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M Loghman-Adham

Publications and source records attributed to M Loghman-Adham.

29 records · Page 2Linked to original sources
PubMed1993

Renal and intestinal Pi transport adaptation to low phosphorus diet in uremic rats.

The normal response of the kidney and intestine to a low-phosphorus diet (LPD) is an increased rate of Na(+)-dependent Pi transport by their brush border membranes (BBM). Dietary phosphorus restriction is used to reduce Pi accumulation in chronic renal failure. It is not known, however, if the uremic state alters the adaptive responses to an LPD. The adaptive response of the renal and intestinal BBM vesicles (BBMV) to LPD in acutely uremic (NX) and sham-operated (SH) control rats placed on a normal diet or an LPD was studied. In renal BBMV, the initial Na+ gradient-dependent Pi transport was lower in NX than in SH rats. Na(+)-independent uptake was unchanged. Thyroparathyroidectomy did not reverse the reduced Pi transport in NX rats. Kinetic studies showed a reduction of the apparent Vmax for Pi in BBMV from NX compared with SH rats (738 +/- 69 and 1,078 +/- 90 pmol/5 s.mg for NX and SH rats, respectively; P < 0.05; N = 5) with no change in the apparent Km. In intestinal BBMV, the initial Na+ gradient-dependent Pi transport was not different between SH and NX rats. There was also no difference in Pi transport kinetics between SH and NX rats. The adaptive response to an LPD persisted in renal and intestinal BBMV from NX rats and was comparable to that observed in SH rats: +54% for SH versus +48% for NX rats in kidney BBMV and +70.2% for SH versus +71.8% for NX rats in intestinal BBMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Role of phosphate retention in the progression of renal failure.

Dietary phosphorus restriction can prevent the progression of renal failure in subtotally nephrectomized rats or in rats with nephrotoxic serum nephritis, independent of protein and caloric intake. Conversely, diets high in phosphorus content result in a more rapid deterioration of renal function. The results are less compelling in indicating that phosphorus restriction can slow the progression of renal failure in the clinical setting. The toxicity of phosphate appears to be related to induction of calcium phosphate precipitation, resulting in tubulointerstitial disease. Most studies of prevention of renal calcification have addressed a single pathway in the development of nephrocalcinosis. These include inhibitors of calcium phosphate precipitation, calcium channel blockers, or an inhibitor of PTH secretion. All of these studies have shown a beneficial effect in preserving renal function. It is possible that a combination of these agents, started early in the course of CRF, may have an additive effect in preventing the progression to ESRD. The discussion of other factors associated with progression of renal failure is beyond the scope of this review. It is obvious that dietary protein restriction, treatment of systemic and intraglomerular hypertension and lipid abnormalities, and prevention of iron overload, all play roles in the preservation of renal function in CRF.

Animals↗
PubMed1992

Mechanisms of heterogeneity of Na(+)-Pi cotransport in superficial and juxtamedullary renal cortex.

To explore the mechanisms of axial heterogeneity of proximal tubular Pi transport, brush border membrane vesicles (BBMV) were prepared from superficial (BBMV-SC) and juxtamedullary (BBMV-JM) cortex of rat kidneys. Na+ gradient-dependent Pi transport was measured after the imposition of an inside-negative electrical potential created by either a K+ gradient ([K+]i greater than [K+]o) or a proton gradient ([H+]i greater than [H+]o) in the presence of ionophores. The initial Na(+)-dependent Pi uptake was higher in BBMV-SC than in BBMV-JM, both in the presence and absence of ionophores. Na(+)-dependent D-glucose uptake remained unchanged. We did not find a significant electrogenic transport component in either BBMV population when the non-specific effect of ionophores on Pi transport was taken into account. The stoichiometry of Na(+)-Pi cotransport was 2:1 in BBMV-SC and BBMV-JM. Phosphonoformic acid (PFA) competitively inhibited Pi transport. The inhibitory constant (Ki) for PFA was lower in BBMV-SC (237 +/- 1.7 microM) than in BBMV-JM (409 +/- 53 microM) (P less than 0.05). Arrhenius plots showed a higher rate of Pi uptake in BBMV-SC compared to BBMV-JM at all temperatures. However, the transition temperatures did not differ. We conclude that axial heterogeneity of Pi transport is not due to differences in electrogenicity or stoichiometry of transport.

Animals↗
PubMed1992

Inhibition of renal Na(+)-Pi cotransporter by mercuric chloride: role of sulfhydryl groups.

We studied the role of sulfhydryl groups in Na(+)-Pi cotransport across the renal brush border membrane (BBM), using HgCl2, an agent which penetrates membranes freely. HgCl2 inhibited the initial Na(+)-dependent 32Pi transport in a dose-dependent manner (IC50 = 54 microM). Na(+)-independent transport was not affected. The inhibitory effect persisted under Na+ equilibrium-exchange conditions. Additionally, HgCl2 had no effect on the diffusional uptake of 22Na up to 1 min incubation. Exposure to HgCl2 had no effect on vesicle integrity as determined by osmotic shrinking experiments. BBM vesicle (BBMV) volume, determined by D-glucose equilibrium uptake, was not affected at low HgCl2 concentrations, but decreased at higher concentrations (greater than 100 microM). Vesicle volumes, determined by flow cytometry, were not changed after exposure to HgCl2. Kinetic studies showed a reduction in the apparent Vmax for Pi transport from 1.40 +/- 0.13 to 0.75 +/- 0.19 nmoles/mg protein/5 sec, without a significant change in the apparent Km. In protection studies, dithiothreitol (DTT) completely protected against inhibition, but Pi, phosphonoformic acid (PFA), and Na+ gave no protection. The data suggest that sulfhydryl groups are essential for the function of Na(+)-Pi cotransporter of renal BBM.

Animals↗
PubMed1992

Dual action of phosphonoformic acid on Na(+)-phosphate cotransport in opossum kidney cells.

Phosphonoformic acid (PFA, foscarnet) was found to exert both an inhibitory and a stimulatory effect on Na(+)-dependent Pi transport in opossum kidney (OK) cells. When added in the uptake media, PFA produced a dose-dependent inhibition of Na(+)-Pi cotransport. PFA had no effect on the Na(+)-dependent transports of methyl-alpha-D-glucopyranoside (AMG) or L-alanine or on amiloride-sensitive Na(+)-H+ antiport. The inhibition of Na(+)-Pi cotransport was competitive [inhibitory constant (Ki) = 6.0 mM], reversible by dilution, and solute specific. When OK cells were incubated with PFA for longer time periods (1-15 h), the Na(+)-Pi uptake measured after removal of PFA was significantly increased, i.e., "upregulated." The extent of Na(+)-Pi cotransport upregulation was dependent on time (greater than or equal to 30 min) and dose of PFA (2-10 mM). The increase in Na(+)-Pi cotransport by upregulation with PFA was due to higher apparent Vmax with no change in apparent Michaelis constant (Km) for Pi and was solute specific: uptakes of AMG or L-proline were not changed. Removal of PFA from culture medium resulted in a fast reversal of upregulation. Upregulation was not inhibited by cycloheximide, actinomycin D, or cordycepin. Solute-specific increase of Na(+)-Pi cotransport was also found when measured in apical membrane vesicles isolated from OK cells. Thus PFA exerts a dual action on the Na(+)-Pi cotransporter of OK cells: 1) acute, competitive inhibition and 2) after prolonged exposure it increases Na(+)-Pi uptake, probably by insertion of Na(+)-Pi cotransporters into apical membrane.

Animals↗
PubMed1992

Phosphate transport in brush border membranes from uremic rats. Response to phosphonoformic acid.

Phosphate retention in chronic renal failure may result in the development of secondary hyperparathyroidism and renal osteodystrophy. Thus, the addition of a specific phosphaturic agent may be beneficial in the treatment of chronic renal failure. Phosphonoformic acid (PFA), a specific and competitive inhibitor of Na(+)-Pi cotransport in renal and intestinal brush border membrane vesicles (BBMV), can induce phosphaturia in thyroparathyroidectomized (TPTX) rats. The aim of this study was to determine if PFA retains its inhibitory activity in uremic intestine and kidney. The effect of PFA, and its derivative phosphonoacetic acid (PAA), added in vitro, on Pi transport in BBMV prepared from the intestine and the remnant kidney of 5/6 nephrectomized (NX) rats was studied. In intestinal BBMV, the time course of Pi transport was not significantly different between NX and sham-operated (SH) control rats. Compared with SH, Na(+)-dependent Pi transport was reduced in BBMV from remnant kidney of NX, with no difference in Na(+)-independent or equilibrium uptakes. The reduced transport was specific for Pi with no change in Na+ gradient-dependent L-proline uptake, suggesting a normal Na+ conductance in uremic BBM. PFA and PAA produced a marked inhibition of Na(+)-Pi cotransport in intestinal and renal BBMV from NX and SH with similar relative inhibitory potency in uremic and control BBMV. It was concluded that the relative inhibitory potency of PFA or PAA on intestinal and renal Na(+)-Pi cotransport is preserved in uremia.

Animals↗
PubMed1991

Characterization of essential sulfhydryl groups of rat renal Na(+)-Pi cotransporter.

Sulfhydryl (SH) groups are essential for the function of the Na(+)-Pi cotransporter of renal brush-border membrane (BBM) as determined by inhibition of Na(+)-Pi cotransport by HgCl2. Recent studies suggest that essential SH groups may be present on the cytoplasmic side of the BBM. We used various maneuvers to differentiate between external and internal SH groups on the Na(+)-Pi cotransporter in renal BBM vesicles (BBMV). The inhibitory potency of p-chloromercuriphenylsulfonic acid (PCMBS), a poorly permeable SH reagent, was about one-half that of p-chloromercuribenzoic acid (PCMB), a highly permeable reagent (half-maximal inhibitory concentrations of 625 and 350 microM, respectively). 5,5'-Dithio-bis-(2-nitrobenzoic acid) (DTNB) and N-ethylmaleimide (NEM) were additive to HgCl2 for inhibition of Pi transport. The highly permeable NEM gave a more pronounced additive effect (+30%) than the less permeable DTNB (+15%). When the intravesicular pH (pHi) and extravesicular pH (pHo) were varied independently, NEM (which reacts mainly at an alkaline pH) inhibited Pi transport only at pHi = 8.5, regardless of pHo. When internal SH groups were blocked by NEM at pH 8.5, PCMB and PCMBS produced similar additive effects. The binding of 14C-labeled phosphonoformic acid was inhibited by both reagents and to the same extent. Both PCMB and PCMBS increased 32Pi efflux from BBMV. The findings are consistent with the presence of essential SH groups on the cytoplasmic side of the BBM, with possible conformational changes induced by modification of the external SH groups.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo.

We examined whether phosphonoformate (PFA) can cause phosphaturia through its direct action on brush-border membrane (BBM) in vivo. Infusion of PFA or of parathyroid hormone (PTH) to thyroparathyroidectomized rats caused a marked increase in fractional excretion of phosphate without changes in excretion of Na+ or of GFR. The PFA-induced phosphaturia was not accompanied by an increase in urinary adenosine-3',5'-cyclic monophosphate (cAMP); moreover, PFA added in vitro did not influence the PTH-sensitive adenylate cyclase and cAMP-phosphodiesterase in proximal convoluted tubules. In BBM vesicles (BBMV) from rats with PFA-elicited phosphaturia, neither the rate of Na+-Pi symport nor Na+-dependent binding of [14C]PFA on BBMV was changed, whereas in BBMV from PTH-infused rats the Vmax of Na+-Pi symport decreased. PFA is almost completely ultrafiltrable; no metabolic transformation of PFA was detected after [14C]PFA exposure to rat renal cortical slices, homogenate, or to blood. We conclude that PFA causes phosphaturia by direct inhibition of Na+-Pi symport across BBM in proximal tubules, acting from the luminal side. Thus PFA (foscarnet) has a unique direct mechanism of phosphaturic effect, via its action on Pi reabsorption in proximal tubules in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Inhibition of Na+-Pi cotransporter in small gut brush border by phosphonocarboxylic acids.

We examined the effect of phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) upon Na+-Pi cotransport in brush-border membrane (BBM) from small gut of rat. Both PFA and PAA inhibited the Na+ gradient-dependent uptake of 32Pi by BBM vesicles (BBMV) prepared from intestinal mucosa but had no effect on Na+-dependent uptakes of D-[3H]glucose, L-[3H]proline, or [14C]succinate. The uptake in the absence of Na+ gradient, or uptake at equilibrium period (180 min), was not affected by PFA or by PAA. A chemical analogue of PFA and PAA, phosphonopropionic acid, had only a minor inhibitory effect and phenylphosphonic acid was inactive. Neither PFA nor PAA influenced the activity of rat intestinal BBM alkaline phosphatase. The BBMV from rat jejunum had a much higher capacity for Na+ gradient-dependent uptake of 32Pi than BBMV from duodenum or ileum. The inhibition of BBMV 32Pi transport across rat jejunum by PFA is competitive. We suggest that PFA and PAA are specific inhibitors of Na+ gradient-dependent uptake of Pi by BBMV from small intestinal mucosa and that they could serve as useful experimental tools for the studies of intestinal Na+-Pi cotransport.

Animals↗
PubMedDate not supplied

Acute hemorrhagic cystitis due to Escherichia coli.

Acute hemorrhagic cystitis in children has been associated with adenovirus type 11 infection as well as with urinary tract infection due to Escherichia coli. In the United States, the incidence of hemorrhagic cystitis due to E. coli appears to be as high as, or higher than that due to adenovirus type 11, but few studies are available. We studied 14 episodes of acute hemorrhagic cystitis in 13 children aged 2-14 years (mean 6.2). Ten were female. Gross hematuria lasted 1-9 days (mean 2.2). Urine cultures were positive (greater than 10(5) colonies/ml) in 6 episodes (43%). One additional patient had a suspected infection. All children grew E. coli. Pyuria was present in 78.5% but did not correlate with positive cultures. IVP was normal in 82%. E. coli appears to be a much more common cause of acute hemorrhagic cystitis in children than heretofore reported.

Acute Disease↗