RESUMO
Therapy with foscarnet is associated with acute renal failure. Prior studies have emphasized foscarnet's proximal tubular toxicity, but there have been isolated reports of foscarnet-induced nephrogenic diabetes insipidus. As a phosphate analog, foscarnet is a competitive inhibitor of NaPO4 cotransport. However, foscarnet's effect on antidiuretic hormone (ADH)-induced transport has not been previously investigated. We studied foscarnet's modulation of transport in the toad urinary bladder. Foscarnet at 10 microM to 10 mM did not alter basal water or urea flux. Urea transport induced by a maximal dose of ADH (24 mIU/ml) was inhibited by 0.1 to 5.0 mM foscarnet. In tissues challenged with 0.5 to 1.0 mIU of ADH per ml, 1.0 to 10 mM foscarnet increased water flow but did not alter urea flux. Foscarnet also increased water flow induced by 1.0 to 10 microM forskolin. In tissues pretreated with 10 microM naproxen, foscarnet did not alter water flow induced by 0.5 to 1.0 mIU of ADH per ml or forskolin. These results indicate that foscarnet stimulates water flow induced by 0.5 to 1.0 mIU of ADH per ml at a site proximal to that of the generation of cyclic AMP and inhibits urea flux induced by a maximal dose of ADH at a separate site. In humans, foscarnet nephrotoxicity is likely not limited to the proximal nephron, but extends to the collecting duct. Patients receiving foscarnet should be closely monitored for disorders of urinary concentration.
Assuntos
Antivirais/farmacologia , Foscarnet/farmacologia , Vasopressinas/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Bufo marinus , Inibidores de Ciclo-Oxigenase/farmacologia , Feminino , Técnicas In Vitro , Naproxeno/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiologiaRESUMO
A 40-year-old man had enlarging painful gluteal masses that developed after 17 years of hemodialysis. Pathologic examination revealed extensive deposition of beta 2-microglobulin amyloid. A bladder biopsy done during evaluation for possible transplantation also showed amyloid deposits. This constellation of findings has not been reported in a patient with beta 2-microglobulin amyloidosis. Patients with dialysis-related amyloidosis should be carefully assessed for systemic involvement. Renal transplantation may prevent further amyloid deposition and provide relief of pain.
Assuntos
Amiloidose/etiologia , Nádegas , Diálise Renal/efeitos adversos , Adulto , Amiloidose/metabolismo , Humanos , Masculino , Bexiga Urinária/metabolismo , Microglobulina beta-2/metabolismoAssuntos
Estro , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Proestro , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/sangue , Fenobarbital/farmacologia , Adeno-Hipófise/metabolismo , Gravidez , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
We have examined the contribution of gonadostatin to the control of gonadotropin secretion throughout the rat estrous cycle. The estrous cycle was simulated in rats ovariectomized on diestrus-1, designated day 1 (D-1) by use of low or high level estradiol and progesterone Silastic implants. The steroid implant regimen simulated the major changes of these hormones in the blood during the course of the estrous cycle. Injections of porcine follicular fluid (pFF) were superimposed on this steroid regimen. Four treatment combinations of steroid and pFF or their controls were tested: 1) steroid implants only, 2) pFF only at a constant dose level, 3) steroid implants and pFF injections at a constant dose level, and 4) steroid implants and pFF injections with reduced levels on simulated proestrus. In group 1 both basal and surge release of LH were similar to those in the intact rat, but both basal and surge release of FSH were significantly elevated above levels observed in the intact rat for the respective periods. In group 2 FSH was suppressed to diestrous levels throughout the course of the experiment, with no surge occurring on D-3. Serum LH levels were slightly elevated above diestrous levels (50-150 ng/ml) with no surge. In group 3 serum levels of both gonadotropins were suppressed to diestrous levels on D-1 and D-2, and a steroid-induced, pFF-attenuated surge occurred on the afternoon of D-3. Group 4 had, with a minor variation, proestrous-like FSH and LH surges on D-3 and basal (diestrous) gonadotropin levels during simulated D-1, D-2, and early proestrus. This study supports previous evidence for estradiol and progesterone control of LH secretion and elaborates the control of FSH secretion. The role of gonadostatin and steroids is demonstrated in the negative feedback regulation of FSH secretion.
Assuntos
Castração , Estro/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Luteinizante/sangue , Proteínas/farmacologia , Animais , Preparações de Ação Retardada , Estradiol/administração & dosagem , Estradiol/sangue , Estradiol/farmacologia , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Inibinas , Gravidez , Progesterona/sangue , Ratos , Ratos Endogâmicos , Fatores de TempoAssuntos
Estradiol/farmacologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/fisiologia , Hormônios Inibidores da Liberação de Hormônio Hipofisário/farmacologia , Animais , Castração , Estradiol/sangue , Retroalimentação , Feminino , Hormônio Foliculoestimulante/sangue , Cinética , Hormônio Luteinizante/sangue , Ratos , Ratos Endogâmicos , SuínosAssuntos
Estradiol/farmacologia , Estro/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Luteinizante/sangue , Proteínas/farmacologia , Animais , Castração , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Inibinas , Fenobarbital/farmacologia , Gravidez , Ratos , SuínosAssuntos
Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hipófise/efeitos dos fármacos , Hormônios Liberadores de Hormônios Hipofisários/farmacologia , Hormônios Testiculares/farmacologia , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Folículo Ovariano , Hipófise/metabolismo , RatosRESUMO
Bovine adenhypophysial tissue was dissociated by sequential enzymatic incubation in a continuous flow system. Dispersed cells separated into discrete fractions after centrifugation in isopycnic bovine serum albumin gradients. The dispersed and separated cells were prepared for microscopic identification and differential counts by centrifugal cytology. Radioimmunoassays for LH, FSH, TSH, and Prl were used to corroborate the differential counts and determine the homogeneity of the fractions. The thyrotrophs banded at an average density (rho) of 1.0417, the FSH-secretory cells at rho = 1.0597, the LH-secretory cells at rho = 1.0458, and the Prl-secretory cells at rho = 1.0126. A 7-16 fold enrichment of different cell populations was possible. In bovine hypophyses each hormone appears to be formed by specific cells: the average TSH concentrations of the thyrotrophs were 5.1 pg/cell for LH- and FSH concentration were 4.7 and 4.9 pg/cell for LH- and FSH-secreting cells, respectively. The average Prl concentration was 4.9 pg/cell for Prl-secreting cells.
Assuntos
Adeno-Hipófise/citologia , Animais , Bovinos , Separação Celular , Centrifugação Isopícnica , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Masculino , Adeno-Hipófise/metabolismo , Prolactina/metabolismo , Tireotropina/metabolismoRESUMO
By studying the metabolic values of a nondiabetic and diabetic uremic population we demonstrated the following: 1. Insulin is higher in diabetic than nondiabetic uremic patients. A slight arteriovenous difference across the dialyzer membrane suggests that insulin is dialyzable in small amounts in man. 2. C-peptides are highest in nondiabetics, lower in maturity onset diabetics, and lowest in juvenile diabetics. 3. Growth hormone is higher in diabetics than nondiabetics, decreased in both groups during hemodialysis, and returns to pre-dialysis levels 2 hrs after the completion of dialysis treatment. 4. Plasma triglycerides are elevated in both popualtions during the fasting state anddrop during hemodialysis, rising slowly towards the end of hemodialysis. 5. The majority of diabetics on hemodialysis have low renin levels and do not respond to volume reduction. In the high renin diabetics and high and low renin nondiabetics the plasma renin levels rise in response to volume reduction during hemodialysis. Renin is not dialyzable in man. 6. Thyroid function tests show that diabetic and nondiabetic patients have measurements in the low normal range. Our results reveal significant information concerning metabolic changes which take place in diabetic and nondiabetic uremic patients on hemodialysis and helps to characterize these populations. This report may have implications in better understanding the nature of the problems encountered in these populations and in their management (Table III).