[Pathophysiological and clinical correlations between endocrine and cardiovascular systems. An inter-systemic model of internal medicine]. / Sistema endocrino ed apparato cardiovascolare: correlazioni fisiopatologiche e cliniche. Modulo intersistemico di medicina interna.

This review focuses on the mechanisms by which thyroid hormones affect the regulation of the cardiovascular system and the thermogenic and hemodynamic variation induced by thyroid disfunction. It is also stressed the hormonal role of the cardiac myocytes realising natriuretic peptides, involved in plasma volume homeostasis and cardiovascular remodelling; its rapid measurement is a useful clinical tool, in the diagnostic and prognostic of left ventricular dysfunction, correlating with the degree of the clinical symptoms. The endothelial layer is a receptor-effector endocrine organ that produces substances that maintain vasomotor balance and vascular-tissue homeostasis. Cardiovascular risk factors causes oxidative stress that alter endothelial function and leads to endothelial dysfunction. On the basis of the present body of evidence there is no doubt that endothelial dysfunction contributes to the initiation, and progression, of atherosclerotic disease and that it could be considered an independent vascular risk factor for the micro- and macrovascular damages in the diabetes disease. In several extrathyroidal pathological condition, as well as in heart failure, the main alteration of the thyroid function is referred to as "low T3 syndrome". This syndrome is due to an adaptative reaction of the metabolic pathway of thyroxine, producing an increased amount of rT3, metabolically inactive, thus decreasing the detrimental metabolic effects of T3, in conditions of critically impaired hemodynamic and metabolic efficiency. Preliminary clinical trials, in heart failure, suggest the prognostic value of the level of circulating T3, as well as usefulness of T3, or of thyromimetic derivatives (DITPA), in chronic treatment of the heart ventricular dysfunction.

[The thyroid nodule: cytomorphofunctional profile-therapeutic approach]. / Il nodulo tiroideo. Definizione citomorfofunzionale e orientamenti terapeutici.

Analyzing a cohort of 16,400 thyroid nodules, sequentially examined since 1982, the value of preoperative echo-guided fine needle aspiration cytology (FNA) in discriminating benign lesion from malignant ones, has been assessed. Ultrasonography provides a useful support not only to guide the diagnostic FNA methodology, but also monitoring therapeutic procedure: evacuation of cyst, alcoholic sclerotization, laser therapy, effects of treatment on the size of the nodular structure. The correct interpretation of the imaging pictures should be rationally anchored to both clinical criteria and to circumstantial anamnestic analysis, as well as to physical examination, laboratory tests, instrumental systems, cytomorphological patterns, immunohistologic and biomolecular studies. The FNA sampling under ultrasonography guidance offers an absolute diagnostic reliability, and it can be confidently applied for planning surgical strategy. By adopting this safe, non invasive, accurate diagnostic tool, that offers the advantage of eliminating unnecessary operation for benign lesions, the number of operation is strikingly reduced, while it allows to identify an higher surgical frequency of malignancy, yielding a prevalence of about 3% of thyroid nodules. FNA is a very profitable cost-effective diagnostic tool, reducing 20% the cost of care, for the evaluation and treatment of patient with thyroid nodule. Preliminary results on the molecular pattern of thyroid nodules, obtained applying a new methodological system, the Laser Capture Microdissection, are underlined; in the next issue of this journal it will be analytically illustrated the diagnostic role of this innovative procedure that appears very promising in obtaining information on the molecular derangements of a single thyroid cell, even at a precancerous stage; thus a preventive surgical treatment of a thyroid nodule genetically characterized can be predicted.

Clinico-pathological significance of cell-type-specific loss of heterozygosity on chromosome 7q21: analysis of 318 microdissected thyroid lesions.

A careful pathological examination often reveals the presence of different lesions at various stages of tumor progression and invasion, even in those thyroid glands presenting with solitary nodules. Each thyroid lesion is composed of many different cell types, reflecting the marked heterogeneity of normal thyroid tissue. Among the different chromosome regions altered in thyroid tumors, 7q21 appears to be specifically involved in malignant tumors, especially of the follicular type. This study was conducted to analyze the loss of heterozygosity (LOH) pattern at 7q21 in pure populations of cells from each single lesion harbored in surgically removed thyroid glands, and to evaluate its clinical significance. One hundred and forty-two thyroid glands were examined, all showing, as a common trait, a goitrous appearance associated with one single lesion in 114 cases and with more than one in the remaining 28 cases. A total number of 318 lesions was analyzed, consisting of 142 goiters (TG), 48 hyperplasias (TH), 80 adenomas (TA) and 48 carcinomas (TC). Five different types of cells were isolated by laser capture microdissection from each lesion. DNA was analyzed by PCR and polyacrylamide gel electrophoresis in search of LOH affecting five microsatellite markers, D7S660, D7S630, D7S492, D7S657, and D7S689. We detected LOH at 7q21 not only in thyroid malignant tumors but also in benign lesions. Allelic loss occurred exclusively in dark nucleus and eosinophilic cytoplasm cells, commonly observed in the follicular type of lesions. In these types of lesions allelic loss frequency increases along with neoplastic transformation (9% in TG, 41% in TH, 68% in TA and 100% in TC), and is directly correlated with thyroid gland volume as well as with the presence of multiple lesions. The highest LOH rate was observed for D7S492, indicating that the recurrent region of deletion was localized at the corresponding genetic locus at 7q21.2, in the same position where the common fragile site FRA7E was previously mapped. LOH at this locus represents an early event in the development of follicular TC and is associated with intense growth of thyroid glands.

Cloning of the mouse insulin receptor substrate-3 (mIRS-3) promoter, and its regulation by p53.

The insulin receptor susbtrate-3 (IRS-3) is a member of a family of intermediate adapter proteins that function as major intracellular targets for phosphorylation by the activated insulin and IGF-I receptors. Among the four IRS proteins identified so far, IRS-3 exhibits a rather peculiar expression pattern during both the embryonic development and adult life, suggesting a different mechanism of regulation of its expression. In this study, we cloned the 5' flanking region of the mIRS-3 gene and analyzed its promoter activity. The mIRS-3 promoter is inhibited by wild-type p53, and this effect is completely abolished by cotransfection of a dominant negative p53. Tumor-derived p53 mutants show variable, but lower suppressing capability than wt p53. In addition, treatment with doxorubicin inhibits endogenous expression of mIRS-3 mRNA in C2C12 and 3T3-L1 cells. The DNA region spanning from nucleotides -287 and -178 in the mIRS-3 promoter is responsible for a 32.2% reduction of the mouse double minute 2 (MDM2) promoter activity, suggesting its involvement in the p53-mediated inhibitory effect. In conclusion, our study demonstrates that the mIRS-3 promoter is regulated by p53 at the transcriptional level. The inhibition of mIRS-3 promoter by wild-type p53, and its de-repression by tumor-derived p53 mutants, appears to be similar to that previously reported for the IGF-I receptor promoter, suggesting a common role of these two genes in p53-mediated cell growth and differentiation.

Utilizaçäo da informática como apoio à responsabilizaçäo dos governantes / Use of informatics as basis a government responsibility

Pretende contribuir para a busca de mecanismos de "accountability" dos governantes, envolvendo um maior controle das atividades do governo. Discorre sobre a administraçäo pública e seus problemas. Apresenta algumas consideraçöes sobre corrupçäo, clientelismo e patrimonialismo. Aborda os conceitos relacionados ao tema do "governo eletrônico". Trata da questäo da divulgaçäo de informaçöes orçamentárias do governo, por meio da Internet. Caracteriza a utilizaçäo da informaçäo por diferentes grupos sociais, apontando meios para utilizaçäo dessas informaçöes no aumento da responsabilizaçäo dos governantes. Através do site da Secretaria da Fazenda, analisa o caso do Governo do Estado de Säo Paulo.