Disease severity in patients infected with Leishmania mexicana relates to IL-1ß.

Leishmania mexicana can cause both localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, yet little is known about factors regulating disease severity in these patients. We analyzed if the disease was associated with single nucleotide polymorphisms (SNPs) in IL-1ß (-511), CXCL8 (-251) and/or the inhibitor IL-1RA (+2018) in 58 Mexican mestizo patients with LCL, 6 with DCL and 123 control cases. Additionally, we analyzed the in vitro production of IL-1ß by monocytes, the expression of this cytokine in sera of these patients, as well as the tissue distribution of IL-1ß and the number of parasites in lesions of LCL and DCL patients. Our results show a significant difference in the distribution of IL-1ß (-511 C/T) genotypes between patients and controls (heterozygous OR), with respect to the reference group CC, which was estimated with a value of 3.23, 95% CI = (1.2, 8.7) and p-value = 0.0167), indicating that IL-1ß (-511 C/T) represents a variable influencing the risk to develop the disease in patients infected with Leishmania mexicana. Additionally, an increased in vitro production of IL-1ß by monocytes and an increased serum expression of the cytokine correlated with the severity of the disease, since it was significantly higher in DCL patients heavily infected with Leishmania mexicana. The distribution of IL-1ß in lesions also varied according to the number of parasites harbored in the tissues: in heavily infected LCL patients and in all DCL patients, the cytokine was scattered diffusely throughout the lesion. In contrast, in LCL patients with lower numbers of parasites in the lesions, IL-1ß was confined to the cells. These data suggest that IL-1ß possibly is a key player determining the severity of the disease in DCL patients. The analysis of polymorphisms in CXCL8 and IL-1RA showed no differences between patients with different disease severities or between patients and controls.

Involvement of the AATn polymorphism of the CNR1 gene in the efficiency of procedural learning in humans.

Procedural learning refers to the acquisition of motor skills and the practice that refines their performance. The striatum participates in this learning through a function regulated by endocannabinoid signaling and other systems. This study relates the efficiency in learning a procedural task with the AATn polymorphism of the CNR1 gene, which encodes for the CB1 receptor. The mirror-drawing star task was solved by 99 healthy young subjects in three trials. The sample was divided into high- and low-performance groups based on performance efficiency. AAT12/14 carriers were more frequent in the former group, while there were more AAT12/13 carriers in the latter, which also made more errors/min. Therefore, we characterized two efficiency phenotypes: high- vs. low-performers associated with the two AATn genotypes, AAT12/14 vs. AAT12/13. The findings suggest that AATn polymorphism modifies CNR1 translation, indicating a different modulation of CB1.

Impact of antigenic and genetic drift on the serologic surveillance of H5N2 avian influenza viruses.

BACKGROUND: Serologic surveillance of Avian Influenza (AI) viruses is carried out by the hemagglutination inhibition (HI) test using reference reagents. This method is recommended by animal health organizations as a standard test to detect antigenic differences (subtypes) between circulating influenza virus, vaccine- and/or reference- strains. However, significant discrepancies between reference antisera and field isolates have been observed during serosurveillance of influenza A viruses in pig and poultry farms. The objective of this study was to examine the effects of influenza virus genetic and antigenic drift on serologic testing using standard HI assays and reference reagents. Low pathogenic AI H5N2 viruses isolated in Mexico between 1994 and 2008 were used for phylogenetic analysis of AI hemagglutinin genes and for serologic testing using antisera produced with year-specific AI virus isolates. RESULTS: Phylogenetic analysis revealed significant divergence between early LPAI H5N2 viruses (1994 - 1998) and more recent virus field isolates (2002 - 2008). Results of the HI test were markedly influenced by the selection of the AI H5N2 virus (year of isolation) used as reference antigen for the assay. These analyses indicate that LPAI H5N2 viruses in Mexico are constantly undergoing genetic drift and that serosurveillance of AI viruses is significantly influenced by the antigen or antisera used for the HI test. CONCLUSIONS: Reference viral antigens and/or antisera need to be replaced constantly during surveillance of AI viruses to keep pace with the AI antigenic drift. This strategy should improve the estimation of antigenic differences between circulating AI viruses and the selection of suitable vaccine strains.