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Biomedical subjects

S Edelstein

Publications and source records attributed to S Edelstein.

At least 37 records · Page 2Linked to original sources

The effect of disodium ethane-1-hydroxy-1,1-diphosphonate on the metabolism of calcitriol in chicks.

Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.

Animals

Migraine and other diseases in women of reproductive age. The influence of smoking on observed associations.

From among the pregnant women in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, we identified 508 who had migraine, and 3192 who had no history of migraine, of taking headache medication during the previous 12 months, and of headaches during the pregnancy. Migraineurs smoked more heavily and had a longer smoking history than their headache-free peers. Among migraineurs, smokers were not more likely to consume analgesics than nonsmokers. Regardless of smoking classification, more migraineurs consumed tranquilizers, amphetamines, and sleeping pills than headache-free women. Among smokers only, migraine was associated with heart disease, thrombosis/phlebitis, asthma, peptic ulcer, and pneumonia. In nonsmokers, migraine was associated with drug sensitivity and other allergies.

Adolescent

Healing of rachitic lesions in chicks by 24R,25-dihydroxycholecalciferol administered locally into bone.

In an attempt to further define the nature of the active metabolite in bone formation, a series of experiments were conducted whereby vitamin D metabolites were administered locally in vivo into the proximal epiphyseal growth plate of the tibiae of rachitic chicks. Local administration of 3 micrograms of 24,25(OH)2D3 in vivo to D-deficient chicks resulted in disappearance of the rachitic lesions in the same leg. Administration of 1 microgram 1,25(OH)2D3 in a similar manner failed to show any sign of healing. Injection of 5 micrograms 25(OH)D3 was followed by recovery from rickets in both the injected right leg and in the vehicle-injected left tibia, although the recovery was more pronounced in the injected leg. Lower doses of 0.3 or 1 microgram 24,25(OH)2D3 failed to reverse the rachitic lesions and induced only minimal recovery. These findings suggest that 24,25(OH)2D3 at the higher doses has a direct local effect on cartilage and bone, while 1,25(OH)2D3 has no such effect in chicks. 25(OH)D3 is probably absorbed from the epiphyses into the blood stream and converted into the active metabolites, which were indeed detected in the blood to exert its systemic effects.

24,25-Dihydroxyvitamin D 3

Ultrasonically controlled retrieval of an intrauterine contraceptive device (IUCD) in early pregnancy.

Removal of an intrauterine contraceptive device (IUCD) in nonpregnant patients under ultrasonic guidance has previously been reported, but results of the method in pregnancy are controversial. In the present study removal of the IUCD was performed in 16 women who conceived with the device in place. Four women were scheduled for pregnancy termination and 12 women wished to continue their pregnancy. Removal was successful in all 16 patients with minimal complications. Fetal loss occurred in one case out of the 12 who wished to continue their pregnancy. The procedure was found to be feasible even in cases with the IUCD located behind the gestational sac. We suggest ultrasonic guided removal of the IUCD during pregnancy to be the method of choice.

Adult

Calbindin-D in peripheral nerve cells is vitamin D and calcium dependent.

The vitamin D-induced calcium-binding protein calbindin-D (CaBP) was localized immunohistochemically in some but not all of the cell bodies and axons within the intestinalis nerve of the chicken. Unlike other nerve tissue thus far examined, the CaBP content of the intestinalis nerve was decreased in vitamin D deficiency and increased in chicken adapted to a calcium-deficient diet. These changes are qualitatively similar to the pattern of response of enterocytes. The inclusion of calcium-containing solutions within the duodenal lumen caused, directly or indirectly, a decrease in the amount of CaBP in this nerve in a dose-dependent manner. The exact role of CaBP in intestinalis nerve cells is unknown but may be in the regulation of intracellular ionic Ca2+ concentrations during excitation, although other functions of CaBP cannot be excluded.

Animals

The metabolism of vitamin D3 during fracture healing in chicks.

The metabolism of vitamin D3 was studied in chicks after experimental fractures were performed on their tibiae. The chicks were fed for 3 weeks a vitamin D-deficient diet but were supplemented with radioactive labeled vitamin D3. The chicks were then divided into two groups. In the first group the right tibia was fractured, whereas the second group served as nonfractured control group. During the following days of fracture healing, the metabolites of [3H]vitamin D3 were measured in callus, epiphysis, diaphysis, plasma, duodenum, and kidney. Histological examination of calluses and bones, measurements of intestinal absorption of calcium, and renal production of dihydroxylated metabolites of vitamin D3 were performed as well. The levels of the dihydroxylated metabolites were increased in the calluses and the levels of [3H]24,25-dihydroxyvitamin D3 were found to coincide with the formation of cartilaginous tissue and with the renal production of this steroid. In the duodenum of the fractured chicks, the levels of [3H]1,25-dihydroxyvitamin D3 dropped significantly during the first week after fracture, coinciding with reduction in the intestinal absorption of calcium. In the plasma during those 3 weeks of healing process the levels of [3H]1,25-dihydroxyvitamin D3 were far below normal. These findings indicate that during the process of fracture repair, changes in the metabolism and expression of vitamin D are taking place in order to meet the new requirements of the body under stress condition of skeletal fracture.

Animals

Levels of active metabolites of vitamin D3 in the callus of fracture repair in chicks.

The levels of the active metabolites of vitamin D were measured in the callus and in the epiphyseal growth plate of chicks given radioactive cholecalciferol during fracture healing. Those levels were correlated with the histological findings. Three groups of chicks were studied: a control group with no fracture, chicks with fractures fixed by Kirschner wire, and chicks with unfixed fractures. A significant increase in the levels of the active metabolites was found in the callus during the first few days after fracture. The levels of 25-hydroxycholecalciferol [25(OH)D3] and of 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were higher when there was no fixation, while those of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] were higher after fixation. The concentrations of these metabolites in the proximal epiphysis of the tibia were similar to those found in the callus. Based on these findings it is suggested that the active metabolites of vitamin D are directly involved in the process of fracture repair.

Animals

Influence of 1,25-hydroxyvitamin D3 on cytosolic free calcium concentrations.

Using isolated cartilage cells from the epiphyseal growth plate of rachitic chicks and utilizing the fluorescence indicator quin2 for measurements of cytosolic free calcium, it has been possible to demonstrate that 1,25-dihydroxyvitamin D3 regulates the concentrations of cytosolic free calcium. The reduction in cytosolic free calcium is associated with inhibition of the activity of alkaline phosphatase. As several hours are required before an effect on cytosolic free calcium can be observed in the cells, it is suggested that the action is dependent on genomic interactions.

Alkaline Phosphatase

Impact of tumor control on survival in carcinoma of the lung treated with irradiation.

The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1-3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course (p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000-6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure (p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled (p = 0.001). In patients surviving 12 months after treatment with 5000-6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 29 months, in contrast to 18 months, if they developed intrathoracic failure (p = 0.05). In patients treated with 4000 cGy, the median survival was 23 months with control and 18 months without control of the intrathoracic tumor [corrected] (p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant (p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Bronchogenic

Use of the beta-carotene rich alga Dunaliella bardawil as a source of retinol.

Dunaliella bardawil, a beta-carotene accumulating halotolerant alga, has been tested as a source of retinol in a chick diet. Chicks were fed diets deficient in retinol or supplemented with retinol, synthetic beta-carotene or dry algae. After an initial lag, chicks grew equally well on diets supplemented with algae, retinol or beta-carotene. Serum and liver analyses revealed a normal content of retinol in all chicks except those grown on the retinol-deficient diet. Chicks fed the algae-supplemented diet contained lutein but no beta-carotene in their serum, even though the ratio of beta-carotene to lutein in the algae was over 15:1. Laying hens fed with an algae-supplemented diet showed enhanced egg yolk colour attributable to a higher lutein content. No beta-carotene was present in the egg-yolk. These studies demonstrate the possibility of using dried Dunaliella bardawil as a dietary supplement which can fully satisfy the retinol requirement and also serve as a yolk-colour enhancing agent.

Animal Nutritional Physiological Phenomena

Metabolic acidosis enhances 1,25(OH)2D3-induced intestinal absorption of calcium and phosphorus in rats.

The effect of metabolic acidosis on the intestinal absorption of calcium (Ca) and phosphorus (P), plasma vitamin D metabolites and urinary excretion of Ca in adult rats treated with a small dose of 1,25(OH)2D3 were investigated. The rats in the experimental group received 1.8% ammonium chloride (NH4Cl) and a commercial chow, and their pair-fed controls received 0.45% NaCl. Both groups were given subcutaneously 1,25(OH)2D3. Intestinal absorption of Ca and P was measured by gut sac uptake of 45Ca and 32P. In the acidotic rats, duodenal, jejunal and ileal 45Ca uptake as well as jejunal and ileal 32P uptake were significantly increased. Plasma 1,25(OH)2D, 25(OH)D and 24,25(OH)2D were similar in both groups. 1,25(OH)2D3 treatment induced a greater calciuria in acidotic rats and increased their fractional excretion (FE) of Ca. An additional experiment showed increased 45Ca uptake by duodenum at a pH of 7.0 compared to pH 7.4. The present study suggests that NH4Cl-induced metabolic acidosis may enhance the effect of 1,25(OH)2D3 on intestinal absorption of Ca and P in the rat. However, the data from the study cannot exclude the possibility that acidosis may have a direct, vitamin D-independent effect on the intestine.

Acidosis

Lead-binding properties of intestinal calcium-binding proteins.

The bovine and chick vitamin D-induced intestinal calcium-binding proteins (CaBP) bind lead. Bovine CaBP binds 2 atoms of lead/molecule, and chick CaBP binds 4 atoms of lead per molecule and these values are identical to those for calcium binding. 45Calcium-displacement studies indicate significantly higher affinities for lead than for calcium for both proteins. All evidence indicates that lead is bound to the 4 high affinity calcium-binding sites on chick CaBP and to the corresponding 2 high affinity sites on bovine CaBP, and that binding of lead to sulfhydryl groups is, relatively, not significant. Calmodulin, troponin C, and oncomodulin also bind lead with high affinities and in preference to calcium, indicating that lead binding is a general property of proteins belonging to the troponin C superfamily of calcium-binding proteins.

Animals

Autoradiographic localization of 24R,25-dihydroxyvitamin D3 in epiphyseal cartilage.

There is emerging evidence for specific binding sites and biologic action for 24,25(OH)2D3 in the epiphyseal cartilage. The present study was undertaken to identify the target cells of 24,25(OH)2D3 in the epiphyses of rat bone using an autoradiographic technique. Pieces of epiphyseal cartilage obtained from 4-day-old vitamin D-deficient rats were incubated for 15 or 60 min with [3H]-24,25(OH)2D3 in the presence or absence of 100-fold excess of 25(OH)D3, 1,25(OH)2D3, or 24R,25(OH)2D3. The pieces were prepared for autoradiographic study by a new modified fixation method. Cytoplasmic and nuclear concentration of radioactivity was observed in all cell layers of the epiphyseal cartilage except for the hypertrophic cartilage zone. The highest concentration of radioactivity was seen in the proliferating chondroblasts of the columnar zone. After 15 min of incubation the radioactivity was seen mainly in the cell membrane and cytoplasm, whereas at 60 min radioactivity was also prominent in the nuclei. The competition with excess of cold metabolites revealed that only 24R,25(OH)2D3 caused a significant decrease in cytoplasmic and nuclear radioactivity. These data support the biochemical studies showing that the epiphyseal cartilage is a target tissue for 24,25(OH)2D3.

24,25-Dihydroxyvitamin D 3

Effect of bicarbonate feeding on intestinal absorption of calcium and vitamin D metabolism in rats.

The effect of bicarbonate (NaHCO3) feeding on intestinal absorption of calcium and phosphorus and vitamin D metabolism was investigated. Gut sac uptake of 45Ca and [32P]phosphate in vitro, as well as the plasma level of vitamin D metabolites, was determined in rats fed with NaHCO3 for 9 days and their pair-fed controls. Duodenal uptake of 45Ca and [32P]phosphate by alkalotic rats was less than duodenal uptake by controls. 1,25(OH)2D plasma level was much higher in alkalotic rats than in their controls, and 25(OH)D slightly higher than in controls. These data suggest that NaHCO3 feeding causes a substantial increase in 1,25(OH)2D plasma level, but interferes with calcium and phosphorus absorption in the duodenum.

24,25-Dihydroxyvitamin D 3

Cholecalciferol metabolites in polycythemic newborns.

Metabolites of cholecalciferol were measured in the sera of healthy and polycythemic newborns at 15.5 and 10.5 h of age (median), respectively. The serum concentrations of 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D were lower in the polycythemic group (P less than 0.003 and P less than 0.001, respectively). As the kidney is the main site of conversion of 25-hydroxyvitamin D to its dihydroxylated metabolites, it is possible that hyperviscosity and subsequent decrease in renal blood flow interfere with the efficiency of the process.

24,25-Dihydroxyvitamin D 3

Photo-affinity label for cellular retinol-binding protein.

A number of retinoid derivatives have been synthesized for use as labels for cellular retinol-binding protein. Introduction of substituents abolished the binding of the derivatives to the protein, except in the case of the photo-reactive derivative, 4-azidoretinol. This compound was found to compete successfully with all-trans-retinol for binding to cellular retinol-binding protein, with a high relative binding affinity. Irradiation of a complex of 4-azidoretinol and a semi-purified preparation of cellular retinol-binding protein from liver resulted in a firm attachment stable to SDS-gel electrophoresis. It is therefore suggested that the irradiated product is held together covalently. A method for the synthesis of 4-azidoretinol is described.

Affinity Labels

Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system.

The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of 203Pb and 47Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] as their only source of the vitamin, the absorption of both 47Ca and 203Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in 47Ca and 203Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)2D3, the intestinal absorption of 47Ca and of 203Pb was increased, as well as the intestinal CaBP levels. Intracardial injection of increasing doses of 1,25(OH)2D3 to rachitic chicks resulted in a concomitant increase in 203Pb absorption in a manner that correlated with the degree of synthesis of CaBP. Ingestion of lead by the chicks was found to impair growth and renal production of 1,25(OH)2D3, resulting in lowered circulating and intestinal content of the hydroxylated metabolites of cholecalciferol.

Animals

Fecal loss of cholecalciferol in gastrectomized rats.

Rats were gastrectomized, and the intestinal absorption and fecal excretion of cholecalciferol were studied following the administration of radioactive cholecalciferol, either by subcutaneous injection or with the aid of a gastric tube. From measurements of radioactivity in feces and sera it has been possible to establish that gastrectomy in rats results in impaired intestinal absorption and increased fecal excretion of cholecalciferol. These findings indicate that gastrectomy alters the nutritional status of vitamin D, and may explain the high incidence of osteomalacia as a complication of gastrectomy.

Animals