Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of the antifungal drug ketoconazole reduces serum 1,25-dihydroxyvitamin D (1,25-D) levels in normal subjects. To determine whether a similar effect occurs in hypercalcemic patients, ketoconazole (200 mg every 8 h for 7 days) was given to nine patients with confirmed primary hyperparathyroidism, three patients with probable primary hyperparathyroidism who were awaiting surgery, and three patients with mild hypercalcemia of uncertain etiology who were being followed. Ketoconazole administration led to a significant reduction in mean serum 1,25-D levels in the hypercalcemic patients [basal, 64 +/- 7 (+/- SEM) pg/mL (154 +/- 17 pmol/L) vs. 36 +/- 5 pg/mL (86 +/- 12 pmol/L) after ketoconazole; P less than 0.001]. Serum total calcium fell slightly but significantly [basal, 11.05 +/- 0.17 mg/dL (2.76 +/- 0.04 mmol/L) vs. 10.77 +/- 0.16 (2.69 +/- 0.04 mmol/L) after ketoconazole; P less than 0.02], but the falls in total serum calcium and serum 1,25-D after ketoconazole treatment were not correlated with one another. Ketoconazole administration did not alter serum ionized calcium, 25-hydroxyvitamin D, phosphate, alkaline phosphatase, or PTH concentrations or urinary cAMP excretion. The responses to ketoconazole were similar in all three patient subgroups. We conclude that short term administration of ketoconazole to hypercalcemic patients causes a substantial fall in serum 1,25-D and a small fall in total serum calcium. These effects render ketoconazole a potentially useful agent for investigation of the importance of 1,25-D in patients with hypercalcemic disorders and for their treatment.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients. 336 Sep 1

Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 +/- 26 U/l (means +/- SEM) to 103 +/- 10 U/l after 6 months (nl less than 120 U/l). Urinary excretion of hydroxyproline decreased immediately and became normal (nl less than 2.3 mumol/lGF) as a mean at day 5 (from 4.6 +/- 0.4 mumol/lGF to 2.1 +/- 0.3 mumol/lGF). Thereafter it remained within the normal range (2.0 +/- 0.2 mumol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.
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PMID:Paget's disease of bone treated in five days with AHPrBP (APD) per Os. 345 56

Serum osteocalcin (BGP) is a new marker of bone turnover that reportedly evaluates bone formation. Thus, its measurement could assess the bone formation rate in tumor-associated hypercalcemia. We measured concentrations of BGP and other parameters of bone metabolism in 54 untreated hypercalcemic cancer patients as compared to 109 healthy subjects. Primary tumor sites were breast (19), lung (11), head and neck (6), multiple myeloma (3), kidney (2), and various (11) or multiple (2). Mean BGP levels were higher in the hypercalcemic subjects, 4.6 +/- 0.4 (SEM) ng/ml, than in the normal subjects, 3.6 +/- 0.1 ng/ml (p less than .05), and were normalized in the 22 patients who could be reevaluated after successful treatment of hypercalcemia with intravenous aminohydroxypropylidene diphosphonate (APD). There was no correlation of BGP levels with age, sex, or renal function. Compared with the Gaussian distribution in the normal subjects, there was a considerable scatter of the data in hypercalcemic patients, suggesting the existence of defined subgroups with abnormally low or abnormally high values. However, we found no significant relationship of BGP concentrations with tumor site or histology or with bone metastatic involvement. We found also no significant correlation between concentrations of serum BGP and total or ionized calcium, alkaline phosphatase, parameters of bone resorption, and indices of parathyroid function. In summary, serum BGP levels were slightly elevated in tumor-associated hypercalcemia and were normalized after successful treatment of hypercalcemia. More importantly, BGP concentrations varied widely even in the subgroups of patients with hypercalcemia accompanying massive bone metastatic involvement or in the patients without detectable skeletal metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum osteocalcin (BGP) in tumor-associated hypercalcemia. 350 43

The acute effects of iron therapy on zinc status during pregnancy were investigated. The 20 subjects studied were healthy and had unremarkable obstetric histories. The mean stage of gestation was 27 weeks (range 21-33 weeks). Initial hematologic indices (mean +/- SEM) were: hematocrit 36.5 +/- 0.4%, serum ferritin 32.6 +/- 6.1 ng/mL, and serum iron 117 +/- 13 micrograms/dL. Iron therapy, prescribed by the obstetric caregivers, provided a total average daily elemental iron intake of 261 mg (range 164-395 mg) from therapy and routine supplements. Laboratory studies of zinc status were obtained immediately before iron therapy and at one and four weeks thereafter. Initial plasma zinc was 62.9 +/- 2.1 micrograms/dL. A mean decline in plasma zinc of 4.0 +/- 1.8 micrograms/dL (P less than .05) was observed from baseline to one week. The decline remained statistically significant after adjustment for the expected physiologic decline over the same interval of gestation. No further decline occurred from one to four weeks. No significant treatment-related effects were observed for neutrophil zinc, mononuclear leukocyte zinc, or serum alkaline phosphatase activity. These results indicate that iron therapy in doses typically prescribed by obstetric caregivers in this country has an acute, measurable effect on maternal zinc status.
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PMID:Acute effects of iron therapy on zinc status during pregnancy. 362 28

The histochemistry and ultrastructure (SEM and TEM) of the spermatheca of Biomphalaria glabrata was investigated to elucidate the function of this organ and to compare its structure and function to similar organs found in other species. The spermatheca has a debris-filled lumen surrounded by a thin wall of tissue. The cells adjacent to the lumen are of three columnar epithelial cell types. Two cell types have abundant microvilli and mammalian cell-like organelle distribution and morphology. The above cell types differ in the electron density of their cytoplasms, nuclear morphologies, and organelle content. The third cell type differs from the other two in its cytoplasmic makeup. However, the most distinctive difference is the presence of large numbers of cilia at the apical surface with no evidence of microvilli. These columnar cells rest on a basal lamina adjacent to a two to three cell thick muscle layer. The entire organ is surrounded by an adventitia of unusual morphology. Histochemical investigation demonstrated that DNAase, RNAase, and protease are present in the lumen, alkaline phosphatase is associated primarily with the microvilli, small amounts of acid phosphatase are concentrated in the midcell area of the columnar epithelium, and ATPase activity is localized in the muscle cells and just below the absorptive surface of the microvillous cells. The luminal contents and adventitial areas are Sudan Black B positive, all areas of the lumen and organ wall are PAS positive, the cell nuclei and amorphous masses in the lumen showed Feulgen staining, and large vesicles in the columnar cells were Oil Red O positive. Apparently, the spermatheca of B. glabrata is both a digestive and absorptive structure. Although this organ shares functional similarities with those found in opisthobranchs and terrestrial pulmonates, the epithelia of the spermatheca differ dramatically in these groups.
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PMID:Structure and function of the spermatheca in a snail host of schistosomiasis, Biomphalaria glabrata. 364 39

The long-term use of glucocorticoid drugs frequently results in the development of osteoporosis. To assess the value of calcium supplementation in preventing this loss of bone, the metabolic effects of administering 1 g of elemental calcium/day have been studied in 13 steroid-treated patients. After 2 mo, the fasting urine hydroxyproline-creatinine ratio decreased from 27.1 +/- 2.5 (SEM) to 21.8 +/- 2.4 (p less than 0.001) and there was an increase in fasting urine-calcium excretion (p less than 0.05). Serum alkaline phosphatase and osteocalcin showed no change. We concluded that calcium supplementation suppresses bone resorption without detectable suppression of indices of bone formation and is, therefore, likely to result in increased bone mass. The safety and low cost of calcium make it a very suitable prophylactic agent in glucocorticoid-treated patients.
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PMID:Calcium supplements in the prevention of steroid-induced osteoporosis. 372 66

The antimycotic agent ketoconazole is known to inhibit several cytochrome P450-dependent enzymes involved in the biosynthesis of steroid hormones from cholesterol. Since 1,25-dihydroxyvitamin D is also a sterol synthesized by cytochrome P450-dependent enzymes, we assessed whether ketoconazole would lower serum 1,25-dihydroxyvitamin D levels. In nine normal men, administration of ketoconazole for 1 week in doses of 300-1200 mg/day led to a dose-dependent reduction in serum 1,25-dihydroxyvitamin D levels (r = -0.64; P less than 0.001). At the highest dose taken by each man (1200 mg/day in six, 900 mg/day in one, and 600 mg/day in two), serum levels of 1,25-dihydroxyvitamin D fell significantly compared to baseline [14 +/- 1 (+/- SEM) vs. 39 +/- 3 pg/ml; P less than 0.001), but there was no change in serum levels of 25-hydroxyvitamin D, PTH, calcium, phosphate, or alkaline phosphatase. Ketoconazole may be potentially useful in exploring the pathogenetic role of 1,25-dihydroxyvitamin D in disorders of calcium metabolism and in treatment of patients with hypercalcemic disorders or renal stone disease.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D. 375 45

Amino-hydroxy-propylidene bisphosphonic acid (APD) is a potent inhibitor of bone resorption. Its oral use in Paget's disease of bone has proved effective and safe when the drug is administered on a long-term basis. Since APD was found not to impair bone mineralization, it was assumed that a long remission would be obtained by administering a high dose of the compound over a very short period of time. Therefore, 12 patients with symptomatic Paget's disease received 1200 mg/d APD orally over 5 consecutive days. Follow-up is 2 months for all patients, 6 months for 6 patients and one year for one patient. Clinical improvement and biochemical remission were observed in all patients. Side effects were negligible (transient nausea in 2 patients and +1 degree C temperature increment noted for 2 days in 3 patients). Urinary hydroxyproline started decreasing within 2 days and became normal as a mean (+/- SEM) after 5 days (1.9 +/- 0.3 mumol/lGF, nl less than 2.3) and in all cases after 15 days. Thereafter it remained within the normal range (1.9 +/- 0.2 mumol/lGF) for 6 months. Plasma alkaline phosphatase activity fell progressively and significantly, and became normal after 1-3 months in all patients but one, a man with very active disease in whom the parameter remained slightly above normal and stable. At the end of the sixth month, mean plasma alkaline phosphatase activity was 100 +/- 13 U/l (nl less than 120 U/l). Plasma calcium and phosphate fell transiently between days 4 and 15.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Paget's disease of bone treated per os with APD in 5 days]. 379 71

Serum osteocalcin (BGP), a vitamin K-dependent gamma-carboxyglutamic acid (GLA) containing bone protein, provides an index of bone turnover in patients with a variety of metabolic bone diseases. BGP increases with increasing age in both sexes, but more so in women. BGP rises above normal when the glomerular filtration rate falls below 30 ml/min. Because of its importance in bone disease, its low mol wt, and the effect of uremia, we measured BGP by RIA in serum and dialysate fluid in patients on hemodialysis (HD) or peritoneal dialysis (PD). In 32 HD patients (22 women and 10 men), serum BGP was not different pre- and postdialysis [67.5 +/- 4.4 (+/- SEM) ng/ml vs. 67.7 +/- 5.2), but was significantly elevated compared to the level in normal subjects (7.3 +/- 0.8 ng/ml). The sex difference previously reported in normal subjects was not found in patients with renal failure. The serum BGP level in 8 PD patients was 49.4 +/- 6.9 ng/ml, with a peritoneal fluid concentration of 27.6 +/- 9.3 ng/ml. The hemodialysate fluid concentration of BGP was 1.7 +/- 0.4 ng/ml, which was significantly lower than the serum BGP levels in the HD patients, the PD patients, and peritoneal fluid (P less than 0.01). A significant correlation existed among BGP, alkaline phosphatase, immunoreactive PTH, creatinine, and blood urea nitrogen. We conclude that BGP is markedly elevated in patients with renal failure, not altered in the serum by HD or PD, but very low in HD dialysate fluid. These findings may reflect a combination of impaired clearance and increased skeletal production. The difference in clearance between the peritoneal and hemodialysis fluid is compatible with the mol wt of BGP. In 15 patients who had successful kidney transplantation, serum BGP was normal despite an elevated serum PTH level.
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PMID:Serum and dialysate osteocalcin levels in hemodialysis and peritoneal dialysis patients and after renal transplantation. 388 31

1.25-Dihydroxyvitamin D concentrations were measured in 10 preterm infants (mean gestational age 29 weeks, range 26-32; mean birthweight 1226 g, range 980-1700). Total parenteral nutrition was begun after birth and partial enteral feeding was started at 1 week of age. Total enteral feeding was achieved at a mean age of 26 days (range 16-47). The daily vitamin D3 intake was about 400 I. U. No clinical, chemical or radiological signs of rickets were observed. The mean 1.25-dihydroxyvitamin D concentration +/- SEM was 103.2 +/- 24.0 pmol/l at 1 week (range 9.6-252.0), 141.6 +/- 26.4 at 3 weeks (range 31.2-324.0), 153.6 +/- 21.6 at 6 weeks (range 67.2- 256.8), 165.6 +/- 24.0 at 9 weeks (range 74.4-307.2) and 153.6 +/- 21.6 at 12 weeks (range 76.8-268.8) postnatal age. The mean values at 6, 9 and 12 weeks were significantly higher (p resp. less than 0.01, less than 0.002 and less than 0.005) than in adults (88.8 +/- 7.2; n = 27). 1.25-Dihydroxyvitamin D concentrations were highly variable and did not correlate with 25-hydroxyvitamin D concentrations, plasma calcium and phosphorus concentrations and plasma alkaline phosphatase levels, nor with illness nor postnatal age. The data demonstrate that preterm infants are capable of producing high plasma levels of 1.25-dihydroxyvitamin D.
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PMID:Plasma 1.25-dihydroxyvitamin D concentrations in preterm infants. 392 55


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