Bioethics and dietetics: education and attitudes.
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Attitude of Health Personnel↗
Biomedical subjects
S Edelstein
Publications and source records attributed to S Edelstein.
Prenatal diagnosis of vitamin D-dependent rickets, type II: response to 1,25-dihydroxyvitamin D in amniotic fluid cells and fetal tissues.
Vitamin D-dependent rickets type II (VDDR-II; hereditary resistance to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]), an autosomal recessive genetic disease that results from a failure to respond to 1,25-(OH)2D3, is characterized by severe rickets, hypocalcemia, growth retardation, and high prevalence of alopecia. We used amniotic fluid cells in the 17th week of gestation to detect VDDR-II in fetuses at risk for the defect. First, we demonstrated in cells obtained from 15 control pregnancies the presence of a specific high affinity 1,25-(OH)2D3 receptor (Kd = 0.3 x 10(-11) mol/L; maximal number of binding sites, 6.1 fmol/mg protein) and 1,25-(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase activity (up to 30-fold increase). Amniotic fluid cells from a woman who had already given birth to a child with VDDR-II contained receptors that bound [3H]1,25-(OH)2D3 normally and responded to 1,25-(OH)2D3 stimulation with a 10-fold increase in 24-hydroxylase activity. The fetus was, therefore, judged unaffected, and a normal baby girl was born. At the age of 16 months she did not demonstrate clinical or biochemical features of VDDR-II. Amniotic fluid cells from another mother of a child with VDDR-II were unable to bind [3H]1,25-(OH)2D3, and the hormone failed to stimulate 24-hydroxylase activity. VDDR-II in this fetus was confirmed after termination of pregnancy by the total inability of 1,25-(OH)2D3 to stimulate 24-hydroxylase activity in tissue explants and cell cultures prepared from the fetus's kidney and skin. In contrast, tissues from dead control fetuses responded to stimulation by 1,25-(OH)2D3 with a 3- to 10-fold increase in 24-hydroxylase activity. Fetal kidney and skin explants and cell cultures also synthesized a [3H]1,25-(OH)2D3-like metabolite from [3H]25-OHD3 as early as the 17th week of gestation. 1,25-(OH)2D3 (10 nM) decreased the in vitro synthesis of the [3H]1,25-(OH)2D3-like metabolite in tissues from dead control fetuses, but not from the affected fetus. Thus, human fetuses at midgestation already have the regulatory mechanisms responsive to 1,25-(OH)2D3 present postnatally. The prenatal diagnosis of VDDR-II is now possible and is indicated in a high risk family.
Adult↗
Biochemical and biomechanical properties of avian callus after local administration of dihydroxylated vitamin D metabolites.
In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union.
24,25-Dihydroxyvitamin D 3↗
Effect of verapamil on intestinal absorption of calcium in the rat.
The effect of verapamil in vitro, and the in vivo effect of both oral and parenteral verapamil administration on intestinal absorption was tested using everted gut sacs of duodenum, jejunum, distal ileum and proximal colon in rats. In the in vivo study, the effect of verapamil on blood levels of calcium, phosphorus and 1.25(OH)2D3, was investigated and a complete calcium balance was performed. In vitro, verapamil (1.5 mM) inhibited calcium absorption by the duodenum and colon only. Oral verapamil led to a reduction in the blood level of 1.25(OH)2D3. However, both oral and parenteral verapamil had no effect on the intestinal absorption, urinary secretion and consequently on the calcium balance.
Animals↗
Establishing a work-site wellness program in a hospital setting.
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Adult↗
Project T.E.A.M.S.
Project T.E.A.M.S. (Training, Education, and Management Skills: Meeting the Needs of Infants Prenatally Exposed to Drugs), funded by a training grant from the National Center on Child Abuse and Neglect, developed skilled interdisciplinary teams to support caregivers and optimize the health and environmental care of infants exposed prenatally to drugs and placed in out-of-home care. Using both didactic and clinical approaches, the 6-month program addressed the medical, developmental, environmental, and physical care needs of drug-exposed infants and toddlers; the special needs of their caregivers; and family dynamics and parenting issues. By enhancing the knowledge and skills of staff from community-based child welfare and health care agencies, this project demonstrated a training approach for enhancing the skills of professionals who serve the growing population of prenatally drug-exposed infants.
Community Health Services↗
Bioavailability of a natural isomer mixture as compared with synthetic all-trans-beta-carotene in rats and chicks.
The unicellular halotolerant alga Dunaliella bardawil was previously shown to contain high concentrations of beta-carotene composed of about equal amounts of the all-trans and 9-cis isomers. One-d-old chicks and 7-wk-old male rats were fed diets supplemented with synthetic all-trans-beta-carotene or dry D. bardawil at equivalent levels of beta-carotene. The chicks were fed diets containing up to 0.025% beta-carotene for 2 mo, and the rats up to 0.1% beta-carotene for 2 wk. Liver analyses at the end of these periods indicated that both species showed at least a tenfold higher accumulation of the algal beta-carotene isomer mixture than of the synthetic all-trans-beta-carotene. The ratio of 9-cis-beta-carotene to the all-trans isomer in the livers of the algae-fed rats and chicks was similar to or higher, respectively, than that present in the algae. Retinol plus retinyl ester accumulated to a similar extent in the rats and chicks fed diets supplemented with synthetic all-trans or the natural isomer mixture of beta-carotene. The preferable accumulation of the natural isomer mixture of beta-carotene suggests that attention should be paid to the different sources of beta-carotene when testing their efficacy in effects other than providing retinol, such as in their possible role in the prevention of some types of cancer.
Administration, Oral↗
Proteoglycan synthesis in vitamin D-deficient cartilage: recovery from vitamin D deficiency.
Vitamin D appears to be required for mineralization of skeletal elements. There is also evidence that cartilage proteoglycans may be involved in the regulation of mineralization. Previous studies have shown an alteration in the structure of the proteoglycans of the epiphyseal growth cartilage as a result of the decrease in serum calcium related to deficiency of dietary vitamin D. Vitamin D deficiency also induces a thickening of the epiphyseal growth plate presumably because of the inhibition of maturation of the growth plate chondrocytes. In order to compare the effect on proteoglycan structure with that on growth plate morphology, the proteoglycans of healing epiphyseal cartilage were characterized. The results indicate that, consistent with previous data, in vitamin D-deficient hatching chicks, the proteoglycans of the growth cartilage, but not of the articular cartilage, are smaller in monomer size with slightly smaller chondroitin sulfate chains whose sulfation pattern is unaltered. Sternal cartilage proteoglycans are unaffected. During recovery from vitamin D deficiency, the proteoglycans isolated from the growth cartilage are still not completely normal one day after supplementation with vitamin D, but are indistinguishable from normal by four days. In addition, the results conflict with those of a previous study in which only growth cartilage of hatchling chicks, not sternal or articular cartilage, was reported to synthesize large proteoglycans. Instead, all of these cartilages in the normal chicken have been found in this study to produce large proteoglycans of a size typical for mammalian cartilage and embryonic chick cartilage.
24,25-Dihydroxyvitamin D 3↗
Mechanical, biochemical, and structural effects of vitamin D deficiency on the chick heart.
The effects of vitamin D deprivation on the chick heart were investigated from three aspects: cardiac contractility (+/- dP/dT), intracellular high-energy phosphorus compounds, and structural differences. Four-week-old vitamin D-deficient chicks were divided into four groups: Group A served as the normal group and received subcutaneous injections of cholecalciferol; Groups B and C were vitamin D-deficient hearts but perfused differently; Group D received daily subcutaneous injections of 5 micrograms of 1,25(OH)2D3. When the isolated spontaneously beating hearts (modified Langendorff preparation) were perfused with Krebs-Henseleit (KH) solution containing a calcium concentration of 2.5mM, the myocardial contractility of the vitamin D-deficient hearts was significantly increased when compared with group A. After the isolated heart had beaten for one hour, the myocardial contractility in the vitamin D-deficient hearts was found to decline to significantly lower values. Presacrifice administration of 1,25(OH)2D3 improved cardiac performance. Vitamin D deficiency resulted in an enhanced rate of decline of the intracellular high-energy phosphorus compounds. No differences were found in the microscopic study. These observations suggest that vitamin D has a role in cardiac function.
Adenosine Triphosphate↗
[Effect of local administration of 24,25-dihydroxyvitamin D3 on bone formation].
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24,25-Dihydroxyvitamin D 3↗
Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study.
Forty primigravid women due to undergo first trimester termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E2 in gel or gel only as placebo. In the PGE2-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of 11.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE2-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15%) patients, fetal demise was observed. The mean induction-abortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE2-gel group. Termination of pregnancy was found to be easier in the PGE2-gel group, compared to the placebo group.
Abortion, Therapeutic↗
Responses of rachitic cartilage cells to metabolites of vitamin D3.
Responses of cultured cartilage cells to metabolites of vitamin D3 were studied. Cells were obtained from the epiphyseal growth plate of rachitic chicks and were exposed to physiological and pharmacological concentrations of three metabolites of vitamin D3, 25 hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). 1,25(OH)2D3 was found to reduce L-[U-14C]leucine incorporation into proteins and Na2 35SO4 incorporation into proteoglycans. The synthesis of 24,25(OH)2D3 from 25(OH)D3 was stimulated upon addition of 1,25(OH)2D3 to the cultures. Physiological concentrations of 24,25(OH)2D3 stimulated protein and proteoglycan synthesis. These findings support the notion that vitamin D3, through its active dihydroxylated metabolites, is directly involved in cartilage cells metabolism and healing of rickets.
24,25-Dihydroxyvitamin D 3↗
Electron microscopic studies of the intracellular polymerization of sickle hemoglobin.
Transmission electron microscopy has been used to study intracellular sickle hemoglobin polymer in unfractionated cells from the arterial and venous blood of patients and after external deoxygenation. We detect polymerized hemoglobin in up to 10% of the cells in the venous circulation, especially in cells that are "cigar-shaped" and appear to be irreversibly sickled. We could not see well-defined polymer in mixed arterial samples; nevertheless, we found electron opaque spots, which could be ferritin granules, hemosiderin, or small aggregates of hemoglobin S. However, upon sequential chemical deoxygenation using 1.0% sodium metabisulphite, polymer formation was seen at oxygen saturation values of 75%-85%. Cells that were physically deoxygenated using gas mixtures containing nitrogen-carbon dioxide-oxygen mixtures were found to contain distinct polymers of deoxyhemoglobin S at oxyhemoglobin saturation values of 50%-75%. As deoxygenation increases, we detect short, randomly arranged polymer in a loose network, with occasional long polymers. Upon further deoxygenation, the length and number of polymer forms increased. Between 0% and 50% saturation, most erythrocytes were full of long, parallel, closely packed polymers that tend to align and run parallel to the cell membrane. In both chemical and physically deoxygenated blood samples, cells were seen at 50%-75% oxyhemoglobin saturation that retained their normal biconcave disc shape, although they contained significant amounts of polymer. The structural changes in sickle erythrocytes seen in vitro due to physical or chemical deoxygenation of cells, may reflect in vivo intracellular changes in the sickle cell patient.
Anemia, Sickle Cell↗
Calcitriol increases Ca2+-ATPase activity.
Treatment with calcitriol of isolated cartilage cells derived from epiphyseal growth plates of rachitic chicks results in reduced intracellular calcium concentrations. The reduction in calcium was found to correlate with increased activity of Ca2+-ATPase. The activities of Na+-K+-ATPase and of Mg2+-ATPase did not change in response to the treatment with calcitriol. It is suggested that calcitriol regulates intracellular calcium by modulating the activity of the Ca2+-pumping ATPase.
Alkaline Phosphatase↗
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↗