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D T Baran

Publications and source records attributed to D T Baran.

At least 73 records · Page 4Linked to original sources
PubMed1986

Differential effects of 1,25-dihydroxyvitamin D3 on cytosolic calcium in two human cell lines (HL-60 and U-937).

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to induce maturational changes in the human promyelocytic leukemia cell line HL-60 and in the human monocytic cell line U-937. Changes in cytosolic calcium have been reported to regulate cellular processes. We used the fluorescent dye Quin 2 to examine the effects of vitamin D metabolites on cytosolic calcium levels in HL-60 and U-937 cells. 1,25-(OH)2D3 (20 nM) increases cytosolic calcium by 24% over a 5-min period in HL-60 but not in U-937 cells. 1,25-(OH)2D3 (0.2 nM and 4 nM) has no effect on cytosolic calcium levels in either cell type. 24,25-(OH)2D3 (20 nM) has no effect on cytosolic calcium in HL-60 cells. Nifedipine (1 mM) has no effect on cytosolic calcium levels over 30 min and likewise does not block the 1,25-(OH)2D3-induced increase in cytosolic calcium in HL-60 cells. However, chelation of extracellular calcium with EGTA (10 mM) blocks the 1,25-(OH)2D3-induced increment in cytosolic calcium, but does not block the 1,25-(OH)2D3-induced maturational changes in HL-60 cells. The data suggest that 1,25-(OH)2D3 but not 24,25-(OH)2D3 increases cytosolic calcium in HL-60 cells within 5 min and the increment is due to increased influx of calcium. 1,25-(OH)2D3 modifies membrane permeability to calcium independent of calcium channels sensitive to nifedipine. Finally, 1,25-(OH)2D3-induced maturational changes in HL-60 cells can take place without an increase in cytosolic calcium.

Aminoquinolines↗
PubMed1986

1,25 Dihydroxyvitamin D increases hepatocyte cytosolic calcium levels. A potential regulator of vitamin D-25-hydroxylase.

1,25 dihydroxyvitamin D (1,25(OH)2D) has been demonstrated to inhibit hepatic 25 hydroxyvitamin D (25 OHD) production. Changes in cytosolic calcium have been shown to regulate cellular processes. Using the fluorescent dye Quin 2, we have investigated the effects of 1,25(OH)2D and 24,25(OH)2D on cytosolic calcium levels in hepatocytes. 1,25(OH)2D exposure for 5 min increases cytosolic calcium levels by 24% at a concentration of 100 pg/ml, 39% at a concentration of 1 ng/ml, and 50% at a concentration of 2 ng/ml. The latter increment occurs in both the presence and absence of extracellular calcium, indicating that 1,25(OH)2D is mobilizing intracellular calcium pools. 24,25(OH)2D, 10 ng/ml, does not increase cytosolic calcium levels while the calcium ionophore A23187, 3 microM, increases levels by 52%. Calcium inhibits hepatic 25 OHD synthesis in liver homogenates in a dose-dependent fashion, which can be prevented by chelation of calcium with EGTA. 1,25(OH)2D and A23187 decrease hepatocyte 25 OHD synthesis. The inhibitory effect of A23187 can be prevented by chelation of extracellular calcium. The data demonstrate that 1,25(OH)2D increases hepatocyte cytosolic calcium, and that these increments in cytosolic calcium may regulate some of the hepatic actions of the vitamin D metabolite.

Animals↗
PubMed1985

End product inhibition of hepatic 25-hydroxyvitamin D production in the rat: specificity and kinetics.

The role of vitamin D metabolites in the regulation of hepatic 25-hydroxyvitamin D production was investigated by examining the effects of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D on the synthesis of [25-3H]hydroxyvitamin D by rachitic rat liver homogenates. Production of [25-3H]hydroxyvitamin D was inhibited by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, but not by 24,25-dihydroxyvitamin D. 25-Hydroxyvitamin D increased the Km of the vitamin D-25-hydroxylase enzyme(s), while 1,25-dihydroxyvitamin D decreased the Vmax with a Ki of 88.7 ng/ml. Inhibition of hepatic 25-hydroxyvitamin D production by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D may be another control mechanism to regulate circulating vitamin D levels.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Acute metabolic acidosis stimulates 3H-25 hydroxyvitamin D production by the rachitic rat liver.

Acute metabolic acidosis alters 1,25 dihydroxyvitamin D metabolism in experimental animals. We have used the NH4Cl-treated rachitic rat as a model to investigate the effect of acidosis on hepatic 25 hydroxyvitamin D (25 OHD) production. NH4Cl ingestion for 4 days was associated with a significant decrease in blood pH (7.44 +/- 0.03 vs 7.17 +/- 0.03, P less than 0.001) and bicarbonate (22.2 +/- 0.9 vs 10.5 +/- 1.6 mEq/liter, P less than 0.001). Acute metabolic acidosis stimulated 3H-25 hydroxyvitamin D production in liver homogenates. Acidosis resulted in a 52% decrease in Km (50.9 nM vs 24.5 nM) and an 11% decrease in the Vmax (554 picomoles/g liver protein/3 h vs 491 picomoles/g liver protein/3 h). The data collectively suggest that an acid load in vivo increases hepatic 25 OHD production and apparently enhances enzyme affinity for substrate.

Acidosis↗
PubMed1985

Inhibitory effect of maternal alcohol ingestion on rat pup hepatic 25-hydroxyvitamin D production.

The mechanisms underlying the teratogenic effects of alcohol are unknown, and may reflect metabolic differences between adult and fetal tissues. The liver is the major site of alcohol metabolism and the sole site of 25 hydroxyvitamin D synthesis. We have compared 25-hydroxyvitamin D production in adult nonpregnant, maternal, and pup livers obtained from vitamin D-deficient animals and examined the effects of alcohol ingestion on hepatic vitamin D metabolism. 25 Hydroxyvitamin D production was comparable in adult nonpregnant and maternal livers, but was decreased in pup livers compared to their maternal controls (1.4 +/- 0.2 versus 0.6 +/- 0.1 pmol/g protein/h, p less than 0.001). Alcohol ingestion for 18 days had no effect on hepatic synthesis of 25 hydroxyvitamin D in the adult livers, but inhibited production by the pup livers (0.6 +/- 0.1 versus 0.3 +/- 0.1 pmol/g protein/h, p less than 0.02). To assess the physiologic significance of these observations, the effect of alcohol on 25-hydroxyvitamin D levels in vitamin D-replete mothers and fetuses was determined. Alcohol had no effect on circulating 25 hydroxyvitamin D levels in the mothers but lowered fetal 25 hydroxyvitamin D content (2.3 +/- 0.3 versus 1.2 +/- 0.3 ng/g fetus, p less than 0.02) without altering fetal weight. The data indicate that differences exist in pup and adult hepatic metabolism of vitamin D and that alcohol has inhibitory effects on pup liver function not expressed in adult tissues.

Animals↗
PubMed1984

Evidence for a defect in vitamin D metabolism in a patient with incomplete Fanconi syndrome.

A patient with incomplete Fanconi syndrome (no metabolic acidosis) presented with muscle weakness and biochemical and radiographic evidence of osteomalacia. Despite hypophosphatemia and increased PTH levels, circulating concentrations of 1,25-dihydroxyvitamin D were inappropriately low. Treatment with the vitamin D metabolite and hydrochlorothiazide was attended by enhanced calcium and phosphorus balance. Impaired vitamin D metabolism may play a role in the pathogenesis of osteomalacia in the Fanconi syndrome.

Adult↗
PubMed1983

1,25 dihydroxyvitamin D-induced inhibition of 3H-25 hydroxyvitamin D production by the rachitic rat liver in vitro.

The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production of 3H-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepatic 3H-25 hydroxyvitamin D production in the liver perfusion (3.6 +/- 0.4 vs 2.0 +/- 0.5 pmol/liver, P less than 0.05) and in liver homogenates (11.9 +/- 0.6 vs 10.1 +/- 0.4 pmol/g liver protein/3 h, P less than 0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 +/- 0.6 vs 9.2 +/- 0.1 pmol/g liver protein/3 h, P less than 0.05) but not in the intact liver (3.6 +/- 0.4 vs 3.4 +/- 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition.

Animals↗
PubMed1983

Effect of phenobarbital treatment on metabolism of vitamin D by rat liver.

Phenobarbital has been postulated to impair hepatic conversion of vitamin D to 25-hydroxyvitamin D [25(OH)D] either by accelerating the conversion of vitamin D to biologically inactive products or by directly inhibiting 25(OH)D production. The effect of a dose of phenobarbital documented to decrease circulating 25(OH)D levels on hepatic vitamin D metabolism has been investigated in rachitic rats with a recycling in vitro hepatic perfusion system. Phenobarbital (75 mg/kg/day) administered intraperitoneally to D-replete rats increased circulating 25(OH)D blood levels after 4 wk of therapy but was attended by decreased levels after 6 and 8 wk. Rachitic rats were then injected daily with phenobarbital for either 4 or 8 wk and the livers removed and perfused at a rate of 15 ml/min for 3 h. The concentrations of [3H]25(OH)D in the hepatic perfusate at 3 h was decreased after both 4 and 8 wk of phenobarbital. Although total [3H]-25(OH)D production (hepatic plus perfusate) was unaffected by phenobarbital, the efficiency of hepatic production was decreased after 8 wk of treatment and the release of [3H]-25(OH)D from the liver into the perfusate was inhibited after both 4 and 8 wk. The data indicate that chronic phenobarbital therapy decreases both the release of [3H]25(OH)D from the liver into the perfusate and the efficiency of hepatic [3H]-25(OH)D production. Phenobarbital-induced inhibition of 25(OH)D release from the liver may be another mechanism for the low 25(OH)D levels noted in humans after long-term phenobarbital therapy.

Animals↗
PubMed1983

Body weight and its effect on immunoreactive parathyroid hormone levels.

Immunoreactive parathyroid hormone (iPTH) levels were measured in 12 obese subjects (140-272% ideal body weight) and 10 normal lean volunteers (93-100% ideal body weight). iPTH values were not significantly different in the two groups and tubular maximum phosphate reabsorption (TmP) was comparable in lean subjects and the 4 obese patients tested. 4 obese subjects were evaluated after an average of 6.7% body weight loss, and neither iPTH levels nor TmP were affected. The data indicate that the biological effects of PTH are not enhanced in the massively obese.

Absorption↗
PubMed1982

Hypercalciuria.

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Absorption↗
PubMed1982

Acquired alterations in vitamin D metabolism in the acidotic state.

Classic (type I) renal tubular acidosis in children in attended by growth retardation and rickets, abnormalities that can be corrected by alkali therapy alone. We have employed the NH4Cl-treated rachitic chick as a model to investigate vitamin D metabolism in the acidotic state. NH4Cl ingestion for 96 h was associated with a rise in serum calcium, a significant decrease in blood pH (7.42 +/- 0.08 vs 7.30 +/- 0.08, P less than 0.005), decreased [3H]1,25(OH)2D3 following [3H]25OHD D3 injections, and enhanced metabolic clearance of administered [3H]1,25(OH)2D3. The data collectively suggest that metabolic acidosis in the chick alters the production and degradation of 1,25(OH)2D3.

Acidosis, Renal Tubular↗
PubMed1982

Alcohol-induced alterations in calcium metabolism in the pregnant rat.

The effect of alcohol ingestion during pregnancy on maternal calcium metabolism was investigated by allowing pregnant rats to ingest Purina Rat Chow ad libitum along with 20% ethanol in their drinking water from day 6 to 19 of pregnancy. Ethanol constituted 50% of the caloric intake and resulted in blood levels of 98 mg/dl on day 19 of gestation. Control rats were pair-fed with rat Chow and dextrimaltose was isocalorically substituted for ethanol in the drinking water. Alcohol consumption was attended by decreased serum levels of calcium (7.3 +/- 0.5 versus 9.5 +/- 0.3 mg/dl, p less than 0.01), and phosphorus (5.7 +/- 0.5 versus 7.5 +/- 0.3 mg/dl, p less than 0.01), as well as by lowered tubular reabsorption of phosphate (88.6 +/- 4.6 versus 95.0 +/- 0.7%, p less than 0.05). The fasting urinary calcium/creatinine ratio (Ca/Cr), an index of bone resorption, was increased in the alcohol-consuming rats (0.41 +/- 0.08 versus 0.24 +/- 0.04, p less than 0.05). In contrast, alcohol administered to nonpregnant female rats for the same time period and resulting in blood levels of 129 mg/dl had no effect on serum calcium, phosphorus, tubular reabsorption of phosphate, or fasting urinary Ca/Cr. The data suggest that alcohol ingestion during pregnancy, a time of increased calcium requirement, produces biochemical changes consistent with secondary hyperparathyroidism.

Animals↗
PubMed1982

Alcohol-induced inhibition of fetal 25-[3H]hydroxyvitamin D and alpha-[14C]aminoisobutyric acid accumulation in the pregnant rat.

Since placental nutrient transport plays a vital role in the development of the fetus, we have evaluated the effect of alcohol ingestion during pregnancy on placental and fetal accumulation of 25-[3H]hydroxyvitamin D and alpha-[14C]aminoisobutyric acid. Pregnant rats were allowed to ingest rat chow ad libitum and were given 20% ethanol in their drinking water from days 6-19 of pregnancy. Ethanol constituted 51% of the caloric intake and resulted in circulating levels of 97 +/- 27 mg/dl. Control rats were pair fed with rat chow, and dextrimaltose was isocalorically substituted for ethanol in the drinking water. Despite pair feeding, alcohol ingestion resulted in decreased maternal and fetal weight gain but increased placental weight gain. Alcohol decreased the fetal accumulation of 25-[3H]hydroxyvitamin D. The transfer ratio of disintegrations per min/g fetal weight to disintegrations per min/g placental weight was lower in the alcohol-exposed animals, whereas the transfer ratio of disintegrations per min/g placental weight to disintegrations per min/ml serum was not altered. Fetal levels of alpha-[14C]aminoisobutyric acid were also decreased. The transfer ratio of disintegrations per min/g fetal weight to disintegrations per min/g placental weight was greater in the alcohol-exposed animals, whereas the transfer ratio of disintegrations per min/g placental weight to disintegrations per min/ml serum was not altered. The data indicate that maternal alcohol ingestion during pregnancy may affect fetal nutrient accumulation by alterations in both maternal metabolism and direct effects on placental function.

Aminoisobutyric Acids↗
PubMed1981

Ultrastructure of the rat epiphyseal growth plate following chronic ethanol ingestion.

We have previously demonstrated that ethanol has a direct toxic effect on the rat skeleton characterized by decreased trabecular bone volume. In the present study, we examined the ultrastructure of the distal radial epiphyseal growth plates in these same animals. Eight weeks of ethanol administration to 12 male rats results in serum alcohol levels of 140 mg/dl but did not alter the width or light microscopic appearance of the radial growth plate. Quantitative electron microscopy failed to demonstrate morphologic evidence of toxicity in the skeletal cells. We conclude that although ethanol appears to have a direct effect on rat bone characterized by enhanced resorption, toxicity is not attended by ultrastructural changes in the skeletal cells.

Animals↗
PubMed1981

Effects off short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man.

These studies were performed to examine the hypothesis that glucocorticoids suppress intestinal calcium absorption in man by decreasing the circulating concentrations of biologically active vitamin D metabolites. Twelve normal adults were equilibrated for 2 weeks on a 600-mg calcium diet. After equilibration, subjects were studied for 12 days before and 14 days during the administration of prednisone (20 mg/day). After 14 days of prednisone administration, intestinal 47Ca absorption had decreased by 31% from initial values (P < 0.001). However, mean serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D did not change significantly from initial values of 28.1 +/- 1.8 and 2.09 +/- 0.17 pg/ml, respectively, and the serum 1,25-dihydroxyvitamin D concentration was slightly increased (baseline, 34.8 +/- 3.3; day 14, 54.0 +/- 7.1 pg/ml; P < 0.02). The fasting serum immunoreactive parathyroid hormone concentration did not change. These results demonstrate that reduced intestinal calcium absorption after glucocorticoid administration cannot be attributed to decreasing circulating concentrations of the major known vitamin D metabolites.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Effect of age on serum immunoreactive parathyroid hormone and its biological effects.

Immunoreactive parathyroid hormone (iPTH) levels, nephrogenous cAMP (ncAMP), and tubular maximum phosphate reabsorption (TmP) were measured in 10 young and 12 healthy volunteers. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Aging was attended by increased iPTH levels (6.9 +/- 0.8 vs. 3.4 +/- 0.4 mu leq/ml; P less than 0.01) as well as increased ncAMP levels (2.48 +/- 0.28 vs. 1.12 +/- 0.21 nmol/100 ml glomerular filtrate; P less than 0.005) and decreased TmP (2.9 +/- 0.2 vs. 4.1 +/- 0.2 mg/100 ml glomerular filtrate; P less than 0.005), indicating that the increased iPTH levels reflected the biological effects of the hormone. A significant positive correlation of iPTH and ncAMP and a significant negative correlation of iPTH and TmP were observed. The Ca:Cr was increased in the older volunteers (0.10 +/- 0.02 vs. 0.05 +/- 0.01; P less than 0.05). The elderly subjects had significantly decreased daily calcium ingestion, serum phosphate and albumin, and creatinine clearance. Our findings suggest that the increased biological effects of PTH in the elderly subjects may contribute to the increases in Ca:Cr and bone loss that occur with age.

Adult↗