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Biomedical subjects

H Fleisch

Publications and source records attributed to H Fleisch.

At least 127 records · Page 7Linked to original sources
PubMed1983

Nature of calcemic effect of 1,25-dihydroxyvitamin D3 in experimental hypoparathyroidism.

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment on the daily fluctuation of plasma calcium concentration ( [Ca]P1) in relation to the feeding-fasting alternation has been studied in vitamin D-replete sham-operated (sham) and thyroparathyroidectomized (TPTX) rats fed a normal Ca diet. 1,25(OH)2D3 was given (26 or 39 pmol/day) intraperitoneally either by single injection or constant infusion using osmotic minipumps. After 7 days of treatment [Ca]P1 was measured at 4-h intervals for 24 h. Pair-fed, sham and TPTX animals received the solvent vehicle intraperitoneally. The results show that in sham rats the very moderate daily fluctuation of [Ca]P1 was not accentuated by 1,25(OH)2D3. A marked fluctuation of [Ca]P1 in relation to the food intake was observed in untreated TPTX as compared with sham rats. In TPTX rats 1,25(OH)2D3 increased the fasting [Ca]P1. In contrast the rise in [Ca]P1 during feeding was not significantly accentuated by 1,25(OH)2D3. The daily fluctuation of [Ca]P1 was the same whether the dose of 1,25(OH)2D3 was given in one single injection or by constant infusion, suggesting that this hormone is not involved in the hour-to-hour regulation of [Ca]P1. In conclusion, in the absence of parathyroid glands, 1,25(OH)2D3 given in doses that stimulate intestinal calcium absorption has a much more pronounced effect on the fasting calcemia than on the rise in calcemia observed during the feeding period. These results suggest that the mobilization of calcium from bone could play an important role in the calcemic effect of 1,25(OH)2D3 when given in the hypoparathyroid state.

Animals↗
PubMed1982

Conductivometric determination of urinary oxalate with oxalate decarboxylase.

An enzymatic method for determination of urinary oxalate is described: the acidified urine samples are extracted with chloroform. This manipulation improves the blank values considerably. 1 ml of extracted urine is incubated with oxalate decarboxylase. The CO2 released from the medium is absorbed by Sr(OH)2. The change in conductivity measured in the Sr(OH)2 solution is linearly proportional to the oxalate concentration in urine and the method is specific for oxalate. The mean recovery is 93.2 +/- 2.5%. The coefficient of variation calculated from 28 determinations is 12.6%. The detection limit is 35 nmol. 1 ml of urine is usually sufficient for determination. The mean 24 h urine oxalate excretion of 11 healthy men and 16 women was 240 +/- 20 mumol.

Carboxy-Lyases↗
PubMed1982

Phosphate transport in brush border membrane vesicles isolated from renal cortex of young growing and adult rats. Comparison with whole kidney data.

Recent clearance studies have demonstrated that the maximal tubular reabsorption of inorganic phosphate (Pi) per ml of glomerular filtrate (max. TRPi/ml GF) of the whole kidney is markedly lower in adult than in young growing rats fed either normal (0.8 g %) or low (0.2 g %) phosphorus diet. In addition, in adult rats clearance studies indicate that enhancement of max. TRPi/ml GF is observed 21 days but not 8 days after starting the low (0.2%) phosphorus diet. In the present work we have studied in the same experimental condition the Na+-dependent Pi uptake in brush border membrane vesicles (BBMV) isolated from renal cortex of either young growing or adult rats. The results of this study indicate that under the low (0.2%) but not under the normal (0.8%) phosphorus diet the Na+-dependent Pi uptake by BBMV was significantly depressed in adult as compared to young growing rats. In adult rats the Pi transport response to Pi restriction monitored at the brush border membrane level was different from that observed by clearance studies in the whole kidney. Indeed, the Pi uptake by BBMV was already enhanced after 8 days of Pi restriction and it did not increase further when studied 21 days after starting the low (0.2%) phosphorus diet. These results suggest that the regulation of the overall transfer of Pi across the renal epithelium may involve other additional modulating factors than the Na+-dependent Pi transport system present in the luminal membrane of the proximal tubule.

Age Factors↗
PubMed1982

Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reduction.

In man as well as in experimental animals progressive renal failure is associated with a decrease in the fractional reabsorption (FR) of inorganic phosphate (Pi). This response has been considered as an adaptation phenomenon and generally attributed to an increase in parathyroid hormone (PTH) secretion. One report indicates that in chronic thyroparathyroidectomized (TPTX) dogs treated with large doses of vitamin D progressive renal failure can also be associated with a fall in FRPi. However, in this latter study the concomittant administration of vitamin D could have accounted for the observed decrease in FRPi. In our study we investigated whether or not chronic reduction in renal mass leads to a similar decrease in maximal net tubular Pi reabsorption per volume of glomerular filtrate (maximal TRPi/ml GF) in the presence and absence of PTH and without pharmacological supplementation in vitamin D. Male rats were either TPTX or sham-operated (intact). One and two weeks later the animals of both groups were either subtotally nephrectomized (NX) in two stages or sham-operated (control). Four weeks after the second renal operation, the glomerular filtration rate (GFR) and the reabsorption of Pi were determined by clearance methodology under acute sodium chloride and Pi infusion, that is, at endogenous and increased plasma Pi concentrations ([Pi]Pl.). Thus maximal TRPi/ml GFR could be determined. In rats with intact parathyroid glands GFR was 1.56 +/- 0.10 (mean +/- SEM) and 0.54 +/- 0.10 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 2.24 +/- 0.07 in control and 1.57 +/- 0.18 mumol/ml (P less than 0.005) in NX. In TPTX rats GFR was 1.66 +/- 0.27 and 0.62 +/- 0.06 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 3.80 +/- 0.20 in control and 2.95 +/- 0.13 mumol/ml (P less than 0.005) in NX. The marked decrease in maximal TRPi/ml GF observed in TPTX after subtotal NX could not be ascribed to any consistent change in plasma calcium. Our study provides conclusive evidence that the decrease in maximal TRPi/ml GF in response to renal mass reduction can occur to the same degree in the presence or absence of PTH.

Adaptation, Physiological↗
PubMed1982

Increase of whole-body calcium and skeletal mass in normal and osteoporotic adult rats treated with parathyroid hormone.

1. The effect of long-term administration of parathyroid hormone (PTH) on whole-body calcium and ash weight of individual bones has been studied in normal and osteoporotic adult female rats in order to examine whether such a treatment could induce a positive calcium balance. 2. Osteoporosis was induced by calcium restriction during pregnancy and lactation. Sequential measurements of whole-body calcium were made by neutron activation. 3. In non-osteoporotic intact and thyroparathyroidectomized rats a daily dose of 75 units of human PTH 1-34 given subcutaneously for 3 weeks increased whole-body calcium. 4. In osteoporotic animals 25-50 units of either bovine PTH 1-84 or human PTH 1-34 given subcutaneously twice daily for 6 weeks increased both whole-body calcium and ash weight of individual bones. Microradiographic examination of the tibiae indicates, however, that PTH administration does not result in the restoration of individual trabeculae lost during the development of osteoporosis. 5. The results show that PTH can enhance skeletal mass in both normal and osteoporotic rats. In osteoporotic animals the restoration of whole-body calcium and ash weight of individual bones is not accompanied by a return of the morphological structure of the tibia to normal.

Animals↗
PubMed1982

Abnormal tubular adaptation to dietary Pi restriction in X-linked hypophosphatemic mice.

The renal handling of inorganic phosphate (Pi) is in part under the control of a powerful mechanism that is independent of parathyroid hormone and has the ability to enhance net tubular Pi reabsorption in response to a reduction in the Pi supply. The decreased renal reabsorption of Pi, the salient feature of the human disease X-linked hypophosphatemia, could be due to a loss of this adaptive capability of the tubular Pi transport system. To investigate this hypothesis, mutant hypophosphatemic (HYP) mice were used as a model of the human disease. Male HYP mice and normal littermates were subjected to high (0.75 g/100 g), low (0.25 g/100 g), or very low (0.03 g/100 g) phosphorus diets for periods varying between 1 and 20 days. Then the overall tubular Pi transport capacity was assessed by determining the maximal net Pi reabsorption per unit volume of glomerular filtrate (max TRPi/ml GF). The results indicate that the marked enhancement of max TRPi/ml GF, which is observed in normal mice after the first day of Pi restriction, is completely absent in HYP mice. In chronically thyroparathyroidectomized animals, 10 days of low phosphorus diet stimulated conspicuous max TRPi/ml GF in normal mice, whereas the same regimen did not significantly change the Pi reabsorptive capacity of HYP counterparts. The results of this study suggest that X-linked hypophosphatemia is a disease with a defect in the mechanism responsible for the adaptation of the tubular Pi transport system to Pi restriction.

Animals↗
PubMed1982

Tubular handling of Pi in young growing and adult rats.

The tubular transport of inorganic phosphate (Pi) is controlled by a parathyroid hormone-independent mechanism that responds to variations in the Pi intake. This adaptation mechanism could also respond to growth-mediated variation in the utilization of Pi by the organism. In the present work we have determined the maximal net Pi reabsorption per volume of glomerular filtrate (max TRPi/ml GF) in the young growing (2-mo) and adult 8- to 9-mo) rats. Max TRP[i/ml GF was significantly lower in intact adult (1.44 +/- 0.06 mumol/ml) compared with intact young growing animals (2.22 +/- 0.12 mumol/ml GF). This difference was maintained after removal of the thyroparathyroid glands; adult, 2.89 +/- 0.25, young, 4.56 +/- 0.25 mumol/ml. It was not associated with a difference in the urinary excretion of cAMP, GFR, renal handling of sodium, plasma calcium, or acid-base status. Administration of growth hormone preparations to adult rats did not raise max TRPi/ml GF to the level observed in young intact animals. With regard to the tubular Pi adaptation to Pi restriction, lowering the phosphorus content in the diet from 0.8 to 0.2 g/100 g resulted in an attenuated and delayed enhancement in max TRPi/ml in adult as compared with the response observed in young growing rats. These results show that the decrease in tubular reabsorption of Pi that occurs when rats become adult in a parathyroid hormone-independent phenomenon. It is suggested that this change is an adaptation of the tubular Pi transport to a reduction in the utilization of Pi in relation to the diminished growth rate of the animals.

Absorption↗
PubMed1982

Interference of dichloromethane diphosphonate with parathyroid hormone effects at the bone but not at the kidney level.

Treatment with dichloromethane diphosphonate (Cl2MDP, 10 mg P/kg s.c. for 3 days) did not abolish the rapid hypocalciuric effect of acute administration of parathyroid hormone (PTH) to thyroparathyroidectomized (TPTX) rats. Cl2MDP impaired, however, the slower hypercalcemic response to PTH. This latter effect of Cl2MDP did not result from increased renal excretion of calcium. Thus, Cl2MDP does not interfere with the kidney but with the bone effect of PTH. This finding explains, at least in part, why, under treatment with Cl2MDP, there is still an effective regulation of plasma calcium.

Animals↗
PubMed1981

[Diphosphonates in the treatment of bone metastases].

The diphosphonates are a group of phosphate compounds which inhibit the growth and dissolution of apatite crystals. These drugs have similar biological effects on bone by inhibiting the osteoclasts, and are also active in preventing pathological calcifications. The diphosphonates have been used successfully in various bone diseases and are now currently used for bone scanning. They are also considered one of the best treatments for Paget's disease. Several experiments in vitro and in vivo have suggested that the diphosphonates are active against bone metastases. Clinical trials have been undertaken and have shown that these compounds are active against malignant hypercalcemia. Further, they may delay the extension of bone destruction due to malignancy.

Animals↗