Influence of metals on rhinosinusal polyposis in Sardinian population (Italy).

Metals have strong toxic effects in humans and can act as immunoregulatory factors. The purpose of our study was to determine whether the concentrations of metals are associated with the clinical course of nasal polyposis (NP). We measured the concentrations of 10 metals and non-metal (Zn, Mn, Se, Fe, Cr, Ni, Pb, Al, Cd, and Cu) in 58 patients with NP, and 29 controls with a healthy nasal mucosa. We used electron microscopy to compare the ultrastructural features of the nasal mucosa between NP patients and healthy controls. Concentrations of metals in nasal polyps and healthy mucosa were determined by mass spectrometry. Transmission electron microscopic (TEM) and scanning electron microscopic (SEM) images of the nasal mucosa were obtained. The mean tissue concentrations of all 10 metals and non-metal were significantly lower in NP patients than in healthy controls (P < 0.05).TEM and SEM revealed changes in the mucosal ultrastructure in NP with progressive fibrosis, devascularisation, and inflammation. Tissue concentrations of metals were lower in NP patients than in healthy controls, and this was particularly evident in massive polyposis.

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

Diet and nutrients are contributing factors that influence blood cadmium levels.

Studies suggested the intake of Cd from diet can be approximately equivalent to that from smoking. Moreover, a mutual metabolic influence between Cd and nutrients has been reported. The purpose of this study was to evaluate the relationship between blood cadmium concentration (BCdC) and food consumption, nutrients intake (Ca, Fe, Zn, vitamin C, and vitamin D), tobacco smoking, and some other variables (age, body mass index, and residence) in 243 adults living in the Italian island of Sardinia (Sassari Province). Specifically, we hypothesized that offal consumption contributes to Cd intakes and blood levels. The BCdC was quantified by graphite furnace atomic absorption spectrometry, and information on personal data was collected through questionnaires. Smoke significantly contributed to the BCdC (P < .001). Nonsmoker subjects who eat offal showed significantly higher BCdC (P = .04). Moreover, slightly higher BCdCs were also observed in nonsmoker subjects who eat rice, fish, and bread. The BCdC positively correlated with age of subjects (r = 0.144; P = .025) and offal daily intake in nonsmokers (r = 0.393; P < .001). The intake of Ca was negatively correlated (r = -0.281; P = .001) with the BCdC in females. The multiple linear regression analysis showed smoking > consumption of offal > body mass index ≈ age as the most important risk factors for the BCdC in the selected population.

Assessment of reference ranges for blood Cu, Mn, Se and Zn in a selected Italian population.

The reference ranges for blood Cu, Mn, Se and Zn of 215 adult subjects non-occupationally exposed and living in the Nuoro province (Sardinia, insular Italy) were assessed. Metals were determined by sector field inductively coupled plasma mass spectrometry after microwave-assisted acid digestion of blood. The blood reference ranges estimated as P5-P95 percentiles (geometric mean, GM) were 776-1495µg/L (1036µg/L) for Cu; 4.73-17.0µg/L (8.91µg/L) for Mn; 106-185µg/L (140µg/L) for Se and 4686-8585µg/L (6418µg/L) for Zn. These results were then stratified for sex, age, alcohol consumption, smoking habit and living area. The GM value of Cu was significantly higher in females (1127µg/L) than in males (957µg/L). Age, alcohol intake, smoking habit and residential area did not influence blood Cu. The GM of Mn was significantly higher in females (9.98µg/L) respect to males (8.01µg/L) and in drinkers (9.67µg/L) compared to non-drinkers (8.38µg/L). The other variables did not change the Mn data. Selenium concentrations did not differ significantly as a function of individuals factors. With reference to Zn, males had GM of 6804µg/L and females of 6031µg/L, and more blood Zn was found in subjects consuming alcohol (6618µg/L) respect to abstainers (6155µg/L). In addition, blood Zn was not affected by age, smoking habit and place of living.

Reference intervals for blood Cd and Pb in the general population of Sardinia (Italy).

The reference values (RVs) for blood Cd and Pb of 215 adult subjects non-occupationally exposed and living in Sardinia (insular Italy) were assessed. Age, sex, smoking, alcohol drinking and living area were used to stratify the reference group. After collection from volunteers, samples were acid digested in a microwave oven and metals were determined by sector field inductively coupled plasma mass spectrometry. The RVs expressed as 5th-95th percentiles (geometric mean, GM) were 0.24-1.82 µg/l (0.53 µg/l) for blood Cd and 13.2-87.3 µg/l (33.4 µg/l) for blood Pb. Females had GM levels of Cd (0.58 µg/l) higher than males (0.49 µg/l); subjects aged <40 years had less Cd (0.44 µg/l) than old subjects (>60 years; 0.56 µg/l); Cd in smokers (1.23 µg/l) was 3-times higher than in non-smokers (0.42 µg/l) and correlated with the number of cigarettes per day. The alcohol intake and place of living did not influence blood Cd. The GM values of blood Pb in males (44.4 µg/l) were higher than in females (24.7 µg/l); subjects less than 40 years-old (27.5 µg/l) showed lower Pb than elderly individuals (>60 years, 41.2 µg/l); drinkers (42.2 µg/l) had Pb 2-times higher than non-drinkers (24.4 µg/l). Blood Pb was not significantly affected by smoking and place of living. As revealed by multiple linear regression, the predictor variables were, in order of weight, smoke ≫ age for blood Cd levels, and sex = age ≫ alcohol for blood Pb levels.

Turning on stem cell cardiogenesis with extremely low frequency magnetic fields.

Modulation of stem cell differentiation is an important assignment for cellular engineering. Embryonic stem (ES) cells can differentiate into cardiomyocytes, but the efficiency is typically low. Here, we show that exposure of mouse ES cells to extremely low frequency magnetic fields triggered the expression of GATA-4 and Nkx-2.5, acting as cardiac lineage-promoting genes in different animal species, including humans. Magnetic fields also enhanced prodynorphin gene expression, and the synthesis and secretion of dynorphin B, an endorphin playing a major role in cardiogenesis. These effects occurred at the transcriptional level and ultimately ensued into a remarkable increase in the yield of ES-derived cardiomyocytes. These results demonstrate the potential use of magnetic fields for modifying the gene program of cardiac differentiation in ES cells without the aid of gene transfer technologies and may pave the way for novel approaches in tissue engineering and cell therapy.