Distribution of IL28B Polymorphism in a Cohort of Italians and Immigrants with HCV Infection: Association with Viraemia, Stage of Fibrosis and Response to Treatment.

Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9 % males, 27.1 % females) is 50 years. 91.5 % % of patients are Caucasian, 8.5 % African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8 % respectively. As regards ethnic group, African people have a prevalence of 35.5 % for CC, while Caucasians have a prevalence of 23.8 % for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges.

[Effect of misclassification of the place of residence on incidence estimates: the example of child cancer in a local health authority in Rome, Italy]. / Misclassificazione della residenza nelle schede di Dimissione Ospedaliera ed effetti sulle stime di incidenza: l'esempio dei tumori in età pediatrica nella ASL RMD.

A study on cancer of the lymphatic and hematopoietic tissue among residents aged 0-14 years was conducted by the Local Health Unit RMD (Rome, Italy; period 2003-09; codes of the International Classification of Diseases, Ninth Revision, Clinical Modification: 200-208). Age and gender Standardized Mortality and Hospitalization Ratios were computed in order to compare observed and expected cases, using municipal rates as reference. Place of residence at the time of admission, as recorded in the Hospital Registry, was compared with the information recorded in the Municipal Registers and the correlation between the two sources was calculated by Cohen's Kappa. No mortality nor morbidity excesses were observed in the study area. Although 14% of children were not confirmed as being resident at the time of admission, the Cohen's Kappa indicates a strong correlation between the Municipal Registry and the Hospital Registry (84%). The analyses restricted to children with ascertained residence did not yield different results. For those whose residence was not confirmed, the mismatch of information between the Municipality Registry and the Hospital Registry needs to be clarified.

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats.

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic beta-cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and beta-cell mass, beta-cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and beta-cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0.05) larger than that of the CD group (556.0+/-8.3 vs 470.0+/-13.1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0.05) in SRD than in CD rats (serum glucose, 8.11+/-0.14 vs 6.62+/-0.17; triacylglycerol, 1.57+/-0.18 vs 0.47+/-0.04). The number of pancreatic islets per unit area increased significantly (P<0.05) in SRD rats (3.29+/-0.1 vs 2.01+/-0.2). A significant increment (2.6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the beta-cell mass (P=0.0025). The islet cell replication rate, measured as the percentage of PCNA-labelled beta cells increased 6.8 times in SRD rats (P<0.03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0.03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of beta-cell mass induced by SRD was accomplished by an enhanced replication of beta cells together with a decrease in the rate of beta-cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.

Mecanismo de producción del aumento de la masa de células B inducido por la administración crónica de sacarosa a ratas normales / Mechanisms producing an increase in B-cell mass induced by the chronic administration of sucrose to normal rats

El objetivo del presente trabajo fue clarificar los mecanismos mediante los cuales una dieta rica en sacarosa produce, en el páncreas de la rata, un aumento de la masa celular B. Se utilizaron ratas Wistar normales, alimentadas durante 30 semanas con una dieta rica en sacarosa (DRS; 63 por ciento o bien con una dieta similar en la que la sacarosa se reemplazó por la misma proporción de almidón (DC). Se estudió el peso corporal, los niveles séricos de glucosa y triacilglicerol, el tejido endocrino, la masa celular B, el grado de replicación de las células B (antígeno de proliferación nuclear celular, PCNA), la neogénesis insular (inmunomarcación de citoqueratina, CK) y la apoptosis de células B (yoduro de propidio). El peso corporal de las ratas DRS fue significativamente mayor (p<0,05) que el registrado en el grupo DC (556,0ñ8,3 vs 470,0ñ13,1). Tanto los niveles séricos de glucosa como los de triacilglicerol (mmol/L) fueron significativamente mayores (p<0,05) en las ratas DRS que en las DC: Glucemia 8,11 ñ 0,14 vs 6,62 ñ 0,17; triacilglicerol 1,57 ñ 0,18 vs 0,47 ñ 0,04. El número de islotes pancreáticos por unidad de área aumentó significativamente (p<0,05) en las ratas DRS (3,29 ñ 0,1 vs 2,01 ñ 0,2). Además, se detectó un incremento significativo (2,6 veces) en la masa de tejido endocrino de los animales DRS, principalmente debido a un aumento en la masa celular B (p=0,0025. El porcentaje de células B insulares en replicación (PCNA positivas) aumentó 6,8 veces en las ratas DRS (p<0,03). El número de células apoptóticas del páncreas endocrino disminuyó significativamente en el grupo DRS (3 veces, p=0,03). No hubo diferencias significativas en el área positiva para CK entre los animales DRS y DC. El aumento de la masa celular B inducido por la DRS se correspondió con un aumento en la replicación de las células B, junto con una disminución en la proporción de dichas células en apoptosis. No hubo evidencias de neogénesisen los islotes. Dichos cambios pancreáticos no pudieron mantener la glucemia de estos animales en valores semejantes a los obtenidos en las ratas DC. Estos resultados muestran que en este modelo de manipulación alimentaria, aunque el aumento de replicación de las células B y la disminución de la apoptosis jugarían un rol importante, la neogénesis insular constituiría el mecanismo compensador decisivo en la adaptación a la mayor demanda de insulina

Troglitazone (CS-045) normalizes hypertriglyceridemia and restores the altered patterns of glucose-stimulated insulin secretion in dyslipidemic rats.

Rats fed a sucrose-rich diet ([SRD] 63% wt/wt) up to 270 days develop stable hypertriglyceridemia, impaired glucose tolerance, and insulin insensitivity. The aim of the present study is to investigate whether the hypoglycemic agent troglitazone introduced as a pharmacologic intervention could improve and/or reverse the whole-body insulin insensitivity and related abnormalities present after feeding normal rats with a SRD long-term. For this purpose, male Wistar rats were fed a SRD for 210 days. While half of the animals continued with this diet for up to 270 days, troglitazone (0.2 g/dL wt/wt) was added to the SRD of the other half for up to 270 days. Troglitazone markedly reduced in vivo the hepatic triglyceride secretion rate (TGSR) and enhanced its removal from the circulation, leading to a normalization of plasma triglyceride levels. It also normalized the whole-body peripheral insulin resistance, the glucose homeostasis, and the elevated free fatty acids (FFAs) without detectable changes in plasma insulin levels. The clear alteration of the biphasic pattern of glucose-stimulated insulin secretion in the in vitro perfused beta-cell islets of rats fed the SRD long-term (270 days) was also completely normalized when the SRD was supplemented with troglitazone for 2 months. The normalization of the altered patterns of glucose-stimulated insulin secretion, as well as the enhancement of peripheral insulin sensitivity without detectable changes in plasma insulin, might be largely a result of the significant action of troglitazone in the decrease of circulating lipids and enhancement of whole-body glucose metabolism.