Citations

1. To investigate whether there is a nyctohemeral rhythm in bone turnover, we measured serum bone Gla-protein (osteocalcin, an index of osteoblast activity) concentration every 2 h and urinary deoxypyridinoline (a marker of bone collagen resorption) excretion for 8 h periods in 10 pubertal girls (aged 10–14 years), 15 premenopausal women (aged 20–49 years) and 17 postmenopausal women (aged 50–75 years). 2. The serum concentration of bone Gla-protein and the urinary excretion of deoxypyridinoline were five times higher in the pubertal girls than in the premenopausal women. The urinary excretion of deoxypyridinoline in the postmenopausal women was twice that in the premenopausal women. 3. There was a nyctohemeral pattern in all age groups with mean night-time increases of 28% (P<0.001) in the urinary excretion of deoxypyridinoline and of 5% (P<0.001) in the serum bone Gla-protein concentration. 4. There also were nyctohemeral patterns in the urinary excretion of calcium (P<0.02), sodium (P<0.001) and potassium (P<0.001), with decreases at night. There was a negative correlation between the night-time changes in the urinary excretion of deoxypyridinoline and calcium, especially in adult women (P<0.01). 5. The serum level of parathyroid hormone increased with age, but this effect was only observed at night (01.00 to 07.00 hours). There was a nyctohemeral rhythm of the serum intact parathyroid hormone level at all ages, with a peak in the afternoon and night. 6. Thus, at night, there is a large increase in bone resorption and a small increase in osteoblastic activity, representing a nyctohemeral rhythm of bone turnover. Although the amplitudes of bone formation and bone resorption are greater during growth, the pattern of nyctohemeral changes present during growth continues up to the age of 75 years.

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51–76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51–79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P < 0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r= 0.61, P < 0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.

1. In canine cutaneous veins, local moderate warming (37°-41°C) augments the responsiveness to postjunctional α1-adrenergic stimulation but depresses that to postjunctional α2-adrenergic activation. Moderate cooling (37°-24°C) has the opposite effect. 2. The effects of warming and cooling on α1-adrenergic responses are buffered by a large receptor reserve, allowing for the predominance of alterations in α2-adrenergic responsiveness.

1. The effect of 1,25-dihydroxyvitamin D [1,25-(OH)2D] on dietary oxalate absorption and postprandial urine supersaturation with calcium oxalate was determined in 11 normal subjects. 2. 1,25-(OH)2D increased the urinary excretion of orally administered [14C]oxalate in the 8 h period after a liquid meal containing 1.875 mmol of calcium and 0.83 mmol of oxalate (P < 0.01), and during a 48 h period when the subjects ingested a diet containing 25 mmol of calcium and 3.3 mmol of oxalate/day (P < 0.01); however, 1,25-(OH)2D administration had no effect on [14C]oxalate excretion when calcium was removed from the liquid meal. 3. 1,25-(OH)2D increased 24 h urinary oxalate excretion from 28.7 ± 2.1 mmol/mol of creatinine to 36.8 ± 2.6 mmol/mol of creatinine (P < 0.05) on the 10 mmol/day calcium diet and from 26.4 ± 2.9 to 33.2 ± 2.2 mmol/mol of creatinine (P < 0.1) on the 25 mmol/day calcium diet. 4. A linear correlation (r = 0.72) was found between plasma 1,25-(OH)2D levels and urinary [14C]oxalate excretion after the liquid meal. 5. 1,25-(OH)2D administration produced postprandial supersaturation of urine with calcium oxalate and calcium oxalate crystalluria. 6. These studies suggest that 1,25-(OH)2D increases oxalate absorption (and urinary excretion) by increasing calcium absorption, which results in less binding of calcium to oxalate in the intestine; therefore more oxalate is available for absorption. The combined effect of increased calcium and oxalate absorption results in postprandial supersaturation of urine with calcium oxalate, with resultant crystalluria.

1. The crystal growth inhibitory activity of mixtures of known inhibitors and of mixtures of known inhibitors with normal urine was determined in calcium oxalate monohydrate and hydroxyapatite seeded crystal growth systems. 2. The inhibitory activity of the mixtures was compared with the measured activity of the individual components of the mixtures. All mixtures had inhibitory activity equal to the sum of the activities of their components, with the exception of RNA/urine mixtures in the calcium oxalate monohydrate system. 3. RNA/urine mixtures had inhibitory activity toward calcium oxalate monohydrate crystal growth which was less than would be predicted from the activity of the RNA and of the urine which were added. This reduced inhibitory activity was shown to be due probably to hydrolysis of RNA by the ribonuclease activity normally present in urine. 4. The results of these experiments make it possible to determine quantitatively the contribution of various naturally occurring urinary crystal growth inhibitors to the total measured inhibition observed in urine.

1. Whewellite (calcium oxalate monohydrate) crystals were found to induce epitaxially the heterogeneous nucleation of brushite (calcium monohydrogen phosphate dihydrate) from its metastable supersaturated solution in approximately one-quarter of the time required for spontaneous precipitation in the absence of added nucleating agents. Scanning electron-microscope observation of the crystalline phase showed brushite crystals originating from the whewellite seed crystals. 2. Crystal growth, upon nucleation, proceeded rapidly, and the metastable solutions quickly approached saturation. 3. Brushite crystals also induced the precipitation of calcium oxalate crystals in about one-quarter of the time required for spontaneous precipitation; however, the rate of crystal growth was considerably slower. In support of the chemical data, scanning electron micrographs showed few crystals of calcium oxalate nucleated on the surface of the brushite seed. 4. The results provide some insight into the cause of stones containing calcium oxalate or calcium phosphate (or both), which form in the normally acid environment of human urine.

1. Perfusion of the human jejunum with low concentrations of glycine-conjugated bile acids in physiological solutions induced net fluid flow that varied between absorption and secretion, with only slight variation of the luminal osmotic and ionic milieu. 2. Transmucosal net flux rates for water and the principal ions were calculated. Regression analysis of the flux data was consistent with the concept of a ‘net transported fluid’ which was iso-osmotic with respect to the lumen, with a superimposed fixed net anion exchange unaffected by the rate or direction of bulk flow. 3. Recalculation of earlier data from comparable studies of the human colon showed similar relationships consistent with varying iso-osmotic bulk flow and fixed ion exchange, the latter differing from that found in the proximal bowel. 4. Studies were performed also in the human ileum. Variable iso-osmotic bulk flow was again encountered, but ion exchange was of a lower magnitude than in the jejunum or colon. Qualitatively, ion exchange in the ileum was intermediate between the jejunum and colon. 5. These analyses suggest that transmucosal bulk flow and ion exchange may be quantitatively and spatially independent processes. They provide support for the hypothesis that bulk flow may be intercellular (and hence extracellular), while ion exchange may take place across the luminal face of the mucosal cell. 6. Secretory agents, such as the dihydroxy bile acids, provide a useful means of analysing solute-solvent flow relationships in greatly differing bulk flow conditions with relatively stable physicochemical parameters.