Graeme Findlay Bryce

DIFFERENCES IN SERUM BONE GLA PROTEIN WITH AGE AND SEX

Serum bone Gla protein (BGP) was measured by radioimmunoassay in 166 healthy men and women aged 30-90 years. Serum BGP levels increased with age in both sexes and were higher in women than in men at all ages. The most striking rise occurred in women after age 40-49. BGP was significantly correlated positively with serum alkaline phosphatase and negatively with midshaft and distal bone mass in both sexes. In women only, BGP levels were significantly positively related to levels of immunoreactive parathyroid hormone (iPTH). When age was included in the multiple regression analysis BGP was still correlated with alkaline phosphatase in both sexes and iPTH in women only. Serum BGP levels were significantly higher in 13 osteoporotic patients than in age-matched controls. It is postulated that with increasing age 1,25-dihydroxyvitamin D levels fall, causing a rise in iPTH and thus in bone turnover, which is reflected by a rise in BGP levels.

The influence of age on bone mineral regulating hormones

The objective of this study was to determine the effect of age on the blood levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) and immunoreactive parathyroid hormone (iPTH) in normal, healthy males and females. A total of 855 normal subjects (361 males and 494 females) were studied. The results show that for healthy males, blood concentrations of 1,25(OH)2D remained essentially constant with increasing age up to age 65, and then the concentrations decreased significantly. For healthy females, 1,25(OH)2D increased up to age 65, and then decreased at a significant rate. Serum iPTH in males increased with advancing age, but the rate of increase was greater after age 65. In females a significant increase in iPTH concentrations did not occur until after age 65. Serum creatinine increased in both males and females with advancing age.

Preliminary evidence of the effect of calcium supplementation on blood pressure in normal pregnant women

In this study the hypothesis that calcium supplementation during pregnancy can modify blood pressure patterns in a population of normal pregnant women was tested. Thirty-six women with normal single pregnancies, between 20 and 35 years of age, in the second trimester of gestation (15 weeks), were randomly assigned to receive 1 gm of calcium per day (n = 11), 2 gm per day (n = 11), or a placebo (n = 14). No differences were observed at the times of admission into the study (baseline) in demographic and clinical variables or in the calcium intake of each group. Baseline blood pressure measures in several positions also were not different. After the initial blood pressure measures (fifteenth week), five follow-up blood pressure measures were obtained. The supplemented groups had significantly lower diastolic blood pressure than the control subjects between the twentieth and twenty-fourth weeks of gestation. Thereafter, an increase in the control group and the group receiving 1 gm of calcium was observed, but levels were similar at term. On the contrary, patients receiving 2 gm of calcium had blood pressure values that remained significantly lower throughout the third trimester. No differences or clear patterns were observed in the blood levels of calcium, magnesium, phosphorus, and proteins between and within groups during gestation. A possible explanation involving parathyroid hormone is attempted.

An improved competitive protein binding assay for 1,25-dihydroxyvitamin D

Abstract A practical procedure for the routine analysis of blood levels of 1,25-dihydroxyvitamin D has been developed. 1,25-Dihydroxyvitamin D was extracted from serum with methylene chloride:methanol. The concentration of acidic lipids in the extract was reduced with an alkaline wash. The serum extract was chromatographed on Sephadex LH-20, which was extracted with methanol prior to use in the columns. The chromatography was aided by a device which simultaneously collected and evaporated the eluates. High pressure liquid chromatography to further purify 1,25-dihydroxyvitamin D was found to be unnecessary. These modifications resulted in negligible 1,25-dihydroxyvitamin D values ( 3 standard curve capable of measuring 1.5 pg of 1,25-dihydroxyvitamin D 3 was achieved with the use of high specific activity 3 H-labeled 1,25-dihydroxyvitamin D 3 (92 Ci/mmol). The sensitivity of the standard curve, combined with changes in the resuspension of the assay sample, reduced the required amount of serum for an assay from 5 to 2 ml. A simplified centrifugation procedure for the separation of bound from free 1,25-dihydroxyvitamin D was attained by the inclusion of bovine γ-globulin in the polyethylene glycol precipitation.

Metabolic consequences of fasting in old lean and obese Zucker rats.

The effects of fasting on lipid and carbohydrate metabolism and plasma insulin and glucagon levels were compared in lean and obese Zucker rats. Sixteen-month-old female and male rats were fasted for periods of 2, 4, 6 and 12 days. Fasting produced significant decreases in hepatic rates of lipid, cholesterol, and glycogen synthesis, as well as circulating levels of triglycerides, cholesterol, phospholipids, and insulin. Significant increases in hepatic lipid levels and serum free fatty acids were noted. When compared to lean rats, obese rats had elevated rates of hepatic lipid and glycogen synthesis, hepatic lipid and glycogen stores, serum triglycerides, cholesterol, phospholipids, and plasma insulin. Lean rats had higher plasma glucagon levels. Sex differences in several parameters were observed. Females demonstrated higher levels of lipid and cholesterol synthesis and serum free fatty acids, whereas serum cholesterol levels and hepatic glycogen stores were higher in males. Following a 12-day fast, carcass fat and protein content were decreased in both lean and obese rats, but the obese animals maintained an obese body composition. It is concluded that fasting results in qualitatively similar metabolic and hormonal changes in both lean and obese rats, but that abnormalities in carbohydrate and lipid metabolism persist in obese rats even after a 12-day fast.

Mitochondrial inclusions in keratinocytes of hairless mouse skin exposed to UVB radiation

Mitochondrial inclusions were observed in keratinocytes during an ultrastructural investigation of the skin of hairless mice exposed to UVB radiation. Mice were irradiated 3 times a week for 5–6 months with sunlamps at individual doses seldom exceeding 0.06 J/cm2. Strips of dorsal skin were processed for electron microscopic examination; blocks were sectioned to include both epidermis and dermis. Mitochondrial inclusions were observed in keratinocytes of the basal, spinous and granular layers. They were spherical in shape and of moderate and homogeneous electron density. Mitochondria toward the upper regions of the epidermis were swollen and had fragmented cristae; mitochondria in the lower areas of the epidermis usually contained smaller and less dense inclusions and intact or partially disrupted cristae. Because mitochondria are essential in providing the energy for cellular function, keratinocyte mitochondrial damage induced by UVB radiation may have serious pathological consequences. Possible mechanisms involved in mitochondrial inclusion formation are suggested.

Ultrastructural effects of UVB radiation and subsequent retinoic acid treatment on the skin of hairless mice

The infrastructure of hairless mouse skin exposed to UVB radiation and followed by retinoic acid treatment was studied to identify alterations induced in both epidermis and dermis. Female mice were irradiated 3 times weekly for 5–6 months; a group of these mice was then treated topically 3 times weekly for 10 weeks with either 25 μg all‐trans‐retinoic acid dissolved in acetone or with acetone alone. Age‐matched, unexposed, untreated mice served as controls. Cutaneous changes induced by UVB radiation included keratinocyte mitochondrial inclusions often accompanied by damaged cristae, duplication of basement membrane, increased number of dermal fibroblasts, inflammatory cells and elastic fibers, and abnormal elastic fibers. Subsequent retinoic acid treatment resulted in more prominent mitochondrial inclusions which sometimes coalesced to form irregular contoured bodies. Also observed were lipid droplets in the stratum corneum, glycogen deposits in keratinocytes and granular material in dilated keratinocyte endoplasmic reticulum. Poorly differentiated epidermis with necrotic or apoptotic cells was present in some specimens. Elastic fibers were fewer and usually morphologically normal. Skin exposed to UVB and treated with vehicle appeared similar to control except for the presence of excess basement membrane and occasional small mitochondrial inclusions. Because of the heightened concern regarding UV radiation‐induced damage to the human skin and the current topical use of retinoids, the cutaneous changes described are considered worthy of attention.

A comparative study of several serotonin receptor antagonists on basal and stimulus induced release of insulin and glucagon in the intact rat.

Abstract Several commonly used serotonin receptor antagonists were studied for their ability to influence basal plasma insulin and glucagon (using 30K antibody) levels as well as the response of these hormones to a glucose or arginine challenge administered systematically to overnight fasted rats. Cyproheptadine, in contrast to other antagonists employed, induced large increases of insulin, glucagon and glucose, although this hyperinsulinemia was of a smaller magnitude when compared with hormone levels observed during an equivalent hyperglycemia resulting from glucose administration. The pancreatic response to a glucose load (increased insulin and decreased glucagon release) and an arginine load (increased insulin and glucagon release) were prevented by cyproheptadine pretreatment. Basal insulin levels were bot consistently altered by methysergide or cinanserin and were slightly elevated by metergoline. Basal glucagon levels were unaffected by these drugs. These three agents potentiated the insulinotropic effect of an arginine load whereas only metergoline exerted a similar effect on the response to glucose loading. Glucagon release in response to these stimuli was not significantly altered by drug pretreatment.