Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls.</p> <p>Methods</p> <p>Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of <it>t</it>-test was set at 0.001.</p> <p>Results</p> <p>Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart.</p> <p>Conclusion</p> <p>In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection, diagnosis, and classification of HCV-related HCC.</p

Heterogeneity and penetration of HIV-1 non-subtype B viruses in an Italian province: Public health implications

SUMMARYThis study assessed changes in prevalence and distribution of HIV-1 non-subtype B viruses in Italian and immigrant patients over two decades in a province in Italy. All HIV-positive patients who underwent genotypic resistance testing were selected. Prevalence of non-subtype B viruses in 3-year periods was calculated. All sequences of non-subtype B and those provided by REGA as unassigned were analysed for phylogenetic relationships. In total, 250/1563 (16%) individuals were infected with a non-subtype B virus. Prevalence increased over time, reaching a peak (31·5%) in 2004–2006. In Italian patients, the most frequent subtypes were B (92·5%) and F1 (4%). F1 subtype was also prevalent in patients from South America (13·6%); in patients of African origin, CRF02_AG (54·9%) and G (12·3%) were the most frequent. HIV-1 non-subtype B infections in Italians were mostly found in patients who acquired HIV sexually. A phylogenetic relationship between F subtypes in Italian and representative HIV-1 sequences from Brazil was found. C subtypes in Italians were phylogenetically related to subtypes circulating in Brazil. Inter-subtype recombinants were also found in the latest years. The HIV-1 epidemic in Brescia province evolved to the point where about 1/3 patients recently diagnosed harboured non-B HIV subtypes. The distribution of HIV-1 non-B subtypes in Italian patients resembled that in South American patients and phylogenetic relatedness between some Italian and South American HIV-1 strains was found. The possible epidemiological link between these two populations would have been missed by looking only at risk factors for HIV acquisition declared by patients. The evidence of inter-subtype recombinants points to significant genetic assortment. Overall our results support phylogenetic analysis as a tool for epidemiological investigation in order to guide targeted prevention strategies

Severity of Coronary Atherosclerosis and Risk of Diabetes Mellitus

Cardio-vascular target organ damage predicts the onset of type 2 diabetes mellitus (DM) in hypertensive patients. Whether an increased incidence of DM is also in relation to the severity of coronary atherosclerosis is unknown

Insulin Resistance Predicts Severity of Coronary Atherosclerotic Disease in Non-Diabetic Patients

Background: Insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) represents a predictor of coronary artery disease (CAD). However, how IR is able to impact the severity of coronary atherosclerosis in non-diabetic patients is unknown. Objectives. We investigated the relation between the IR and the extent and severity of coronary atherosclerosis in non-diabetic patients referred to coronary angiography (CA) Methods: Consecutive patients undergoing to CA for acute coronary syndromes or stable angina were analyzed. The IR was assessed by mean of the homeostasis model assessment of insulin resistance (HOMA-IR) whereas the SYNTAX score (SS) was used as index of the severity of coronary atherosclerosis Results: Overall, 126 patients were included, with a median SS of 12 (IQR 5.25–20.5). Patients were divided in four groups according to the distribution in quartiles of SS (SS1-2-3-4). A significant correlation between HOMA-IR and SS was observed, especially in women. A progressive increase of HOMA-IR was observed in parallel with the increasing severity (from SS1 to SS4) and extension (1-2-3-vessel disease) of coronary atherosclerosis. Multivariable analysis showed that the HOMA-IR was the strongest independent predictor of severe (SS4) and extensive (three-vessel disease) coronary atherosclerosis. Conclusion: Insulin resistance goes hand in hand with the extension and severity of coronary atherosclerosis in non-diabetic patients. The HOMA index is an independent predictor of three-vessel disease at CA. The HOMA index could be useful for risk stratification of CAD even in absence of T2D

Animal welfare in studies on murine tuberculosis : assessing progress over a 12-year period and the need for further improvement

There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains.Nuno H. Franco is funded by Fundação para a Ciência e Tecnologia (SFRH/BD/38337/2007). This work is funded by FEDER funds through the Operational Competitiveness Programme - COMPETE and by national funds through FCT - Fundação para a Ciência e Tecnologia under the project FCOMP-01-0124-FEDER-022718 (PEst-C/SAU/LA0002/2011

Perceived efficacy of herbal remedies by users accessing primary healthcare in Trinidad

BACKGROUND: The increasing global popularity of herbal remedies requires further investigation to determine the probable factors driving this burgeoning phenomenon. We propose that the users' perception of efficacy is an important factor and assessed the perceived efficacy of herbal remedies by users accessing primary health facilities throughout Trinidad. Additionally, we determined how these users rated herbal remedies compared to conventional allopathic medicines as being less, equally or more efficacious. METHODS: A descriptive cross-sectional study was undertaken at 16 randomly selected primary healthcare facilities throughout Trinidad during June-August 2005. A de novo, pilot-tested questionnaire was interviewer-administered to confirmed herbal users (previous or current). Stepwise multiple regression analysis was done to determine the influence of predictor variables on perceived efficacy and comparative efficacy with conventional medicines. RESULTS: 265 herbal users entered the study and cited over 100 herbs for the promotion of health/wellness and the management of specific health concerns. Garlic was the most popular herb (in 48.3% of the sample) and was used for the common cold, cough, fever, as 'blood cleansers' and carminatives. It was also used in 20% of hypertension patients. 230 users (86.8%) indicated that herbs were efficacious and perceived that they had equal or greater efficacy than conventional allopathic medicines. Gender, ethnicity, income and years of formal education did not influence patients' perception of herb efficacy; however, age did (p = 0.036). Concomitant use of herbs and allopathic medicines was relatively high at 30%; and most users did not inform their attending physician. CONCLUSION: Most users perceived that herbs were efficacious, and in some instances, more efficacious than conventional medicines. We suggest that this perception may be a major contributing factor influencing the sustained and increasing popularity of herbs. Evidence-based research in the form of randomized controlled clinical trials should direct the proper use of herbs to validate (or otherwise) efficacy and determine safety. In the Caribbean, most indigenous herbs are not well investigated and this points to the urgent need for biomedical investigations to assess the safety profile and efficacy of our popular medicinal herbs

“Gli aspetti innovativi dell’informativa finanziaria nelle “entità” del settore pubblico: gli IPSAS 5, 15, 18, 19 e 21”

Per il citato lavoro, che rappresenta un contributo alla ricerca della Scuola Superiore della Pubblica Amministrazione “Principi e metodi di contabilità economico-patrimoniale per lo Stato e le Pubbliche Amministrazioni nel quadro teorico ed operativo internazionale” (coordinatore Prof. L. Anselmi, anni 2007/2008), sono stati assolti gli obblighi di pubblicazione direttamente dall’autore, ai sensi della Legge 15.4.2006 n. 106 e del D.P.R. 03.05.2006, n. 252