Biomedical subjects

Tatiana Mancini

Publications and source records attributed to Tatiana Mancini.

6 recordsLinked to original sources

PubMed2006

Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic patients undergoing CABG.

BACKGROUND: Type 2 diabetes mellitus (DM) is known to negatively affect biological properties of venous vasculature, and, particularly, to reduce endothelium-derived nitric oxide release. This condition might influence venous graft function following coronary artery bypass surgery (CABG). The aim of this study was to evaluate the functional effects of a NO-releasing aspirin (NORA) on vein grafts (VG) of diabetics and control patients undergoing elective CABG. METHODS: In 40 consecutive ischemic heart disease patients, the effects of NORA were tested on segments of saphenous vein conduits harvested during elective CABG. Twenty patients had type-2 DM (mean age 69+/-2), whereas 20 patients had no DM (NDM) and represented the control group (mean age 67+/-4). Functional responses were tested by exposing VGs to NORA and to standard vasoactive agents in an organ-bath preparation. Histological features of VGs were also assessed by light and electronic microscopy. RESULTS: Significant impairment of endothelial-dependent vasodilation (acetylcholine induced) was documented in VGs of DM subjects. NORA induced a significant and comparable vascular relaxation in all venous segments of NDM and DM patients (56+/-12% of maximal relaxation vs 61+/-11% in the control group, respectively). Histology showed variable extent of vascular layer and cellular abnormalities in VGs of diabetics (intimal hyperplasia, calcific deposition, endothelial cell degeneration) likely responsible of the endothelial functional impairment, whereas control group VG showed preserved structures. CONCLUSIONS: This preliminary study confirms the impairment of endothelium-dependent vasodilative property of VGs in DM patients. It also indicates that NORA effectively induces vasodilation of VGs which was effective also in DM patients thereby representing a promising therapy for diabetics undergoing CABG with the use of VGs, although further studies are mandatory to conclusively assess the safety and benefits of this pharmacological agent.

Acetylcholine↗

PubMed2005

Expression of growth hormone-releasing hormone receptor splicing variants in human primary adrenocortical tumours.

OBJECTIVE: Several splice variants (SVs) of GHRH receptor (GHRH-R) have been identified in various human cancers through which GHRH antagonists may exert their IGF-II-mediated antiproliferative action. Because the overexpression of the IGF-II gene is a frequent feature of adrenal carcinoma, we searched for the presence of GHRH-R SVs in these tumours. METHODS AND RESULTS: The expression of GHRH-R SVs was assessed by nested PCR in 45 human adrenocortical tumours. We have amplified 720-, 566- and 335-bp PCR products only in carcinomas. Their sequence revealed three open reading frames, corresponding to SV1, SV2 and SV4 of GHRH-R. SV2 was detected in five of 24 cancers examined, whereas the incidence of SV1 and SV4 was lower. Their simultaneous expression was observed in one carcinoma. No PCR products for SV3 or wild-type GHRH-R were found in carcinomas; mRNA for wild-type GHRH-R or SVs of GHRH-R were not observed either in adenomas or in normal adrenal or in NCI-H295R cells. Interestingly, all carcinomas which expressed SVs were also positive for the presence of GHRH mRNA. CONCLUSION: This is the first time that the expression of splice variants of GHRH-R has been demonstrated in human adrenal carcinoma. This study raises the possibility that splice variants might play a role in adrenal carcinogenesis and might offer the possibility for new therapeutic strategies at least in a subgroup of adrenal carcinomas.

Adenoma↗

PubMed2004

Cushing's syndrome and bone.

Structural and functional impairment of skeletal system is a relevant cause of morbidity and disability in patients with Cushing's syndrome (CS). Approximately 30-50% of patients with CS experience fractures (particularly at the spinal level) consistent with the 50% incidence of osteoporosis. Growth failure, pubertal arrest are the hallmarks of CS in children and growing adolescents leading to reduced final adult height and peak bone mass. The decrease in osteoblast number and function, through different mechanisms, seems to play a central role in the bone loss in CS. Patients with CS have decreased serum levels of osteocalcin and alkaline phosphatase. Considering the preferential bone loss in the cancellous skeleton it is reasonable to measure BMD, possibly with Dual X-rays absorptiometry (DEXA) at lumbar spine, in all patients with CS. Patients cured from CS have increased prevalence of spine damage: therefore, a radiological follow-up of the skeleton should be included in the management of patients with CS not only during the active phase but also after cure. Glucocorticoid-induced osteoporosis is reversible. The recovery of bone loss in CS is slow, taking approximately ten years to become complete. In the meanwhile, patients with severe osteopenia are exposed to a high risk of fracture. Alendronate may induce a more rapid improvement in BMD than cortisol normalization alone and it could be useful in patients with persistent postsurgical hypercortisolism to prevent further bone loss. The decision to discontinue antiresorptive therapy should be based on clinical monitoring and DEXA measurements.

Absorptiometry, Photon↗

PubMed2004

Cardiovascular risk in Cushing's syndrome.

Chronic cortisol hypersecretion causes central obesity, hypertension, insulin resistance, dyslipidemia, protrombotic state, manifestations which form a metabolic syndrome in all patients with Cushing's syndrome. These associated abnormalities determine an increased cardiovascular risk not only during the active phase of the disease but also long after the "biomedical remission". Clinical management of these patients should be particularly careful in identifying global cardiovascular risk. Considering that remission from hypercortisolism is often difficult to achieve care and control of all cardiovascular risk factors should be one of the primary goals during the follow up of these patients. Extending the indications of the recent consensus on Cushing's syndrome, we suggest to carry out an OGTT to avoid underestimation of diabetes mellitus, an echocardiography and Doppler ultrasonography of the epiaortic vessels in all patients at diagnosis and during follow-up.

Adult↗

PubMed2004

High cardiovascular risk in patients with Cushing's syndrome according to 1999 WHO/ISH guidelines.

OBJECTIVE: In patients with Cushing's syndrome (CS) cardiovascular complications determine a mortality rate four times higher than in an age- and gender-matched population. Therefore, we calculated the global cardiovascular risk in patients with CS. DESIGN AND PATIENTS: We applied the World Health Organization--International Society of Hypertension (WHO/ISH) 1999 guidelines for the estimation of cardiovascular risk in 38 females and 11 males with CS; 27 pituitary adenomas, 15 adrenal adenomas, four adrenal carcinomas and three ectopic ACTH-secreting tumours. The risk of major cardiovascular events was estimated considering the combined effect of several risk factors (hypertension, diabetes, etc.), organ damage (left ventricular hypertrophy (LVH), proteinuria, etc.) and associated pathologies. Four categories of absolute cardiovascular disease risk were defined (low, medium, high, very high). RESULTS: Eighty per cent of patients presented a 'high' or 'very high' cardiovascular risk; 85.1% of the patients were hypertensive with a mild-moderate hypertension (68%). Forty-seven per cent of patients were diabetics and 41.3% were obese. Hyperlipidaemia was less frequent (37.5%). Fasting glycaemia was the only cardiovascular risk factor that correlated with a degree of hypercortisolism. Duration of disease correlated with the presence of obesity (P < 0.0008) and hypertension (P < 0.03) but not with the presence of diabetes or dyslipidaemia and seemed to be the only significant predictor of cardiovascular risk (P = 0.03). CONCLUSIONS: Patients with active CS present a remarkably increased cardiovascular risk. Considering that the biochemical cure of hypercortisolism is often difficult to obtain, especially in Cushing's disease, and that cardiovascular risk could persist even after the 'cure', control of risk factors should be one of the primary goals of the therapy.

Adult↗

PubMed2003

Functional and nonfunctional adrenocortical tumors demonstrate a high responsiveness to low-dose adrenocorticotropin.

Aldosterone-producing adenomas (APAs) demonstrate exquisite sensitivity to endogenous ACTH. We previously showed an ACTH receptor overexpression in APAs compared with the other adrenal tumors. To evaluate the meaning of such findings, we investigated the response of aldosterone, cortisol, and 17OH progesterone (17OHP) to 1 microg ACTH in 42 patients with adrenocortical tumors (23 NHAs, 9 APAs, and 10 CPAs) and 10 normal subjects (C). All 52 subjects were responsive to ACTH, and hormone peak levels were reached at 30 min. The aldosterone peak level was significantly higher in APAs [mean +/- SEM: 84.3 +/- 13.1 ng/dl (2335.1 +/- 362.9 pmol/liter)] than in other tumors and control (C). Cortisol peak levels was higher in CPAs [37.1 +/- 3.9 microg/dl (1023.9 +/- 107.6 nmol/liter)] than in NHAs (P < 0.01), in C (P < 0.01) and in APAs (P = n.s.). 17OHP peak levels were significantly higher in patients with adrenocortical tumors toward C. In summary: 1) low-dose ACTH induces an important stimulation in all tumors, suggesting preservation of high responsiveness to ACTH; 2) this is especially true for aldosterone in APA and could be of primary importance when performing diagnostic tests for hyperaldosteronism; and 3) 17OHP-hyperresponsiveness to low-dose ACTH is the most common alteration both in functional and nonfunctional tumors.

17-alpha-Hydroxyprogesterone↗