Plasma vitamin D-binding globulin in vitamin D deficiency, pregnancy and chronic liver disease.

Plasma concentrations of vitamin D-binding globulin were measured by radial immunodiffusion in healthy subjects, pregnancy, and during oestrogen therapy. Subjects with disorders of vitamin D metabolism (dietary deficiency, malabsorption, anticonvulsant therapy, chronic liver disease) were also studied. Neither sex nor age influenced the plasma vitamin D-binding globulin concentration in healthy subjects, but there was a significant increase in concentration during pregnancy and oestrogen therapy. Elevated levels were found in vitamin D deficient elderly but not younger subjects, while levels in subjects with chronic liver disease were significantly reduced. Normal levels of vitamin D-binding globulin were present in hypervitaminosis D and no vitamin D-binding globulin was detected in human milk. No correlation was observed between plasma 25-hydroxycholecalciferol levels and plasma vitamin D-binding globulin concentrations.

Impaired mononuclear phagocyte function in patients with severe acute pancreatitis: evidence from studies of plasma clearance of trypsin and monocyte phagocytosis.

Activated proteases in plasma are complexed by alpha 2-macroglobulin. Although the complexes retain peptidase activity, they are usually eliminated promptly by mononuclear phagocytes. In severe acute pancreatitis, almost 30% of plasma alpha 2-macroglobulin becomes complexed, suggesting impaired clearance. In the present study, plasma [methyl-14C]trypsin clearance and monocyte phagocytosis were investigated. Attacks complicated by major organ-system failure, pancreatic pseudocyst, abscess, or necrosis were graded severe (median Ranson score 5.5). Plasma [methyl-14C]trypsin half-life was significantly increased in severe attacks (N = 7, median 21.1 min), compared to mild attacks (N = 14, median 15.4 min, P < 0.05) and healthy controls (N = 4, median 10.8 min, P < 0.02). Monocyte phagocytosis was significantly lower in severe attacks (N = 9, median 3.6%) compared to mild attacks (N = 20, median 20.8%, P < 0.01) and healthy controls (N = 8, median 26.9%, P < 0.01). Plasma [methyl-14C]trypsin half-life and monocyte phagocytosis were significantly inversely correlated (r = -0.51, P < 0.01). Impaired clearance of circulating trypsin in acute pancreatitis is potentially deleterious but may be reversed by stimulating mononuclear phagocytes.

Vitamin D status of residents of an old people's home and long-stay patients.

The vitamin D status of residents of an old people's home and long-stay patients was assessed by means of plasma 25-hydroxycholecalciferol (25-OHD) estimations. The residents of the old people's home had a higher mean plasma 25-OHD concentration than long-stay patients. Both groups had diets with vitamin D intakes of less than 2.5 micrograms (100 IU) per day and the conclusion is that solar exposure is the major determinant of the concentration of circulating 25-OHD.

The role of peptidases in cancer of the rectum and sigmoid colon.

Increased levels of peptidases are found in some human carcinomas and may be related to invasive potential. We therefore measured the activity of four peptidases in 50 specimens of tumour and normal colonic wall from patients with a rectal or sigmoid carcinoma, and correlated this with the stage, differentiation, fixity of the tumour and presence of venous invasion, determined histologically. Since acute phase reactant proteins (APRP) may inhibit these proteolytic enzymes we have also measured serum levels of two relevant APRPs, alpha 1 acid glycoprotein (AGP) and C-reactive protein (CRP) pre-operatively. Activity of cathepsin B, cathepsin H and collagenase-like peptidase (CLP) was determined fluorimetrically and collagenase photometrically. Significantly elevated activity of cathepsin B, CLP and collagenase was found in tumour compared with normal colonic wall (median values: (nmol (mg protein)-1 min-1) Cat B 0.71 and 0.42 (P less than 0.001), CLP 25.24 and 12.25 (P less than 0.0001) and collagenase 0.49 and 0.31 (P less than 0.001). There was no correlation between the activity of these enzymes expressed as a ratio of tumour/colonic wall, and differentiation or Dukes' stage of the tumour. However, there was significant elevation of activity of cathepsin B in tumours with local spread (n = 13) compared with those with no spread (n = 37) (median values 2.76 and 1.36 respectively (P less than 0.001] and also in tumour with venous invasion (n = 24) compared with tumours without (n = 26) (median values 1.82 and 1.18 respectively (P less than 0.01]. Pre-operative serum levels of CRP were inversely correlated with the activity of CLP and cathepsin H and collagenase in the tumours (rs = 0.332, 0.359 (P less than 0.05) and 0.302 (P = 0.05) respectively). Thus certain peptidases are raised in rectal and sigmoid tumours. Activity of cathepsin B appears related to local tumour invasion. APRP may have a role in inhibiting the activity of these enzymes. These findings may have therapeutic implications.

Changes in skinfold thickness with increasing age.

Skinfold thickness measurements on 626 normal subjects of both sexes between the ages of 5 months and 73 years demonstrated a tri-phasic relationship between loss of skin thickness and age. Measurements for infants of either sex were indistinguishable and high, falling rapidly to levels which only changed slightly over the period 20-60 years. Thereafter, massive loss of skin-thickness occurred in both sexes. Throughout the major portion of adult life the values obtained for females were significantly lower than those for males. It is suggested that the three phases may be associated with progressive dehydration, failure to synthesize collagen and frank degradation of the collagen of the dermis.

Intestinal cholecalciferol absorption in the elderly and in younger adults.

1. A method for assessing cholecalciferol absorption in man is described. 2. The intestinal absorption of [3H]cholecalciferol was studied in 20 female geriatric patients, most of whom were vitamin D-depleted. 3. The plasma [3H]cholecalciferol response after oral ingestion was significantly lower than that of a group of younger female subjects. 4. The plasma response of labelled polar metabolites of cholecalciferol was also lower in the geriatric than in the younger group, suggesting that increased removal of label by conversion into more polar metabolites could not account for the reduced plasma [3H]cholecalciferol response. 5. There was no evidence that alteration in gastrointestinal motility could account for the different rate of appearance of the labelled vitamin in the plasma in the two groups. 6. It is suggested that there is a defect in intestinal absorption of cholecalciferol in the elderly.

Response of plasma-25-hydroxyvitamin D to ultraviolet irradiation in long-stay geriatric patients.

The response of plasma-25-hydroxyvitamin D (25[OH]D) to different exposures to ultraviolet irradiation has been studied in patients in long-stay geriatric wards. Increases sufficient to bring the plasma-25(OH)D into the normal range may be obtained with doses less than those required to produce erythema. The provision of such background irradiation may be a suitable method of preventing vitamin-D deficiency in elderly subjects who receive very little exposure to sunlight.