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H Fleisch

Publications and source records attributed to H Fleisch.

At least 163 records · Page 9Linked to original sources
PubMed1980

Chronic thyroparathyroidectomy and tubular handling of phosphate: increased reabsorption in late but not in early proximal tubule.

The fractional reabsorption (FR) of inorganic phosphate (Pi) along the proximal tubule depends upon both the filtered load of Pi (FLPi) and the tubular reabsorptive capacity of the Pi transporting system. To assess the actual effect of parathyroid hormone on the reabsorptive capacity only, the influence of Pi load has to be eliminated. In this study FRPi was determined by free-flow micropuncture along superficial nephrons of chronically (48 h) thyroparathyroidectomized (TPTX) and pair-fed sham-operated (SHAM) rats at identical FLPi [TPTX 3.07 +/- 0.14 (n = 26) and SHAM 3.07 +/- 0.11 (n = 26) mumol/min +/- SEM]. The micropuncture results indicate that in the ranges of tubular fluid over plasma inulin concentration [TF/P)In] 1.00-1.49 and 1.50-1.99, no difference in FRPi between TPTX and SHAM could be detected. It is only between a TF/PIn of 2.0 and 2.49 that chronic TPTX resulted in a significant increase in FRPi. Accordingly the present study indicates that chronic TPTX increases FRPi in late but not in early portions of proximal tubule. Thus in the early proximal tubule the tubular reabsorptive capacity of the Pi transporting system appears to be unaffected by chronic removal of the parathyroid glands. From this result it can be inferred that the increased plasma concentration of Pi which follows the removal of the parathyroid glands, particularly in the chronic stage, will lead to an apparently paradoxical decrease in FRPi in early proximal tubule as a mere consequence of the increased filtered load of Pi.

Absorption↗
PubMed1980

Use of dermestid beetles for cleaning bones.

Various parts of the skeleton of normal and osteoporotic rats were compared with respect to their dry weight, ash weight, and calcium content when the bones were cleaned by Dermestes maculatus beetles or manually. Both techniques gave similar results. This was also true when whole body calcium measured by neutron activation and total skeletal calcium from bones cleaned by the beetles were compared. Thus dermestid beetles are useful as a technique to clean bones, especially for the parts of the skeleton which are difficult to dissect by hand.

Animals↗
PubMed1980

Effects of pyrophosphate and diphosphonates on the dissolution of hydroxyapatites using a flow system.

Pyrophosphate and diphosphonate ions have been said to diminish the dissolution of hydroxyapatite crystals, because they lower the equilibrium concentrations of calcium and phosphate ions in the bulk solution around hydroxyapatite crystals in a closed system. However, in a closed system these effects are not necessarily due to an effect on dissolution alone. In this paper we have used a continuous flow system to study the effects of pyrophosphate and two diphosphonates, ethane-1-hydroxy-1,1,-diphosphonate and dichloromethane diphosphonate, on the dissolution of hydroxyapatite. All three compounds decreased markedly the rate of dissolution of hydroxyapatite as well as the exchangeable pools of calcium and phosphate ions around the crystals.

Calcium↗
PubMed1980

Calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D.

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.

Animals↗
PubMed1980

Effect of diphosphonate treatment on phosphate transport by renal brush border vesicles.

Treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in doses of 10 mg P/kg s.c. for 7 days inhibits bone mineral retention and decreases the tubular capacity to reabsorb inorganic phosphate (Pi) in thyroparathyroidectomized (TPTX) rats. In the present work we show that pretreatment with EHDP depressed Na+-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex of TPTX rats. The effect of EHDP was observed after feeding both high (1.2%) and low (0.2%) phosphorus diets. The EHDP-induced changes observed in vitro at the brush border level parallel the variations in the overall tubular Pi transport capacity as assessed by clearance techniques in conscious rats. Na+-dependent glucose uptake by BBMV, as well as alkaline phosphatase activity in cortical homogenates and in the BBMV were not affected by EHDP treatment. Accordingly, EHDP, given in doses that block bone mineral retention, appears to specifically affect the Na+-dependent transport of Pi across the luminal membrane of proximal tubules of renal cortex.

Animals↗
PubMed1980

Mechanisms of stone formation: role of promoters and inhibitors.

This paper represents a review on the role played by promoters and inhibitors in the formation of urinary stones. It appears that both mechanisms are, together with the degree of supersaturation, important in the development of urolithiasis. For the promoting activity emphasis has shifted towards the role of crystals of one salt inducing epitactically the precipitation of another salt. For the inhibitors it is important to distinguish the effect on crystal growth and aggregation. While citrate, pyrophosphate and magnesium are probably the most relevant for crystal formation, glycosaminoglycans play the primary role for aggregation. This field is still at its beginnings, and it might be rewarding to focus future investigations both in the laboratory and clinically along these directions.

Calcium↗
PubMed1979

Effects of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on rabbit articular chondrocytes in culture.

Investigations were carried out to assess the effects of disodium 1-hydroxyethane-1,1-diphosphonate and disodium dichloromethanediphosphonate (compounds containing a P-C-P bond) on isolated rabbit articular chondrocytes in culture. Studies on growth behaviour showed that both diphosphonates displayed inhibitory actions, dichloromethanediphosphonate producing the larger effect. Both compounds inhibited the uptake of 2-deoxy-d-glucose, dichloromethanediphosphonate once more being the more potent of the two. The uptake of alpha-aminoisobutyrate was considerably increased by chondrocytes treated with dichloromethanediphosphonate, whereas 1-hydroxyethane-1,1-diphosphonate showed no effects. The biosynthesis of sulphated extracellular macromolecules secreted by the cells into the pericellular space as well as into the growth medium was greatly increased by dichloromethanediphosphonate but not by 1-hydroxyethane-1,1-diphosphonate. The stimulatory effect was dose-dependent. Short-term exposure of already confluent cells to dichloromethanediphosphonate as opposed to growing the cells to confluence in the presence of the diphosphonate revealed that the stimulatory effects were already evident after 24h, indicating that cell division is not necessarily required to produce the observed effects. The increment in proteoglycan synthesis was still evident with cells that were exposed continuously to the diphosphonate in primary as well as secondary culture. Pulse-chase experiments together with studies on the enzyme arylsulphatase revealed that the appearance of increased amounts of proteoglycans was the result of a stimulation in synthesis and not due to an inhibition in turnover.

Aminoisobutyric Acids↗
PubMed1979

Increase in alkaline phosphatase activity in calvaria cells cultured with diphosphonates.

1. Dichloromethanediphosphonate and to a lesser degree 1-hydroxyethane-1,1-diphosphonate, two compounds characterized by a P-C-P bond, increased the alkaline phosphatase activity of cultured rat calvaria cells up to 30 times in a dose-dependent fashion. 2. Both diphosphonates also slightly inhibited the protein synthesis in these cells. 3. Thymidine, an inhibitor of cell division, did not inhibit the induction of the enzyme, indicating that the increase in enzyme activity was not due to the formation of a specific population of cells with high alkaline phosphatase activity. 4. The effect on alkaline phosphatase was suppressed by the addition of cycloheximide, an inhibitor of protein synthesis. 5. After subculturing the stimulated cells in medium without diphosphonates, the enzyme activity fell almost to the control value. 6. Bovine parathyrin diminished the enzyme activity of the control cells and the cells treated with dichloromethanediphosphonate; however, at high concentration the effect of parathyrin was greater on the diphosphonate-treated cells than on the control cells. 7. The electrophoretic behaviour, heat inactivation, inhibition by bromotetramisole or by phenylalanine, and the Km value of the induced enzyme were identical with that of the control enzyme.

Alkaline Phosphatase↗
PubMed1979

Phosphate transport by rat renal brush border membrane vesicles: influence of dietary phosphate, thyroparathyroidectomy, and 1,25-dihydroxyvitamin D3.

In the present work we have investigated whether the changes in the renal handling of inorganic phosphate (Pi) induced by 1) dietary Pi, 2) removal of parathyroid glands and 3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are associated with alterations in the Na-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex. Sham-operated (SHAM) or thyroparathyroidectomized (TPTX) rats treated or not with 26 pmol/day of 1,25(OH)2D3 i.p. were fed low (0.2%) or high (1.2%) P diet for 7 days. The results showed that in SHAM, TPTX and TPTX+1,25(OH)2D3 the Pi uptake by BBMV was greater after low than high Pi diet. It was greater in TPTX than in SHAM counterparts fed either diets. In TPTX fed low or high Pi diet 1,25(OH)2D3 decreased the Pi uptake to the level observed in SHAM. A striking parallelism was found between variations in Pi uptake by BBMV and in the tubular Pi reabsorption of the whole kidney. The Na-dependent glucose, the mannitol uptake by BBMV, and the alkaline phosphatase activity in cortical homogenates and BBMV were not affected by the various treatments. Thus, dietary Pi, chronic TPTX and 1,25(OH)2D3 appear to specifically affect the Na-dependent Pi transport system bound to the brush border membranes of renal cortical tubules. The alterations observed at this membrane level could account, at least in part, for the changes induced by these factors on the overall tubular reabsorption of Pi.

Animals↗
PubMed1979

Diphosphonates.

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Animals↗
PubMed1979

Renal handling of calcium: influence of parathyroid hormone and 1,25-dihydroxyvitamin D3.

The influence of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the renal Ca handling was studied in vitamin D-replete rats. The relation between plasma concentration ([Ca]P) and urinary Ca (UCaV/ml GF) was ascertained by clearance techniques over the [Ca]P range of 1.4-3.4 mM varied by infusion of Ca gluconate. Chronic thyroparathyroidectomy (TPTX) decreased the plasma Ca threshold from about 2.3 to 1.5 mM. Between [Ca]P 1.4 and 3.4 mM there was a linear increase in UCaV/ml GF corresponding to 35-50% of the increment in filtered load. In TPTX, PTH (2.5 IU/h i.v.) shifted the Ca threshold from 1.5 to 2.3 mM, without changing the slope of UCaV/ml GF on [Ca]P. The effect of TPTX on the renal Ca handling was not corrected by doses of 1,25(OH)2D3, which increased the intestinal Ca absorption of TPTX rats to normal level. In intact and TPTX rats disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given at doses which inhibit the production of 1,25(OH)2D3 did not change the tubular Ca handling. Furthermore, 1,25(OH)2D3 had no effect in EHDP-treated TPTX rats. Therefore, tubular Ca handling does not appear to be altered in response to chronic endogenous variation or physiologic supplementation of 1,25(OH)2D3 in vitamin D-replete rats. This is in contrast to the marked alteration observed after TPTX or PTH administration.

Animals↗
PubMed1979

Resistance to the phosphaturic and calcemic actions of parathyroid hormone during phosphate depletion. Prevention by 1,25-dihydroxyvitamin D3.

Recent observations indicate that in thyroparathyroidectomized (TPTX) rats fed a low (0.2 g/100 g) phosphorus diet, the tubular phosphaturic response to parathyroid hormone (PTH) remains markedly blunted even when it is assessed at normal or high plasma concentration and filtered load of inorganic phosphate (Pi). Because 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] decreases the tubular capacity to reabsorb Pi when chronically administered to TPTX rats, we have studied whether this vitamin D(3) metabolite could specifically increase the phosphaturic response to PTH in phosphate-deprived animals. The results show that in Vitamin D-replete TPTX rats fed a low (0.2 g/100 g) phosphorus diet, 1,25(OH)(2)D(3) (2 x 13 pmol/d i.p. for 7 d) markedly enhanced the acute tubular phosphaturic response to PTH (2.5 IU/h i.v.) without affecting the action of the peptide hormone on Ca reabsorption and cyclic-3',5'-AMP excretion. The influence of 1,25(OH)(2)D(3) on the phosphaturic response to PTH could not be ascribed to an increased plasma concentration and(or) filtered load of Pi during the administration of the peptide hormone. However, it could be, at least in part, related to the elevation in the basal level of plasma Pi which was observed in the 1,25(OH)(2)D(3)-treated animals. The results also indicate that 1,25(OH)(2)D(3) significantly enhanced the calcemic response to PTH, which was blunted in these conditions of phosphate deprivation. Unlike 1,25-(OH)(2)D(3), 25-hydroxyvitamin D(3) did not unmask the phosphaturic effect of PTH in phosphate-depleted animals, even when given in doses 100 times larger. Thus, 1,25(OH)(2)D(3) displays a selective and powerful activity in preventing the occurrence of tubular resistance to the phosphaturic action of PTH during Pi depletion. This finding suggests the existence of an important interaction between dietary Pi, 1,25(OH)(2)D(3), and PTH in the homeostasis of phosphate.

Animals↗
PubMed1979

Regulation of the metabolism of 25-hydroxyvitamin D3 in primary cultures of chick kidney cells.

A primary chick kidney cell culture is described, capable of forming 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], and 1,24,25-trihydroxyvitamin D3 [1,24,25(OH)3D3] over several days. The apparent Km values were 0.125 microM for the 1-hydroxylase and 2.1 microM for the 24-hydroxylase. Exogenous 1,25(OH)2D3 decreased 1-hydroxylase and increased 24-hydroxylase within 4 h. 24,25(OH)2D3 produced similar effects, but only in the absence of fetal calf serum. R and S isomers of 1,24,25(OH)3D3 were about fives times less active than 1,25(OH)2D3. Bovine parathyroid hormone stimulated the 1- and reduced the 24-hydroxylase in 6 h, but this only occurred in cultures either previously treated with 1,25(OH)2D3 and EGTA to lower Ca to 0.8 mM or in cultures grown in the presence of 25-hydroxyvitamin D3 (25(OH)D3). Under the latter condition, the sensitivity to bovine parathyroid hormone was enhanced, 0.04 U/ml producing a maximum response. Synthetic aminoterminal tetratriacontapeptide (1-34) human parathyroid hormone was equally effective. In the absence of D metabolites, estradiol for 6 h produced a dose-dependent inhibition of the 1-hydroxylase, but no change in the 24-hydroxylase. Progesterone, testosterone, and corticosterone had no significant effect. In cultures grown in the presence of 25(OH)D3 no reproducible effects were obtained with either 1 microM estradiol or 1 microM testosterone, alone or in combination, but 5 microM corticosterone decreased the 1- and increased the 24-hydroxylase. Changes in Ca and P concentrations of the medium as well as addition of ethane-l-hydroxy-1, 1-diphosphate for 48 h did not affect any of the hydroxylase activities. The modulation of the hydroxylase activities by vitamin D3 metabolites and parathyroid hormone suggests that these factors regulate the renal hydroxylase by direct actions, whereas it would appear that ethane-1-hydroxy-1,1-diphosphate, Ca, P, and steroid may exert their influence indirectly.

Animals↗