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Biomedical subjects

A S Brem

Publications and source records attributed to A S Brem.

At least 37 records · Page 2Linked to original sources
PubMed1993

Activity of 11 beta-hydroxysteroid dehydrogenase in toad bladder: effects of 11-dehydrocorticosterone.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) transforms circulating glucocorticoids to their "biologically inert" 11-dehydro derivatives. Isoforms of 11 beta-OHSD with different cofactor requirements and biochemical properties [Michaelis constant (Km) and maximal velocity (Vmax)] exist in the kidney. Since epithelial cells derived from the toad bladder also contain this enzyme, we wished to further characterize its properties in prepared cell homogenates. 11 beta-OHSD from toad bladder demonstrated a clear preference for NAD+ over NADP+ as a cofactor similar to that observed in renal cortical collecting duct (CCD) cells. Furthermore, 11 beta-OHSD had a rapid onset of action. The apparent Km for corticosterone was 16.3 x 10(-8) M, a value comparable to that observed for enzyme from CCD, and a Vmax of 4.8 x 10(-12) mol.mg protein-1.min-1. The end product, 11-dehydrocorticosterone (compound A), influenced enzyme activity; it increased 11 beta-OHSD activity at corticosterone concentrations below the apparent Km for the enzyme and inhibited 11 beta-OHSD activity at corticosterone concentrations above the Km for the enzyme. The inhibitory effects of compound A appeared noncompetitive with an apparent equilibrium constant (Ki) of 2.8 x 10(-7) M. Consistent with its inhibitory action on 11 beta-OHSD, compound A (10(-6) M) enhanced the short-circuit current response to corticosterone (10(-7) M) in the intact toad bladder (experimental 2.03 +/- 0.33 vs. control 1.40 +/- 0.17 times above baseline; n = 7, P < 0.01). Thus 11 beta-OHSD in toad bladder resembles the isoform found in CCD, and compound A may be biologically important as a regulator of 11 beta-OHSD.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

Central nervous system and renal investigations in patients with Lowe syndrome.

We describe three patients with Lowe (oculocerebrorenal) syndrome, emphasizing primarily the central nervous system and renal pathology. Using magnetic resonance imaging, we noted diffuse high T2 signals periventricularly, indicating significant white matter destruction, which may be responsible in part for the mental retardation, seizure disorder, hypotonia, and areflexia observed in the patients. In contrast to previously published reports, there was minimal renal tubular dysfunction; however, proteinuria was significantly increased in all patients. We believe that the observed proteinuria is primarily the result of glomerular pathology rather than renal tubular dysfunction and may represent a net loss of negative charges within the glomerular filter. This loss of charge may be linked to the increased excretion of glycosaminoglycans in the urine.

Adolescent↗
PubMed1992

Effect of carbenoxolone sodium on steroid-induced sodium transport in the toad bladder: further studies.

The licorice derivative, carbenoxolone sodium, is a potent inhibitor of the enzyme 11 beta-hydroxysteroid dehydrogenase. When this enzyme is suppressed or is absent, endogenous glucocorticoids induce mineralocorticoid-like sodium retention by the kidney. Carbenoxolone sodium administered in vivo to an adrenalectomized rat has also recently been shown to enhance the mineralocorticoid response to submaximal concentrations of aldosterone, deoxycorticosterone (DOC) and 11-dehydrocorticosterone (compound A). In the present studies conducted on the urinary bladder isolated from the Dominican toad, Bufo marinus, a concentration of carbenoxolone sodium shown previously to increase glucocorticoid-induced sodium transport (2.5 x 10(-5) M) did not appear to alter the response to submaximal concentrations of aldosterone 10(-8) M, DOC 10(-7) M, or compound A 10(-5) M. These findings are consistent with the view that in the whole animal carbenoxolone sodium may modify additional steroid metabolic pathways and/or physiological processes in several organs to produce the enhanced renal response to mineralocorticoids and compound A.

Aldosterone↗
PubMed1992

Electrolyte disorders associated with respiratory distress syndrome and bronchopulmonary dysplasia.

In understanding the various electrolyte disorders associated with respiratory failure, one has to appreciate how the otherwise healthy premature infant maintains extracellular fluid homeostasis. The same physiologic processes that regulate body fluids are affected to varying degrees in the infant with respiratory failure. Maintenance of sodium conservation by the kidney is of critical importance for survival and growth. The immature kidney tends to exhibit excessive sodium wasting especially early on, but appropriate positive sodium balance is achieved generally within the first week. Appropriate reduction in extracellular fluid occurring during the first week or so of life is expected and if it is not allowed to occur may result in dilutional hyponatremia and an increase in pulmonary interstitial water. Diuretics, when used to promote an increase in lung compliance, can themselves generate significant morbidity. Sodium depletion, hypokalemia, alkalosis, and calcium wasting all can either be caused by or exaggerated by the loop diuretics. Thus, one must consider the maturational state of the infant, the infant's response to pulmonary failure, and iatrogenic factors influencing the outcome.

Acid-Base Equilibrium↗
PubMed1991

Primary renal lymphoma.

Lymphomatous involvement of the kidneys is a common manifestation of systemic non-Hodgkin's lymphoma but associated renal dysfunction is uncommon. In contrast, lymphoma originating within the kidneys is a rare event. We report a case of primary renal lymphoma presenting with renal insufficiency and hypertension in a 10-year-old boy.

Child↗
PubMed1991

Changes in intracellular sodium during the hydroosmotic response to vasopressin.

During vasopressin (VP)-induced water movement, toad urinary bladder epithelial cells undergo unique morphological changes. The osmolality within these responding cells remains relatively stable despite the large transcellular transport of water. We hypothesized that the hydroosmotic response to VP may be associated with a net increase in sodium either as an aid in maintaining the intracellular osmolality or as part of a Na-Ca exchange process. Changes in intracellular sodium (Nai) were monitored over time in individual hemibladders using 23Na NMR. Hemibladders were mounted as bags on glass pipets and filled with deionized water. During NMR studies, the serosal bath consisted of aerated 2.4 mM HCO3 amphibian Ringer's (pH 8.1) made up with 15% D2O containing the shift reagent, dysprosium tripolyphosphate (1 mM). This reagent allowed for visualization of Nai by shifting the extracellular Na signal; it did not affect basal or VP stimulated water flow, short-circuit current, or high energy phosphate metabolism as seen by 31P NMR. Changes in Nai were determined by integrating the area under the unshifted Na peak at each measurement and expressing differences as a ratio relative to baseline. The initial Nai signal from unstimulated hemibladders remained stable in these tissues over at least 180 minutes. Within 30 minutes of VP (20 mU/ml) exposure, however, the Nai peak increased 2.47 times above pretreatment baseline (N = 16, P less than 0.001). The Nai signal returned toward baseline values with removal of VP from the serosal bath but only after approximately 90 minutes. When change in cell shape and water movement were prevented by having isotonic sorbitol in the mucosal bath, VP produced no change in the Nai signal (N = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

11-Dehydrocorticosterone, a glucocorticoid metabolite, inhibits aldosterone action in toad bladder.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) metabolizes glucocorticoid hormones and diminishes their ability to induce sodium transport. In these studies, we determined the location of this enzyme in toad bladder and assessed the biological role for its 11-dehydro end product. Employing a polyclonal antibody directed toward 11 beta-OHSD and immunofluorescence techniques, we located the enzyme in the epithelial cell layer of the toad bladder. Although corticosterone (10(-7) M) can partially suppress aldosterone (10(-7) M)-stimulated short-circuit current (SCC), a clear excess of corticosterone (10(-6) M) did not inhibit the aldosterone-induced induced (10(-8) M) rise in SCC (n = 6). The 11-dehydro product of corticosterone, 11-dehydrocorticosterone (compound A) added to the serosal bath suppressed aldosterone (10(-8) M) peak SCC (360 min) in a dose-dependent fashion reaching 46 +/- 5% of control values at 10(-5) M (n = 6; P less than 0.001). Compound A (10(-5) M) in the mucosal bath also was capable of partially inhibiting the peak aldosterone rise in SCC to 63 +/- 7% of control values with aldosterone at 10(-8) M (n = 6; P less than 0.01) and to 64 +/- 10% of control values with aldosterone at 10(-7) M (n = 9; P less than 0.01). Compound A alone at 10(-5) M did not have any effect on SCC. Isolated toad bladders were not able to transform compound A (at 10(-8) and 10(-5) M) back to corticosterone. Thus the 11-dehydro end product of 11 beta-OHSD (compound A) may play a biologic role by regulating a component of mineralocorticoid-induced sodium transport.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

Disorders of potassium homeostasis.

Derangements in potassium homeostasis affect the body's bioelectric processes, including muscle contraction, nerve conduction, and myocardial electric pacing. Changes in extracellular potassium concentration occur with altered routes of elimination (renal or gastrointestinal) or with pathologic shifts in potassium from one body fluid compartment to another. The therapeutic interventions may either restore a normal resting potential for excitable cells or affect the threshold potential. Thus, an understanding of the basic pathophysiology is the foundation for treatment.

Humans↗
PubMed1989

Effect of carbenoxolone on glucocorticoid metabolism and Na transport in toad bladder.

In humans, diminished 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme activity has been associated with sodium retention and hypertension. These studies show that the toad bladder, another target tissue epithelium displaying steroid-induced sodium transport, possesses the enzyme 11 beta-OHSD. The toad urinary bladder rapidly transformed corticosterone (3 x 10(-8) M) (50% by 10 min and 90% by 180 min) with 11-dehydrocorticosterone being the major metabolite. The 11-dehydrocorticosterone produced reached an apparent plateau when the tissue incubations were repeated with higher concentrations of corticosterone (10(-7) and 10(-6) M). Carbenoxolone sodium (2.5 x 10(-5) M), a water soluble derivative of glycyrrhetinic acid, markedly inhibited the metabolism of corticosterone (3 x 10(-8) M) to 11-dehydrocorticosterone similar to previous observations in the mammalian kidney. Carbenoxolone sodium (2.5 x 10(-5) M) did not significantly affect short-circuit current (SCC) in toad bladders when added to either the serosal or mucosal bath. However, when carbenoxolone sodium was added to the mucosal bath and 60 min later corticosterone 10(-6) M was placed in the serosal bath, bladders generated a SCC 2.07 +/- 0.17 (mean +/- SE) times above base line at 360 min compared with 1.48 +/- 0.11 in bladders exposed to corticosterone alone (P less than 0.02). In parallel experiments, carbenoxolone sodium in the mucosal bath enhanced the rise in SCC induced by cortisol 10(-6) M; 1.66 +/- 0.16 times above base line at 360 min compared with 1.07 +/- 0.14 with cortisol alone (P less than 0.02). We conclude that the toad bladder contains 11 beta-OHSD and inhibition of this enzyme with carbenoxolone sodium is associated with amplification of glucocorticoid-induced transepithelial sodium transport in this tissue. However, since the quantity of 11-dehydro-product produced appears to be limited, other factors in addition to inhibition of 11 beta-OHSD may play a role in this amplification of sodium transport.

Animals↗
PubMed1989

Linear growth of children with nephrotic syndrome: effect of alkylating agents.

Growth velocity measurements were assessed in 12 children with steroid responsive but frequent relapsing or dependent nephrotic syndrome prior to and following treatment with either cyclophosphamide or chlorambucil and alternate day prednisone. Patients averaged 6 +/- 3 years (mean +/- SD) of age at the time of treatment. All of the patients underwent renal biopsy prior to treatment; 5 of the 12 showed mesangial proliferation; and in 10 of the 12, IgM deposits were seen within the mesangium of the glomerulus. Growth rates before treatment with the alkylating agent were 4.3 +/- 1.3 cm/y increasing to 8.7 +/- 2.5 cm/y (P less than .001) after therapy despite the relapses that occurred in 5 of the patients in the year following treatment. Short-term side effects of the treatment were minimal. The significant increase in growth associated with diminished use of steroids makes the use of alkylating agents reasonable for children with nephrosis who show signs of decreased growth velocity.

Child↗
PubMed1989

Perceived aluminum-related disease in a dialysis population. A report from the End-Stage Renal Disease Network 28.

A survey to assess the perceived prevalence of aluminum-related disease was conducted by the Medical Review Board of the End-Stage Renal Disease Network 28 from 1986 to 1987. Responses were obtained for 855 of 3000 patients on dialysis representing 17 of 39 participating dialysis units within the network. Almost 40% of the patients surveyed had been receiving dialysis therapy for over 3 years. Patients on hemodialysis (83% of the study group) had the water used to prepare the dialysate pretreated. Serum aluminum determinations were obtained in 240 (28%) of the 855 patients; other methods of assessing body aluminum burden were performed in less than 10% of the survey population. When obtained, elevated serum aluminum measurements were more likely to be found with each year patients were given dialysis and with each year patients were treated with oral aluminum gels. With the exception of patients with bone pain, clinical signs and symptoms did not correlate with elevated serum aluminum. However, the prevalence of muscle weakness, bone pain, fractures, and dementia in the survey group did correlate with years on dialysis and/or years receiving oral aluminum gels. Data gathered from this survey are consistent with the view that signs and symptoms suggestive of an increased body aluminum burden occur in the minority of patients on dialysis. Nevertheless, patients at risk for aluminum intoxication (years on dialysis, years receiving gels, patients with clinical signs) may not be adequately identified.

Aluminum↗
PubMed1988

Psychosocial characteristics and coping skills in children maintained on chronic dialysis.

Psychosocial character traits and coping skills were examined in 12 children with end-stage renal failure. Six of the children were maintained on in-center hemodialysis and 6 were treated with home peritoneal dialysis. All of the patients felt a lack of ability to control their lives. The incidence of anxiety, depression, and hostility did not appear to vary from a population of healthy adolescents. Personal and social adjustment scores were, on average, on the 20th percentile. Coping skills appeared to be most influenced by the mode of dialysis treatment. Home peritoneal dialysis patients utilized self-reliance as a coping process more often than their counterparts on hemodialysis. We conclude that children maintained on chronic dialysis therapy demonstrate reasonable psychological adjustment with some differences in social and emotional functioning when compared with healthy children, and that the type of treatment chosen may influence the development of certain coping skills.

Adaptation, Psychological↗
PubMed1988

Infants of azotemic mothers: a report of three live births.

Women with severe renal failure rarely conceive, and when they do become pregnant these women often deliver prematurely. The clinical course of mothers with renal failure has been described, but little attention has been given to the offspring. In this report, we provide data on three infants born prematurely to mothers either on dialysis or with severe renal failure. The infants were the appropriate size for gestational age and demonstrated no obvious physical abnormalities. Laboratory data, including renal function, was also within normal limits. Renal size in the two infants studied by ultrasound was near or above the 95th percentile when corrected for gestational age. The premature birth appeared to be a function of maternal complications rather than a primary in utero growth disturbance.

Adolescent↗
PubMed1988

Time-dependent aldosterone metabolism in toad urinary bladder.

Aldosterone (Aldo) metabolism was examined in the toad bladder. Bladders were incubated with [3H]aldosterone (10(-7) M) for 5 h, 1 h, or 10 min. Tissues were analyzed for metabolites using high-pressure liquid chromatography (HPLC). In separate experiments, Na+ transport was assessed by the short-circuit current (SCC) technique. Following a 5-h tissue incubation, about 25% of the [3H]-aldosterone was converted into metabolites including a polar monosulfate metabolite, 20 beta-dihydroaldo (20 beta-DHAldo), small quantities of 5 beta-reduced products, and a variety of 5 alpha-reduced Aldo products including 5 alpha-DHAldo, 3 alpha,5 alpha-tetrahydroaldo (3 alpha,5 alpha-THAldo), and 3 beta,5 alpha-THAldo. Tissues metabolized approximately 10% of the labeled hormone into the same compounds by 1 h. Measurable quantities of these metabolites were also synthesized by bladders exposed to Aldo for only 10 min and then incubated in buffer for an additional 50 min without Aldo. Bladders pretreated with the spironolactone, K+-canrenoate (3.5 X 10(-4) M), and stimulated with Aldo (10(-7) M) generated a peak SCC 44 +/- 6% of that observed in matched pairs stimulated with Aldo (P less than 0.001; n = 6). K+-canrenoate also markedly diminished [3H]aldosterone metabolism at both 5 and 1 h. Thus, metabolic transformation of Aldo begins prior to hormone-induced increases in Na+ transport. Both the generation of certain metabolites (e.g., 5 alpha-reductase pathway products) and the increase in Na+ transport can be selectively inhibited by K+-canrenoate.

Aldosterone↗
PubMed1987

Long-term renal risk factors in children with meningomyelocele.

We studied renal function and structure in 42 patients with meningomyelocele, 28 treated with intermittent catheterization and 14 with ileal loop diversion. Patients were observed for a minimum of 60 months. Nine of the 28 patients who underwent intermittent catheterization had evidence of unilateral or bilateral reflux, and all patients with ileal loop diversion had free ureteral reflux. Bacteriuria was present in 38% +/- 5% of cultures obtained from patients with catheterization and in 70% +/- 7% of cultures from those with diversion (P less than 0.001). Four (14%) of 28 patients with catheterization had worsening renal function or anatomic appearance by intravenous pyelogram, and required a diversion. Three (28%) of 14 patients with diversion had changes in renal structure or function. Eight of 31 patients from both groups studied with voiding cystourethrography before the onset of therapy had small, noncompliant, trabeculated bladders; all seven patients who had worsening in function or anatomic appearance were from this subset (P less than 0.01). None of the patients with flaccid or distensible bladders demonstrated these changes. Renal disease was unrelated to the level of neurologic function. A small, noncompliant, trabeculated bladder is a risk factor associated with loss of renal function in patients with meningomyelocele.

Adult↗
PubMed1987

Psoas muscle abscess due to Pasteurella multocida.

A 9-year-old girl with meningomyelocele, an ileal conduit and a living related kidney transplant presented with a progressive gait disturbance. Radiographic evaluation included a computerized tomography scan that disclosed a large right psoas muscle abscess. The abscess cavity was drained percutaneously and culture of its contents yielded Pasteurella multocida. This case illustrates an unusual presentation of a psoas muscle abscess caused by an uncommon organism that was diagnosed and treated by nonoperative methods.

Abscess↗