Triclabendazole-resistant Fasciola hepatica: β-tubulin and response to in vitro treatment with triclabendazole

Resistance in Fasciola hepatica to triclabendazole (Fasinex) has emerged in several countries. Benzimidazole resistance in parasitic nematodes has been linked to a single amino acid substitution (phenylalanine to tyrosine) at position 200 on the [beta]-tubulin molecule. Sequencing of [beta]-tubulin cDNAs from triclabendazole-susceptible and triclabendazole-resistant flukes revealed no amino acid differences between their respective primary amino acid sequences. In order to investigate the mechanism of triclabendazole resistance, triclabendazole-susceptible and triclabendazole-resistant flukes were incubated in vitro with triclabendazole sulphoxide (50 [mu]g/ml). Scanning and transmission electron microscopy revealed extensive damage to the tegument of triclabendazole-susceptible F. hepatica, whereas triclabendazole-resistant flukes showed only localized and relatively minor disruption of the tegument covering the spines. Immunocytochemical studies, using an anti-tubulin antibody, showed that tubulin organization was disrupted in the tegument of triclabendazole-susceptible flukes. No such disruption was evident in triclabendazole-resistant F. hepatica. The significance of these findings is discussed with regard to the mechanism of triclabendazole resistance in F. hepatica.

5-Fluorouracil: mechanisms of action and clinical strategies

5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

Quadratic Forms on Complex Random Matrices and Multiple-Antenna Systems

This research published in the foremost international journal in information theory and shows interplay between complex random matrix and multiantenna information theory. Dr T. Ratnarajah is leader in this area of research and his work has been contributed in the development of graduate curricula (course reader) in Massachusetts Institute of Technology (MIT), USA, By Professor Alan Edelman. The course name is "The Mathematics and Applications of Random Matrices", see http://web.mit.edu/18.338/www/projects.html

Welfare Effort and Poverty from the Monetary and Capabilities Approach: A Cross-Country Analysis in Latin American and the Caribbean (1990-2010)

There is abundant empirical evidence on the negative relationship between welfare effort and poverty. However, poverty indicators traditionally used have been representative of the monetary approach, excluding its multidimensional reality from the analysis. Using three regression techniques for the period 1990-2010 and controlling for demographic and cyclical factors, this paper examines the relationship between social spending per capita —as the indicator of welfare effort— and poverty in up to 21 countries of the region. The proportion of the population with an income below its national basic basket of goods and services (PM1) and the proportion of population with an income below 50% of the median income per capita (PM2) were the two poverty indicators considered from the monetarist approach to measure poverty. From the capability approach the proportion of the population with food inadequacy (PC1) and the proportion of the population without access to improved water sources or sanitation facilities (PC2) were used. The fi ndings confi rm that social spending is actually useful to explain changes in poverty (PM1, PC1 and PC2), as there is a high negative and signifi cant correlation between the variables before and after controlling for demographic and cyclical factors. In two regression techniques, social spending per capita did not show a negative relationship with the PM2. Countries with greater welfare effort for the period 1990-2010 were not necessarily those with the lowest level of poverty. Ultimately social spending per capita was more useful to explain changes in poverty from the capability approach.

Malignancy and mortality in a population-based cohort of patients with coeliac disease or 'gluten sensitivity'

Aim: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland.

Methods: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated.

Results: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin anti-bodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population.

Conclusion: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity. © 2007 The WJG Press. All rights reserved.