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Biomedical subjects

J B Puschett

Publications and source records attributed to J B Puschett.

At least 73 records · Page 4Linked to original sources
PubMed1984

Interference by prostaglandin E2 with the phosphaturic effects of nonhormonal agents.

The purpose of the present study was to evaluate the ability of prostaglandin (PG) E2 to alter phosphate excretory patterns induced by the nonhormonally mediated phosphaturic maneuvers, bicarbonate loading (BIC), volume expansion (VE) and acetazolamide administration (Az). Acute clearance studies were performed in chronically thyroparathyroid-ectomized dogs. The dosage of PGE2 utilized was free of excretory or hemodynamic effects. After BIC, percentage of phosphate excretion (%EP) increased from 4.8 to 14.0%, (P less than .05). In contrast, BIC preceded by PGE2 infusion produced no phosphaturia. Additionally, PGE2 blunted the increases in Na and HCO3 excretion associated with BIC. VE (5-6% b.wt.) increased %EP from 6.0 to 14.2%, (P less than .01). However, VE after PGE2 treatment did not result in a phosphaturia. Az increased %EP from 4.7 to 28.5%, (P less than .02). When PGE2 was infused before Az, %EP rose from 1.9 to 7.1%, (P less than .02) in response to Az. However, the increment in %EP over base line was reduced from 23.8 to 3.6% by PGE2 pretreatment (P less than .005). PGE2 did not alter the effects of VE or Az on sodium or bicarbonate excretion. Thus, PGE2 blunts or abolishes the phosphaturic effect of each of these maneuvers independent of its action on sodium or bicarbonate transport. We conclude that PGs have a specific action on phosphate transport events induced by certain nonhormonal factors, revealing a hitherto unappreciated role for these agents in modulating tubular reabsorptive processes.

Acetazolamide↗
PubMed1984

Difference between 1-84 parathyroid hormone and the 1-34 fragment on renal tubular calcium transport in the dog.

Acute clearance studies were performed in chronically thyroparathyroidectomized dogs to determine similarities and differences between the effects of 1-34 and 1-84 parathyroid hormone (PTH) on urinary calcium excretion. In a small (physiological) dose, 1-84 PTH caused no mean change in percentage calcium excretion, while the 1-34 fragment was frankly calciuric. At this dose, the two hormone preparations were equally phosphaturic. Fragments of PTH in the range 25-84 did not alter calcium or phosphate transport. We conclude that the entire molecule is required in order for the distal nephron effect of the hormone to enhance net calcium transport in the kidney to become manifest.

Adenylyl Cyclases↗
PubMed1983

Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic amp and parathyroid hormone.

The aims of the study were to determine whether 8-bromo-cyclic AMP (8BcAMP) in vivo mimics the inhibitory action of parathyroid hormone (PTH) on phosphate transport across the brush border membrane (BBM) of the renal proximal tubule, and to examine whether changes in BBM transport are accompanied by changes in the rate of renal gluconeogenesis. Thyroparathyroidectomized dogs were anesthetized and equilibrated, and control urine collections were obtained prior to removing the left kidney. Subsequent intravenous infusion of 8BcAMP at 50 mg/hr for 2 hr increased fractional excretion of phosphate from 4 +/- 1 (controls) to 29 +/- 4% (P less than 0.001) without changing glomerular filtration. In BBM vesicles isolated from the renal cortex, the initial Na+-dependent transport of phosphate was decreased from 747 +/- 135 (controls) to 564 +/- 126 pmoles per mg per 0.25 min after 8BcAMP (P less than 0.025), but Na+-independent phosphate uptake and Na+-dependent L-proline uptake were not changed significantly. Renal gluconeogenesis in the same animals was increased from 2.5 +/- 0.3 (controls) to 5.3 +/- 0.5 mumoles glucose per g tissue per hr after infusion of 8BcAMP (P less than 0.001). Infusion of PTH, like 8BcAMP, inhibited BBM phosphate transport and stimulated renal gluconeogenesis. We conclude that the inhibitory action of cyclic AMP and PTH on BBM phosphate transport is accompanied by stimulation of gluconeogenesis which suggests, indirectly, that changes in gluconeogenesis may be part of the intracellular mechanism for regulating BBM phosphate uptake in response to certain stimuli.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Parathyroid hormone: effects of the 3-34 fragment in vivo and vitro.

The biologically active fragment ofparathyroid hormone, consisting of residues 1-34, and its in vitro antagonist, fragment 3-34, were administered separately or in combination to chronically thyroparathyroidectomized dogs. These fragments were also studied in vitro with dog renal cortical membranes. Fragment 3-34 inhibited the stimulation of adenylate cyclase by fragment 1-34 in vitro, but had no agonist or antagonistic effects on renal phosphate transport in vivo.

Adenylyl Cyclases↗
PubMed1983

Influence of vitamin D status and chronic administration on the renal tubular effects of 1,25-dihydroxy vitamin D3.

Previous studies from this laboratory have demonstrated that the acute infusion of the vitamin D3 derivative, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) is antiphosphaturic when administered with small "permissive" amounts of parathyroid hormone (PTH). To determine the effect of chronic administration of this metabolite, studies were performed in both vitamin D-deficient (-D) and vitamin D-fed (+D) rats which had been pretreated with 1,25(OH)2D3 for 6 days and then infused with either the metabolite alone, the metabolite with a small "permissive" dose of parathyroid hormone (PTH) or neither. The results indicate that in the -D animals, 1,25(OH)2D3 infusion alone results in antiphosphaturia without the presence of PTH. However, in the +D rats, PTH was required, despite 1,25(OH)2D3 pretreatment, for the acute infusion of the metabolite to enhance phosphate reabsorption. Thus, both vitamin D and parathyroid status are important in determining the effect of 1,25(OH)2D3 on the renal tubular transport of phosphate.

Animals↗
PubMed1983

Direct effect of metolazone on sodium-dependent transport across the renal brush border membrane.

Studies with clearance and micropuncture techniques indicate that metolazone inhibits transport of sodium and phosphate in the proximal tubule. The present study is focused on transport across the luminal BBM of the proximal tubule to determine whether metolazone has any direct effect on this initial step in transtubular reabsorption. Addition of metolazone (0.01 to 1.00 mM) to isolated renal BBM vesicles caused dose-dependent inhibition (30% to 70%) of the initial uphill phase of Na+ gradient-dependent phosphate transport but did not inhibit the uptake at equilibrium. There were no significant changes in Na+-independent phosphate transport and phosphate transport under nongradient conditions when metolazone was present at 1.0 mM. The initial Na+ gradient-dependent BBM transport of both D-glucose and L-proline was markedly inhibited by 1.0 mM metolazone, indicating the nonspecific inhibitory action of the drug. Metolazone also inhibited efflux of D-glucose and L-proline from vesicles. Neither acetazolamide nor chlorothiazide at 0.1 to 1.0 mM inhibited BBM transport of phosphate, D-glucose, or L-proline. Metolazone did not change significantly BBM transport of Na+, suggesting that inhibition of Na+-dependent transport was not due to major changes in Na+ flux. These in vitro data indicate that metolazone inhibition of phosphate reabsorption in vivo may be due, in part, to a direct effect of metolazone on transport across the BBM of the proximal tubule.

Acetazolamide↗
PubMed1982

Acute effects of a "physiological" dose of 1,25-dihydroxy vitamin D3 on renal phosphate transport.

The renal phosphate transport response of thyroparathyroidectomized, vitamin D-deficient rats to the infusion of 1,25-dihydroxy vitamin D3 (1,25 D3) was studied with and without the simultaneous administration of a small (or "permissive") non-phosphaturic amount of bovine parathyroid hormone (bPTH). Although phosphate excretion (UPV) was unaltered by the infusion of either 0.1 U (= .0025 microgram or 6 pmoles) of 1,25 D3 or 0.2 U bPTH per hour for 6 hours, their combined administration reduced UPV from 14.8 +/- 1.6 to 10.3 +/- 1.2 microgram/min. (P less than .05). There were no alterations in inulin excretion. These data verify that: 1) 1,25 D3 is antiphosphaturic in this experimental setting in a very low dose which may represent a "physiological" amount of the metabolite; and 2) to enhance phosphate transport, the 1,25 D3 requires the presence of a small ("permissive") amount of PTH.

Animals↗
PubMed1982

Potentiation by calcium of the proximal tubular transport effects of parathyroid hormone.

Previous studies from this laboratory have demonstrated that a low ('physiological') dose of parathyroid hormone (PTH) effects a phosphaturia in chronically thyroparathyroidectomized (TPTX), hypocalcemic dogs, similar in magnitude to that seen in normal intact animals, without altering proximal tubular reabsorption. In addition, cyclic AMP did not increase following this amount of PTH, despite the phosphaturia. Since calcium is an important modulator of transport events, we studied the effects of restoring serum calcium (Ca) to normal before administering a physiological dose of PTH (0.3-0.5 U/kg). In hypocalcemic dogs given only physiological amounts of PTH, percentage phosphate excretion (%EPO4) rose from 3.81 +/- 1.48 to 18.29 +/- 5.69% (p less than 0.025) without any alteration in proximal tubular function. Ca infusion alone likewise did not change %EPO4 or proximal tubular transport. However, calcium-infused dogs given a physiological dose of PTH showed a reduction in proximal tubular fractional phosphate reabsorption from 0.73 +/- 0.04 to 0.63 +/- 0.04 (p less than 0.005), as well as an increase in %EPO4 (from 5.64 +/- 1.69 to 15.86 +/- 2.82%, p less than 0.001), without any increase in urinary or tissue cyclic AMP. We conclude that the elevation of the serum Ca to normal restores the ability of PTH in physiological amounts to alter proximal tubular PO4 transport. The data also suggest that this action of PTH is mediated by Ca, rather than by the adenylate cyclase system.

Absorption↗
PubMed1981

Diabetic nephropathy: natural course, survivorship and therapy.

Diabetes mellitus is a disease with major social and economic consequences. End-stage renal disease (ESRD) due to diabetes occurs in as many as 30% of patients with juvenile diabetes, providing a large percentage (up to 33%) of all patients in need of therapy for ESRD. We have reviewed the natural course of the nephropathy in type I diabetes mellitus and the results of dialysis and transplantation therapy with particular regard to survival and morbidity. Comparisons of the survival of diabetic patients among peritoneal dialysis, hemodialysis, and transplantation are complicated by the lack of sufficient data for peritoneal dialysis and by the bias introduced by patient/treatment selection methods. Presently, it appears that transplantation with a living related donor graft offers the best survival for both graft and patient, with a definite reduction of morbidity associated with the complications of diabetes. Cadaveric transplantation is approximately the equivalent of hemodialysis in patient survival at 1 year and also appears to offer a somewhat diminished morbidity. Peritoneal dialysis data are sparse and skewed by patient selection. However, there is some emerging evidence that therapy with this modality may be associated with a delay in progression of retinopathy, when compared with hemodialysis.

Adult↗
PubMed1981

Inhibition of the renal tubular effects of parathyroid hormone on phosphate transport by prostaglandin E2.

The infusion of PGE2 into TPTX dogs abolishes the phosphaturic action of PTH in vivo. This effect occurs only if PGE2 infusion precedes the administration of PTH. The infusion of PGE2 in vivo induces a state of refractoriness of PTH-sensitive adenylate cyclase in renal middle medulla from TPTX dogs in vitro. These results suggest that PGE2 inhibits the biological effects of PTH, in part by altering the events related to PTH activation of renal adenylate cyclase. These effects of PGE2, a local mediator, suggest that the renal tubular cell may modulate its responses to multiple and antagonistic stimuli by altering local renal prostaglandins.

Adenylyl Cyclases↗
PubMed1980

Mechanism of the phosphaturia due to chlorothiazide.

CTZ caused a phosphaturia when baseline phosphate excretion was not already high. Furthermore, when th influence of PTH is withdrawn, the excretion of phosphate appears to be largely affected by changes in urinary pH.

Animals↗