Geographical and epidemiological analysis of oncological incidence in paediatric and adolescent ages in a municipality of North-Western Italy: Vercelli, years 2002-2009.

INTRODUCTION: This study of the geographical incidence on the oncological mortality in young age (0-44 years) in the City of Vercelli, was aimed to address the concerns of the population and the request of municipal administrators. A detailed and sophisticated study for a City of medium-small size is due for the presence of various sources of pressure, such as a MSW incinerator just a few kilometres from the city and an intensive agricultural activity that characterizes the entire area. MATERIALS AND METHODS: The study is based on the census analysis of the population, and of the hospital admission cards, and it considers epidemiological standardized estimators and spatial analysis through Bayesian models, as well. RESULTS: Both approaches highlight Major risks for the area south of the city for major tumours such as total cancer in women (SIR / SMR significant excess of about 50%), colorectal (mean increments SMR / SIR between 3 and 4 times), ovary (mean increments SMR / SIR between 3:04 and times), and nervous system (increases 3 times for both indicators). CONCLUSION: These results deserve further studies through inferential case-control and cohort analysis, given the marginal role of the possible occupational hazards in the aetiology of juvenile cancer disorders.

Incidence of oncological pathologies 2002-2010 in the southwestern Piedmont area, province of Vercelli, neighbouring municipalities of former nuclear sites.

The Vercelli Province counts two former nuclear installations: a radioactive waste disposal area in Saluggia and a former nuclear power plant in Trino. This study takes also into account four other neighbouring municipalities, counting 20,000 total inhabitants. We studied the incidence of neoplastic pathologies in the 2002-2010 period. The data sources were Hospital Discharge Form (SDO), histological reports from the Registry of Hospital Charts (RHC) and Italy's National Statistics Institute (ISTAT) reports, and the Cancer Register of Turin. The research highlights the excesses for all type of cancers (SIR=1,11; IC 1,04-1,18), including the ones of nervous system (SIR=2,23 IC 1,47-2,98), leukaemia (SIR=1,94 IC 1,35-2,52), and bones (SIR=12,0 IC 9,22-14,7), according to different aggregation levels by age, sex and housing area. Considering such results, previous studies, and the environmental and occupational risk factors in the area, we believe that further epidemiological and environmental studies should be conducted in this area.

Exploration study on mortality trends in the territory surrounding an incineration plant of urban solid waste in the municipality of Vercelli (Piedmont, Italy) 1988-2009.

BACKGROUND: The places, where the incinerators are located, often present problems of heterogeneous people having different environmental factors. It becomes important to evaluate the possible etiologic role of various environmental risk factors and try to quantify as they affect in the excess epidemiological. METHODS: This study considers the ISTAT index mortality due to all causes occurred from 1988 to 2009 referred to ten municipalities at south of Vercelli (Piedmont, North Western Italy) placed nearby the active incinerator from 1977 (10 latent years). The risks were calculated considering this area at risk versus the municipalities placed at North of Vercelli and versus the Vercelli. RESULTS: Some significant statically excesses emerged in the South area such as neoplasia of nervous system, liver and total of tumours. CONCLUSIONS: The study presents some drawbacks, but it is a work creditable of widening by specific research ad hoc such as cohort and/or control where it is possible to verify various environmental, occupational and occasional factors.

Modulation of DMT1 activity by redox compounds.

Iron(II) exacerbates the effects of oxidative stress via the Fenton reaction. A number of human diseases are associated with iron accumulation including ischemia-reperfusion injury, inflammation and certain neurodegenerative diseases. The functional properties and localization in plasma membrane of cells and endosomes suggest an important role for the divalent metal transporter DMT1 (also known as DCT1 and Nramp2) in iron transport and cellular iron homeostasis. Although iron metabolism is strictly controlled and the activity of DMT1 is central in controlling iron homeostasis, no regulatory mechanisms for DMT1 have been so far identified. Our studies show that the activity of DMT1 is modulated by compounds that affect its redox status. We also show that both iron and zinc are transported by DMT1 when expressed in Xenopus laevis oocytes. Radiotracer uptake and electrophysiological measurements revealed that H(2)O(2) and Hg(2+) treatments result in substantial inhibition of DMT1. These findings may have a profound relevance from a physiological and pathophysiological standpoint.

A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.

Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells. Ireg1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA contains a functional iron-responsive element (IRE). IREG1 stimulates iron efflux following expression in Xenopus oocytes. We conclude that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease, hereditary hemochromatosis.

Rat erythrocyte susceptibility to lipid peroxidation after chronic ethanol intake.

Erythrocytes, from 2- and 7-month-old rats chronically fed with a liquid diet containing ethanol, were analyzed for their susceptibility to lipid peroxidation estimated as thiobarbituric acid reactive substance (TBARS) products. In spite of a lower alcohol consumption, adult rats were the more affected by the ethanol treatment. Erythrocyte membranes prepared from alcoholic animals were more sensitive to lipid peroxidation than those prepared from control rats. In both age groups lipid analysis revealed similar changes: 1) an increased cholesterol/phospholipid molar ratio mainly derived from a higher content of cholesterol that accounts for the lower membrane fluidity and the higher tolerance to the disordering effect exerted by ethanol in vitro; 2) an increase of phospholipid unsaturated fatty acids, especially C20:4; 3) a modification of the phospholipid pattern, characterized in the ethanol group by an increase of PE and decrease of PE and decrease of PC levels; moreover, significant increases of the anionic phospholipids were detected in the adult group.

Leucine transport in Xenopus laevis oocytes: functional and morphological analysis of different defolliculation procedures.

L-leucine uptake in stage V Xenopus laevis oocytes was affected by the specific methods used to remove the follicle cells. In the presence of 100 mM NaCl, L-leucine uptake was reduced by 67.5% +/- 5.7 when defolliculation was performed enzymatically by collagenase treatment, whereas the reduction was 30.5% +/- 6.4 after mechanical defolliculation. The Na(+)-dependent uptake of 0.1 mM L-leucine was 18.6 +/- 4.6 pmol oocyte-1 40 min-1 in folliculated oocytes and 5.6 +/- 1.9 in collagenase defolliculated oocytes (means +/- SE). L-leucine uptake was not affected by the removal of the follicular layer if defolliculation occurred after the transport period; radiolabeled L-leucine is therefore not taken up into a compartment that is removed by the defolliculation process. The different L-leucine uptake rates observed in folliculated and defolliculated oocytes were not due to non-specific L-leucine binding to membranes. L-leucine kinetics showed that the L-leucine Vmax and Km values were lower in oocytes deprived of the follicular layer than in control oocytes enveloped in intact follicular layers. The Vmax and Km values of Na(+)-dependent L-leucine transport, calculated from data obtained the day after defolliculation by collagenase treatment, were: 16 +/- 1.5 pmol oocyte-1 40 min-1 and 57 +/- 21 mumol (mean +/- SD). The Na(+)-activation curve of 0.1 mM L-leucine was hyperbolic in folliculated oocytes and sigmoidal in defolliculated oocytes. The morphological analysis performed in parallel with the transport experiments showed that after defolliculation, the fibers forming the vitelline membrane tended to be arranged in a more regular orthogonal array, and the number of oocyte microvilli was reduced after collagenase treatment. Mechanical defolliculation did not appreciably affect the oocyte microvilli, however this procedure did not completely remove all follicle cells. The damage to collagenase treated oocytes was reversible, and the functional and structural features of most oocytes improved upon subsequent in vitro incubation. The recovery process seemed to involve protein synthesis in view of the increased value of L-leucine Vmax, and microscopic observation showing recovery of the microvillar apparatus.

Age-related effects of chronic ethanol intake on physical properties, lipid composition and galactosyltransferase activity of rat small intestine microsomes.

The effect of a 4-week ethanol administration on: (1) glycoprotein content of brush border membrane (BBM): (2) galactosyltransferase activity; (3) lipid composition and fluidity of intestinal microsomes prepared from young and adult rats was investigated. In spite of a lower alcohol consumption, the more dramatic effects of treatment have been observed in the older rats, where BBM protein-bound hexoses and microsomal galactosyltransferase activity were significantly decreased. On the contrary, these parameters were unaffected in young rats. However, both rat groups were similarly affected in having their microsomal cholesterol contents significantly increased. Microsomal membranes from ethanol-fed adult rats were less fluid compared to control rats: the high fluorescence anisotropy value could be related to the high cholesterol/phospholipid ratio and to the decrease of the unsaturated fatty acids C22:4 and C22:6.

Age related changes in functions and physicochemical properties of rat jejunal brush border membrane after chronic ethanol administration.

1. We investigated the chronic effects of a 4 week treatment with ethanol on functions and physicochemical properties of BBM of young and adult rats (2 and 7 months old respectively). 2. In the ethanol treated groups the cholesterol/phospholipid and the protein/lipid ratios as well as the D-glucose uptake and lactase specific activity and Vmax were increased. In spite of a minor alcohol consumption the adult group was the more affected. 3. Membranes from the ethanol fed rats were less fluid and more tolerant to the in vitro addition of ethanol.

L-carnitine and carnitine ester transport in the rat small intestine.

L-carnitine and its esters (acetyl-L-carnitine and propionyl-L-carnitine) at pharmacological doses (1, 5 and 10 mM) are absorbed by the rat jejunum by simple diffusion. Partition coefficients of carnitine esters determined in lipophilic media (diethyl ether/water and olive oil/water) are greater than that of L-carnitine. It would therefore seem that esters diffuse more easily through the lipid component of the intestinal barrier. The transport of acetyl- and propionyl-L-carnitine at pharmacological doses seems to be linearly and positively correlated with K+ transport but not with Na+ transport.

Postnatal maturation of rat intestinal membrane: lipid composition and fluidity.

1. We studied the lipid composition and the fluidity of small intestine brush border membrane (BBM) of rats of different age: 'very young' (5-7 weeks old), 'young' (9 weeks old), 'adult' (30 weeks old) and 'old' (85 weeks old). 2. Fluorescence anisotropy, as assessed by 1,6-diphenyl-1,3,5-hexatriene probe (DPH), was increased from very young to adult rats. 3. In agreement with these results the lipid composition in adult animals showed a lower lipid/protein ratio (derived mainly from a lower content of total polar lipids) and an increase of cholesterol esters and sphingomyelin (SM) saturation index. 4. A marked decrease of the order parameter was observed in the 'old' group, accompanied by a decreased cholesterol/phospholipid ratio. 5. The percentage distribution of membrane phospholipids significantly changed during development, but the modifications were not correlated with the anisotropy of DPH.

Effects of cholesterol and alfa-2-recombinant interferon on cell growth and cell antigen production in the HT 29 cells, an established cell line of human colon adenocarcinoma.

HT 29 cells, an established cell line of human colon adenocarcinoma, were grown in RPMI 1640 medium without or with cholesterol at 25, 50, 100 micrograms/ml concentrations. In some experiments 100 or 200 U/ml alfa-2-A recombinant Interferon were added to the medium. Only in the case of the highest cholesterol concentration there was a reduced number of cells at confluence. Moreover, only the production of CEA increased in the presence of cholesterol. Interferon did not affect cell growth appreciably but stimulated CEA release into the medium during the first three days of culture. Morphological analysis of cells in the presence of cholesterol seems to indicate an attempt of the cells to differentiate.

Effects of semistarvation on transintestinal D-glucose transport and D-glucose uptake in brush border and basolateral membranes of rat enterocytes.

The present work shows that semistarvation (8-10 g of food for 10 days) increases net D-glucose, Na+ and water transport in the everted and perfused rat jejunum. A linear and positive correlation between cell sugar concentration and transport was found in control and semistarved rats, but the phenomenon was more relevant only in semistarved animals. Membrane vesicle experiments showed that semistarvation increases sugar overshoot only in brush border membrane vesicles, while this situation does not occur in basolateral membrane vesicles. The effect of partial food deprivation seems to enhance net sugar transport by increasing sugar entry across the apical membrane of enterocytes.

Intestinal sugar transport during ageing.

Ageing effects on sugar intestinal transport were studied by using the everted sac and the brush-border membrane vesicle techniques. Four age groups of rats were used: very young, young, adult and old animals. Net transintestinal transport of D-glucose and intracellular sugar accumulation were greater in young than in very young, adult and old rats. Net Na+ transport was high in very young and young animals and then it declined with age. In brush-border membrane vesicle experiments D-glucose overshoot was smaller in the groups of animals where net sugar transport was less. In old rats, however, the overshoot did not occur. Short-circuiting of vesicles with valinomycin showed that the driving forces for sugar accumulation, i.e. the chemical potential gradient of Na+ and the electrical potential gradient, played different roles during ageing. In very young animals the chemical potential gradient seems to be responsible for D-glucose overshoot; in young rats both gradients are important while in adult animals the electrical potential gradient represents the main driving force.