmotic flow parameters, whereas the whole thickness of the epithelium, particularly the intercellular space, plays the dominant role in regulation of diffusional permeability.

Animals↗
PubMed1975

Antagonism of the effects of furosemide by indomethacin in normal and hypertensive man.

Furosemide and the prostaglandin synthetase inhibitor, indomethacin, were administered singly and in combination to four normal subjects and six patients with essential hypertension in order to determine whether the antihypertensive, natriuretic and other effects of furosemide could be altered by inhibition of prostaglandin synthesis. In all subjects indomethacin treatment alone resulted in a significant elevation of blood pressure and a fall in plasma renin without any change in sodium excretion. Furosemide alone resulted in a significant blood pressure fall with a rise in plasma renin and urinary aldosterone with a marked increase in urinary sodium loss. These effects were either obviated or blunted by addition of indomethacin. The results are compatible with hypothesis that the antihypertensive and natriuretic effects of furosemide might be mediated at least in part by prostaglandin synthesis. In addition, the effects of indomethacin should be considered when using this drug in hypertensive patients and in subjects requiring diuretic therapy.

Aldosterone↗