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Biomedical subjects

S Adler

Publications and source records attributed to S Adler.

At least 163 records · Page 9Linked to original sources
PubMed1988

Inhibition of rat glomerular visceral epithelial cell growth by heparin.

The effect of several glycosaminoglycans and sulfated polysaccharides on the growth of cultured rat glomerular visceral epithelial cells (GEC) was studied in vitro. Heparin, one preparation of heparan sulfate proteoglycan, dextran sulfate, and pentosan polysulfate significantly inhibited the growth of several GEC clones studied (36.0-77.1% inhibition at 100 micrograms/ml). Other glycosaminoglycans studied did not affect GEC growth. Growth inhibition by heparin was dose related and did not appear to reflect cytotoxicity. Heparins with high or low affinity for antithrombin inhibited growth to similar degrees. When heparin was fractionated into high- and low-anticoagulant activity fractions by physicochemical means the high activity fraction displayed significantly greater growth inhibition. The degree of growth inhibition significantly correlated with serum concentration in the media (r = 0.64; P less than 0.001). Removal of heparin binding factors from serum resulted in a loss of this correlation as well as less overall growth inhibition. These experiments suggest that interactions of GEC with heparan sulfates and other heparin-like molecules in the extracellular matrix may be important in the control of GEC growth.

Animals↗
PubMed1988

Determination of rat brain buffering in vivo by 31P-NMR.

Buffering capacity of most tissues is composed of both rapid and slow phases, the latter presumably due to active acid extrusion. To examine the time course of brain buffering the brain pH of Sprague-Dawley rats was measured using 31P-nuclear magnetic resonance. The effect on brain pH of 30- or 58-min exposures to 20% CO2 followed by 30- or 38-min recovery periods, respectively, was studied. Brain pH reached its lowest value after a 15-min exposure to elevated CO2, thereafter slowly and steadily increasing. During recovery brain pH rose rapidly in the first 5 min exceeding control brain pH by 0.08 pH units. Brain pH fell during the next 30 min despite increases in blood pH and decreases in blood CO2 tension. Calculated intrinsic brain buffering rose steadily threefold during the last 40 min of CO2 exposure and during the final 30 min of recovery. These data show that in rat brain there is a temporally late buffering process, most likely active acid extrusion, requiring greater than 30 min for full activation and at least 30 min for discontinuation.

Animals↗
PubMed1988

Cerebral blood flow in chronic cocaine users: a study with positron emission tomography.

Occurrence of cerebrovascular accidents has been associated with cocaine abuse. We investigated the relative distribution of cerebral blood flow (CBF) in groups of chronic cocaine users, and of normal controls. Relative CBF was measured using positron emission tomography and 15 oxygen-labelled water. The cocaine users showed areas of deranged CBF as evidenced by patchy regions of defective isotope accumulation throughout their brain. The chronic cocaine users showed decreased relative CBF in the prefrontal cortex when compared with normal subjects. The repeated scans of some cocaine users, after 10 days of cocaine withdrawal, continued to show decreased relative CBF of the prefrontal cortex. We hypothesise that some of the widespread defects in CBF in the cocaine users could reflect the effects of vasospasm in cerebral arteries exposed chronically to the sympathomimetic actions of cocaine.

Adult↗
PubMed1988

A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene.

Binding of ligand to the estrogen receptor, a member of the steroid receptor gene family, rapidly increases PRL gene transcription. A 15 base pair core sequence 5'TTGTCACTATGTCCT-3' greater than 1.5 kilobase upstream from the rat PRL gene transcription start site is necessary for receptor binding, demonstrates interaction with the receptor DNA binding domain, and confers estrogen regulation. Transient cotransfection of expression plasmids encoding mutant estrogen receptors with a luciferase reporter plasmid under regulation of the rat PRL estrogen regulatory element were used to investigate the minimal information necessary and sufficient for activation of gene transcription. These analyses confirmed the absolute requirement for the receptor DNA binding domain in positive regulation of transcription, and revealed that removal of amino-terminal domains reduced, but did not abolish transcriptional effects. In contrast, truncation of the receptor immediately carboxy-terminal to the DNA binding domain resulted in constitutive activation of the receptor. The observations that removal of the steroid binding domain results in a constitutively active transcriptional factor, and that the amino-terminal domains are not required for transcriptional effect provides evidence that for two members of the steroid receptor gene family (the glucocorticoid and estrogen receptors), a relatively short DNA binding domain is sufficient for transcriptional activation. These results are likely to be prototypic for other members of this family of transcriptional factors.

Animals↗
PubMed1988

Smart ratio systems.

Explore the source record for details and available documents.

Emergency Medical Service Communication Systems↗
PubMed1988

The effect of serum potassium on theophylline-induced seizures.

Generalized seizures may be associated with therapeutic or intentional theophylline overdose. Toxic levels of theophylline are also associated with a fall in potassium which could potentiate theophylline-induced seizures. To evaluate the role of serum potassium concentration in theophylline-induced seizures we investigated the seizure threshold in normokalemic and hyperkalemic rats during theophylline infusion to toxic levels. Hyperkalemic rats were prepared with intraperitoneal amiloride and potassium chloride and had a mean +/- SEM initial potassium of 5.29 +/- 0.15 mEq/L. Control animals received either amiloride or potassium and had initial serum potassium concentrations of 4.00 +/- 0.08 and 3.93 +/- 0.16 mEq/L, respectively. Potassium levels after 30 minutes of theophylline infusion were 4.11 +/- 0.18 mEq/L in the hyperkalemic rats and 3.47 +/- 0.06 and 3.51 +/- 0.12 mEq/L in the control animals. There were no significant differences in the serum theophylline concentrations at time of seizure, nor was there a correlation between serum potassium concentration and theophylline concentration at time of seizure. Since the preservation of normokalemia does not influence the onset of seizures in theophylline toxicity, this suggests that the potassium level has little effect on seizure activity in this model.

Animals↗
PubMed1988

Relationship between cerebrospinal fluid dynamics and reversible spinal cord ischemia during experimental thoracic aortic occlusion.

This study was designed to assess the effects of hemodynamic changes and cerebrospinal fluid dynamics on spinal cord function during experimental thoracic aortic occlusion. We investigated the effects of dopamine, sodium nitroprusside, and sodium thiopental in this model. Proximal and distal aortic pressures and cerebrospinal fluid pressure were measured during occlusion in 12 adult mongrel dogs under control conditions and during drug interventions. Spinal cord function was assessed by spinal somatosensory evoked potentials recorded during 3-minute intervals of reversible spinal cord ischemia. By multiple regression analysis, the degree of spinal cord ischemia was positively related to the cerebrospinal fluid pressure (p = 0.0092) and negatively related to the percent change in cerebrospinal fluid pressure (p = 0.028); there were no significant drug effects on cerebrospinal fluid pressure or on the degree of spinal cord ischemia. This study indicates that cerebrospinal fluid pressure is an important factor in determining the degree of spinal cord ischemia during aortic occlusion and suggests that measures to reduce cerebrospinal fluid pressure will mitigate the degree of spinal cord ischemia.

Animals↗
PubMed1987

Enhanced glomerular prostaglandin formation in experimental membranous nephropathy.

To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN). PHN is a model of membranous nephropathy mediated by antibody and complement independent of inflammatory cells. Five days following induction of PHN by injection of heterologous antibody to rat proximal tubular brush border antigen (Fx1A) rats developed proteinuria 36.5 +/- 34 (controls 3.8 +/- 1 mg/day). Treatment with cobra venom factor, which depleted complement C3 levels to less than 10% of baseline, prevented the development of proteinuria (6.9 +/- 2 mg/day). The development of subepithelial, glomerular immune-complex deposits and proteinuria was associated with a significant stimulation of glomerular PGE2 (87%) and TXB2 (183%) formation. This increment in glomerular prostanoid biosynthesis was significantly inhibited (PGE2 increased 22%, TXB2 increased 75%) in animals that were complement depleted with cobra venom factor. Cobra venom factor had no effect on glomerular prostanoid formation in normal rats. In additional experiments we tested the hypothesis that TXA2 may contribute to mediation of proteinuria in PHN. We utilized a thromboxane synthetase inhibitor UK38485. UK38485 reduced glomerular TXB2 formation by 80% without influencing glomerular deposition of 125I-labeled antibody, and did not alter levels of urine protein excretion in rats with PHN (control 42 +/- 21, UK 38485, 39 +/- 24 mg/day, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Participation of the myeloperoxidase-H2O2-halide system in immune complex nephritis.

Neutrophils (PMNs) mediate injury in experimental glomerulonephritis (GN) in part via the release of reactive oxygen species, particularly hydrogen peroxide (H2O2). Recent kidney perfusion studies demonstrate that H2O2 can cause glomerular injury by reaction with halides in the presence of the PMN cationic enzyme myeloperoxidase (MPO) to form oxidants which can oxidize and halogenate tissue. We sought evidence for participation of the MPO system in a model of PMN-mediated immune complex (IC) GN. A PMN-dependent model of GN was developed in rats by perfusing the renal artery with concanavalin A followed by anticoncanavalin A antibody. PMN depletion abolished glomerular PMN infiltration and significantly reduced proteinuria (35 +/- 7 mg/day vs. 113 +/- 10, P less than 0.001). Rats that received Na125I (5.0 microCi) three and six hours following disease induction had more 125I incorporation in glomeruli and GBM at 48 hours than similarly treated rats that were PMN depleted (1200 cpm vs. 88 cpm, P less than 0.01). Glomerular iodination could not be demonstrated in a PMN-independent model of nephrotoxic nephritis induced with noncomplement fixing anti-GBM antibody. These data indicate that this model of PMN-mediated IC GN is associated with activation of the MPO-H2O2-halide system, which may participate in mediating glomerular injury.

Animals↗
PubMed1987

Biphasic effect of oxygen radicals on prostaglandin production by rat mesangial cells.

Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, as assessed by 51Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E2 (PGE2) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased to 38.1 +/- 9.7 or 30.8 +/- 6.9% of control levels (P less than 0.05) when cells were stimulated with the calcium ionophore A23187 (1 microgram/ml) or AA (10(-6) M), respectively. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B2 production was similarly decreased to 83.1 +/- 7.6 (0.05 less than P less than 0.10) or 54.9 +/- 2.5% (P less than 0.05). This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H2O2 was the responsible metabolite. High levels of H2O2 (5 x 10(-4) M) suppressed PGE2 production to 44.0 +/- 4.1 or 17.4 +/- 6.2% of A23187- or AA-stimulated production (P less than 0.05). Lower levels of H2O2 resulted in significant stimulation of base-line PGE2 production. Analysis of release of [3H]AA-labeled metabolites from A23187-stimulated cells showed no effect of H2O2 on phospholipase activity. Thus ROS can stimulate or inhibit AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury.

Animals↗
PubMed1987

New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system.

Reactive oxygen species, particularly hydrogen peroxide (H2O2), participate in neutrophil-mediated glomerulonephritis. However, the mechanism of H2O2 neptrotoxicity is unknown. Myeloperoxidase (MPO), a neutrophil cationic enzyme that localizes in glomeruli, can react with H2O2 and halides to form highly reactive products. We tested the hypothesis that the MPO-H2O2-halide system may induce glomerular injury by infusing MPO followed by H2O2 in a chloride-containing solution into the renal artery of rats. Controls received MPO or H2O2 alone. MPO-H2O2-perfused rats developed significant proteinuria, endothelial cell swelling, and epithelial cell foot process effacement, whereas control kidneys were normal. In the presence of free 125I, MPO-H2O2-perfused rats incorporated large amounts of 125I, localized to the glomerular basement membrane and mesangium by autoradiography, into glomeruli. Glomerular iodination was greatly decreased or absent in controls. The MPO-H2O2-halide system causes glomerular injury and may be important in neutrophil-mediated glomerulonephritis.

Animals↗
PubMed1987

A rat model for hyperkalemia.

It is often necessary to have a small animal model for hyperkalemia for use in electrolyte and acid base experiments. In reviewing the literature, we found a paucity of such animal models, especially for acute hyperkalemia. We have had difficulty in inducing acute hyperkalemia in rats using potassium chloride alone either intravenously or intraperitoneally and felt the need for an easily reproducible small animal model for hyperkalemia. We gave experimental animals a combination of intraperitoneal amiloride 3 mg/kg and potassium chloride 2 meq/kg in two divided doses while control animals received only the potassium chloride. Initial serum potassiums were similar but at 2 hr, the experimental group had significantly higher serum potassium levels which were sustained throughout the 8 hr of the experiment. Arterial blood gas revealed no significant difference in blood pH values at all time points during the experiment. We conclude that the combination of amiloride and potassium chloride is useful to produce acute hyperkalemia in rats and that this hyperkalemia is sustained beyond 6 hr. This model is convenient for use in metabolic experiments requiring the use of acutely hyperkalemic rats.

Amiloride↗
PubMed1987

Identification of risk factors for spinal cord ischemia by the use of monitoring of somatosensory evoked potentials during coarctation repair.

The infrequency of spinal cord infarction and paraplegia after occlusion of the descending thoracic aorta has effectively precluded statistical identification of risk factors. Reversible spinal cord ischemia (SCI), however, is more common, can be detected by intraoperative neurophysiologic monitoring, and can lead to irreversible spinal cord damage. Spinal somatosensory evoked potentials (SEPs) were monitored intraoperatively in 38 patients (18 days to 18 years) undergoing coarctation repair (1982-1986). Although no patients sustained perioperative neurologic dysfunction, 10 of 38 (26%) patients developed reversible SCI, as reflected by greater than 75% loss of SEP N1-P1 interpeak amplitude during aortic occlusion (mean clamp time, 29.1 +/- 1.1 min). During occlusion, seven of 38 (18%) sustained complete loss of the SEP; uniform and prompt (1 to 6 min after clamp release) recovery of the signal occurred in these patients with reperfusion following completion of the repair (n = 6), or temporary institution of partial occlusion (n = 1). By multiple regression analysis the degree of SCI was negatively related to the distal aortic pressure (mean 32.4 +/- 2.4 mm Hg, p = .03), and the occlusion PCO2 (mean 33.1 +/- 1.1 mm Hg; p = .013), and positively related to the change in proximal systolic pressure with aortic occlusion (mean 19.8 +/- 3 mm Hg, p = .003). We conclude that: (1) distal hypotension and SCI commonly occur during aortic occlusion for coarctation repair, and (2) intraoperative interventions that can potentially influence distal aortic perfusion and/or PCO2 should be used judiciously.

Aortic Coarctation↗
PubMed1987

Low molecular weight proteinuria exacerbates experimental ischemic renal injury.

To determine whether tubular reabsorption of low molecular weight proteins (LMWPs) alters ischemic tubular injury, rats were infused with 25 mg of lysozyme (isoelectric point (pI) 11.3), cytochrome C (pI 10.6), ribonuclease (pI 8.7), or myoglobin (pI 7.0), and during this time 25 minutes of bilateral renal artery occlusion (RAO) was induced. RAO control rats received either saline or 25 mg of albumin. Renal injury was assessed 24 hours later by blood urea nitrogen, creatinine, and histology. Lysozyme, ribonuclease, and myoglobin each exacerbated ischemic damage (increased tubular necrosis, cast formation, azotemia), but to comparable degrees (e.g., blood urea nitrogen range 75 +/- 8 to 100 +/- 5 mg/dl versus controls, 29 +/- 2 to 36 +/- 7; p less than 0.01). Rendering lysozyme anionic (pI 4.5) by succinylation did not diminish its acute renal failure-potentiating effect. Cytochrome C which is freely filtered but poorly reabsorbed had a minimal impact on the ischemic process. Infusion of LMWPs did not alter blood pressure, renal blood flow, or induce renal injury in the absence of RAO. During a sublethal ischemic event (10 minutes of RAO) LMWP infusion exacerbated proximal tubular luminal membrane damage before an adverse effect on other critical determinants of cell integrity were apparent (adenine nucleotide pools, oxidant stress). We conclude that endocytic LMWP reabsorption by proximal tubules can exacerbate superimposed ischemic tubular necrosis independent of any direct nephrotoxic protein effect. This action is not influenced by protein isoelectric point and appears to be mediated by a primary intensification of ischemic luminal membrane damage.

Animals↗