Consensus Document on substitution therapy with DHEA in the elderly.
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Biomedical subjects
Publications and source records attributed to Graziano Ceresini.
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OBJECTIVE: Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. DESIGN: We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). MAIN OUTCOME: ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. CONCLUSIONS: This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.
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In the laboratory environment, rodents are usually housed in unisexual groups, which are assembled after weaning. Housing of unfamiliar subjects has been described, however, as a stressful social setting for rodents and other mammals. Aim of the present study was to evaluate whether the age at which house mice are grouped might affect their behavior and physiology. Male or female unisexual groups were formed at different ages: at weaning, i.e., before puberty (JUV); at adolescence, i.e., after puberty (AD); and controls were raised with siblings since birth (CON). Results show that age at group formation induced several behavioral and physiological alterations in males but not in females. Specifically, when compared to controls, JUV males showed higher aggression, smaller preputial gland, and a marked reduction of neophobia in the free exploratory paradigm. Fewer changes occurred in the AD males, which showed reduced neophobia in the free exploratory paradigm and, when adults, a reduction in body weight. Females were not affected by the experimental treatment. Surprisingly, the basal corticosterone assessed at the nadir was lower for both males and females JUV and AD respect to CON. In conclusion, it is clear that mixing groups at different ages has profound effects on mouse behavior and physiology.
PURPOSE: To examine whether serum insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations, determined early after the onset of stroke, are predictive of clinical outcome in elderly patients. METHODS: The sample comprised 85 patients (mean [+/- SD] age, 83 +/- 7.4 years; range, 67 to 99 years; 34% male) who were admitted with acute stroke to a geriatric ward between January 1998 and June 2000, and 88 control patients who were similar in age and sex. Clinical and laboratory assessments, computed tomographic scan of the head, carotid ultrasonography, and electrocardiography were employed to define the clinical and etiologic stroke subtype. Fasting blood samples were collected within 24 hours of admission for IGF-I and IGFBP-3 measurement. Univariate and multiple logistic regression analyses, with adjustment for other related clinical covariates, were used to assess the relation of IGF-I and IGFBP-3 to poor outcome, defined as severe disability (Barthel index <60/100) or death, at 1 month (or at discharge), 3 months, and 6 months. RESULTS: Mean (+/- SD) IGF-1 levels were lower in patients with stroke than in controls (69 +/- 45 ng/mL vs. 102 +/- 67 ng/mL, P adjusted for age = 0.001). The mean IGF-1/IGFBP-3 molar ratio was also lower in stroke patients (0.12 +/- 0.07 vs. 0.19 +/- 0.09, P adjusted for age <0.0001). However, there was no relation of hormone levels to either the clinical subtype of stroke or the extent of neurologic impairment. IGF-1 levels were inversely related to poor outcome (mainly death) at 3 and 6 months, independent of other clinical covariates that were highly predictive of outcome, such as age and stroke scale score on admission (hazard ratio for death at 6 months for each 20-ng/mL increase = 0.7; 95% confidence interval: 0.5 to 0.9). An independent association of the molar ratio with death at 3 and 6 months was also found. CONCLUSION: Low levels of circulating IGF-1 may predict the clinical outcome of stroke in elderly patients.
The reduction of muscle mass and increased protein catabolism in aging can determine the occurrence of metabolic alterations-such as hyperglycemia and reduced insulin sensitivity-in elderly subjects with diabetes mellitus. Therefore, the aim of the study was to evaluate the effect of nutritional supplementation with oral amino acid mixture (OAAM) in elderly subjects with type 2 diabetes. This approach was conducted in an attempt to antagonize muscle catabolism by means of increased endogenous protein synthesis and to improve glucose metabolism and insulin sensitivity. A randomized, open-label, crossover study was conducted in poorly controlled (glycosylated hemoglobin level [HbA(1c)] >7%) elderly subjects (age range, 65 to 85 years) with type 2 diabetes. OAAM significantly reduced fasting and postprandial blood glucose and HbA(1c), whereas all parameters remained substantially unchanged in the group treated with placebo. Fasting insulin levels and insulin resistance increased at baseline in all subjects with diabetes and decreased during OAAM supplementation. These results persisted also after crossover from OAAM to placebo. No changes in blood lipid levels, creatinine, homocysteine, and urinary albumin excretion rate were observed throughout the study, whereas a mild but significant increase of high-density lipoprotein cholesterol was found after OAAM supplementation. We suggest that increased amino acid availability for skeletal muscle function and strength could ameliorate metabolic control and insulin sensitivity in elderly patients with poorly controlled type 2 diabetes.
BACKGROUND: It has been suggested that the reduced production of dehydroepiandrosterone sulfate (DHEAS) may be partially responsible for the decline of muscle strength and mass that often occurs with aging. However, this hypothesis has been only tested in small series of normal volunteers, with little consideration for potential confounders. Using data from a representative sample of 558 men (20-95 years) we tested the hypothesis that circulating DHEAS is independently associated with muscle strength and mass. METHODS: Data are from InCHIANTI, an epidemiological study conducted in the Chianti geographic area (Tuscany, Italy). DHEAS serum levels were related to lower extremity muscle strength assessed by hand-held dynamometry and calf muscle area estimated from quantitative computerized tomography. Confounders included age, anthropometrics, physical activity, smoking, energy and alcohol intake, albumin, lipids, interleukin-6, comorbidity, depressive symptoms, and disability in activities of daily living. RESULTS: In fully adjusted models predicting lower extremity muscle strength and calf muscle area, we found significant age*log DHEAS interactions, suggesting that the relationship between DHEAS levels and muscle parameters differs across the life span. In age-stratified models adjusted for confounders, serum DHEAS was an independent predictor of muscle strength (p <.02) and mass (p <.01), but only for men between 60 and 79 years of age. After adjusting these models for serum-free or bioavailable testosterone, results were unchanged. CONCLUSIONS: In men aged 60-79 years, circulating DHEAS is an independent correlate of muscle strength and calf muscle area. The possible causal role of declining DHEAS in age-related sarcopenia should be further explored in longitudinal studies.
Raloxifene is one of the most important selective estrogen receptor modulators currently employed for the treatment of postmenopausal osteoporosis. However, it has also been suggested that this compound affects the vascular system. We evaluated both carotid blood flow resistance and endothelium-dependent vasodilation in 50 healthy postmenopausal women randomly assigned to receive, in a double blind design, either raloxifene (60 mg per day; N=25 subjects) or placebo (N=25 subjects) for 4 months. Indices of carotid blood flow resistance, such as the pulsatility index (PI) and resistance index (RI), as well as the flow-mediated brachial artery dilation were measured both at baseline and at the end of treatment. Changes in PI were -1.86+/-2.24 and -2.15+/-2.22% after placebo and raloxifene treatment, respectively, with no significant differences between groups. Changes in RI were -0.77+/-1.72 and -1.81+/-1.54% after placebo and raloxifene treatment, respectively, with no significant differences between groups. At the end of the treatment period, the increments in artery diameter measured after the flow stimulus were 10.79+/-2.39 and 6.70+/-1.23% for placebo and raloxifene, respectively, with no significant differences between groups. These results demonstrate no significant effects of raloxifene on either carotid blood flow resistance or brachial artery flow-mediated dilation in postmenopausal women.
The degree of cardiovascular stress responsivity and its possible implications for the onset and progression of cardiovascular pathologies seem to be linked to the individual strategy of behavioral coping with stressors. This study was designed to investigate the relationship among cardiac autonomic, endocrine and behavioral responses to real-life stress episodes. Thirty university students were exposed to two brief social challenges (stress interviews), during which the state of sympathovagal balance (time-domain indexes of heart rate variability) and a number of non-verbal behaviors were quantified. Psychometric measurements were also obtained via SPRAS questionnaire, administered just after each stress interview. Samples of saliva were collected for cortisol determination immediately prior and after the experimental session. Subjects showing higher levels of sympathetic dominance were characterized by higher scores of submissive behavior, larger cortisol increments, and higher perception of psychophysiological arousal. A clear consistency in the individual response to the two stress interviews was found, at the behavioral, physiological and psychophysiological level. Finally, the gender of the subjects did not clearly influence their stress responsivity. These results support the hypothesis of a close relationship between the degree of physiological arousal and the style of behavioral adaptation to social stressors.
OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.