Genotoxicity Evaluation of the Soybean Isoflavone Genistein in Human Papillary Thyroid Cancer Cells. Study of Its Potential Use in Thyroid Cancer Therapy.

Genistein is one of the several known isoflavonic phytoestrogens found in a number of plants, with soybeans and soy products being the primary food source. The aim of the study is to evaluate if genistein is able to exert antineoplastic action in primary human papillary thyroid cancer (PTC) cells. Thyroid tissues were treated with genistein (1-10-50-100 µM). Cell viability, proliferation, DNA primary damage and chromosomal damage were evaluated. An antiproliferative effect was induced by the highest doses of genistein, and such an effect was synergistically enhanced by the cotreatment with the antineoplastic drug sorafenib. Comet assay did not show any genotoxic effect in terms of primary DNA damage at all the times (4 and 24 h) and tested doses. A reduction of hydrogen peroxide-induced DNA primary damage in primary thyrocytes from PTC cells pretreated with genistein was observed. Data suggest that genistein exerts antineoplastic action, does not induce genotoxic effects while reduces oxidative-induced DNA damage in primary thyrocytes from PTC cells, supporting its possible use in therapeutic intervention.

n-TiO2 and CdCl2 co-exposure to titanium dioxide nanoparticles and cadmium: Genomic, DNA and chromosomal damage evaluation in the marine fish European sea bass (Dicentrarchus labrax).

Due to the large production and growing use of titanium dioxide nanoparticles (n-TiO2), their release in the marine environment and their potential interaction with existing toxic contaminants represent a growing concern for biota. Different end-points of genotoxicity were investigated in the European sea bass Dicentrarchus labrax exposed to n-TiO2 (1mgL(-1)) either alone and combined with CdCl2 (0.1mgL(-1)) for 7 days. DNA primary damage (comet assay), apoptotic cells (diffusion assay), occurrence of micronuclei and nuclear abnormalities (cytome assay) were assessed in peripheral erythrocytes and genomic stability (random amplified polymorphism DNA-PCR, RAPD assay) in muscle tissue. Results showed that genome template stability was reduced after CdCl2 and n-TiO2 exposure. Exposure to n-TiO2 alone was responsible for chromosomal alteration but ineffective in terms of DNA damage; while the opposite was observed in CdCl2 exposed specimens. Co-exposure apparently prevents the chromosomal damage and leads to a partial recovery of the genome template stability.

Does the crystal habit modulate the genotoxic potential of silica particles? A cytogenetic evaluation in human and murine cell lines.

Crystalline silica inhaled from occupational sources has been classified by IARC as carcinogenic to humans; in contrast, for amorphous silica, epidemiological and experimental evidence remains insufficient. The genotoxicity of crystalline silica is still debated because of the inconsistency of experimental results ("variability of silica hazard"), often related to the features of the particle surfaces. We have assessed the role of crystal habit in the genotoxicity of silica powders. Pure quartz (crystalline) and vitreous silica (amorphous), sharing the same surface features, were used in an in vitro study with human pulmonary epithelial (A549) and murine macrophage (RAW264.7) cell lines, representative of occupational and environmental exposures. Genotoxicity was evaluated by the comet and micronucleus assays, and cytotoxicity by the trypan blue method. Cells were treated with silica powders for 4 and 24h. Quartz but not vitreous silica caused cell death and DNA damage in RAW264.7 cells. A549 cells were relatively resistant to both powders. Our results support the view that crystal habit per se plays a pivotal role in modulating the biological responses to silica particles.

Genomic and chromosomal damage in the marine mussel Mytilus galloprovincialis: Effects of the combined exposure to titanium dioxide nanoparticles and cadmium chloride.

Titanium dioxide nanoparticles (TiO2-NPs) continuously released into waters, may cause harmful effects to marine organisms and their potential interaction with conventional toxic contaminants represents a growing concern for biota. We investigated the genotoxic potential of nanosized titanium dioxide (n-TiO2) (100 µg L(-1)) alone and in combination with CdCl2 (100 µg L(-1)) in Mytilus galloprovincialis after 4 days of in vivo exposure. RAPD-PCR technique and Micronucleus test were used to study genotoxicity. The results showed genome template stability (GTS) being markedly reduced after single exposure to n-TiO2 and CdCl2. Otherwise, co-exposure resulted in a milder reduction of GTS. Exposure to n-TiO2 was responsible for a significant increase of micronucleated cell frequency in gill tissue, while no chromosomal damage was observed after CdCl2 exposure as well as after combined exposure to both substances.

Safety of fondaparinux in the prevention of venous thromboembolism in elderly medical patients: results of a single-center, retrospective study.

AIM: Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality in acutely ill medical patients. Fondaparinux is recommended for the prevention of VTE in this setting, but little information is available on its safety and effectiveness in unselected, "real world" patients. The aim of this paper was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients. METHODS: Single center, retrospective study. All patients >60 years, admitted for acute medical disease, bedridden for at least four days and treated with fondaparinux were evaluated. Occurrence of objectively documented, symptomatic VTE, and of bleeding events during the treatment period and follow-up were reported. RESULTS: Two hundred and ten patients (median age 81 years) were treated with fondaparinux. Seventy patients received fondaparinux 1.5 mg daily, 140 received the 2.5 mg daily dose. However, 29 patients in the first group (with a CrCl≥50 mL/min) and 84 patients in the last group (with a CrCl<50 mL/min) did not receive the correct dose of fondaparinux. During treatment, one episode (0.48%, 95% CI 0.1% to 2.6%) of major bleeding and 6 episodes (2.86%, 95% CI 1.3% to 6.1%) of clinically relevant non major bleeding were recorded. Only one thromboembolic event (0.48%, 95% CI 0.1% to 2.6%) was documented. Thirty-nine patients died; no death was related to VTE, unlike one death was due to major bleeding. Cancer was the only significant predictor of bleeding at statistical analysis. CONCLUSION: In elderly acutely ill hospitalized medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Comparison in in-vivo response between a bioactive glass and a non-bioactive glass.

The authors report on the in-vivo comparison, in the rabbit, between the response to a bioactive glass and the response to a non-bioactive glass. Implants have been performed in muscle and bone. Two different glasses were investigated, namely B01 and I02. B01 is a glass designed to be degradable and resorbable and has a percentual molar composition of: SiO2 49.6%; P2O5 2.7%; CaO + MgO + Na2O + K2O + Al2O3 47.7% with a 1 : 1 CaO/Na2O ratio. I02 is a sodium-calcium-silicate non-resorbable glass lacking P2O5 and has a percentual molar composition of: SiO2 70.7%; CaO + MgO + Na2O + K2O + Al2O3 29.3%. In-vivo tests were planned as: (a) intramuscular implants of glass cylinders in the rectus femoris and retrievals took place at 2, 16 and 43 weeks; (b) intraosseus implants of glass cylinders in the distal femural canal and retrievals took place at 8 and 43 weeks. Histology and light microscopy analysis followed. Bioactive degradable glass elicits a favorable response both in muscle and bone; a gradual degradation process leads to disruption and partial resorption of the material and a tight apposition is promoted with the newly formed bone. The non-bioactive sodium-calcium-silicate glass (named I02) may elicit, like the bioactive degradable B01, a favorable response which is characterized by the absence of inflammatory or other adverse reactions; anyway it does not change its structure at an optical microscopic level and it does not promote any tight apposition with bone.

[Thyroid function in the euthyroid elderly subject: evidence of low T3 syndrome]. / La funzionalità tiroidea negli anziani eutiroidei: evidenza di una "sindrome a bassa T3".

The presence of a low T3 syndrome was confirmed in elderly euthyroid patients. The condition is characterised by lower circulating total (TT3) and free triiodothyronin (FT3) than in adults with no clinical symptoms of hypothyroidism. A total of 133 subjects over 65 were studied as we used 204 adult controls aged 18-65. Among the indices of thyroid function studied only TT3 and FT3 were founded to be statistically reduced among the elderly.