215 research outputs found

    Endocrine and physical determinants of bone mass in late postmenopause

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    To analyze the relative contribution of endocrine and physical factors to bone mineral density (BMD) in late menopause, we studied biochemical markers of bone turnover as well as sex and calciotropic hormones in 53 women (mean age 61 +/- 5.3 years), 5 to 23 years after natural menopause. BMD was measured at the lumbar spine and proximal femur by dual energy radiography. Stepwise regression analysis showed that age and PTH levels were the two major factors that significantly accounted for spinal BMD, with a final r(2) = 0.27. Plasma androstenedione was the only other variable that contributed, albeit not significantly, to spine BMD increasing the r(2) by 2%. Conversely, body mass was the main contributor to femoral BMD at all sites. While serum calcium and urinary hydroxyproline were significant determinants of neck BMD, urinary hydroxyproline and age provided significant source of variation for trochanteric BMD, and circulating FSH for BMD in the Ward's area. The final models gave r(2) values of 0.35, 0.31, and 0.23, for neck, trochanter and Ward's areas, respectively. Thus, determinants of bone density differentially affect the vertebral and proximal femoral sites. While increasing age and PTH, probably reflecting a subclinical vitamin D deficiency, explain a decreased vertebral bone density, body mass appears to affect mostly the proximal femur. Circulating androgens play a secondary role. A persistently increased bone turnover state is conducive to lower bone density in late postmenopausal women

    Analysis of K-ras mutations in the stool of patients with colorectal cancer

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    Mutated cellular ras genes have been detected in many tumor types, though with varying frequencies: for example, it is well known that between 40-50 % of colon carcinoma show mutations in one allele of the Kirsten ras gene, involving preferentially the codon 12 in which the most frequent change is the transition GGT to GAT; they may be found in the stools of the colorectal cancer patients. Purpose of our study is that to analyze stools of the normal subjects and of patients with colorectal tumor for the transition GGT to GAT in codon 12 of K-ras and, in the present paper, we report the most reproducible procedure to obtain purified DNA from stools

    Age-related decline of bone mass and intestinal calcium absorption in normal males

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    Although about 25% of all hip fractures occur in men, little is known about the pattern of their age-related bone loss and its main determinants. The aim of this cross-sectional study was to evaluate the age-related changes of intestinal calcium absorption, bone mass, and bone turnover in normal men. In 70 normal males (age 17-91 years), we measured spinal and forearm bone density (FBD) (by DXA), fractional intestinal calcium absorption (by oral test), serum immunoreactive parathyroid hormone (PTH), dietary calcium intake (diet records), biochemical markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin, urine calcium, creatinine, and hydroxyproline), and 1,25(OH)2D3 serum levels. Vertebral bone density (VBD) showed a modest decline before age 50 and a greater decline after age 50, whereas FBD presented a significant decrease with advancing age starting at age 40, suggesting a predominant age-related cortical bone loss. Intestinal calcium absorption (47CaFA) and serum 1,25(OH)2D3 also presented an age-related decline similar to FBD. Simple correlation analysis revealed that age was significantly related to 47CaFA (r = 0.60), calcium intake (r = 0.32), VBD and FBD (r = 0.79 and 0.63, respectively), serum 1,25(OH)2D3 (r = 0.69), and serum iPTH (r = 0.72). No significant correlation was found between age and biochemical markers of bone remodeling. Partial correlation and stepwise variable selection analyses, using 47CaFA and bone mass as dependent variables, showed that in normal males, serum 1,25(OH)2D3 and dietary calcium intake were the main contributors (64%) to 47CaFA variability, whereas only age accounted for 63% of VBD and age and dietary calcium accounted for 45% of FBD variability. These results indicate that bone loss in men accelerates after age 50 years and that among other factors, intestinal calcium malabsorption and 1,25(OH)2D3 serum levels play a role

    An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss

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    In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of 99mTc-methylene-dichloro-bisphosphonate (99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or placebo. Treatment with sCT significantly increased VMC by 2.7 +/- 0.9% at 6 months, and 3.3 +/- 0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6 +/- 0.5%, and -3.5 +/- 0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P less than 0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis

    Biological activity of different calcitonins in men

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    Calcitonin has been isolated and its structure defined from several species, including man. Synthetic preparations of several calcitonins are available for clinical use. Of these, porcine (pCT), human (hCT), and salmon (sCT) have been synthetized according to their natural sequences, while eel calcitonin (cCT) is available as amino-suberic acid derivative (ASU-eCT). The different molecular configuration results in different biological potency and tolerability. Currently, the potency of calcitonin in man is evaluated by its capacity of lowering serum calcium and stimulating cAMP plasma levels after acute infusion. In normal subjects, cAMP stimulation seems to be a more sensitive test, since plasma calcium in normal subjects is poorly affected by an acute treatment with calcitonin. On the other hand, the side effects are usually assessed by clinical observation, on the basis of duration and intensity of the symptoms. Our experience, emerging from several studies devoted to comparing the biological activity and tolerability of different calcitonin preparations in humans, indicates that the hypocalcemic effect and the increase of plasma cAMP are produced by all peptides, according to the potency order sCT greater than hCT greater than ASU-eCT. For all peptides, the most constant side effect is flushing, and the frequency order of side effects is hCT greater than sCT = ASU-eC
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