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  • 1
    ISSN: 1432-2013
    Keywords: Jejunal absorption ; Ca and Na transport ; Saline loading ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate whether intestinal calcium absorption parallels that of sodium following extracellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium. sodium and water were studied in rats by perfusing jejunal loops in situ. After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using45Ca, increased significantly (P〈0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again, the b-l calcium flux increased but to a significantly lesser extent (P〈0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P〈0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone was unchanged after expansion with the calcium containing solution but increased following calcium-free infusion. It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree by calcium-free Ringer infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2013
    Keywords: Phosphate (Pi) transport ; Isolated rat enterocytes ; Calcitriol (1,25(OH)2 vitamin D3) ; Vitamin D deficiency ; Methyl esters of cisvaccinic acid and transvaccinic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present work we studied rapid in vitro effects of calcitriol (1,25(OH)2 vitamin D3) on the intestinal transport of inorganic phosphate (Pi). Enterocytes from vitamin D replete (D+) as well as vitamin D depleted (D−) rats were isolated mechanically from the duodeno-jejunum. In this model, Pi uptake was a temperature and Na+-dependent phenomenon. The in vitro-addition of calcitriol (1 pM) resulted in a significant enhancement of initial Pi uptake rate by enterocytes from D+ (P〈0.01) and D− (P〈0.05) rats. This effect which was Na+-dependent, was observed within the time of 20 min, but not before. A similar effect on Pi uptake rates of D+ or D− enterocytes could be elicited by the in vitro addition of the methyl ester of cis-vaccinic acid (MCVA) which is thought to increase membrane fluidity by modifying the lipid composition of the cell membrane. The stimulatory effect of calcitriol on Pi uptake rate was blunted in the presence of the methyl ester of transvaccinic acid (MTVA) thought to decrease membrane fluidity. Enterocyte Pi efflux rate constant (o KPi) remained unchanged in the presence of calcitriol (1 pM). In conclusion, the study demonstrates a rapid in vitro effect of calcitriol on Pi uptake by isolated enterocytes from D+ and D− rats. It suggests, but does not prove, that the hormone may act via an action independent of genomic nuclear activation.
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  • 3
    ISSN: 1432-2013
    Keywords: Vitamin D3 ; Polyamine metabolism ; Difluoromethyl-ornithine ; 1-Alpha-hydroxyvitamin D3 ; Intestinal calcium transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Evidence is accumulating that 1,25(OH)2D3 may stimulate calcium transport from the intestinal lumen extremely rapidly by a mechanism which appears independent of de novo protein synthesis. To investigate this rapid action of 1,25(OH)2D3, the rate of calcium uptake by isolated enterocytes from duodena of young rats was determined in vitro as the uptake of45Ca from 1–15 min. Prior in vitro exposure of cells to 1,25(OH)2D3 (100 pM) for 20 min significantly increased the rate of calcium uptake (p〈0.001), an effect unaltered by 50 μM cycloheximide. Incubation with 100 pM 1-alpha-hydroxyvitamin D3 produced the same effect (p〈0.01). In contrast, exposure to 10 pM 1,25(OH)2D3, as well as to 100 pM or to 1,000 pM 25-hydroxyvitamin D3 induced no significant change. Because both 1,25(OH)2D3 and starvation may stimulate key enzymes in polyamine metabolism, we investigated the effects of (i) difluoromethyl-ornithine (CHF2-Orn), a specific irreversible inhibitor of ornithine decarboxylase and (ii) varying the timing of feeding prior to sacrifice. Both in vitro CHF2-Orn and feeding prior to sacrifice significantly decreased the baseline rate of calcium uptake (p〈0.05) and reduced the effect of 1,25(OH)2D3. Increased duration of starvation significantly increased the baseline rate of calcium uptake (p〈0.02) without changing the increment in rate of calcium uptake induced by 1,25(OH)2D3. The study suggests (i) that the early action of 1,25(OH)2D3 on the influx process of intestinal calcium transport may involve a different molecular specificity from that involved in the genomic action of 1,25(OH)2D3 and (ii) that changes in polyamine metabolism may play a part in this process.
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  • 4
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La parathyroïdectomie chez les sujets urémiques est indiquée seulement en présence d'un hyperparathyroïdisme grave. Dans quelques cas elle peut être insuffisante ou au contraire elle peut se solder par un hypoparathyroïdisme grave. La récidive est également toujours possible en raison de la persistance de l'insuffisance rénale. En conséquence une réintervention peut être nécessaire. Les auteurs rapportent 25 cas de réinterventions chez 21 sujets appartenant à une série de 248 malades qui ont été opérés pour hyperparathyroïdisme secondaire. Neuf d'entre eux avaient subi une parathyroïdectomie dans une autre formation chirurgicale. Six patients furent réopérés alors que l'intervention initiale avait été incomplète laissant en place de 1 à 3 parathyroïdes. Dans 7 cas la réintervention fut pratiquée après une parathyroïdectomie subtotale qui avait été d'abord suivie de succès et il fut alors trouvé des fragments résiduels hypertrophiques et une parathyroïde en surnombre. Sept patients subirent une parathyroïdectomie totale avec réimplantation parathyroïdienne immédiate dans 5 cas. Chez 5 sujets une réintervention concernant la greffe fut nécessaire mais c'est seulement chez 3 d'entre eux que fut constaté l'hypertrophie des fragments greffés. Dans 3 cas l'autogreffe secondaire fut réalisée avec du tissu conservé par le froid. L'analyse de ces cas démontre la difficulté de localiser les sites uniques et multiples où siègent les éléments hyperfonctionnels et ce malgré la mise en oeuvre de nombreuses techniques de diagnostic. Actuellement sur le plan pratique les auteurs essaient de réséquer la totalité du tissu parathyroïdien lorsqu'ils réinterviennent pour traiter l'hyperparathyroïdisme récidivant. S'il en résulte un hypoparathyroïdisme ils procèdent alors à une autre transplantation à l'aide de tissu conservé par le froid.
    Abstract: Resumen La paratiroidectomía (PTx) en pacientes urémicos sólo se realiza en caso de hiperparatiroidismo severo. En algunos casos la PTx puede resultar insuficiente o, por el contrario, dar lugar a hipoparatiroidismo manifiesto. La recurrencia del hiperparatiroidismo siempre es posible debido a la falla renal persistente, lo cual puede requerir reoperación. En el presente trabajo presentamos los resultados en 25 reoperaciones realizadas en 21 pacientes que son parte de una serie de 248 casos operados por hiperparatiroidismo secundario. Nueve pacientes tuvieron la PTx inicial en otra institución. Seis pacientes fueron reoperados después de una cirugía inicial que resultó incompleta al dejar una a 3 glándulas en su lugar. En 7 casos la reoperación fue realizada después de una PTx subtotal inicialmente exitosa. En estos casos encontramos remanentes hipertróficos, y una glándula supernumeraria en un paciente. Siete pacientes recibieron PTx total con reimplantación inmediata de paratiroides en 5 casos. La reoperación sobre el transplante fue juzgada como necesaria en 5 pacientes, aunque solo se observó hipertrofia de los fragmentos transplantados en 3 de ellos. En 3 casos se realizó autotransplante secundario usando tejido criopreservado. El análisis de nuestros casos demuestra las dificultades en localizar una fuente única o múltiple de superproducción de hormona paratiroidea a pesar de la disponibilidad de numerosos métodos de diagnóstico. Desde el punto de vista práctico, actualmente nosotros tratamos de resecar todo el tejido paratiroideo en casos de reoperación por hipertiroidismo recurrente. Si este procedimiento resulta en hipoparatiroidismo, o si se presenta hipoparatiroidismo inesperado, procedemos entonces con un autotransplante tardío de paratiroides utilizando tejido criopreservado.
    Notes: Abstract Parathyroidectomy (PTx) in uremic patients is only performed in case of severe hyperparathyroidism. In some instances, PTx may be either insufficient or, on the contrary, lead to intolerable hypoparathyroidism. Recurrence is always possible because of persistent renal failure. Reoperations may, therefore, be necessary. We report here on 25 reoperations done in 21 patients who are part of a series of 248 patients operated on for secondary hyperparathyroidism. Nine patients had initial parathyroidectomy (PTx) at another institution. Six patients underwent reoperation after initial surgery, which was incomplete leaving 1–3 glands in place. In 7 patients reoperation was done after initially successful, subtotal PTx. In these we found hypertrophic remnants and a supernumerary gland in 1. Seven patients had total PTx, with immediate parathyroid reimplantation in 5 instances. Reoperation on the graft was judged necessary in 5 patients, but hypertrophy of grafted fragments was observed in only 3 of them. In 3 patients secondary autografting was performed with cryopreserved tissue. The analysis of our cases shows the difficulties of localizing unique or multiple sites of parathyroid hormone overproduction despite the availability of many diagnostic approaches. From a practical point of view, we try at present to resect all parathyroid tissue in case of reoperation for recurrent hyperparathyroidism. If hypoparathyroidism results by this procedure or in case of hypoparathyroidism obtained unexpectedly, we then proceed to delayed parathyroid autotransplantation with cryopreserved tissue.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 10 (1996), S. 348-350 
    ISSN: 1432-198X
    Keywords: Hyperparathyroidism ; Parathyroid hormone ; Skeletal resistance ; Parathyroid hormone receptor ; Renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic renal failure is characterized by a resistance to the hypercalcemic action of parathyroid hormone (PTH). This resistance probably involves several mechanisms, including a disturbance of vitamin D metabolism, a desensitization of the skeleton by high PTH levels, hyperphosphatemia, uremic toxins, and acidosis. We have explored the possibility that a downregulation of the recently cloned PTH/PTHrp receptor might also be involved. We found a marked decrease in the expression of the receptor mRNA in the kidney and the bone of uremic rats; other authors have found a decrease in the heart and the liver. The reduced expression in the kidney was accompanied by a diminished stimulability of renal adenylate cyclase activity, suggestive of a functional depression of the hormonal response in this target tissue. It is probable that the downregulation of the PTH/PTHrp receptor plays an important role in the skeletal resistance to the calcemic effect of PTH in chronic renal failure.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 10 (1996), S. 348-350 
    ISSN: 1432-198X
    Keywords: Key words: Hyperparathyroidism ; Parathyroid hormone ; Skeletal resistance ; Parathyroid hormone receptor ; Renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Chronic renal failure is characterized by a resistance to the hypercalcemic action of parathyroid hormone (PTH). This resistance probably involves several mechanisms, including a disturbance of vitamin D metabolism, a desensitization of the skeleton by high PTH levels, hyperphosphatemia, uremic toxins, and acidosis. We have explored the possibility that a downregulation of the recently cloned PTH/PTHrp receptor might also be involved. We found a marked decrease in the expression of the receptor mRNA in the kidney and the bone of uremic rats; other authors have found a decrease in the heart and the liver. The reduced expression in the kidney was accompanied by a diminished stimulability of renal adenylate cyclase activity, suggestive of a functional depression of the hormonal response in this target tissue. It is probable that the downregulation of the PTH/PTHrp receptor plays an important role in the skeletal resistance to the calcemic effect of PTII in chronic renal failure.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0827
    Keywords: SHR-WKY rats ; Calcium ; Calcitriol ; Intestine ; Calbindin ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary the response pattern of plasma calcitriol level and related intestinal adaptation to short-term moderate calcium (Ca) restriction was examined in adolescent male, spontaneously hypertensive rats (SHR) and normotensive WKY control rats. Twelve-week-old SHR and WKY fed a low (0.1%) Ca diet for 3, 6, or 12 days were compared with rats of either strain fed a normal (1.0%) Ca diet. Plasma calcitriol response was measured and duodenal adaptation to Ca restriction was investigated by evaluating active Ca transport, calbindin-D9K (CaBP9K) protein, CaBP9k mRNA, and alkaline phosphatase activity (ALP). Under the normal Ca diet, no significant difference between strains was observed for all five parameters. In response to the low Ca diet, the SHR and WKY showed a similar increase (nearly 50%) in plasma calcitrol, starting at day 3 of this diet. However, only the WKY displayed the expected duodenal adaptation: active Ca transport increased at day 6 and CaBP9K as well as ALP increased at day 3 of the low Ca diet. The stimulation of the latter three parameters was maintained until day 12 of Ca restriction. Moreover, CaBP9K mRNA was increased in WKY after 3 days of Ca restriction. In contrast, the SHR had either no or only a minor increase of duodenal parameters in response to Ca restriction. Finally, a significant and positive correlation between Ca transport and plasma calcitriol and between Ca transport and CaBP9K was found in WKY but not in SHR. In conclusion, this study showed that the adolescent SHR was able to increase calcitriol production but unlike the WKY, it failed to fully adapt at the intestinal target level during a 12-day low Ca diet. Thus, our results provide further evidence for an impairment of the vitamin D endocrine system in adolescent SHR as demonstrated by an abnormal intestinal responsiveness to circulating calcitriol during moderate, short-term Ca restriction.
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  • 8
    ISSN: 1432-2013
    Keywords: Albumin loading ; Parathyroid hormone ; Rat jejunum ; Na and Ca transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preferential plasma volume expansion by infusion of hyperoncotic albumin solution dialyzed against distilled water (calcium-poor albumin) decreases sodium reabsorption in the dog proximal renal tubule during hydropenia. No such decrease is observed when infusing a calcium-rich hyperoncotic albumin solution. A possible role of parathyroid hormone (PTH) has been postulated. To investigate whether similar changes could be observed in intestinal electrolyte and water absorption, the effects of systemic hyperoncotic albumin infusion on jejunal transport of water, sodium, and calcium were studied in hydropenic rats by perfusing proximal jejunum in situ. It was further sought whether PTH could play a direct role in jejunal electrolyte and water transfer. Following infusion of calcium-poor, sodium-poor hyperoncotic albumin solution (group I), net jejunal absorption of water, sodium, and calcium decreased significantly when compared to control. Concurrently, lumen-to-mucosa (1-m) calcium flux, measured using 45 Ca, diminished significantly. Following infusion of calcium-rich, sodium-poor hyperoncotic albumin solution (group II), no changes in net or unidirectional fluxes were observed. After infusion of calcium-rich, sodium-rich hyperoncotic albumin solution (group III), net jejunal absorption of water and sodium, but not of calcium, were found significantly decreased when compared to control. Plasma ionized calcium increased 10 min after calcium-rich hyperoncotic albumin loading, but decreased significantly at that time when the calcium-poor hyperoncotic albumin solution was infused. However, 30 min after each of the calcium-rich and calcium-poor albumin infusion, plasma ionized calcium was increased in both groups of rats. Plasma immunoreactive PTH was unchanged 30 min after expansion with the calcium-rich solution but it increased significantly after expansion with the calcium-poor solution. Intravenous infusion of bovine PTH (group IV) resulted in a decrease of net jejunal water, sodium, and calcium flux. The decrease in net calcium transport was accompanied by a decrease in 1-m calcium flux. No such changes were observed when PTH was replaced by vehicle (group V). It is concluded that: (1) hyperoncotic albumin infusion induces jejunal water, sodium, and calcium flux changes dependent on the calcium and sodium content of the infused solution: calcium-poor, sodium-poor hyperoncotic albumin infusion leads to a decrease in net jejunal electrolyte and water absorption possibly via stimulation of PTH secretion; (2) sodium-poor hyperoncotic albumin infusion does not modify per se these fluxes in the hydropenic rat; (3) exogenous PTH infusion as well as endogenous stimulation of PTH secretion results in a comparable decrease of jejunal water, sodium, and calcium absorption.
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  • 9
    ISSN: 1432-2013
    Keywords: Sorbitol ; d-Alanine ; Ca uptake ; Ileal cells ATP ; Ca channel blockers ; Calmodulin antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of sorbitol on Ca uptake by isolated ileal epithelial cells was investigated. Intestinal cells were isolated from rat ileum by mechanical vibration.45Ca uptake was approximately 2 times higher in cells exposed to 200 mM sorbitol ofd-alanine than in control cells. This enhancing effect of sorbitol on percentage Ca uptake decreased with increasing Ca concentrations in the incubation medium suggesting an effect on Ca entry velocity. The addition of 10 μM nifedipine or 200 μM verapamil to the incubation medium was devoid of any effect on Ca uptake in ileal cells, whereas 100 μM trifluoperazine or chlorpromazine abolished the stimulatory effect of sorbitol. Finally, the effect of sorbitol on isolated cells was independent of a measurable change of cellular ATP content. In conclusion, the stimulatory effect of sorbitol on ileal Ca uptake is probably exerted through mechanisms other than an increase in intracellular ATP concentration. Sorbitol may enhance enterocyte Ca transport via a direct interaction with calmodulin and/or the Ca pump. It may also exert its effect through an inhibition of the basolateral Na Ca exchanger.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of bone and mineral metabolism 12 (1994), S. S87 
    ISSN: 1435-5604
    Keywords: PTH/PTHrP receptor ; uremia ; secondary hyperparathyroidism ; PTH/PTHrP receptor mRNA expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Resistance to the action of PTH has been well characterized in the setting of chronic renal failure. Most evidence points to post-receptor abnormalities in its pathogenesis. The recent cloning of the PTH/PTHrP receptor (PTH-R) has permitted us to examine whether in a 5/6 nephrectomy rat model (CRF) the expression of the PTH-R gene is modified. First, we have found that the renal PTH-R mRNA expression is markedly decreased in CRF compared to normal rats. Diminished PTH-R transcripts were associated with a lower PTH-induced cAMP production in renal membranes in CRF suggesting a decrease in the PTH-R number or post-receptor modifications. Second, thyroparathyroidectomized (TPTX) rats with normal renal function had no change in the renal PTH-R expression whereas TPTX-CRF rats still showed a decreased renal PTH-R mRNA expression suggesting that high plasma PTH levels were not etiologically important in the observed down-regulation. Despite the renal PTH-R down-regulation, CRF rats had a normal renal handling of calcium. They also had a higher phosphate excretion than control rats. TPTX-CRF rats showed a decrease in renal tubular calcium reabsorption and a phosphate retention when compared with CRF animals with intact parathyroid glands. This suggests that a few available PTH-R in the kidney allow PTH to exert, to a certain extent, its physiological role in this experimental model of uremia. In conclusion, these findings indicate a down-regulation of the renal PTH-R expression in CRF which appears to be independent of parathyroid gland function. The relevance of this phenomenon in the setting of the secondary hyperparathyroidism of uremia remains to be elucidated.
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