Expression of nucleoside-metabolizing enzymes in myelodysplastic syndromes and modulation of response to azacitidine.

The nucleoside analog azacitidine (AZA) is used in the treatment of myelodysplastic syndromes (MDS), but 30-40% of patients fail to respond or relapse after treatment. Hence, to identify new molecular alterations that allow for identification of patients unlikely to respond to AZA could impact the utility of this therapy. We determined the expression levels of genes involved in AZA metabolism: UCK1, UCK2, DCK, hENT1, RRM1 and RRM2 using quantitative PCR in samples from 57 patients with MDS who received AZA. Lower expression of UCK1 was seen in patients without a response to AZA (median 0.2 vs 0.49 for patients with response to AZA, P=0.07). This difference in UCK1 expression was not influenced by aberrant methylation of the UCK1 promoter. In addition, the seven polymorphic loci found in the coding sequence were not associated with UCK1 gene expression nor AZA response. Silencing of UCK1 by siRNA leads to blunted response to AZA in vitro. The univariate analysis revealed that patients expressing lower than median levels of UCK1 had a shorter overall survival (P=0.049). Our results suggest that expression level of UCK1 is correlated with clinical outcome and may influence the clinical response to AZA treatment in patients with MDS.

[Assessment of congenital malformation risk in the progeny of the military and civilian personnel of the Salto di Quirra military base: preliminary results]. / Valutazione del rischio di malformazioni congenite nella progenie del personale militare e civile del Poligono Interforze del salto di Quirra: risultati preliminari.

INTRODUCTION: We evaluated the congenital malformation rate in the progeny of the personnel of the Salto di Quirra military base in Sardinia. METHODS: During 2011, we gathered questionnaire information on the reproductive history of 389 employees, more then 99% of those eligible for routine health surveillance. RESULTS: the observed congenital malformation rate (20.1 x 10(-3), 95% CI 6.3 - 33.8) was lower than that reported by the Italian Registries of Congenital Malformations, and it did not vary by exposure to radiofrequency, elf electromagnetic fields, and solvents, and by jobs associated with alleged exposure to nanoparticles or alpha radiation. CONCLUSIONS: Our findings suggest that the documented or alleged occupational exposures among the PISQ workforce did not increase the congenital malformation rate in the progeny.

Faecal occult blood test-based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer.

BACKGROUND: The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported. METHODS: All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen-detected cancers and other colorectal cancers diagnosed within the target age group. RESULTS: Some 38,693 (49.6 per cent) of 78,083 individuals had a FOBT and 2392 (6.2 per cent) had a positive result. Colorectal cancer was diagnosed in 4.6 per cent and advanced adenoma in 32.7 per cent. PPVs were 4.0 per cent for cancer, 28.1 per cent for advanced adenoma and 36.6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non-screened cohorts. Compliance for colonoscopy was 92.0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non-manual work. CONCLUSION: These results justify extension of colorectal cancer screening to other regions of Italy.

Cannabaceae pollen in the atmosphere of Brianza, Northen Italy.

AIM: We have noted several patients suffering for rhinitis and/or asthma symptoms in the summer months without positive skin tests for pollens blossoming in the corresponding season. So we tried to determine the pollination pattern of pollens usually not tested, because no company produces the corrisponding extract. METHODS: We determined airborne pollination by means of a volumetric pollen trap for five years from 2001 to 2005. RESULTS: We found, in addition to well-known aeroallergens, a significant percentage of Cannabaceae from the end of July to mid September with the highest concentration in 2004 (140 gr/m3). DISCUSSION: The potential allergenicity of Cannabis pollen was supported in the United States, where they found some patients with rhinitis or asthma during the pollen seasons and positive prick test for Cannabis, but the clinical significance of Cannabaceae pollen as an aeroallergen in Europe is still undefined.

Calcium protects differentiating neuroblastoma cells during 50 Hz electromagnetic radiation.

Despite growing concern about electromagnetic radiation, the interaction between 50- to 60-Hz fields and biological structures remains obscure. Epidemiological studies have failed to prove a significantly correlation between exposure to radiation fields and particular pathologies. We demonstrate that a 50- to 60-Hz magnetic field interacts with cell differentiation through two opposing mechanisms: it antagonizes the shift in cell membrane surface charges that occur during the early phases of differentiation and it modulates hyperpolarizing K channels by increasing intracellular Ca. The simultaneous onset of both mechanisms prevents alterations in cell differentiation. We propose that cells are normally protected against electromagnetic insult. Pathologies may arise, however, if intracellular Ca regulation or K channel activation malfunctions.