The use of mouse ribs in organ culture improves the in vitro bone resorption assay

This study investigated in vitro bone resorption determining the calcium release in ribs, long bone and calvaria prelabelled with 45Ca from 17 day mouse fetuses, both in the absence and in the presence of specific stimuli, such as parathyroid hormone and calcitonin. 10- 7 M rat parathyroid hormone (1-34) (rPTH (1-34)) stimulated bone resorption (evaluated through the ratio treated ribs/control ribs) in 93% of the organ cultures, while lower success rate was obtained using calvaria and long bone from the same animals. In the absence of test substances, no differences were observed in paired ribs from the same fetus, while corresponding ribs from different fetuses showed considerable differences. Within every single hemythorax, bone resorption varies according to the rib position either in control ribs, or in those ones treated with rPTH (1-34). In the presence of rPTH (1-34), bone resorption showed to be dose-dependent producing a maximal response at 10- 6 M, a minimal response at 10- 8 M and a half-maximal response at 5x10-8 M. Salmon calcitonin (sCT) had no effect upon basal resorption, while it acted as a potent inhibiting agent in PTH response. The conspicuous number of samples which can be obtained from a relatively low number of mice, the reproducibility of results, together with the hormone sensitivity make the fetal mouse rib model an excellent tool for evaluating bone resorption in vitr

Multiple endocrine neoplasia type 2

Abstract Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and other hyperplasia and/or neoplasia of different endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been estimated at approximately 1:30,000. Two different forms, sporadic and familial, have been described for MEN2. Sporadic form is represented by a case with two of the principal MEN2-related endocrine tumors. The familial form, which is more frequent and with an autosomal pattern of inheritance, consists of a MEN2 case with at least one first degree relative showing one of the characteristic endocrine tumors. Familial medullary thyroid carcinoma (FMTC) is a subtype of MEN2 in which the affected individuals develop only medullary thyroid carcinoma, without other clinical manifestations of MEN2. Predisposition to MEN2 is caused by germline activating mutations of the c-RET proto-oncogene on chromosome 10q11.2. The RET gene encodes a single-pass transmembrane tyrosine kinase that is the receptor for glial-derived neurotrophic growth factors. The combination of clinical and genetic investigations, together with the improved understanding of the molecular and clinical genetics of the syndrome, helps the diagnosis and treatment of patients. Currently, DNA testing makes possible the early detection of asymptomatic gene carriers, allowing to identify and treat the neoplastic lesions at an earlier stage. In particular, the identification of a strong genotype-phenotype correlation in MEN2 syndrome may enable a more individualized treatment for the patients, improving their quality of life. At present, surgical treatment offers the only chance of cure and therefore, early clinical and genetic detection and prophylactic surgery in subjects at risk are the main therapeutic goal.</p

In Vitro Effects of Oestrogens, Antioestrogens and SERMs on Pancreatic Solid Pseudopapillary Neoplasm-Derived Primary Cell Culture

Background: Solid-pseudopapillary neoplasms of the pancreas (SPNs) are uncommon tumours usually frequent in young women. Although the pathogenesis of SPNs is uncertain a potential influence of the sex hormone milieu on the biology of these tumours has been suggested. The controversial expression of oestrogen receptors (ERs) in SPNs, provide a rationale for studying the effects of oestrogenic molecules on SPN development