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Biomedical subjects

M Maggio

Publications and source records attributed to M Maggio.

At least 19 recordsLinked to original sources

Correlates of bone quality in older persons.

PURPOSE OF THE STUDY: In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. METHODS: Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCT scans and other variables used in the analysis presented here. The final study population included 807 persons (372 men and 435 women, age range 65-96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. RESULTS: In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. CONCLUSIONS: Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption.

Aged↗

Acute changes in circulating hormones in older patients with impaired ventricular function undergoing on-pump coronary artery bypass grafting.

OBJECTIVES: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB. DESIGN: Intervention case study. METHODS: 19 patients (12 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with coronary artery disease and an ejection fraction <40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG. RESULTS: After surgery, serum IGF-I levels decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women. CONCLUSION: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG.

Aged↗

The hormonal pathway to frailty in older men.

Frailty, which is a state of high vulnerability that imparts a high risk of developing adverse health outcomes, affects many elderly subjects, especially men and women aged 80 yr and older (1). Although many different definitions of frailty have been proposed (2), a large portion of the recent literature has focused on the definition developed by L. Fried et al. (1) using the data from the Cardiovascular Health Study. Although this definition has not been officially recognized as the "gold standard" for the diagnosis of frailty, nonetheless most of the studies on frailty in the last 5 yr have used this definition. Several mechanisms have been hypothesized to have an important role in the development of frailty, including inflammation, coagulation and oxidative stress (3). Many authors implicate age-related hormonal changes to be directly or indirectly involved in the development of the frailty syndrome (4). Alterations in hypothalamic- pituitary-testicular, hypothalamic-pituitary-adrenal (HPA) and GH-IGF-I axes that accompany aging have been associated with single components of frailty, such as reduced muscle strength, bone strength or poor mobility (5, 6). However, most of these studies have focused on single hormonal changes rather than evaluating the parallel effect of aging on multiple hormonal axes. In addition, no interventional studies have specifically targeted frail older subjects (7). Since frailty by definition is a multi-system disorder, it is unlikely that changes in one axis (leading to a change in a single hormone) will explain the complexity of the dysregulation leading to frailty. Therefore, global measures of endocrine dysregulation that can discriminate between specific endocrine diseases and endocrine senescence should be developed. Observational and interventional studies will be needed to better define the role of "hormonal dysregulation", alone and in combination with other pathways, in the development of frailty in older men.

Aged, 80 and over↗

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Aged↗

Thyroid disease in the elderly: sex-related differences in clinical expression.

Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women >60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects >70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.

Aged↗

The relationship between testosterone and molecular markers of inflammation in older men.

Aging is accompanied by a pro-inflammatory state expressed by the increasing levels of inflammatory cytokines, including interleukin-6 (IL- 6), tumor necrosis factor alpha (TNF-alpha) and interleukin- 1beta (IL-1beta). At the same time, aging is associated with a decrease in serum testosterone (T) levels. There is evidence from many experimental studies that IL-6, TNF-alpha and IL-1beta inhibit T secretion by their influence on the central (hypothalamic-pituitary) and peripheral (testicular) components of the gonadal axis. On the other hand, observational and interventional studies suggest that T supplementation reduces inflammatory markers in both young and old hypogonadal men. Preliminary data from 473 older male participants of the InCHIANTI population showed a significant inverse relationship between T and soluble IL-6 receptor (sIL-6r) levels (a soluble portion of the IL-6 receptor that may enhance the biological activity of IL-6) but not with other markers of inflammation. This study, together with previous observations, suggests that a close relationship exists between the development of a pro-inflammatory state and the decline in T levels, two trends that are often observed in aging men. In the context of this paradigm, we discuss androgen deprivation therapy, a treatment used in men with metastatic prostate cancer as an ideal model to improve our understanding of the relationship between T and inflammatory markers. We advocate the notion that changes in inflammatory markers and T in aging men are causally linked. However, longitudinal and interventional studies are needed to confirm that T can be used therapeutically, based on its anti-inflammatory properties.

Aged↗

Effects of vitamin A administration on serum thyrotropin concentrations in healthy human subjects.

Retinoids play an important role in the regulation of normal growth and development. Their biological action is mediated by a nuclear receptor that belongs to the steroid/thyroid hormone receptors superfamily. Retinoic acid has been shown to inhibit the secretion and synthesis of thyrotropin (TSH); however, little is known on the effects of retinoids on TSH secretion in normal human subjects. In the present study, we evaluated serum TSH concentration following both vitamin A (vit A) and the combined vit A and triiodothyronine (T(3)) administration. Basal and thyrotropin-releasing hormone (TRH)-stimulated TSH serum concentrations were measured in healthy young subjects in the following experimental conditions: (1) after 10 days of treatment with vit A orally administered as retinol at a dose of 50,000 IU/d; (2) after 10 days of oral placebo (PL) treatment; (3) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of PL treatment; and (4) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of vit A treatment. Serum TSH concentrations were also measured during vit A administration in healthy elderly subjects according to the following protocol: (1) after 10 days of treatment with PL; and (2) after 10 days of treatment with vit A at the same dose used for young subjects. In young subjects, basal serum TSH levels were found to be similar in the 4 different treatment conditions. In the same group of subjects, each of the 4 experimental conditions induced an increase in serum TSH, which rose from basal values of 1.80 +/- 0.31 to a peak of 11.92 +/- 1.75 microIU/mL (P <.001) during the PL treatment, from basal values of 1.81 +/- 0.22 to a peak of 10.81 +/- 1.00 microIU/mL (P <.001) during vit A treatment, from basal values of 1.72 +/- 0.28 to a peak of 9.92 +/- 1.10 microIU/mL (P <.001) during PL + T(3) treatment, and from basal values of 1.79 +/- 0.30 to a peak of 9.51 +/- 1.12 microIU/mL (P <.001) during vit A + T(3) treatment. The 2-way repeated measure analysis of variance revealed no significant differences among treatments. In old subjects, basal serum TSH levels were similar in the 2 experimental conditions and were not different from those observed in young subjects. In these subjects, serum TSH levels increased significantly in response to the TRH stimulus from basal values of 2.16 +/- 0.3 to a peak of 10.27 +/- 0.55 microIU/mL (P <.001) during PL treatment and from basal values of 2.10 +/- 0.51 to a peak of 7.82 +/- 1.4 microIU/mL (P <.001) during vit A treatment. No significant effects of treatment were found in this group of subjects on TRH-induced TSH levels; however, TSH responses were somewhat lower during vit A treatment with a difference close to statistical significance. These results suggest that TSH secretion is poorly affected by vit A administration in healthy human subjects; the data also indicate that any cooperation between T(3) and vit A is unlikely to occur in the regulation of TSH secretion.

Administration, Oral↗

Hepatocyte growth factor/scatter factor released during peritonitis is active on mesothelial cells.

Peritonitis causes mesothelial detachment that may result in persistent peritoneal denudation and fibrosis. We investigated whether hepatocyte growth factor (HGF), a scatter factor that induces detachment from substrate and fibroblastic transformation of several cell types, is produced during peritonitis and is active on mesothelial cells. We studied 18 patients on peritoneal dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum, peritoneal fluid, and supernatant of peripheral blood mononuclear cells and peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial cells and the human mesothelial cell line MeT-5A were conditioned with recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly higher in serum and peritoneal fluid of peritonitic than uncomplicated patients. Mononuclear cells of peritonitic patients produced more HGF than cells of uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of peritonitic patients caused mesothelial cell growth, detachment, transformation from epithelial to fibroblast-like shape, overexpression of vimentin, and synthesis of type I and III collagen. In conclusion, HGF released during peritonitis causes a change in mesothelial cell phenotype and function. HGF may affect the healing process facilitating repair through mesothelial cell growth, but may contribute to peritoneal fibrosis inducing cell detachment with mesothelial denudation and collagen synthesis.

Ascitic Fluid↗

Hemodialysis prevents liver disease caused by hepatitis C virus: role of hepatocyte growth factor.

UNLABELLED: Hemodialysis prevents liver disease caused by hepatitis C virus: Role of hepatocyte growth factor. BACKGROUND: Hemodialysis increases markedly the serum levels of hepatocyte growth factor (HGF) so that regular dialysis treatment (RDT) mimics the regular administration of HGF as a drug. Therefore, we have studied the effects of dialysis-associated HGF production on the severity of liver damage caused by hepatitis C virus (HCV). METHODS: Biochemical tests of liver function and liver biopsy were performed in 10 patients on RDT and in 11 patients without renal disease (WRD) converted to anti-HCV serum-positive test for the same time (48 +/- 4 months). The HGF serum concentration was measured by enzyme immunoassay. In patients on RDT, HGF was measured just before starting a dialysis session (T0), at 15 and 240 minutes of dialysis (T15 and T240), and 24 hours later (T24 hr). RESULTS: Serum HGF was similar in WRD (average 0.17 ng/ml) as in RDT at T0 (0.25 ng/ml). In RDT serum HGF increased markedly at T15 and T240 (5.51 and 2.67 ng/ml, respectively, P < 0. 001 vs. WRD and T0) and was still higher than baseline at T24 hr (0. 41 ng/ml, P < 0.05). Both grade of necroinflammatory activity and stage of fibrosis were significantly lower in RDT than in WRD (both, P < 0.001). The number of apoptotic hepatocytes was also significantly reduced in patients on RDT compared with patients WRD. CONCLUSION: These results show that HCV-related liver disease is more benign in patients on RDT. The phenomenon may depend on the marked and prolonged HGF release caused by dialysis.

Acute Disease↗

The insulin-like growth factor axis and plasma lipid levels in the elderly.

The activity of the hypothalamic-GH-insulin-like growth factor (IGF) network declines with age. It has recently been shown that increased cardiovascular mortality occurs in adults with GH deficiency. As hypercholesterolemia is common in GH-deficient adults, and because there is experimental evidence that GH may play a role in regulating plasma cholesterol, we decided to investigate the activity of the GH-IGF axis in an elderly population by measuring serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and to study their relationship with blood lipid levels. One hundred and thirty-two elderly subjects, 52 men and 80 women, were studied (age range, 60-91 yr). Men had significantly lower levels of IGFBP-3, high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) compared to the women, whereas IGF-I and IGF-II were only slightly lower. Using linear regression analysis, we observed an inverse relationship of age with IGF-I (r = -0.35; P < 0.001), IGF-II (r = 0.40; P < 0.001), IGFBP-3 (r = 0.52; P < 0.001), body mass index, and lipid levels. Univariate regression analysis showed a strong and positive correlation of both IGF-I and IGFBP-3 with HDL-C and ApoA1. Partial correlation analysis, after adjustment for age and body mass index, showed that IGFBP-3 and IGF-II were still significantly and positively related to HDL-C and ApoA1. Furthermore, a strong association was documented among IGF-I, IGF-II, and IGFBP-3. These data demonstrate that even in an elderly population, further aging is accompanied by a progressive decline in circulating IGF-I, IGF-II, and IGFBP-3, suggesting a continuing diminution of the GH-IGF axis throughout aging. Moreover, the strong correlation between HDL-C and an index of GH secretion, such as IGFBP-3, suggests that GH might play an important role in lipid metabolism in healthy elderly subjects.

Aged↗

Immunity to tetanus in the 3-20 year age group in Italy.

In Italy, systematic mandatory tetanus immunization of children started in 1968. In 1989, immunity against tetanus was assessed in a random sample of 758 healthy subjects aged 3-20 y, from four Italian cities. There were 257 subjects 3-5 y old all residing in Southern Italy and 501 subjects 11-20 y old from both the South and North. The overall prevalence of non-immune subjects was 19.1%, without difference by sex. The rates of subjects lacking protective antibody titres was 25.3% in children 3-5 y old (all coming from South and the islands), 11.5% in those 11 y old, and 18.9% in the 18-20 y age-group, respectively. Subjects 11-20 y old residing in the South and the islands were more likely to be non-immune that those residing in the North (20.2% vs 6.0%; P < 0.01). Socio-demographic indicators such as lowest paternal education and largest family size were both unassociated with lack of protective antibodies. These findings indicate that an high rate of children in South of Italy do not have protective antibody levels, probably as consequence of lack of compliance with the vaccination programme. More efforts should be addressed to decrease geographical inequalities in the delivery of health care.

Adolescent↗

Concomitant evaluation of plasma galanin and catecholamine levels during a cold pressor test in healthy human male and female subjects.

The neuropeptide galanin (GAL) is localized in the peripheral and central nervous systems as well as in the adrenal medulla where it coexists with catecholamines. We evaluated the changes in GAL plasma levels as well as systolic and diastolic blood pressures and in the plasma levels of epinephrine and norepinephrine (NE) in normal human male and regularly menstruating female subjects during the activation of the sympathoadrenal system by a cold pressor test. The test was performed by immersing the hand of the subject in 1 degree C cold water for 4 min. Blood samples were collected both under basal conditions and at subsequent intervals during the cold stimulus as well as at the end of the recovery phase. The values were compared with those obtained when the same subjects were sham tested. As expected, systolic and diastolic blood pressures increased in both sexes during the cold test; the systolic blood pressure values were significantly (p < 0.05) higher in males. Epinephrine and NE levels rose significantly above baseline in both male and female subjects after the cold stimulus; the NE increments were significantly (p < 0.05) higher in males. The basal GAL levels were found to be variable but not sexually dimorphic. In both sexes, during cold stimulus and recovery phase, GAL values were found to be not significantly different from those detected during the sham test. These results demonstrate that the release of GAL in peripheral blood is not associated with that of catecholamines in response to the cold pressor test.

Adult↗

Characteristics of Escherichia coli strains belonging to enteropathogenic E. coli serogroups isolated in Italy from children with diarrhea.

Fifty-five Escherichia coli strains belonging to enteropathogenic E. coli (EPEC) serogroups were examined for phenotypic and genetic factors associated with virulence. The strains were isolated in Italy from children with diarrhea and identified as EPEC by clinical laboratories using commercially available antisera. O:H serotyping showed that 35 strains (27 of O26, O111, and O128 serogroups) belonged to 11 serotypes considered to be classical EPEC O:H serotypes. The other 20 isolates were classified as 15 nonclassical EPEC O:H serotypes. All the potential EPEC virulence factors associated with bacterial adhesion (localized adherence, fluorescentactin staining test positivity, presence of the attaching and effacing [eaeA] gene), the production of verotoxin, and the positivity with the enterohemorrhagic E. coli probe were significantly more frequent among isolates belonging to classical than nonclassical serotypes. Strains displaying an aggregative adhesion and hybridizing with the enteroaggregative DNA probe were found in serogroups O86, O111, and O126. Verotoxin-producing isolates belonged to serogroups O26, O111, and O128. Only one of the isolates hybridized with the EPEC adherence factor (EAF) probe, but 33 strains gave positive results with the eae probe, confirming that the former is more suitable in epidemiological studies in European countries. These results indicate that up to 75% of strains identified as EPEC by commercial antisera may possess potential virulence properties and/or belong to classical EPEC O:H serotypes and suggest that O grouping is still a useful diagnostic tool for presumptive identification of diarrheagenic E. coli in clinical laboratories.

Adhesins, Bacterial↗