Polymorphisms of toll-like receptor 2 and 4 genes in Chagas disease

The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2) and TLR4 gene polymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln) polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6% and 1.8% respectively). The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Toll-like receptors (TLRs) recognise pathogen-derived molecules and influence immunity to control parasite infections. This study aimed to evaluate the mRNA expression of TLRs 2 and 4, the expression and production of the cytokines interleukin (IL)-12, interferon (IFN)- 47;, tumor necrosis factor (TNF)- 45;, IL-17, IL-10 and transforming growth factor (TGF)- 46; and the production of nitric oxide (NO) in the spleen of mice infected with Leishmania chagasi. It also aimed to evaluate any correlations between mRNA expression TLR2 and 4 and cytokines and NO production. Infection resulted in increased TLR2-4, IL-17, TNF- 45; and TGF- 46; mRNA expression during early infection, with decreased expression during late infection correlating with parasite load. IFN- 47; and IL-12 mRNA expression decreased at the peak of parasitism. IL-10 mRNA expression increased throughout the entire time period analysed. Although TGF- 46;, TNF- 45; and IL-17 were highly produced during the initial phase of infection, IFN- 47; and IL-12 exhibited high production during the final phase of infection. IL-10 and NO showed increased production throughout the evaluated time period. In the acute phase of infection, there was a positive correlation between TLR2-4, TNF- 45;, IL-17, NO, IL-10 and TGF- 46; expression and parasite load. During the chronic phase of infection, there was a positive correlation between TLR2-4, TNF- 45;, IL-17 and TGF- 46; expression and parasite load. Our data suggest that infection by L. chagasi resulted in modulation of TLRs 2 and 4 and cytokines.

Managing IT, April/May 2002. Vol.2, No.4

Newsletter for Information Technology Department

Iowa Community Empowerment Newsletter, August 2001, Vol. 2, no. 4

Monthly newsletter for the Iowa Department of Public Health

Inside Iowa's DOC, April 2005, Vol. 2, no. 4

Newsletter from the Department of Corrections

Innovative Outstanding Weatherization Assistance News, October 2004, Vol.2, no.4

Quarterly newsletter from the Division of Cimmunity Action Agenices, part of the Department of Human Rights.

Innovative Outstanding Weatherization Assistance News, October 2004, Vol.2, no.4

Quarterly newsletter from the Division of Cimmunity Action Agenices, part of the Department of Human Rights.

Subtype-specific Modulation of Acid-sensing Ion Channel (ASIC) Function by 2-Guanidine-4-methylquinazoline.

Acid-sensing ion channels (ASICs) are neuronal Na(+)-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mm, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH.

Iowa Department of Elder Affairs Legislative Update and Addendum to Update, February 3, 2006, Vol. 2, no. 4

Iowa Department of Elder Affairs provides a brief summation of a Departmental program or other important Departmental information in each Legislative Update. The Legislative Update is produced for informational and educational purposes only.

Team Diversity Newsletter, Vol 2, no.4, September/October 1997

Newsletter produced by Iowa Civil Right Commission for the community about the community.

Innovative Outstanding Weatherization Assistance News, October, 2004, Vol.2, no.4

This is a quarterly newsletter for the Iowa Weatherization Program. The purpose of the newsletter is to share with you information on all aspects of the program as well as spotlight a couple of agencies in each issue. We will provide information on upcoming events, training schedules, monitoring schedules and general news about the program. There will be a section of questions we have received from you and the answers provided.

Secure & Prepared, February 21, 2006, Vol.2, no.4

Secure & Prepared is a bi-weekly publication of the Iowa Homeland Security & Emergency Management Division for those involved in the homeland security system in the state of Iowa.