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Biomedical subjects

K Cashman

Publications and source records attributed to K Cashman.

10 recordsLinked to original sources
PubMed1999

The effect of moderately and severely restricted dietary magnesium intakes on bone composition and bone metabolism in the rat.

Forty 3-week-old male rats, Wistar strain, average weight 59 g, were randomized by weight into five groups of eight rats each. Three groups were fed ad libitum on a semi-purified diet containing (per kg) 400 (adequate), 200 (moderately Mg-restricted) or 20 (severely Mg-restricted) mg Mg for 3 weeks while two groups were pair-fed with the Mg-adequate diet in the same quantities as those consumed by the two Mg-restricted groups respectively. While weight gains and food conversion efficiency values for the Mg-restricted groups were similar to those of the corresponding pair-fed control groups, serum and kidney Mg, and femoral dry weight were reduced by 70, 7 and 9% respectively in the severely Mg-restricted group and were unaffected in the moderately Mg-restricted group. Significant reductions were observed in urinary pyridinoline (Pyr) (by 44 and 34%) and deoxypyridinoline (Dpyr) levels (by 40 and 33%) (markers of bone resorption), serum osteocalcin levels (by 46 and 28%) (marker of bone formation), femoral Mg levels (by 52 and 14%) and osteocalcin mRNA levels (by 46 and 22%) compared with the corresponding pair-fed controls, in the severely and moderately Mg-restricted groups respectively, and these reductions, except for those in urinary Pyr and Dpyr, were more marked in the severely Mg-restricted group. Femoral Ca and P concentrations were unaffected by dietary Mg restriction. These results show that not only severe but also moderate dietary restriction of Mg over 21 d results in qualitative changes in bone (i.e. reduced Mg concentration) as well as in aberrant bone turnover in young growing rats (i.e. severely depressed rates of bone formation and bone resorption), which may impair bone development and bone strength.

Amino Acids↗
PubMed1999

The effect of magnesium supplementation on biochemical markers of bone metabolism or blood pressure in healthy young adult females.

OBJECTIVES: To investigate the effects of increasing Mg intakes, above the usual dietary intake, on blood pressure and on biomarkers of bone metabolism in healthy young adult females. DESIGN: A double-blind, placebo-controlled, randomised crossover Mg intervention trial. SETTING: The study was conducted in the Department of Nutrition, University College, Cork, Ireland. SUBJECTS: Twenty-six healthy (normotensive) adult females aged 20-28 y were recruited from University College, Cork. INTERVENTION: Subjects were randomly assigned to their self-selected diets (approximately 11 mmol Mg/d) or their self-selected diet with a 10 mmol/d Mg supplement as Mg(OH)2 (approximately 22 mmol Mg/d) for 28 d followed by cross-over to the alternative diet for a further 28 d. During each dietary period urines (last 3 d) and blood (morning of 27 d) were collected and blood pressure was measured on the morning of 28 d. RESULTS: Increasing Mg intake from the usual level (11 mmol/d) to 22 mmol/d for 28d increased urinary excretion of Mg by 36% and erythrocyte Mg content by 5% but had no effect on serum Mg, Ca, PTH, osteocalcin or bone-specific alkaline phosphatase (biomarkers of bone formation), urinary pyridinium crosslinks of collagen (biomarkers of bone resorption), or on blood pressure. CONCLUSION: Increasing the mean Mg intake in healthy young adult females above the usual dietary intake, which is currently above the US EAR (estimated average requirement), but below the US RDA for Mg, does not affect blood pressure or the rate of bone turnover.

Adult↗
PubMed1999

Effect of dietary copper intakes on biochemical markers of bone metabolism in healthy adult males.

OBJECTIVE: To investigate the effects of changing from a medium (1.6 mg Cu/d) to a low (0.7 mg Cu/d) or a high (6.0 mg/d) Cu intake on biochemical indices of bone turnover in healthy adult males. DESIGN: A longitudinal intervention trial. SETTING: The study was conducted at the Institute of Food Research, Norwich, UK. SUBJECTS: Eleven healthy adult males aged 20-59 y were recruited from Norwich Research Park. INTERVENTION: Subjects were given medium (1.6 mg/d), low (0.7 mg/d) and high (6.0 mg/d) intakes of Cu, in that order, over consecutive 8 week periods with a minimum of 4 week washout periods. On the last d of each dietary period fasting first void urine and blood were collected. RESULTS: Serum caeruloplasmin or Cu (indices of Cu status), serum osteocalcin (biomarker of bone formation), urinary creatinine (Cr) were unaffected by dietary Cu intake. Urinary Pyr/Cr and Dpyr/Cr (biomarkers of bone resorption) were significantly increased (P < 0.05) (by 30% and 25%, respectively), when subjects were switched from the medium to the low Cu diet and were significantly decreased (P < 0.05) (by 30%) and 22% respectively), when subjects were switched from the low to the high Cu diet. CONCLUSION: The findings of the present study could have implications for bone health in individuals with marginal Cu intakes. Thus, further studies are warranted to better define the relationship of marginal Cu intakes to bone health.

Adult↗
PubMed1998

Inter and intra-individual variations in urinary excretion of pyridinium crosslinks of collagen in healthy young adults.

OBJECTIVES: To investigate the inter- and intra-individual variation in the excretion of pyridinium crosslinks of collagen in first morning void urine samples in healthy young adults. DESIGN: An observational study in which urinary pyridinium crosslinks of collagen were measured in fasting first void urine samples over five consecutive days. SETTING: The study was conducted in the Department of Nutrition, University College, Cork, Ireland. SUBJECTS: A total of 17 healthy young adults (11 females and 6 males) aged 22-26 y were recruited from University College, Cork. The subjects were without any history of bone or articular disease, and with no intake of medicine that could affect bone or cartilage metabolism. RESULTS: There were large intra-individual variations in the excretion of both pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in first morning void urine samples and the ratios of intra- to inter-individual variation were high. In comparison, inter-individual variation in excretion of crosslinks was relatively low. No significant day-to-day variation was observed either in Pyr or Dpyr excretion when either five, four or three consecutive days or four or three non-consecutive days of urine sampling were used. However, there were significant differences between any two consecutive or non-consecutive days in both Pyr and Dpyr excretion. CONCLUSIONS: The relatively large day-to-day variation in urinary excretion of the pyridinium crosslinks emphasises the need to use multiple samples to characterise the crosslink excretion of an individual. The present study demonstrates that urine sampling for these crosslinks necessitates at least a 3 d collection to ensure that day-to-day effects are not a significant source of variation included in the data analysis.

Adult↗
PubMed1998

Intestinal calcium absorption in the aged rat: evidence of intestinal resistance to 1,25(OH)2 vitamin D.

We investigated the role of circulating 1,25-dihydroxycholecalciferol (1,25(OH)2D) and intestinal resistance to 1,25(OH)2D in the diminished intestinal calcium absorption capacity of the senescent rat. We measured plasma 1,25(OH)2D, total and unoccupied duodenal vitamin D receptor, duodenal calbindin D9k protein (calbindin D), and net dietary calcium absorption in rats at several ages. As expected, circulating 1,25(OH)2D, calbindin D, and net calcium absorption decreased with age. However, no age-related changes were evident in intestinal vitamin D receptor levels. We then measured duodenal calcium absorption from in situ intestinal loops after continuous s.c. infusion of 1,25(OH)2D for up to 6 days and found that despite a marked elevation of plasma 1,25(OH)2D duodenal calcium absorption was significantly lower in old compared with young rats. To assess calcium absorption over a wide physiological range of plasma 1,25(OH)2D, in a dose-response study we altered plasma 1,25(OH)2D by continuous infusion of 1,25(OH)2D (at 0, 4, or 14 ng/100 g BW/day) for 9 days. We found that the slope of the linear regression between plasma 1,25(OH)2D and duodenal Ca transport in old rats was only 46% of that observed in young rats, suggesting an age-related resistance of the duodenal calcium transport process to the hormonal action of 1,25(OH)2D. Collectively, our observations suggest a dual defect in vitamin D metabolism in old animals: one defect related to the low circulating levels of 1,25(OH)2D and a second defect related to a relative intestinal resistance to the action of 1,25(OH)2D, which is apparently not due to a reduction in intestinal vitamin D receptor levels.

Absorption↗
PubMed1996

The effects of aging on the bone inductive activity of recombinant human bone morphogenetic protein-2.

We examined the effects of gain on the ectopic bone-forming ability of recombinant human BMP-2 (rhBMP-2) in rats and investigated the mechanism by which aging might affect this type of bone. Bone formation induced after 12 days of sc implantation of 5 micrograms rhBMP-2 was reduced as animals aged from 1-16 months. The osteocalcin messenger RNA levels of implants also declined in aging animals. When the implant period was doubled, 16-month-old rats formed amounts of bone equivalent to those in 3-month-old rats. Increasing the dose of rhBMP-2 increased bone formation in older rats. To get a response comparable to that seen in 1-month-old rats given 5 micrograms rhBMP-2 for 12 days, 3-month-old rats required 30 micrograms rhBMP-2, whereas 16-month-old rats required 60 micrograms. Treatment with either GH or 1,25-dihydroxyvitamin D3 during the 12-day implantation period returned the bone formation in 16-month-olds rats to that in 3-month-old rats. These studies show that aging blunts rhBMP-2 inducted bone formation in rats. We speculate that the decreased response may be due in part to a decrease in the number of mesenchymal stem cells present in order rats or to a change in the responsiveness of these target cells to rhBMP-2.

Aging↗
PubMedDate not supplied

The genetics of osteoporosis: vitamin D receptor gene polymorphisms and circulating osteocalcin in healthy Irish adults.

BACKGROUND: A relationship between bone turnover and the vitamin D receptor (VDR) genotype is reported in Australian subjects of UK-Irish descent. There is conflicting evidence of linkage between the VDR genotype and differences in bone mineral density. No such study has been carried out on a resident Irish population. AIMS: This study examined the relationship between serum osteocalcin (a marker of bone turnover) and VDR genotype in Irish adults. METHODS: One hundred and eighteen healthy Irish adults aged between 19 and 67 were recruited and had two fasting blood samples taken. One sample was analysed for osteocalcin by enzyme immunoassay. The other was used to isolate genomic DNA and determine VDR genotype. RESULTS: Tt was the most prevalent VDR genotype (53%) and tt (15%) the least prevalent in this group of healthy Irish adults. The tt VDR genotype was associated with significantly higher levels of serum osteocalcin (29% and 40%) than the Tt or TT VDR genotypes. CONCLUSIONS: These findings suggest that healthy Irish adults with the tt VDR genotype have higher rates of bone turnover than those with Tt or TTVDR genotypes. They may have a higher risk of low bone mineral density and osteoporosis in later life.

Adult↗
PubMedDate not supplied

Apolipoprotein E gene polymorphisms and serum cholesterol in healthy Irish adults: a proposed genetic marker for coronary artery disease risk.

BACKGROUND: The apolipoprotein (Apo) E gene, and thus its gene product, plays a central and pervasive role in lipid metabolism by serving as a ligand for lipoprotein receptors. Polymorphisms of this gene have been associated with variation in lipid phenotypes in some Caucasian and Asian populations, but not in others. No such study has been carried out in a resident Irish population. AIM: A study was designed to examine the relationship between serum cholesterols and Apo E genotype in a cohort of healthy Irish adults. METHODS: One hundred healthy Irish adults, aged 19-65 years, were recruited from the Cork City area. Two fasting blood samples were collected from each subject. One was assayed for serum cholesterols--total and low-density lipoprotein (LDL), and high-density lipoprotein (HDL)--while the other sample was used for isolation of genomic DNA and determination of Apo E genotype. RESULTS: While the E2 (12%) was the least prevalent, E3 was the most prevalent Apo E genotype (66%) in this group of healthy Irish adults. A significant Apo E gene-dosage effect was evident, whereby individuals with the Apo E2 genotype had a lower level of total cholesterol, E3 had intermediate levels, and E4 had a higher level. Moreover, those with the Apo E4 genotype had a significantly higher level of LDL cholesterol compared to E2 or E3 genotypes. There was no significant difference in mean serum adjusted HDL-cholesterol levels between the three Apo E genotypes. CONCLUSION: These findings suggest that healthy Irish adults with the Apo E4 genotype have higher serum total and LDL-cholesterol levels than those with E2 or E3 Apo E genotypes and therefore may have a higher risk of atherosclerotic coronary artery disease and coronary heart disease in later life.

Adult↗