Safety of type 2 diabetes treatment with repaglinide compared with glibenclamide in elderly people: A randomized, open-label, two-period, cross-over trial.
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Aged↗
Biomedical subjects
Sebastiano Bruno Solerte
Publications and source records attributed to Sebastiano Bruno Solerte.
Current guidelines for adult GH replacement.
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Adult↗
Defect of a subpopulation of natural killer immune cells in Graves' disease and Hashimoto's thyroiditis: normalizing effect of dehydroepiandrosterone sulfate.
BACKGROUND: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves' disease (GD) and Hashimoto's thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. OBJECTIVE: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. DESIGN: We studied 13 patients with recent onset Graves' disease, 11 patients with Hashimoto's thyroiditis at first diagnosis and 15 age-matched healthy subjects. METHODS: NK cells were concentrated at a density of 7.75x10(6) cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16+/CD56+cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-beta (IFN-beta) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-alpha (TNF-alpha) from NK cells. RESULTS: Lower spontaneous, IL-2- and IFN-beta-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P<0.001). A decrease in spontaneous and IL-2-modulated TNF-alpha release from NK cells was also found in both groups of patients (P<0.001). The co-incubation of NK cells with IL-2/IFN-beta+DHEAS at different molar concentrations (from 10(-8) to 10(-5) M/ml/NK cells) promptly normalized NKCC and TNF-alpha secretion in GD and HT patients. CONCLUSIONS: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.
Adjuvants, Immunologic↗
Decreased release of the angiogenic peptide vascular endothelial growth factor in Alzheimer's disease: recovering effect with insulin and DHEA sulfate.
Changes of vascular endothelial growth factor (VEGF) secretion have recently been demonstrated in patients with Alzheimer's disease (AD). Since VEGF has been involved in brain angiogenesis, neuroprotection and cerebromicrovascular exchange of substrates and nutrients, the study of VEGF could have important relapses into the pathogenesis and treatment of AD. Within this context, 35 healthy subjects (16 of young and 19 of old age), 18 patients with dementia of the vascular type (VAD) and 22 with dementia of the Alzheimer's type (AD) were included in the study. VEGF levels were determined in the supernates of circulating natural killer (NK) immune cells isolated by immunomagnetic separation (pure CD16 + CD56 + NK cells at a final density of 7.75 x 10(6) cells/ml). VEGF was measured in spontaneous conditions (without modulation) and after exposure of NK cells with IL-2, lipopolysaccharide (LPS), dehydroepiandrosterone sulfate (DHEAS), LPS + insulin, amyloid-beta (Abeta) fragment 1-42, the inactive sequence Abeta(40-1) and Abeta(1-42) + insulin. A significant decrease in VEGF released by NK cells was demonstrated in AD subjects compared to the other groups. No differences of VEGF levels were found between healthy subjects of old age and the VAD group. The incubation with LPS and DHEAS significantly increased, in a dose-dependent manner, VEGF levels in AD as well as in healthy subjects of young and old age and in VAD patients. The incubation of NK cells with Abeta(1-42) completely suppressed VEGF generation in AD subjects, also reducing VEGF release in the other groups. The co-incubation of NK with LPS + insulin, at different molar concentrations, significantly restored (4- and 6-fold increase from LPS alone) VEGF in AD, also enhancing VEGF secretion in healthy subjects and the VAD group, while the co-incubation of NK with Abeta(1-42) + insulin promptly abolished the negative effects of Abeta(1-42) on VEGF release. These data might suggest that the decreased VEGF secretion by peripheral immune cells of AD subjects could have a negative role for brain angiogenesis, neuroprotection and for brain microvascular permeability to nutrients, increasing brain frailty towards hypoxic injuries. On the contrary, insulin and DHEAS could have beneficial effects in AD, as well as in VAD and in physiological aging, by increasing, in a dose-dependent fashion, VEGF availability by peripheral and resident immune and endothelial cells, so contributing to increase its circulating pool.
Adult↗
Endocrine pancreatic dysfunction in HIV-infected children: association with growth alterations.
BACKGROUND: The pancreatic endocrine system normally guarantees a quick and efficient response to daily metabolic perturbations, but associated data for human immunodeficiency virus (HIV)-infected patients are lacking. A prospective study was performed to evaluate pancreatic endocrine secretion and its possible association with failure to thrive among HIV-infected children. METHODS: Fourteen well-nourished, prepubertal, HIV-infected children (6 boys and 8 girls; age range, 5-11 years), none of whom were receiving protease inhibitors, and 16 clinically healthy sex- and age-matched children formed the patient group and the control group, respectively. At yearly follow-up examinations, insulin, glucagon, C-peptide, and glucose levels were measured; the ratio of insulin to glucose, the ratio of insulin to glucagon, and the homeostasis model assessment (HOMA) index were calculated; the glucagon test was administered; and growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, cortisol, and lipid patterns were evaluated. RESULTS: Insulin, glucagon, C-peptide, glucose, and HOMA measurements were significantly higher among patients, compared with control subjects, at all 3 follow-ups performed to date. The glucagon test revealed a normal glycemic response in all the healthy control subjects and a significantly impaired response in 11 patients. A significant correlation emerged between the ratio of insulin to glucagon and the growth velocity of HIV-infected children. CONCLUSION: To our knowledge, the present study provides the first evidence of altered pancreatic endocrine secretion and its association with growth failure among HIV-infected children.
Blood Glucose↗
Insulin-like growth factor I (IGF-I) and IGF-binding protein 3 response to growth hormone is impaired in HIV-infected children.
To better characterize the somatotropic axis in HIV-infected children the circadian rhythm of growth hormone (GH), and basal and stimulated (by an insulin-like growth factor I [IGF-I] generation test) plasma levels of IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3), were evaluated in 16 children (9 boys and 7 girls; age range, 7-11 years) with HIV infection. All patients were free from active opportunistic infection or liver disease at the time of the study. Sixteen age- and sex-matched healthy children (10 boys and 6 girls; age range, 7-11 years) served as control subjects. GH rhythmometric data were analyzed by single and population mean cosinor analysis. As regards the IGF-I generation test, biosynthetic human GH (hGH, 0.1 IU/kg, 0.033 mg/kg) was administered subcutaneously for 4 days and blood samples were taken from fasting subjects at baseline and on the morning after the last GH injection for measurement of IGF-I and IGFBP-3. Plasma GH levels fell within normal limits in the HIV-seropositive patients and were similar to those of healthy children (1.31 +/- 1.18 vs. 1.57 +/- 1.16 microg/liter, respectively; mean +/- SD). The population mean cosinor analysis shows that the GH circadian rhythm reached statistical significance both in the HIV-seropositive children and in the control group. Despite this, the IGF-I and IGFBP-3 levels were significantly lower in HIV-infected children than in the control group (75.6 +/- 57.2 vs. 233.3 +/- 52.5 ng/ml, p < 0.001 and 2.09 +/- 0.17 vs. 3.89 +/- 0.24 mg/liter, p < 0.01, respectively; mean +/- SD); moreover, the response of IGF-I and IGFBP-3 to the IGF-I generation test was significantly lower in HIV-infected children than in the control group (86.3 +/- 55.8 vs. 257.5 +/- 53.4 ng/ml, p < 0.001 and 3.14 +/- 0.43 mg/liter, p < 0.01, respectively; mean +/- SD). It appears that circadian GH secretion is normal in children with HIV infection, but the response to exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.
Child↗