Violence Against Women: Representations, Interpretations, and Education.

Cultural representations of violence against women have been mystified, eroticized, and depicted as heroic, camouflaging, and trivializing acts of violence as a societal norm for thousands of years. This themed issue invites people to re/claim identities and power, and enter into a global cultural discourse connected with cross-disciplinary channels and creative work.

No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis.

PURPOSE: As (131)I therapy, used to achieve ablation of thyroid gland remnant, can cause chromosome damage in cultured peripheral lymphocytes especially, we investigated whether administration of radioiodine may induce early genome damage in peripheral T lymphocytes of adolescents with differentiated thyroid carcinoma (DTC). METHODS: We studied 11 patients, aged 14.8 +/- 3.1 years, who assumed (131)I (range: 1.11-4.44 GBq) to ablate thyroid remnant. A blood sample for micronucleus assay and for evaluating expression of some genes involved in the DNA repair or the apoptosis pathways was obtained from each patient 1 h before (T(0)) and 24 (T(1)) and 48 h (T(2)) post-radioiodine administration. RESULTS: Compared to T(0), we did not find any difference in the number of micronucleated cells at both T(1) and T(2) in any subject. Nine out of 11 patients had altered expression levels in a majority of the DNA repair and apoptosis genes at T(1), which decreased at T(2). CONCLUSIONS: We demonstrated for the first time that peripheral cells of DTC children and adolescents who received (131)I at a mean dosage of 3.50 +/- 0.37 GBq did not show chromosome damage within 48 h from the end of radiometabolic therapy. This may be due to a prompt activation of the cell machinery that maintains the integrity of the genome to prevent harmful double-strand breaks from progressing to chromosome mutations, either by repairing the lesions or by eliminating the most seriously damaged cells via apoptosis.

Licoflavone C attenuates the genotoxicity of cancer drugs in human peripheral lymphocytes.

Flavonoids exhibit a wide spectrum of biological activities that can lead to beneficial effects for human health. The search for cytotoxic, genotoxic and/or antimutagenic natural compounds is therefore of great relevance, especially in cancer chemotherapy. In view of this, we screened the potential genotoxicity/antigenotoxicty of licoflavone C (LFLC) - a naturally occurring prenyl-flavone extracted from Genista ephedroides - using the micronucleus (MN) assay on stimulated and cytochalasin B-blocked human lymphocytes. LFLC did not increase the spontaneous MN level up to 600 microM final concentration where a strong toxicity was seen to occur. We therefore performed an antigenotoxicity assay against the two mutagenic anticancer drugs, mitomycin C (MMC) and daunorubicin (DAU), using two non-toxic LFLC concentrations (0.1 microM and 1.0 microM). The MN frequencies induced by 0.025 microg/ml or 0.05 microg/ml DAU were significantly lowered by 45.4% or 46.6% and 41.8% or 44.8% at LFLC 0.1 and 1.0 microM, respectively. After treatment with 0.085 microg/ml or 0.17 microg/ml MMC, we detected a reduction in genotoxicity of 35.1% or 37.0% and of 38.0% or 35.8% at LFLC 0.1 and 1.0 microM, respectively. In conclusion, LFLC was proven to be protective toward the chromosome damage induced by DAU or MMC in cultured human peripheral lymphocytes.

Genetic advances, biochemical and clinical features and critical approach to treatment of patients with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is an hereditary form of rickets due to isolated renal tubular phosphate wasting and impaired production of 1,25-dihydroxyvitamin D [1,25(OH)2D]. XLH is caused by mutations in the PHEX (phosphate regulating gene with homology to endopeptidases) gene, which is located on Xp22.1. The pathogenetic mechanisms by which mutations in the PHEX gene cause XLH are not completely known. Hypophosphatemia associated with disproportionate short stature and bone deformities of the lower limbs are the main findings in XLH patients. Some studies have shown that conventional treatment with vitamin D metabolites, such as 1,25(OH)2D3 or 1 alpha-hydroxyvitamin D3, combined with inorganic phosphate salts is able to improve serum phosphate concentrations and linear growth, as well as healing rickets. However, some patients may have poor beneficial effects by this therapy. On the other hand, some important treatment complications, such as hypervitaminosis D, nephrocalcinosis and secondary/tertiary hyperparathyroidism may occur during the current therapy. Despite conventional treatment, some patients may require surgical correction of bone deformities. In the light of the recent genetic advances the mechanisms that could be involved in the pathogenesis of XLH are discussed. Furthermore, the article reviews the effects of the medical treatment providing current recommendations for the management of XLH patients.

High incidence of central precocious puberty in a bounded geographic area of northwest Tuscany: an estrogen disrupter epidemic?

The potential health consequences of human exposure to environmental estrogen disrupters are not known. Because many chemical compounds are environmentally persistent, toxic and estrogen-active, they can dysregulate the hypothalamic-pituitary-gonadal axis, potentially inducing reproductive disorders such as central precocious puberty (CPP). We performed a multi-center analysis of CPP distribution in northwest Tuscany (NWT), an area of 5990 km2 with 1,280,895 inhabitants. Study criteria consisted of recorded CPP diagnoses and prescriptions of gonadotropin-releasing hormone analogs from January 1, 1998 to December 1, 2003. Although similar CPP prevalences were found in four major cities of NWT (Livorno, Lucca, Massa and Pisa) (mean 30.4 per 100,000 children, standard deviation 18.6; p > 0.05), Viareggio area (< 300 km2) with 19,219 child inhabitants (0-14 years of age) had the highest CPP prevalence: more than 161 CPP cases per 100,000 children. Living in Viareggio area significantly increased the risk of CPP (relative risk (RR) 5.73, 95% confidence interval (CI) 3.5-9.3; rate/risk difference 0.133%, p < 0.05). Annual CPP incidence in the Viareggio area was relatively constant and significantly higher than in other NWT areas (RR 5.04, 95% CI 2.3-11.2; rate/risk difference 0.03%, p < 0.05). Indeed, 47% of total NWT cases were distributed in the countryside (300?km2) surrounding Viareggio. Specifically, three villages - Camaiore, Pietrasanta and Stazzema - in Viareggio presented the highest CPP frequency: 216.1, 393.5 and 274.0 CPP cases per 100,000 children, respectively (RR 9.59, 95% CI 1.71-16.6; rate/risk difference 0.26%, p < 0.05). Owing to the definite geographic distribution of CPP and because increasing distance (km) from Pietrasanta rarefied CPP frequency, we suggest environmental factors (e.g. estrogen disrupter pollution) as major CPP determinants in NWT.

Pubertal changes in biochemical markers of growth.

Puberty is a crucial period of life during which dramatic hormonal changes induce notable modifications in linear growth, bone mass and body composition. These changes are associated with variations in some biochemical parameters such as markers of bone turnover and leptin, which may reflect changes in bone growth and fat mass, respectively. Children with growth hormone (GH) deficiency have reduced concentrations of bone markers, which increase during GH administration, while the levels of leptin decrease. There have been few studies analysing the behaviour of bone markers during puberty in GH-treated GH-deficient patients and no studies analysing the behaviour of leptin. Results from a longitudinal study showed that there was no change in serum osteocalcin, carboxy-terminal propeptide of type I procollagen, and cross-linked carboxy-terminal telopeptide of type I collagen levels during puberty in GH-treated GH-deficient children. Some studies have shown that changes in markers of bone turnover and leptin after short-term GH treatment may predict the growth response (at 6-12 months) to GH administration in GH-deficient children. At present, insufficient data are available for the clinical use of these parameters as markers of growth response during pubertal development and as predictors of long-term growth response to GH treatment in children with GH deficiency. Nevertheless, the use of more and possibly new markers might improve the accuracy of growth prediction models in the future.

Human immunodeficiency virus-1 tat induces hyperproliferation and dysregulation of renal glomerular epithelial cells.

Human immunodeficiency virus-associated nephropathy (HIVAN) is etiologically related to the viral infection, but the mechanisms of virus-induced renal injury remain undetermined. Peculiar histopathological features of HIVAN are the enhanced proliferation and the loss of differentiation markers of glomerular epithelial cells (podocytes). We found that podocytes were not permissive to HIV-1 replication. In this study we investigated the effects of the HIV-1 regulatory protein Tat on primary cultures and on a continuous line of podocytes. Our results demonstrated that Tat induced hyperproliferation of these cells in a dose-dependent manner. This activity was primarily mediated by the basic domain of the viral protein. Proteoglycans were required for this phenomenon because Tat-induced increase of podocyte growth was significantly impaired by inhibition of proteoglycan synthesis with beta-D-xyloside. In podocyte cultures Tat promoted both the transcription and the release of basic fibroblast growth factor, which contributed to the enhanced cell proliferation. Moreover, Tat deregulated the podocyte phenotype causing down-regulation of maturity markers such as WT-1 and synaptopodin, alteration of cytoarchitecture, and impairment of permselectivity. Together, these results demonstrate that the interaction of extracellular Tat with podocytes can induce alterations that mimic the pathological changes of podocytes detected in HIVAN.

Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement.

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8.