The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure.

Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected, or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

Stratifying risk for celiac disease in a large at-risk United States population by using HLA alleles.

BACKGROUND & AIMS: Susceptibility to celiac disease (CD) is related to HLA-DQ2 and DQ8 alleles and the heterodimers they encode. The objective of this study was to stratify risk for CD on the basis of HLA-DQ genotype. METHODS: DNA from 10,191 subjects who are at risk for CD was analyzed for HLA-DQ haplotypes. Individuals with CD were identified as those who tested positive for anti-endomysial immunoglobulin A (EMA+) in an immunofluorescence assay. RESULTS: Samples homozygous for DQ2.5 (HLA-DQA1 05-DQB1 02) or DQ2.2/DQ2.5 (HLA-DQA1 05-DQB1 02 and HLA-DQA1 0201-DQB1 02) comprised 5.38% of the total; 28.28% of these were EMA+ (95% confidence interval [CI], 24.55-32.26). Of the samples that were DQ2.5 heterozygous (HLA-DQA1 05-DQB1 02); 9.09% were EMA+ (95% CI, 7.82-10.51). Among samples in which HLA-DQ8 (HLA-DQA1 03-DQB1 0302) was detected, 8.42% of homozygotes (95% CI, 3.71-15.92) and 2.11% of heterozygotes (95% CI, 1.43-3.00) were EMA+. Samples with DQ2.2/DQ8 or DQ2.5/DQ8 comprised 5.08% of the total, and 11.78% of these were EMA+ (95% CI, 9.13-14.87). HLA-DQ2 and HLA-DQ8 were absent in 4283 samples (42.03% of the total); 0.16% of these samples were EMA+ (95% CI, 0.07-0.34). CONCLUSIONS: High-resolution, sequence-specific oligonucleotide probe typing with 35 DQA1-specific and 37 DQB1-specific probes of DNA from more than 10,000 subjects was used to stratify risk of CD in an at-risk U.S. population. DQ2 homozygosity (DQ2.5/DQ2.2+2.5) increased risk for CD, estimated by the rate of EMA positivity, compared with the entire sample population and other DQ genotypes. These data suggest a quantitative relationship between the type/proportion of DQ heterodimers and the risk of CD and identify potential immunotherapeutic targets.

Effects of topical L-selenomethionine with topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

BACKGROUND: The antioxidants selenium and vitamin E can be effective in reducing acute and chronic ultraviolet (UV)-induced skin damage. OBJECTIVE: This study investigated whether topical L-selenomethionine with topical RRR-alpha-tocopherol (Eol) or oral RRR-alpha-tocopheryl acetate (Eac) can reduce the incidence of UV-induced skin damage more than treatment with each alone. METHODS: Skh:2 hairless pigmented mice were treated with lotion vehicle, L-selenomethionine lotion, Eol lotion, oral Eac, L-selenomethionine plus Eol lotion, or L-selenomethionine lotion plus oral Eac and exposed to UVB. Skin pigmentation was scored, and the number of skin tumors per animal was counted weekly. RESULTS: Mice treated with selenium and vitamin E had significantly less acute and chronic UV-induced skin damage. CONCLUSION: Topical L-selenomethionine alone and combined with vitamin E gave the best protection against UV-induced blistering and pigmentation. In protecting against skin cancer, topical Eol and topical L-selenomethionine plus oral Eac were best. Significant synergy of L-selenomethionine with vitamin E was not observed.

Advances in clinical laboratory tests for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a generic term that refers to Crohn's disease and chronic ulcerative colitis (UC). The CD and UC are considered to be distinct forms of IBD; but there is a subgroup of CD with a UC-like presentation. The genetic factors play a significant role in IBD. IBD is associated with a strong familial pattern. Recent studies support the hypothesis that IBD patients have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract. The serologic responses seen in Crohn's disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides and E. coli. The pANCA antibody seen in UC and CD has been demonstrated to react with epitopes of H1 histone, Bacteroides caccae (Ton-B linked outer membrane protein), Pseudomonas fluorescens-associated bacterial protein I-2, mycobacterial histone 1 homologue called Hup B. In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies: (a) pANCA, (b) ASCA, (c) anti-pancreatic antibody, (d) OmpC antibody and (e) I-2 antibody and antibodies to anaerobic coccoid rods. The application of a panel of markers with the use of an algorithm (i.e. IBD First Step) can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The serologic markers are useful for the diagnosis and management of CD and UC patients.

Overview on induction mechanisms of autoimmunity

Auto-imunidade pode ser definida como uma falha do siste ma imunológico em reconhecer como "self" alguns antígenos do próprio organismo e inclui tanto as respostas humoral quanto a celular dirigidas a constituintes próprios. A auto-imunidade é tradicionalmente vista como patológica, induzindo doenças mediadas por lesoes imunológicas. As doenças auto-imunes foram recente mente separadas em quatro classes: órgao-específicas, células-específicas, órgao-específicas "paradoxais" e multissistêmicas. Diversos mecanismos têm sido pro postos para explicar a quebra de tolerância; os mais importantes sao o by-pass de célula T (sinal iniciador de células T alternativo ou ativaçao policlonal de células B), liberaçao de antígenos seqüestrados, perda de atividade supressora, mimetismo molecular, proteínas de estresse (heat shock proteins) e anticorpos antiidiotipo. A suscetibilidade a doenças auto-imunes é provavelmente multifato rial e poligênica. A associaçao com antígenos HLA está bem documentada, variando desde a baixa prevalência de antígenos de classe I em doenças auto-imunes órgao-específicas até a impressionante associaçao entre espondilite anquilosante e o HLA-B27. Uma possível relaçao entre opoptose e auto-imunidade foi recentemente admitida