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Biomedical subjects

M Pedrazzoni

Publications and source records attributed to M Pedrazzoni.

At least 37 records · Page 2Linked to original sources

Effects of nandrolone decanoate on bone mass in established osteoporosis.

A double-blind, randomized, placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of nandrolone decanoate on the bone mineral density (BMD) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover. The patients received intramuscular injections of placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months. Overall, vertebral BMD increased by 2.9% in the nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD showed a slight but transient improvement, with a subsequent return to basal levels in the nandrolone decanoate group, whereas there was a progressive decrease in the placebo group. Patients treated with nandrolone decanoate also complained less of bone pain. Urinary hydroxyproline decreased significantly in treated patients, whereas osteocalcin tended to increase, but the change was not significant. HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the nandrolone decanoate group. Two patients treated with nandrolone decanoate withdrew from the study because of hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis.

Alkaline Phosphatase↗

Seasonal variation in the incidence of hip fractures in Emilia-Romagna and Parma.

Though some reports suggest the existence of seasonal changes in hip fracture incidence, with a peak in winter months, other investigations have failed to confirm this finding. In this study we present data on the month-to-month variability of hip fractures in Emilia-Romagna, a region of Northern Italy with a population of approximately four million inhabitants, and in Parma, a province of Emilia-Romagna (population of approximately 400,000). Data on cervical and trochanteric fractures were obtained from two sources: a) records of all operative procedures in the five orthopaedic centres serving the area of the Parma province; and b) a computerised database of all hospital discharges from public and private hospitals of Emilia-Romagna. In both cases, the analysis gave similar results, with no evidence of a consistent seasonal pattern in hip fracture rates.

Age Factors↗

Effects of chronic heroin abuse on bone and mineral metabolism.

Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1-2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4-24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p < 0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p < 0.01), whereas parathyroid hormone was lower than in controls (p < 0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p < 0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation.

Adult↗

Impaired PRL response to hyperthermia in alcoholic men.

The aim of this study was to evaluate the release of PRL to sauna-induced hyperthermia in 10 chronically alcohol-addicted male subjects after a few weeks of abstinence. In contrast with normal men the alcoholic men showed higher basal levels of PRL and the exposure to hyperthermic stress did not stimulate in PRL secretion. These results indicate that chronic alcohol abuse is associated with functional pituitary alterations similar to other states of addiction.

Adult↗

Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males.

The purpose of this investigation was to assess the chronic effects of marihuana smoking on the basal and stimulated secretion of the pituitary hormones luteinizing hormone (LH), follicle-stimulating (FSH) and prolactin (PRL). Ten male chronic marihuana users and 10 age- and sex-matched healthy volunteers were studied by measuring hormone levels before and after i.v. administration of thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). The basal and stimulated levels of LH were reduced in marihuana users, whereas FSH and PRL levels and responses were not different from the control subjects. The chronic use of marihuana may selectively impair the hypothalamic control mechanisms regulating LH secretion.

Adult↗

Spontaneous release of interleukin-I and interleukin-6 by peripheral blood mononuclear cells after oophorectomy.

1. We studied the changes in interleukin-1 and interleukin-6 secretion by peripheral blood mononuclear cells from 12 premenopausal women after oophorectomy and seven premenopausal women who had undergone simple hysterectomy. 2. The results showed that 1 month after surgery interleukin-1 secretion increased by 414 +/- 171% (mean +/- SEM) and interleukin-6 secretion increased by 1354 +/- 481% in oophorectomized women, whereas only non-significant fluctuations in the secretion of both cytokines (-9% +/- 29% for interleukin-1 and -31% +/- 19% for interleukin-6) were seen in the women who had undergone simple hysterectomy. The difference between the two groups was significant (P = 0.035 for interleukin-1 and P = 0.003 for interleukin-6). In addition, oophorectomy, but not simple hysterectomy, was followed by significant increases in plasma ionized calcium concentration (P < 0.05), plasma alkaline phosphatase activity (P < 0.01) and plasma osteocalcin concentration (P < 0.02), and a reduction in plasma parathyroid hormone level (P < 0.01). 3. We conclude that ovary ablation may modify cytokine secretion by peripheral blood mononuclear cells. If this phenomenon occurs in the bone microenvironment, it could be important in the loss of bone observed after oophorectomy. However, the possibility of an independent alteration induced by the lack of gonadal hormones but unrelated to bone turnover cannot be excluded.

Adult↗

Longitudinal study of bone loss after thyroidectomy and suppressive thyroxine therapy in premenopausal women.

The effects of suppressive doses of L-thyroxine on the appendicular and axial bone mineral content were followed for 12-36 months after total or subtotal thyroidectomy in 15 premenopausal women. Compared to age-matched controls, these patients had a more marked bone loss of the spinal bone mineral content (2.6 +/- 1.9% vs 0.2 +/- 1.2% per year). The changes in radial cortical bone density were not significantly different from the control group. We conclude that when a suppressive therapy with L-thyroxine is necessary the rate of bone loss should be monitored at regular intervals.

Adult↗

Calcitonin nasal spray reduces opioid withdrawal syndrome without modification of endogenous opioid secretion.

It has been suggested that the well known analgesic effect of calcitonin (CT) may result from an enhanced secretion of opioid peptides. The purpose of this double-blind, controlled study was therefore to evaluate the effectiveness of CT on the opiate withdrawal syndrome. 20 drug addicts were randomly allocated to receive either 200 UI/day of salmon CT (n = 10) or placebo (n = 10) by nasal spray, after the abrupt withdrawal of low-dose methadone (20 mg/day). The severity of the withdrawal syndrome was evaluated by means of a score derived from a symptom check-list. Plasma beta-endorphin, glucose and insulin levels were measured before and after CT administration. The subjects treated with spray CT had significantly lower score than those treated with placebo. Beta-endorphin levels did not show any significant variation in both groups. An inhibitory action of CT on insulin secretion was observed. Our data suggested that CT might be considered a useful supportive measure for opiate withdrawal. CT action does not seem to involve the opioid system, but is probably mediated by a direct action on specific receptors or by a modulation of noradrenergic pathways.

Administration, Intranasal↗

Intermittent treatment with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of postmenopausal osteoporosis.

Since data on the efficacy of 4-amino-2-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of osteoporosis are not yet available, we have examined in an open, randomized study, the effects of an intravenous intermittent treatment with this drug on the vertebral and radial bone mass in postmenopausal osteoporosis. Forty postmenopausal osteoporotic women were randomly assigned to one of two groups, one treated with AHBuBP (5 mg/day on two consecutive days every 3 months for one year; n = 20), the other with oral calcium (n = 20). The bone mineral density (BMD) of the spine increased significantly in women receiving AHBuBP, whereas it tended to decrease in patients given calcium. The differences in the vertebral BMD changes between groups was highly significant (P less than 0.01). Radial BMD tended to increase in patients treated with AHBuBP, and to decrease in patients receiving calcium. The difference in the linear trends was statistically significant (P less than 0.05). The side effects of AHBuBP (a transient acute phase reaction in 3 out of 20 subjects) were slight and well-tolerated. A good effect of AHBuBP was observed also on back pain (P less than 0.05). We conclude that intermittent treatment with AHBuBP is capable of increasing spinal BMD and conserving radial BMD in postmenopausal osteoporosis and may represent a convenient therapeutic choice in this condition.

Aged↗

Vertebral mineral content in diet-dependent and diet-independent hypercalciuria.

The vertebral mineral content was measured using dual photon absorptiometry in 41 calcium stone patients with idiopathic hypercalciuria. These patients had been previously divided into 2 groups (diet-dependent and diet-independent hypercalciuria) during a low sodium and low calcium diet. In some of the patients (11 with diet-dependent and 11 with diet-independent hypercalciuria) the vertebral mineral content was evaluated in relation to serum ionized calcium, intact parathyroid hormone, alkaline phosphatase and osteocalcin determined after a low sodium and low calcium diet. The vertebral mineral content, expressed as Z-VMD, was normal in diet-dependent and lower in diet-independent hypercalciuric stone patients (-0.30 +/- 1.19 versus -0.26 +/- 1.18, p less than 0.02). In 7 of 21 patients (33.3%) the vertebral mineral content was less than 2 standard deviations of the normal value, indicating a true involvement in bone metabolism. Serum intact parathyroid hormone and osteocalcin levels were not different from the controls in both groups, while alkaline phosphatase activity and ionized calcium were higher in diet-independent hypercalciuric patients. Serum ionized calcium was negatively correlated with bone vertebral density. The results suggest that an increased bone turnover may be a primary event in causing hypercalciuria in calcium stone patients unable to decrease urinary calcium to less than the calcium intake.

Absorptiometry, Photon↗

Impairment of cytokine production in mice fed a vitamin D3-deficient diet.

C57Bl/6 female mice fed a Vitamin D (VIT-D)-deficient diet had serum levels of 25-hydroxyvitamin D decreasing with the time of diet exposure (3 and 8 weeks). Cytokine production (IL-6, TNF and IL-1) by peritoneal macrophages cultured in vitro with a standard stimulus, LPS, evaluated in the supernatants as biological activity, was significantly reduced in VIT-D-deficient animals. The defect in monokine production was partial and was evident at suboptimal LPS concentrations and incubation times. I-A antigen expression, induced in macrophages by in vitro exposure to IFN-gamma, was not modified in VIT-D-deficient mice, but IFN-gamma-inducible macrophage cytotoxicity to tumour target cells was significantly decreased in VIT-D-deficient animals. Moreover, basal and Poly I:C-induced NK activity was not modified by VIT-D deficiency. Thus, macrophage functions, such as cytokine production and tumour cytotoxicity induction, are down-modulated in vitro by VIT-D deprivation. To give more support to the relevance of VIT-D availability for cytokine production, TNF and IL-6 have been evaluated in the sera of control and VIT-D-deficient mice given LPS as a model stimulus. Serum peak levels of both cytokines were at least halved in VIT-D-deprived mice. Thus, VIT-D deficiency may represent a model of partial defect of monokine production.

Animals↗

Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients.

Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP. A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed. Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M. Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes). Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3-treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines. In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity. In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals. Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell-mediated immunity, or bone resorption. The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration.

Acquired Immunodeficiency Syndrome↗

Calcitonin secretion rate in elderly normal subjects.

The aim of the study was to investigate the metabolic clearance rate (MCR) and the secretion rate (SR) of calcitonin (CT) in elderly men and women (mean age +/- SE: 75 +/- 3 and 78 +/- 3 yr, respectively). The basal levels of CT were higher in men than in women (9.6 +/- 3.2 vs 6.0 +/- 1.5 pg/ml; p less than 0.05). The MCR was not significantly different between sexes (905 +/- 54.2 vs 810 +/- 165.1 l/day). In contrast, CT SR was significantly higher in male subjects compared to women (8.7 +/- 3.1 vs 4.8 +/- 1.5 micrograms/day; p less than 0.05). These findings suggest that only a few units of CT are secreted daily by elderly subjects and that the lower basal values of the hormone in women are probably the result of a lower production rate.

Aged↗

Salmon calcitonin given by nasal spray or by injection does not increase beta-endorphin levels in normal men.

It has been suggested that the analgesic action of calcitonin (CT) might involve a stimulation of beta-endorphin (beta-EP) release. To verify whether salmon CT modifies the circulating levels of beta-EP, and whether the route of administration plays any role in this response, we have studied 10 healthy male volunteers, aged 30-40 yr. Each of them was studied on 4 different days, after administration of placebo or salmon CT (100 UI) by the intravenous, intramuscular and nasal route, in random order. Ionized calcium tended to decrease, especially after intravenous CT, but there was no change in plasma beta-EP levels, regardless of the route of administration. It is therefore unlikely that circulating beta-EP mediates any biological effect of CT.

Administration, Intranasal↗

Metyrapone effects on beta-endorphin, ACTH and cortisol levels after chronic opiate receptor stimulation in man.

The aim of this study was to evaluate beta-endorphin, ACTH, and cortisol plasma levels during metyrapone administration in man after chronic opioid receptor stimulation. Metyrapone (750 mg every 4 hr for 6 doses) was administered to ten male heroin addicts, who had been on a maintenance therapy with methadone for at least 6 months and to ten healthy sex- and age-matched volunteers. Before metyrapone administration the basal levels of cortisol and ACTH were significantly decreased in addicts as compared to normal controls, while plasma beta-endorphin was not different. The response of beta-endorphin and ACTH to metyrapone administration was significantly blunted in addicts (p less than 0.01). These results suggest that the chronic stimulation of opiate receptors can impair the function of the anterior pituitary gland.

Adrenocorticotropic Hormone↗

Circulating opioid peptides during thermal stress.

In the present study we have examined the response of endogenous opiates (beta-EP and Met-enk) and ACTH to a particular type of thermal stimulus such as sauna in 8 young healthy subjects. Sauna-induced hyperthermia resulted in an increase of plasma beta-EP and ACTH, but appeared to have no significant effect on circulating Met-enk. The different responses of ACTH, beta-EP and Met-enk to heat exposure indicate that hyperthermia represents a form of stress, which can trigger off a well-defined neuroendocrine reaction.

Adrenocorticotropic Hormone↗

Impaired prolactin response to hyperthermia in heroin addicts.

The response of PRL, FSH and LH to sauna-induced hyperthermia was examined in 8 male former heroin addicts (studied after 14-24 days of abstinence) and 8 age- and sex-matched control subjects. The basal levels of PRL tended to be higher in former drug users than in control subjects (p = 0.07). After sauna, there were no changes in the addict group, whereas a significant increase was observed in normal subjects (p less than 0.001). Baseline plasma LH and FSH levels were significantly lower in former drug users (p = 0.02), but no change was found after sauna in either group. These findings are consistent with the existence of a deficient adaptation to thermal stress in chronic drug users, even after a relatively short drug-free period.

Adolescent↗

Osteocalcin levels in diabetic subjects.

Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.

Adult↗