Pathway analysis for identification of potential biomarkers in severe cutaneous drug hypersensitivity reactions

Purpose: To construct a cluster model or a gene signature for Stevens-Johnson syndrome (SJS) using pathways analysis in order to identify some potential biomarkers that may be used for early detection of SJS and epidermal necrolysis (TEN) manifestations. Methods: Gene expression profiles of GSE12829 were downloaded from Gene Expression Omnibus database. A total of 193 differentially expressed genes (DEGs) were obtained. We applied these genes to geneMANIA database, to remove ambiguous and duplicated genes, and after that, characterized the gene expression profiles using geneMANIA, DAVID, REACTOME, STRING and GENECODIS which are online software and databases. Results: Out of 193 genes, only 91 were used (after removing the ambiguous and duplicated genes) for topological analysis. It was found by geneMANIA database search that majority of these genes were coexpressed yielding 84.63 % co-expression. It was found that ten genes were in Physical interactions comprising almost 14.33 %. There were < 1 % pathway and genetic interactions with values of 0.97 and 0.06 %, respectively. Final analyses revealed that there are two clusters of gene interactions and 13 genes were shown to be in evident relationship of interaction with regards to hypersensitivity. Conclusion: Analysis of differential gene expressions by topological and database approaches in the current study reveals 2 gene network clusters. These genes are CD3G, CD3E, CD3D, TK1, TOP2A, CDK1, CDKN3, CCNB1, and CCNF. There are 9 key protein interactions in hypersensitivity reactions and may serve as biomarkers for SJS and TEN. Pathways related gene clusters has been identified and a genetic model to predict SJS and TEN early incidence using these biomarker genes has been developed.

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-γ, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Clinical evaluation of two materials in the restoration of abfraction lesions

Aim: To evaluate the clinical performance of a composite resin (CR) and a resin-modified glassionomer cement (RMGIC) for the treatment of abfraction lesions. Methods: Thirty patients with abfraction lesions in at least two premolar teeth were selected and invited to participate in this study. All restorations were made within the same clinical time frame. One tooth was restored with CR Z100TM (3M, St. Paul, MN, USA), and the other was restored with RMGIC VitremerTM (3M). The restorations were assessed immediately and 1, 6 and 12 months after the restoration, using modified US Public Health Service (USPHS) criteria: marginal integrity, marginal discoloration, wear, retention, secondary caries and hypersensitivity. The statistical analysis was based on Friedman ANOVA test and Mann-Whitney test, considering p<0.05 for statistical significance. Results: Both materials demonstrated satisfactory clinical performance after one year. In the individual analysis of each material, there was a significant difference (p<0.05) in the criteria marginal integrity and wear, for both CR and RMGIC. RMGIC exhibited more damage one year after the restoration. Comparing both materials, it was found a significant difference only for marginal discoloration, while the RMGIC restorations showed the worst prognosis after a year of evaluation. There was no significant difference in the number of retentions, caries or hypersensitivity between CR and RMGIC. Conclusions: It was concluded that CR exhibited the best clinical performance according to the cost-effectiveness and evaluation criteria used in this study.

Immunomodulatory activity of methanol extract of Adansonia digitata L

Purpose: To evaluate the immune-modulatory activities of various plant parts Adansonia digitata L. using delayed-type hypersensitivity rat model. Methods: Defatted leaf, root bark and fruit pulp of A. digitata were extracted with methanol. Immunomodulatory activity of the methanol extracts (250 and 500 mg/kg) were evaluated in sheep RBC (SRBC)-induced delayed-type hypersensitivity model, cell mediated immune re-sponse and phagocytic activity using carbon clearance test. Results: The extracts exhibited significant increase in delayed-type hypersensitivity reaction, indicating the ability of the extracts to stimulate T-cells. It also increased SRBC induced anti-body titer in immunesuppressed rats, and produced significant increase in phagocytic index by rapid removal of carbon particles from the blood stream. Conclusion: These results indicate that methanol extracts of the leaf, root bark and fruit pulp of A. digitata hold promise as immunemodulatory agents.