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Biomedical subjects

A S Brem

Publications and source records attributed to A S Brem.

At least 55 records · Page 3Linked to original sources
PubMed1987

Metabolic derivatives of aldosterone.

Metabolism of aldosterone during the latent period prior to the action of the hormone may be of physiological importance. In the rat, liver metabolizes aldosterone in a sex-dependent manner; larger quantities of neutral polar and reduced aldosterone derivatives are found in male rat kidney; correlating with the larger physiological responses of male rats to aldosterone. The target tissues, mammalian kidney and toad urinary bladder, are also capable of metabolizing aldosterone in situ to neutral polar, 5 alpha- and 5 beta-reduced, and monosulfate derivatives. The 5 alpha-reduced metabolites possess significant antinatriuretic activity and are preferentially synthesized by rat kidney nuclei. The metabolic pathways leading to the synthesis of 5 alpha-reduced metabolites and their subsequent neutral polar derivatives appear to be regulated by dietary sodium and can be inhibited by antimineralocorticoids. At concentrations somewhat higher than aldosterone, these 5 alpha-reduced metabolites also can recreate the development of hypertension and suppress plasma renin activity in young adrenalectomized spontaneously hypertensive rats. Thus, several of the metabolically transformed aldosterone derivatives can be correlated with physiological regulation and/or expression of the actions of the hormone.

Aldosterone↗
PubMed1987

Cytosolic calcium and the action of vasopressin in toad urinary bladder.

The effects of experimental procedures believed to increase cytosolic calcium on basal and vasopressin-stimulated osmotic water flow and transepithelial sodium transport were examined in the toad urinary bladder. Exposure of isolated toad bladders to quinidine, calcium ionophores (A23187, X537A), or low-sodium or potassium-free serosal solutions resulted in a dose-dependent decrease in the hydrosmotic response to vasopressin or exogenous adenosine 3',5'-cyclic monophosphate (cAMP). The degree of inhibition of cAMP-induced water flow induced by low-sodium or potassium-free serosal bathing media varied, and in a similar manner, with the serosal calcium concentration. The effects of quinidine sulfate (2 X 10-4 M), X537A (2 X 10(-5) M), and low serosal sodium (20 mM), but not that of A23187 (10(-5) M), were readily reversible. Exposure to quinidine (4 X 10(-4) M), A23187 (10(-5) M), X537A (5 X 10(-6) M), or low serosal sodium (2 mM) also inhibited the basal short-circuit current (SCC). Vasopressin, 4-20 mU/ml, completely overcame the inhibition of the SCC induced by quinidine, A23187, or low serosal sodium, but a submaximal dose of hormone (4 mU/ml) failed to fully reverse the inhibitory effect of X537A, 5 X 10(-6) M. These results are consistent with the view that 1) a Na-Ca exchange process operates across the basolateral surface of the granular epithelial cells of the toad urinary bladder in vivo, and 2) the level of free calcium in the granular cell cytosol plays a modulatory role in the control of apical membrane water and sodium permeability by vasopressin, and in the regulation of the basal rate of transepithelial sodium transport.

Animals↗
PubMed1986

The effects of antimineralocorticoids on synthesis of aldosterone metabolites in target tissues.

[3H]Aldosterone is transformed into several metabolites by subcellular fractions of rat kidney. 80-90% of the metabolites synthesized by nuclei and plasma membranes are 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo in ratios of 1:2 and 1:1 respectively; small quantities of 3 beta,5 alpha-THAldo are also synthesized. In contrast, kidney cytosol metabolizes Aldo principally to 5 beta-reduced products with co-chromatograph with 5 beta-DHAldo and 3 alpha,5 beta-THAldo. Several polar neutral metabolites, as well as sulfate and acidic metabolites are also synthesized by the cytosol fraction. Similar 5 alpha-reduced metabolites, 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo are also synthesized when [3H]aldosterone is incubated in vitro with toad urinary bladder for 1 and 5 h. Significant quantities of 5 beta- and 20 beta-reduced products and sulfate and acidic metabolites are also synthesized. The metabolism of [3H]aldosterone in both target tissues is significantly inhibited by aldosterone antagonists. Several of the reduced metabolites of aldosterone synthesized in kidney and toad bladder possess significant mineralocorticoid activity. 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo possess 1/10 and 1/30 and 3 alpha,5 beta possesses 1/80-1/100 of the antinatriuretic activity of Aldo. It is suggested that the metabolism of Aldo in its target tissues may be linked to regulation or expression of the hormone's actions.

Aldosterone↗
PubMed1986

Fluctuations in intracellular pH associated with vasopressin stimulation.

Intracellular pH (pHi) was estimated in paired hemibladders isolated from Dominican toads (Bufo marinus) by the tissue distribution of [14C]5,5'-dimethyl-2,4-oxazolidinedione and [3H]inulin. Tissues were incubated with isotopes for 30 min to correlate changes in pHi with the approximate time of peak vasopressin (VP)-induced water flow. At serosal pH 7.1 in the presence of an osmotic gradient, the intracellular hydrogen ion concentration [( H+]i) after 30 min of VP (20 mU/ml) stimulation was 8.29 +/- 0.23 X 10(-8) M (pHi 7.08) compared with 5.19 +/- 0.46 X 10(-8) M (pHi 7.28) in unstimulated paired controls (n = 5, P less than 0.001). The cyclic AMP (cAMP) analogue 8-(p-chlorophenylthio)-cAMP (10(-5) M) mimicked the VP effects. A similar change was observed at serosal bath pH 8.2, where [H+]i was 1.67 +/- 0.06 X 10(-8) M (pHi 7.78) with VP vs. 1.11 +/- 0.04 X 10(-8) M (pHi 7.95) in matched controls (n = 8, P less than 0.001). In all cases, the hydroosmotic response was associated with a significant decrease in inulin space. When the osmotic gradient was eliminated with Ringer solution or isotonic sorbitol in the mucosal bath, VP produced a smaller decrease in pHi (approximately 0.08 pH units) at both serosal pH. 31P-nuclear magnetic resonance spectra showed a similar downward trend in pHi with cell swelling. When vasopressin was removed from the bath, pHi and inulin space in stimulated hemibladders returned to pretreatment values within 30 min, and the tissues were again capable of a maximum hydroosmotic response if rechallenged with the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Mineralocorticoid activity of 19-hydroxyaldosterone, 19-nor-aldosterone, and 3 beta-hydroxy-delta 5-aldosterone: relative potencies measured in two bioassay systems.

The mineralocorticoid (MC) activities of 19-hydroxyaldosterone (19-OH-Aldo) and 19-nor-aldosterone (19-nor-Aldo) were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall MC activity is expressed as the ability to decrease the urinary Na+ to K+ ratio; antinatriuretic activity is represented by decreases in the urinary Na+ to creatinine ratio, and kaliuretic activity by increases in the K+ to creatinine ratio. All measurements were made on urine collected 1-3 h postinjection. In this assay, 19-OH-Aldo was 1/100th to 1/140th as active as Aldo, and 19-nor-Aldo possessed MC activity similar to that of Aldo; both steroids possessed antinatriuretic and kaliuretic activities. In contrast, when assayed in vitro in the isolated toad urinary bladder, the natriferic responses of both 19-OH-Aldo and 19-nor-Aldo (10(-8), 10(-7), and 10(-6) M) were not significantly different from those caused by equivalent concentrations of Aldo. 3 beta-Hydroxy-delta 5-Aldo is active as a MC in the adrenalectomized male rat, being 1/20th to 1/35th as active as Aldo, but, in contrast to 19-OH-Aldo, was less active in the isolated toad bladder system. 19-OH-Aldo, 19-nor-Aldo, and 3 beta-hydroxy-delta 5-Aldo could represent important new classes of Aldo analogs.

Adrenalectomy↗
PubMed1985

Effects of bilirubin on transepithelial transport of sodium, water, and urea.

Urinary concentrating defects and renal salt wasting have been described in the hyperbilirubinemic Gunn strain strain of rat. Homozygous animals demonstrate significant reductions in renal medullary urea and sodium ion concentrations. These observations are consistent with possible bilirubin associated disorders in the transepithelial transport of water and solute. To test this hypothesis, measurements of active sodium transport and passive water and urea fluxes were made in hemibladders isolated from the Dominican toad, Bufo marinus. Tissues were exposed to amphibian bicarbonate Ringer's solution containing 0.1 mM bilirubin with 0.05% bovine serum albumin (BSA) or BSA alone. Vasopressin-stimulated sodium transport, as reflected by short circuit current (SCC), was inhibited by 18 +/- 6% in the presence of bilirubin (N = 10; P less than 0.02). Cyclic AMP (p-Cl-phenylthio cAMP 10(-5) M) stimulated SCC was inhibited to a similar degree in the presence of bilirubin. The inhibition was noted only when bilirubin was in the serosal bath, and it could be abolished with BSA 0.5%. Bilirubin had no effect on the increase in SCC induced by higher concentrations of cyclic AMP (10(-4) M), aldosterone, or amphotericin B. Furthermore, bilirubin had no effect on the hydro-osmotic response to vasopressin and vasopressin-induced changes in urea permeability. These findings show that short-term exposure to bilirubin exerts a tissue-specific effect on the vasopressin-stimulated active transport of sodium but has no effect on the vasopressin-induced fluxes of water and urea.

Aldosterone↗
PubMed1985

Anion transport inhibitors: effects on water and sodium transport in the toad urinary bladder.

Acidification of the medium bathing the serosal surface of the toad urinary bladder results in impairment of the water permeability response to vasopressin. The magnitude of the hydrosmotic response to a maximal concentration of either vasopressin or the cyclic nucleotide analogue 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (C1PhS-cAMP) was progressively reduced when serosal bath pH was decreased from 8.5 to 6.5. The disulfonic stilbenes SITS and DIDS and the diuretic furosemide, agents known to interfere with anion transport and with the regulation of intracellular pH in other tissues, inhibited the water flow response to vasopressin and C1PhS-cAMP in a pH-dependent manner when added to the serosal bathing medium. Inhibition of the hydrosmotic response to 10(-5) M C1PhS-cAMP was estimated to be half-maximal at 1.5 X 10(-4) M SITS, 2 X 10(-5) M DIDS, and 1 X 10(-5) M furosemide. The degree of inhibition induced by the anion transport inhibitors varied inversely with the concentration of exogenous cyclic nucleotide. SITS, DIDS, and furosemide had no effect on either basal or vasopressin-stimulated short-circuit current at serosal pH 8.5; all three agents inhibited basal short-circuit current at pH 7.1 but had no effect on the natriferic response to vasopressin. These results are consistent with the view that changes in intracellular hydrogen ion and/or anion concentration can selectively inhibit the increase in water permeability elicited by vasopressin at a step(s) distal to the generation of cAMP.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Continuous-cycling peritoneal dialysis for children: an alternative to hemodialysis treatment.

Treatment of end-stage renal failure in children is invasive and prolonged. Although kidney transplantation is often the desired therapy, children usually require some form of life-sustaining dialysis until a suitable donor is found. Home continuous-cycling peritoneal dialysis (CCPD) is a useful alternative to in-center hemodialysis for these children. Adequate biochemical control of the uremic state can be achieved with continuous-cycling peritoneal dialysis. Peritonitis remains the major complication of this form of dialysis, averaging approximately one episode per 12 patient-months. Growth rates of children maintained on continuous-cycling peritoneal dialysis appear to be equivalent to growth rates of children treated with hemodialysis. The advantage of continuous-cycling peritoneal dialysis lies in the fact that exchanges occur during the evening hours and parental intervention is minimized.

Adolescent↗
PubMed1983

Juvenile nephronophthisis with blindness in a three-month-old infant. Senior's syndrome associated with relative parathyroid insufficiency.

Juvenile nephronophthisis is a slowly progressive renal disease with onset in infancy, characterized by impaired renal concentrating ability. The combination of juvenile nephronophthisis and tapeto-retinal degeneration, renal-retinal dystrophy, may cause blindness in infancy, and renal failure in the first decade of life. This syndrome has not been previously described as a cause of renal failure in young infants. We report an infant who presented at three months of age with blindness and renal insufficiency. In addition, this infant had a disproportionate degree of hypocalcemia and hyperphosphatemia compatible with relative parathyroid gland insufficiency. We propose that this was due to an inability of this infant's parathyroid glands to undergo compensatory hypertrophy, rather than a specific defect in parathyroid function associated with renal-retinal dystrophy.

Biopsy, Needle↗
PubMed1983

Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone.

The mineralocorticoid activities of the two dihydro- and the four tetrahydroisomers of the ring A-reduced derivatives of aldosterone were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall mineralocorticoid activity is expressed as the ability to reduce the urinary Na+/K+ ratio; antinatriuretic activity is represented by decreases in urinary Na+/creatinine; kaliuretic activity is shown by increases in K+/creatinine. All measurements were made on urine collected in the period 1-3 h postinjection. Measurements of overall activity indicate that the potency of aldosterone is greater than 5 alpha-dihydroaldosterone (DHA) greater than 3 alpha, 5 alpha-tetrahydroaldosterone (THA) greater than 3 alpha, 5 beta-THA greater than 3 beta, 5 alpha-THA greater than 5 beta-DHA greater than 3 beta, 5 beta-THA. Measurements of individual cation effects indicated that reduced derivatives generally, and the 5 alpha-reduced derivatives in particular, have greater antinatriuretic than kaliuretic activity. For example 5 alpha-DHA possesses between 7% and 17% of the antinatriuretic activity of aldosterone but only 0.7-2.7% of the kaliuretic activity. 5 alpha-DHA and 3 alpha, 5 beta-THA at concentrations of 10(-7)M were also shown to have mineralocorticoid activity in the isolated toad bladder; both caused an increase in the short circuit current across this epithelium although not to the level shown by a similar concentration of aldosterone. 5 beta-DHA appeared to be inactive at this dose.

Adrenalectomy↗
PubMed1982

Protein-losing enteropathy in systemic lupus erythematosus.

A 12-year-old girl, who was later found to have systemic lupus erythematosus (SLE), had a protein-losing enteropathy. Histologic documentation of intestinal lymphangiectasia in the absence of congestive heart failure, retroperitoneal masses, or constrictive pericarditis marks this case as demonstrating a unique association of SLE with intestinal lymphangiectasia.

Adrenal Cortex Hormones↗
PubMed1982

A prospective comparison of urinary tract infections in patients treated with either clean intermittent catheterization or urinary diversion.

Clean intermittent catheterization (CIC) has replaced urinary diversion as the treatment of choice for patients with neurogenic bladder. Yet, no well controlled studies are available assessing the efficacy of CIC over ileal loop diversion (ILD). Consequently, a one-year pospective study was carried out comparing short-term patient morbidity, infection rates, and bacterial organisms in 33 children with meningomyelocele. Twenty-four of the children were treated with CIC whereas nine children had an ILD. A minimum of four cultures per year were obtained on each patient. Patients maintained on CIC had 36.8% of their cultures positive for bacteriuria whereas children with ILD had 61.8% of their cultures positive (P less than .001). The incidence of bacteriuria associated with clinical signs and symptoms was similar in both groups. Four of 24 children treated with CIC had sterile urine whereas none of the children with ILD were persistently free from bacteriuria. Only five of 24 children receiving CIC had 50% or more of their cultures positive as contrasted with seven of nine children with an ILD (P less than .01). Escherichia coli accounted for approximately one third of organisms recovered from infected urine in both groups. Although the short-term morbidity associated with both treatment modalities is similar, the incidence of asymptomatic bacteriuria in children maintained on CIC is significantly less than in children with ILD. Whether this factor plays a role in determining long-term morbidity is a subject for further study.

Adolescent↗
PubMed1980

Urinary tract infection in pediatric renal transplantation.

Urinary tract infection is a frequent complication following renal transplantation and represents a potential focus for systemic infection in the immunosuppressed transplant recipient. The incidence, etiologic factors, temporal pattern, bacteriology, and prognostic significance of urinary tract infection were determined by analysis of 85 renal allografts in 69 patients. Significant bacteriuria occurred after 49 of 85 transplants (58 per cent). The incidence of infection was not related to success or source of the allograft, but was related to patient gender. Urinary tract infections developed in 68 per cent of females, while only 43 per cent of males became infected (p less than 0.05). Escherichia coli caused most first infections (30 per cent), while Pseudomonas aeruginosa and E. coli were equally responsible for recurrent infections (25 per cent each). Children with previous reconstructive urologic surgery had similar allograft success (63 per cent) and infection rates (53 per cent) as our other children (61 per cent and 58 per cent, respectively). No apparent correlation was noted between episodes of infection and graft rejection. Thorough preoperative assessment and preparation and prompt, specific treatment minimize the adverse influences of urinary tract infection.

Adolescent↗
PubMed1977

Toxicity from tea ingestion in an infant: a computer simulation analysis.

A seven-week-old infant presented with tonic posturing and nervous irritability after concentrated tea ingestion. The tea was analyzed and found to contain caffeine, a methylxanthine central nervous system stimulant. With the aid of a computer, projected blood levels were calculated over a thirty-hour time period and comared to the infant's clinical status. It is recommended that beverages containing xanthines be given to infants and small children with caution.

Caffeine↗