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Biomedical subjects

K Hruska

Publications and source records attributed to K Hruska.

At least 19 recordsLinked to original sources
PubMed1990

PTH receptor coupling to phospholipase C is an alternate pathway of signal transduction in bone and kidney.

The parathyroid hormone (PTH) receptor is coupled via a guanine nucleotide-binding regulatory protein (G protein) to phospholipase C (PLC). Binding of PTH to its receptor leads to activation of PLC with the subsequent hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 generation leads to the release of intracellular calcium stores, which produces an increase in the intracellular calcium concentration. DAG activates protein kinase C (PKC). Both IP3 metabolites and PKC may play a role in returning the intracellular calcium concentration back to base line, by stimulating the movement of calcium from the intracellular to the extracellular compartment, as well as by sequestering calcium within intracellular organelles. PKC appears to be important in the development of desensitization and downregulation of the PTH receptor to PTH. Activation of PLC may be important in modulating the well-known effects of PTH on bone and kidney and also may be relevant to recently described actions, such as the possible role of PTH as a growth factor in skeletal tissue. Important issues that need to be addressed in this field include 1) characterization of the PTH receptor, 2) the possible role of low-molecular-weight G proteins in PTH signal transduction, and 3) further description of the role of alternate pathway signal transduction in producing the effects of PTH.

Animals↗
PubMed1990

Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) is a heterogeneous disorder frequently observed in patients with nephrolithiasis. At one extreme of its clinical spectrum is fasting hypercalciuria (FH), a condition characterized by increased bone resorption and turnover. In previous studies we have shown that monocytes from patients with high turnover osteoporosis and from women in early postmenopause elaborate increased amounts of interleukin-1 (IL-1), a cytokine that stimulates bone resorption in vitro and in vivo. Since IL-1 could also mediate the resorptive mechanism of FH and cause a clinically significant bone loss, we have studied the relationship of IH, vertebral mineral density, bone turnover, and monocyte IL-1 activity in 47 patients with absorptive hypercalciuria (AH), 23 with FH, and 38 nonhypercalciuric subjects with recurrent nephrolithiasis (controls). Vertebral mineral density, as measured by quantitative computer tomography, was decreased in each of the three patient groups, but was significantly lower in FH patients than in AH patients or control subjects. Twenty-four-hour total urinary hydroxyproline excretion was increased in FH patients compared to that in AH patients or controls, but blood levels of osteocalcin were not. Monocytes from FH subjects yielded significantly more IL-1 (alpha + beta) activity than those from AH patients or controls; levels of IL-1 activity in monocytes of AH and control patients were similar. In IH subjects, significant correlations were found between IL-1 and hydroxyproline (r = 0.70; P less than 0.0001), IL-1 and quantitative computer tomography values (r = -0.49; P less than 0.005), and IL-1 and urinary calcium (r = -0.36; P less than 0.05). Serum PTH levels were within normal limits in all subjects and were similar in the three study groups, 1,25-Dihydroxyvitamin D3 levels, although higher in IH patients than in controls, were not significantly different in FH and AH subjects. Increased IL-1 activity and decreased vertebral mineral density are features of a subset of patients with IH. Although a cause-effect relationship remains to be established, increased monocytic IL-1 activity, rather than elevated PTH or 1,25-dihydroxyvitamin D3 levels, could underlie the resorptive component of FH.

Adult↗
PubMed1988

Characterization of a (Ca2+ + Mg2+)-ATPase system in the osteoblast plasma membrane.

A high affinity, calmodulin-sensitive (Ca2 + Mg2+)-ATPase was demonstrated in the plasma membrane preparation of three different osteosarcoma cell lines previously demonstrated to respond to parathyroid hormone with an increase in cytosolic calcium and a decrease in pH. The maximal velocity of the enzyme activity in the membrane preparations ranged from 0.83 to 2.42 nmol Pi released per min per mg protein with half-saturation constants of 26 nM of free Ca. The enzyme activity was not affected by Na+, K+, ouabain and azide, and exhibited an absolute requirement for Mg2+ ions. These results suggest a possible role for a membrane Ca2 + Mg2+-ATPase in initiating and perpetuating the ionic control of osteoblastic function.

Animals↗
PubMed1979

[Effect of chorionic gonadotropin administration on the concentration of testosterone in the blood of boars].

In intact boars, intravenous administration of 100 to 6000 I. U. chorionic gonadotropin elicited a pronounced rise in the plasma level of testosterone, depending on the time interval from the administration of chorionic gonadotropin and on the size of the administered dose. In the blood of castrated boars such an application of choronic gonadotropin did not influence the concentration of testosterone. It was inferred that the rise in the levels of blood testosterone in boars after administration of chorionic gonadotropin was specific for testicular incretion and indicated the endocrine reserve of the testes. There is a discussion concerning the importance of the functional testing of the incretion capacity of testes for differential diagnosis different forms o incretion hypogonadism.

Animals↗
PubMed1978

[Variation of the serum testosterone level in boars during 24 hours and during a period of several days].

Seven sexually mature boars were studied in two-hour intervals for 8 to 32 hours, as to the variation of testosterone levels in the blood plasma. Blood samples were obtained by means of a cannula inserted in the v. cava cranialis. The hormone level under study showed marked fluctuation. The coefficient of variation of testosterone concentration ranged from 12.7% to 35.2% in the individual animals and for the whole part of the study it was 33.0%. It appeared impossible to derive seriously any regular periodicity of testosterone concentration in boar blood in the 24-hour period from the analysis of the variation of the levels of the hormone in individual animals during the period under study. Further, the study revealed a marked fluctuation of testosterone levels in the blood plasma of twelve sexually mature boars in the course of several days' study. The coefficient of variation of testosterone concentration in individual animals ranged from 18.1% to 106.5%, reaching 77.0% for the whole part of study. The analysis of variance showed statistically significant differences of hormonal levels in individual boars in which the fluctuation of testosterone was studied in the 8- to 32-hour period as well as in several days' period. This proved the role of the animals' individuality in determining the concentration of testosterone in their blood. The discussion concerns the importance of these findings for the evaluation of the role of basal testosterone levels in the blood in classifying the incretion function of the gonads and in the diagnosis of incretion hypogonadism of boars.

Age Factors↗
PubMed1978

[Effect of bilateral orchidectomy on serum testosterone levels in boars].

Bilateral orchidectomy caused a marked decrease in the concentration of testosterone in the bood plasma of boars already in the early post-castration stage of three hours after the operation. In the period from 3 to 207 days after castration, the pre-operation levels of plasma testosterone decrease by 84.4%, on an average. Adreno-cortical compensation of the concentration of the hormone did not occur in the post-castration period. The conclusion is that the levels of testosterone in the blood of boars are mostly of testicular origin and can be considered as the main criterion of the incretion function of the testes. The discussion concerns the practical importance of the determination of testosterone levels in the blood of boars for clinical evaluation of the hormonal function of the testes and for diagnostics of incretion hypogonodism.

Animals↗
PubMed1977

Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog.

Previous studies from this laboratory demonstrated that secondary hyperparathyroidism in dogs with chronic renal disease may occur, at least in part, as a consequence of the need for progressive adaptation in renal phosphorus (P) excretion that occurs as glomerular filtration rate falls. However, the studies were of relatively short duration. Moreover, no information emerged regarding a potential role of calcium malabsorption in the pathogenesis of secondary hyperparathyroidism. The short duration of the protocol did not lend itself to the study of the effect of P control or the administration of vitamin D in the pathogenesis of renal osteodystrophy. In the present studies, 14 dogs with experimental chronic renal disease were studied serially for a period of 2 yr. Each animal was studied first with two normal kidneys on an intake of P of 1,200 mg/day. Then, renal insufficiency was produced by 5/6 nephrectomy. The dogs then were divided into three groups. In group I, 1,200 mg/day P intake was administered for the full 2 yr. In group II, P intake was reduced from the initial 1,200 mg/day, in proportion to the measured fall in glomerular filtration rate, in an effort to obviate the renal adaptation in P excretion. In group III, "proportional reduction" of P intake also was employed; but in addition, 20 mug of 25(OH)D(3) were administered orally three times a week. In group I, parathyroid hormone (PTH) levels rose throughout the 2-yr period reaching a final concentration of 557+/-70 U (normal 10-60). In group II, values for PTH remained normal throughout the 1st yr, increased modestly between the 12th and the 18th mo, but then did not rise after the 18th mo. In group III, no elevation of PTH levels was observed at any time; however, these animals were hypercalcemic. Histomorphologic analyses of the ribs of these dogs were performed serially throughout the 2-yr period. A linear relationship was obtained between the osteoclastic resorption surface and the concentration of circulating immunoreactive PTH. The osteoid volume was greater in group I animals when compared to those in group II. None of the morphologic abnormalities associated with renal osteodystrophy were observed in the animals in the third group.

Animals↗
PubMed1977

Ischemic bowel disease following bilateral nephrectomy or renal transplant.

In a 2 year period five patients developed pathologically proved ischemic bowel disease (IBD) following either renal transplantation or bilateral nephrectomy in preparations for transplantation. This entity accounted for 42% of all major gastrointestinal complications in this transplant unit. Three patients presented with abdominal pain and ileus, and two patients developed massive lower gastrointestinal hemorrhage. All five patients had nonocclusive ischemic disease because obstruction of a major intestinal vessel could not be documented in any case. Each patient was treated with bowel resection and three of the five patients survived. Although sepsis, shock, and large doses of immunosuppressive drugs have been implicated in predisposing such patients to IBD, these factors were not uniformly present in our cases. Blood volume redistribution with transient episodes of hypotension, especially during postoperative hemodialysis, may be significant. IBD in uremic patients can occur in the presence or absence of renal transplantation and may be the cause of massive intestinal hemorrhage in these individuals.

Adult↗
PubMed1977

Hyperphosphatemia.

Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.

Acromegaly↗
PubMed1976

Selective uptake of intact parathyroid hormone by the liver: differences between hepatic and renal uptake.

Hepatic and renal extraction of immunoreactive parathyroid hormone (i-PTH) was studied in awake dogs with explanted kidneys and chronic indwelling hepatic vein catheters. After a single injection of bovine PTH 1-84 (b-PTH 1-84), hepatic arteriovenous (A-V) differences for immunoreactive PTH (i-PTH) was 39% at 2 min after injection but decreased to 0% by 25 min, despite high levels of i-PTH in the arterial circulation. Gel filtration of arterila and hepatic venous samples obtained when hepatic A-V differences for i-PTH were demonstrable revealed hepatic uptake of the intact hormone and addition of a smaller COOH-terminal fragment, eluting just after the intact hormone, to the hepatic venous blood. Gel filtration of samples obtained 20-30 min after injection of b-PTH was demonstrable) revealed no detectable intact hormone in the circulation. Levels of COOH-terminal fragments of the hormone at the time were identical in arterial and hepatic venous samples. In additional experiemtns no hepatic A-V difference was observed after the injection of the synthetic bovine PTH 1-34 (syn b-PTH 1-34). By comparison there was a demonstrable A-V difference of 20% across the kidney for both intact PTH and COOH-terminal fragments that persisted until i-PTH disappeared from the circulation. The kidney also demonstrated an A-V difference of 22% after injection of syn b-PTH 1-34. These studies demonstrate selective extraction of intact PTH but not of its fragments by the liver. The kidney, on the other hand, extracted the intact hormone and both COOH and NH2 terminal fragments. The studies demonstrate that the kidney was the only organ of those examined that detectably removed the fragments of PTH from the circulation.

Animals↗
PubMed1976

[Concentration of testosterone in the blood of sexually immature boars after stimulation with chorionic gonadotropin].

Levels of testosterone concentration in blood increased significantly in sexually immature boars after application of chorionic gonadotropin. Existence of considerable function reserve and readines of the incretion component of gonads were proved in sexually immature boars. The paper discusses a possibility of utilizing this phenonmenon in diagnostics of disorders of the incretion testicular function in individuals of the animal species under study in their pre-puberal age.

Animals↗
PubMed1975

Effect of 25-hydroxycholecalciferol on calcium absorption in chronic renal disease.

Calcium absorption was measured in eight uremic patients before and after eight days of treatment with 100 or 500 mug of 25-hydroxycholecalciferol (25(OH)D3) per day. Fractional calcium absorption was estimated by administering 47Ca i.v. and orally on separate days and counting forearm radioactivity four hours later. Calcium absorption in four patients with residual renal function rose from 16.3 +/- 2.5 to 40.8 +/- 5.5% after treatment. In order to determine if the increased calcium absorption was mediated by an increase in the production of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) by virtue of increased substrate delivery to the 25-hydroxycholecalciferol-1-hydroxylase system present in the residual renal tissue, identical studies were performed in four anephric patients. Calcium absorption in these patients averaged 15.7 +/- 2.2% during the control period and rose to 46.0 +/- 11.1% after treatment. Increments in serum calcium after treatment were similar in both groups of patients; the mean concentration rose from 9.6 +/- 0.3 to 11.0 +/- 0.6 mg/100 ml. The results indicate that 25(OH)D3 can improve calcium absorption in the absence of renal tissue suggesting that its conversion to 1,25(OH)2D3 may not be necessary for its effect on the gastrointestinal tract in the uremic patient.

Absorption↗