Biomedical subjects

S Perrini

Publications and source records attributed to S Perrini.

6 recordsLinked to original sources

PubMed2006

[Multiple arterial ischemic strokes in a child with moyamoya disease and Mycoplasma pneumoniae infection].

Moyamoya disease is a rare disorder characterised by a progressive occlusion or stenosis of the distal portions of bilateral internal carotid arteries with the development of a network of collateral vessels. Pediatric patients show transient ischemic attacks or strokes; diagnosis is made on the basis of clinical and radiographic findings. The case of a 2-year-old female, which after a Mycoplasma pneumoniae infection presented multiple cerebral strokes is reported. A diagnosis of moyamoya disease was made on the basis of neuroradiological findings; neurological complications due to Mycoplasma infection are reported and the relationship between disease and infection are discussed.

Carotid Artery, Internal↗

PubMed2005

Associated hormonal declines in aging: DHEAS.

DHEA and its sulfate prohormone DHEAS are the most abundant circulating adrenal steroid hormones in humans. DHEA exerts its actions on peripheral target tissues either indirectly, following its conversion to androgens, estrogens or both, or directly, as a steroid hormone interacting with either a nuclear or a membrane receptor. In humans, DHEA shows a characteristic pattern of secretion throughout life. Serum DHEA concentrations decline with advancing age and vary with gender, ethnicity, and environmental factors. Epidemiological studies show an inverse relationship between plasma DHEA(S) levels in men and age-related illnesses, including cardiovascular and metabolic diseases, immune disorders, malignancies, and neurological dysfunction. This has generated great interest on the putative role of DHEA in age-associated illnesses. Administration of DHEA to rats and mice reduces visceral fat accumulation, and improves insulin resistance in experimental models of diet-induced obesity and/or Type 2 diabetes. In addition, recent studies in vitro have shown that DHEA has the capacity to improve endothelial function by increasing nitric oxide (NO) synthesis. Replacement of DHEA in patients with adrenal insufficiency has been shown to exert beneficial effects on well-being, mood, and sexuality. By contrast, in healthy individuals, the physiological age-associated decline in circulating DHEA(S) per se does not justify DHEA supplementation, since the effects of this hormone on metabolic abnormalities, endothelial function in vivo, and cardiovascular events are contradictory. However, these results do not exclude the possibility that DHEA treatment may prove beneficial in specific subgroups of elderly subjects.

Adrenal Insufficiency↗

PubMed2001

Effects of streptozocin diabetes and diabetes treatment by islet transplantation on in vivo insulin signaling in rat heart.

The insulin signaling cascade was investigated in rat myocardium in vivo in the presence of streptozocin (STZ)-induced diabetes and after diabetes treatment by islet transplantation under the kidney capsule. The levels of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit, insulin receptor substrate (IRS)-2, and p52(Shc) were increased in diabetic compared with control heart, whereas tyrosine phosphorylation of IRS-1 was unchanged. The amount of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) and the level of PI 3-kinase activity associated with IRS-2 were also elevated in diabetes, whereas no changes in IRS-1-associated PI 3-kinase were observed. Insulin-induced phosphorylation of Akt on Thr-308 was increased fivefold in diabetic heart, whereas Akt phosphorylation on Ser-473 was normal. In contrast with Akt phosphorylation, insulin-induced phosphorylation of glycogen synthase kinase (GSK)-3, a major cellular substrate of Akt, was markedly reduced in diabetes. In islet-transplanted rats, the majority of the alterations in insulin-signaling proteins found in diabetic rats were normalized, but insulin stimulation of IRS-2 tyrosine phosphorylation and association with PI 3-kinase was blunted. In conclusion, in the diabetic heart, 1) IRS-1, IRS-2, and p52(Shc) are differently altered, 2) the levels of Akt phosphorylation on Ser-473 and Thr-308, respectively, are not coordinately regulated, and 3) the increased activity of proximal-signaling proteins (i.e., IRS-2 and PI 3-kinase) is not propagated distally to GSK-3. Islet transplantation under the kidney capsule is a potentially effective therapy to correct several diabetes-induced abnormalities of insulin signaling in cardiac muscle but does not restore the responsiveness of all signaling reactions to insulin.

Adaptor Proteins, Signal Transducing↗

PubMed2000

The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells.

Glucose transport in insulin-regulated tissues is mediated by the GLUT4 and GLUT1 transporters. Using the yeast two-hybrid system, we have cloned the sentrin-conjugating enzyme mUbc9 as a protein that interacts with the GLUT4 COOH-terminal intracellular domain. The mUbc9 enzyme was found to bind directly to GLUT4 and GLUT1 through an 11-aa sequence common to the two transporters and to modify both transporters covalently by conjugation with the mUbc9 substrate, sentrin. Overexpression of mUbc9 in L6 skeletal muscle cells decreased GLUT1 transporter abundance 65%, resulting in decreased basal glucose transport. By contrast, mUbc9 overexpression increased GLUT4 abundance 8-fold, leading to enhanced transport stimulation by insulin. A dominant-negative mUbc9 mutant lacking catalytic activity had effects opposite to those of wild-type mUbc9. The regulation of GLUT4 and GLUT1 was specific, as evidenced by an absence of mUbc9 interaction with or regulation of the GLUT3 transporter isoform in L6 skeletal muscle cells. The mUbc9 sentrin-conjugating enzyme represents a novel regulator of GLUT1 and GLUT4 protein levels with potential importance as a determinant of basal and insulin-stimulated glucose uptake in normal and pathophysiological states.

3T3 Cells↗

PubMed2000

[Fetal growth restriction and insulin-like growth factors].

The insulin-like growth factors (IGFs) and their receptors are implicated in pre- and postnatal growth and development. It is believed that the alteration in their activity may contribute to intrauterine growth restriction (IUGR). The aim of this experimental study was to relate some metabolic alterations, involving insulin-like growth factor pathway, in the placenta of pregnancies complicated by intrauterine growth restriction. Placental samples were obtained from six uncomplicated pregnancies and four pregnancies complicated by IUGR. These samples were then stained by immunohistochemical technique, using monoclonal antibodies. Our data have not shown a significant difference in the IR, the Shc isoforms and Akt levels between normal and IUGR placentas. The IUGR placentas had significantly lower levels of IRS-2 expression and higher levels of p85 transcription. IGF-I receptor binds to its ligand and activates two intracellular processes mainly a Shc-mediated pro-mitotic pathway and an anti-apoptotic pathway mediated by IRS and Akt. The diminished activity of one of the two pathways may alter the mitosis/apoptosis balance. Because of the low number of samples and the knowledge about the enzymatic pathways, we have not been able to associate our data to any biological consequence. We can only demonstrate that the enzymatic differences between IUGR and controls tend to the pro-apoptotic processes. It seems to be an other in vivo aspect in favour of the placental role in the IUGR pathogenesis.

Female↗

PubMed1996

Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal obese women.

OBJECTIVE: To determine whether any androgen is independently related with parameters of body fat accumulation and distribution in obese women. DESIGN: Circulating insulin and androgen levels (total testosterone (T), free testosterone (FT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, sex hormone binding globulin (SHBG)) and the parameters of body fat accumulation and distribution (body mass index, waist-to-hip ratio, total body fat volume (TBF), visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were determined in a population of non-diabetic obese women. SUBJECTS: 28 premenopausal obese women, recruited at the Verona University Hospital Outpatient Clinic. MEASUREMENTS: TBF, VAT and SAT area were quantified by computed tomography. Hormone levels were measured by RIA. RESULTS: SHBG showed an inverse correlation with BMI (r: -0.452, P < 0.05), WHR (r: -0.388, P < 0.05), TBF (r: -0.509, P < 0.01), VAT (r: -0.378, P < 0.05) and SAT (r: -0.449, P < 0.05). DHEA was negatively associated with BMI (r: -0.376, P < 0.05), TBF (r: -0 < 0.05), VAT (r: -0.662, P < 0.001) and SAT (r: -0.401, p < 0.05). T was found to be inversely related with VAT (r: -0.401, P < 0.05). Androstenedione was positively correlated with WHR (r: 0.383, P < 0.05). DHEAS and FT did not show significant associations with BMI, WHR, or any CT-parameters. Stepwise multiple regressions were performed for all androgens: one of the age-adjusted androgens was considered as the dependent variable for each analysis, and insulin, VAT, SAT and all other androgens were entered into the regression model. DHEA was the only hormone to show an independent association (negative) with both SAT (t-value: -3.683, P < 0.01) and VAT (t-value: -2.252, P < 0.05), whereas DHEAS showed an independent positive correlation with SAT (t-value: -2.241, P < 0.05). CONCLUSIONS: Among the androgens, DHEA seems to be the most sensitive to body fat accumulation in premenopausal obese women.

Adipose Tissue↗