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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 181 records · Page 10Linked to original sources

Normal vitamin D and mineral metabolism in essential hypertension.

The effects of dietary sodium upon serum and urinary calcium and selected vitamin D metabolites were studied in two groups (n = 10 each) of age and gender matched, white normotensive subjects and patients with normal-renin hypertension. Isocaloric diets were consumed on a metabolic ward with sequential daily sodium intake of 109 meq for 5 days and 9 meq and 259 meq for 6 days each. Values for serum and urinary calcium, phosphorus, magnesium and electrolytes, creatinine clearance, plasma immunoreactive parathyroid hormone, and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar in both study groups on each diet. Measurements of plasma renin activity and serum aldosterone levels were higher in the hypertensive than in the normotensive group on each diet (p less than .05-.01). Serum 1,25-dihydroxyvitamin D and urinary calcium increased on the high sodium diet in the normotensive (p less than .05) and the hypertensive groups (p less than .01). When the data for normotensive subjects and hypertensive patients were pooled by gender, males had a 1 1/2 to 3 times the urinary calcium excretion than females, regardless of diet. The present study indicates that there are no differences in the selected components of calcium and vitamin D metabolism in response to sodium intake in patients with essential hypertension and normal plasma renin activity as compared to normal controls.

Adult↗

Oxygen and carbon isotopic compositions of gases respired by humans.

Oxygen-isotope fractionation associated with respiration in human individuals at rest is linearly related to the fraction of the O2 utilized in the respiration process. The slope of this relationship is affected by a history of smoking, by vigorous exercise, and by the N2/O2 ratio of the inhaled gas. For patients who suffer anemia-related diseases, the slope of this relationship is directly proportional to their level of hemoglobin. These results introduce a new approach for studying the mechanisms of O2 consumption in human respiration and how they are affected by related diseases.

Adult↗

Demonstration of reduced mitogenic and osteoinductive activities in demineralized allogeneic bone matrix from vitamin D-deficient rats.

Osteoinduction is the formation of ectopic bone that follows implantation of demineralized allogeneic bone matrix (DABM) and is believed to be secondary to the release of associated inductive factors from bone matrix. To clarify the role of vitamin D in osteoinduction, we implanted DABM from vitamin D-deficient rats (-D rats) into normal rats (+D rats). Because mitogens and osteocalcin might be involved in osteoinduction, these were measured. Mitogenic activity in extracts from mineralized allogeneic bone matrix (ABM) and DABM from both +D and -D rats was determined with an assay that utilizes monolayer cultures of embryonic chick calvarial cells. Osteocalcin in serum and DABM was measured by radioimmunoassay. DABM from -D rats did not promote osteoinduction as effectively as DABM from +D rats. Resorption of implant matrix from -D rats was diminished compared with resorption of matrix from +D rats (P less than 0.01), and the decrease was attributed to a corresponding decrease in the number of osteoclasts in the implants (P less than 0.02). Bone formation (P less than 0.01) and total implant mineralization (P less than 0.001) were significantly reduced in implants from -D rats, and the reductions corresponded with a decline in the number of osteoblasts (P less than 0.05). Mitogenic activity in DABM from +D rats was only slightly decreased as compared with activity in ABM, but DABM from -D rats contained significantly less activity (P less than 0.001). No mitogenic activity was identified in implants of DABM from either +D or -D rats 3 wk after implantation. Serum osteocalcin was significantly higher in -D as compared with +D animals. In contrast, the concentrations of osteocalcin in DABM from the two groups of animals were not significantly different from each other. These findings indicate that the diminished osteoinductive activity of DABM from -D rats results from deficiency of one or more mitogenic factors that are essential for inducing the proliferation and differentiation of bone cells at the implant site and that osteocalcin does not play a role in this regard.

Animals↗

Creatine kinase elevation after neuroleptic treatment.

Two cases of asymptomatic elevation of creatine kinase levels after oral neuroleptic treatment are described. One patient was successfully challenged with a different neuroleptic. The authors discuss possible reasons for creatine kinase elevation.

Adult↗

Serum and urinary markers of bone remodeling: assessment of bone turnover.

It appears that at present, serum BGP is the one bone protein that has the most promise for assisting in the diagnosis and management of high turnover metabolic bone disease states. If further studies confirm its usefulness in osteoporosis as a predictor of rapid bone loss without the need for bone biopsy, this serum marker will then not only allow early detection but also an appropriate choice of therapy in osteoporosis, i.e. the use of specific inhibitors of high turnover states such as estrogen, calcitonin, or bisphosphonates. In addition, it may also permit more accurate follow-up of patients suffering from diseases such as primary hyperparathyroidism after surgery. In low turnover osteoporosis, it may also serve a useful function to observe whether the osteoblast can be stimulated to enhance bone formation with therapies such as fluoride, anabolic steroids, PTH, etc. As yet, additional measurements, such as bone histomorphometry and other bone mineral markers, are required for definitive diagnosis. Hopefully, the availability of specific well-characterized antibodies against BGP may define its role more accurately. Recently, several other new bone proteins have been identified but at present they have very limited clinical application. Future studies into the structure-function relationship of these bone proteins may identify those markers which will be most relevant to the diagnosis and treatment of metabolic bone disease.

1-Carboxyglutamic Acid↗

Serum bone gla protein and the vitamin D endocrine system in the oophorectomized rat.

Because of the importance of estrogen in osteoporosis, the effects of decreased estrogen production using sensitive measurements of bone mineral metabolism were studied in oophorectomized rats. Serum levels of ionized calcium, bone gla protein (BGP), vitamin D metabolites (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D), and estradiol were measured before and serially for 6 weeks after oophorectomy in the rat. In addition, static and dynamic indices of bone histomorphometry were determined after double tetracycline labeling. Fifty Sprague-Dawley female rats (approximately 250 g) were studied. Twenty-five rats underwent oophorectomy (O), while the remaining rats were sham operated. Estrogen deficiency was noted in the O group within a week after surgery (estradiol, 2.45 +/- 0.78 vs. 27.9 +/- 4.15 pg/ml; P less than 0.05). Serum ionized calcium levels, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH levels did not differ between the two groups during the length of the study. Serum BGP levels were the same in both groups until the second week postoophorectomy, after which BGP remained significantly elevated in the O animals (121.7 +/- 5.95 vs. 76.7 +/- 3.87; P less than 0.001). Bone histomorphometry revealed increased osteoid volume (4.4 +/- 0.9% vs. 2.3 +/- 0.7%), osteoblast surface (26.5 +/- 2.4% vs. 3.2 +/- 1.2%), tetracycline surface (18.9 +/- 4.1% vs. 6.8 +/- 2.2%), as well as osteoclast surface (8.2 +/- 1.4% vs. 2.5 +/- 2%) in all O animals compared with those in the sham-operated group. These data indicate that oophorectomy and decreased estrogen result in increased bone turnover with elevated BGP levels. The marked BGP elevation within 2 weeks postoophorectomy suggests that estrogen withdrawal results in rapid altered bone mineral metabolism. The lack of concomitant increase in circulating PTH levels suggests that other factors may be mediating the bone loss following surgical oophorectomy.

Animals↗

Bone mineral metabolism in experimental diabetes mellitus: osteocalcin as a measure of bone remodeling.

The etiology of diabetic osteopenia has not been established. The value of serum osteocalcin (BGP) as a marker of the bone abnormalities and the possible role of the polyol pathway in diabetic osteopenia were investigated. Three groups of rats were studied over 7 weeks: group D (n = 12), rats with streptozotocin (55 mg/kg)-induced diabetes given saline by gavage; group DS (n = 12), rats with streptozotocin-induced diabetes given the aldose reductase inhibitor sorbinil (25 mg/kg) daily by gavage; and group C (n = 6), saline-injected controls. Circulating levels of ionized calcium, BGP, amino-terminal PTH, and glucose were measured on days 0, 7, 14, 28, and 49. Tibial bone specimens were examined for the presence of aldose reductase by immunocytochemistry and by histomorphometry after tetracycline labeling. Diabetic rats with or without sorbinil treatment failed to gain weight [group D, 234 +/- 26 g; group DS, 217.0 +/- 40 g; group C, 310 +/- 33 g (mean +/- SD)]. Serum BGP levels decreased significantly in the diabetic rats within 7 days and remained lower throughout the study. BGP values on day 7 were: group D, 47.7 +/- 4.9 ng/ml; group DS, 65.9 +/- 5.5 ng/ml; and group C, 90.4 +/- 4 ng/ml (mean +/- SEM). Serum PTH levels were similar in all groups, except for day 49, when an increase in the D group was observed. Bone histomorphometry showed decreased bone remodeling in the D group, which confirmed the serum BGP findings. Aldose reductase was detectable in the small blood vessels and in bone itself. Sorbinil failed to influence the biochemical or bone histomorphometric abnormalities associated with diabetes. Serum BGP may be a valuable marker for the decreased bone remodeling in insulinopenic diabetes.

Aldehyde Reductase↗

Cyclosporin-A in vivo produces severe osteopenia in the rat: effect of dose and duration of administration.

Cyclosporin-A (CsA) inhibits the in vitro bone-resorbing effects of cytokines. We investigated the in vivo effects of CsA on rat bone mineral metabolism. Three groups of male Sprague-Dawley rats were administered vehicle or low dose (7.5 mg/kg) or high dose (15 mg/kg) CsA for 14 and 28 days. Ionized calcium, PTH, serum bone Gla protein, blood urea nitrogen, creatinine, magnesium, and 1,25-dihydroxyvitamin D were determined serially. No significant changes in calciotropic hormones or renal function were noted. Significant bone resorption and trabecular bone loss occurred in the high dose group by day 14 and in both groups by day 28. Bone Gla protein was significantly increased within 2 weeks in both dosage groups (P less than 0.005), reflecting increased bone remodeling. CsA in vivo resulted in an unexpected and significant increase in bone remodeling, with striking bone loss. These effects are dependent on the duration and dose of CsA and appear to be mediated at a local level.

Animals↗

Low-dose streptozocin-induced diabetes in mice. Electron microscopy reveals single-cell insulitis before diabetes onset.

We investigated the morphology of mouse islets 5 days after completion of low-dose streptozocin treatment of C57BL/6 mice by electron microscopy. At this stage, mice were still normoglycemic and light microscopy did not reveal massive islet infiltration. The electron-microscopic investigation revealed two characteristics indicative of ongoing islet cell destruction. In all islets investigated, lysed islet beta-cells were recognized by disrupted plasma membranes and concomitantly decreased plasma contrast. Many of the lysed islet beta-cells still contained numerous insulin granules. We also found immunocytes scattered throughout the islets, most of which could be identified as macrophages. Some were found engaged in phagocytosis of islet beta-cell debris. This early stage of islet lesion termed single-cell insulitis is followed by the well-known later stage of massive infiltration easily recognized in light microscopy. Administration of silica particles to mice treated with low-dose streptozocin inhibited macrophage infiltration of islets as shown by immunocytochemistry with macrophage-specific monoclonal antibody F4/80. In parallel, the development of hyperglycemia was suppressed. The observations favor a pathogenic role of macrophages in islet destruction.

Animals↗

Treatment of the geriatric dentally phobic patient.

The elderly patient, who is phobic or exceedingly anxious established behavior patterns years ago when dentistry was not as advanced as today and when dental experiences were unpleasant and uncomfortable. The elderly phobic patient may view his role as a passive participant as he was in his youth; that is, he fears that the dentist will treat him as he was treated by an unsympathetic dentist years ago. In order to create acceptable, positive experiences for the phobic or anxious patient, the first appointment should give the patient an opportunity to know the dentist and office staff. The dentist can take this opportunity to reassure the patient that pain does not have to be a part of dental treatment. It is imperative that the dentist and staff involve the patient and instill trust. One must always have the patient's perspective in mind and constantly, by word or deed, assure the patient that he will always be in control of decisions and treatment. The dentist must not view the geriatric patient as different from his other patients. He or she must be perceptive and deliberate in the initial encounter and early relationship and determine what is the best treatment for that patient. The dentist must be realistic about the goals and requirements of that patient, for whom the dentist's ultimate objective should be to achieve quality dental care, done expeditiously, without fear and pain.

Aged↗

Long term administration of prostaglandin inhibitors in vivo fail to influence cartilage and bone mineral metabolism in the rat.

Non-steroidal anti-inflammatory drugs are potent inhibitors of prostaglandin synthesis. Prostaglandins have been reported to stimulate bone resorption and to enhance 1,25(OH)2D3 production in vitro. In patients with osteoarthritis of the hip, non-steroidal anti-inflammatory drugs are associated with localized accelerated bone destruction. The mechanisms for some of the in vivo effects are unknown. The effects of prostaglandin inhibitors on normal bone and mineral homeostasis has not been established. Therefore 15 male Sprague-Dawley rats were given daily injections of indomethacin, 2 mg/kg s.c., for either 4 or 8 weeks (a dose known to inhibit fracture healing) and compared to 13 control rats given vehicle alone. Serum Ca, BGP and 1,25(OH)2D were measured serially until day 56 in nine of those administered indomethacin and in seven of the control animals. Bone histomorphometry with double tetracycline labelling and cartilage histology were performed after sacrifice on days 28 and 56. Compared to control animals serum ionized calcium, BGP and 1,25(OH)2D levels were not altered by indomethacin administration. Quantitative histomorphometric indices of bone formation and resorption as well as cartilage histology were not significantly different between the two groups. With time, however, serum bone Gla protein fell in the control and indomethacin-treated groups, while calcium and 1,25-dihydroxyvitamin D remained stable. The age related decline in this serum marker of bone turnover was accompanied by a parallel reduction in the level of bone remodelling activity. These reductions in bone formation and bone resorption were not retarded or enhanced by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Unusual stable isotope ratios in amino acid and carboxylic acid extracts from the Murchison meteorite.

Much effort has been directed to analyses of organic compounds in carbonaceous chondrites because of their implications for organic chemical evolution and the origin of life. We have determined the isotopic composition of hydrogen, nitrogen and carbon in amino acid and monocarboxylic acid extracts from the Murchison meteorite. The unusually high D/H and 15N/14N ratios in the amino acid fraction (delta D = 1,370% after correction for isotope exchange; delta 15N = 90) are uniquely characteristic of known interstellar organic materials. The delta D value of the monocarboxylic acid fraction is lower (377%), but still consistent with an interstellar origin. These results confirm the extraterrestrial origin of both classes of compound, and provide the first evidence suggesting a direct relationship between the massive organo-synthesis occurring in interstellar clouds and the presence of pre-biotic compounds in primitive planetary bodies. The isotope data also bear on the historical problem of distinguishing indigenous material from terrestrial contaminants.

Amino Acids↗

Cellular immunity and T-lymphocyte subsets in young children with acute measles.

The changes occurring in the T-cell subsets during acute symptomatic measles were examined in ten malnourished and 18 well nourished hospitalized children younger than 5 years of age (median age 14 months). A significant decrease in total lymphocyte count was observed, which was due mainly to a decrease in helper/inducer T lymphocytes, whereas the suppressor/cytotoxic T-lymphocyte subset remained unchanged. Consequently, helper/suppressor ratio decreased significantly during the acute phase of the disease. A reduced response to mitogens (PHA, Con A, PWM) was also observed. Malnourished infants showed a trend toward a deeper depression in both helper and suppressor T cells during the acute phase than well nourished children, whereas the helper/suppressor ratio remained similar in the two groups.

Acute Disease↗