The effects of early developmental exposure to 3,3'4,4'5-pentachlorobiphenyl (PCB 126) on developing mink (Neovison vison) and domestic chick (Gallus domesticus) brains

Polychlorinated biphenyls (PCBs) are environmental toxicants that bioaccumulate in the body. PCB 126 is the most toxic PCB congener due to its ability to mimic the effects of dioxins. Here, I examined the effects of early developmental PCB 126 exposure in two animal models. In the first experiment, American mink kits were exposed prenatally and postnatally to PCB 126. The effects of early exposure were examined in the hippocampus, neocortex and corpus callosum. PCB 126 exposure had no effect on the hippocampus, but decreased volume of both the neocortex and corpus callosum. In the second experiment, chick eggs were injected with PCB 126 and the effects of embryonic exposure in the brain were examined in the telencephalon and hippocampus. Overall, I found no effects of PCB 126 on the chick brain. Taken together, my two experiments suggest PCB 126 has effects on the brain, but species sensitivity may differ.NSERC and AITF funding to Dr. Iwaniu

Apolipoprotein A-I infiltration in rheumatoid arthritis synovial tissue: a control mechanism of cytokine production?

The production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) by monocytes is strongly induced by direct contact with stimulated T lymphocytes, and this mechanism may be critical in the pathogenesis of rheumatoid arthritis (RA). Apolipoprotein A-I (apoA-I) blocks contact-mediated activation of monocytes, causing inhibition of TNF-α and IL-1β production. This study examined the hypothesis that apoA-I may have a regulatory role at sites of macrophage activation by T lymphocytes in inflamed RA synovial tissue. Synovial tissue samples were obtained after arthroscopy from patients with early untreated RA or treated RA and from normal subjects. As determined by immunohistochemistry, apoA-I was consistently present in inflamed synovial tissue that contained infiltrating T cells and macrophages, but it was absent from noninflamed tissue samples obtained from treated patients and from normal subjects. ApoA-I staining was abundant in the perivascular areas and extended in a halo-like pattern to the surrounding cellular infiltrate. C-reactive protein and serum amyloid A were not detected in the same perivascular areas of inflamed tissues. The abundant presence of apoA-I in the perivascular cellular infiltrates of inflamed RA synovial tissue extends the observations in vitro that showed that apoA-I can modify contact-mediated macrophage production of TNF-α and IL-1β. ApoA-I was not present in synovium from patients in apparent remission, suggesting that it has a specific role during phases of disease activity. These findings support the suggestion that the biologic properties of apoA-I, about which knowledge is newly emerging, include anti-inflammatory activities and therefore have important implications for the treatment of chronic inflammatory diseases

MANAGING TOURIST SATISFACTION: THE CASE OF A RESORT IN GAUTENG, SOUTH AFRICA

MANAGING TOURIST SATISFACTION: THE CASE OF A RESORT IN GAUTENG, SOUTH AFRIC

The active metabolite of leflunomide, A77 1726, increases the production of IL-1 receptor antagonist in human synovial fibroblasts and articular chondrocytes

Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis. In this study, we investigated the effect of A77 1726 – the active metabolite of leflunomide – on the production of IL-1 receptor antagonist (IL-1Ra) by human synovial fibroblasts and articular chondrocytes. Cells were incubated with A77 1726 alone or in combination with proinflammatory cytokines. IL-1Ra production was determined by ELISA. A77 1726 alone had no effect, but in the presence of IL-1β or tumour necrosis factor-α it markedly enhanced the secretion of IL-1Ra in synovial fibroblasts and chondrocytes. The effect of A77 1726 was greatest at 100 μmol/l. In synovial fibroblasts and de-differentiated chondrocytes, A77 1726 also increased IL-1β-induced IL-1Ra production in cell lysates. Freshly isolated chondrocytes contained no significant amounts of intracellular IL-1Ra. A77 1726 is a known inhibitor of pyrimidine synthesis and cyclo-oxygenase (COX)-2 activity. Addition of exogenous uridine did not significantly modify the effect of A77 1726 on IL-1Ra production, suggesting that it was not mediated by inhibition of pyrimidine synthesis. Indomethacin increased IL-1β-induced IL-1Ra secretion in synovial fibroblasts and de-differentiated chondrocytes, suggesting that inhibition of COX-2 may indeed enhance IL-1β-induced IL-1Ra production. However, the stimulatory effect of indomethacin was consistently less effective than that of A77 1726. A77 1726 increases IL-1Ra production by synovial fibroblasts and chondrocytes in the presence of proinflammatory cytokines, and thus it may possess chondroprotective effects. The effect of A77 1726 may be partially mediated by inhibition of COX-2, but other mechanisms likely concur to stimulate IL-1Ra production

Física téorica online: um desafio para o ensino superior

O objetivo deste trabalho é apresentar as etapas de construção da disciplina Fisica Teórica I na modalidade online. Esta disciplina apresenta um índice de reprovação de cerca de 40% na modalidade presencial, sendo um dos principais motivos de abandono nos cursos de Engenharia ainda no ciclo básico. Percebe-se que boa parte das reprovações ocorre devido às deficiências trazidas pelos alunos em matemática e física. No curso regular não há carga horária suficiente para sanar estas deficiências e cumprir o conteúdo integralmente. Este aspecto motivou a construção da disciplina na modalidade online para cursos presenciais. A disciplina foi construída permitindo-se flexibilidade de caminhos, incluindo revisão de conteúdos do ensino médio. Desta forma, pretende-se suprir as deficiências da formação com as quais os estudantes ingressam na universidade, reduzindo, assim a taxa de reprovação e consequente evasão. A disciplina foi implantada no primeiro periodo letivo de 2013 e a resposta por parte dos alunos foi positiva e encorajadora. Trabalhos adicionais estão sendo produzidos para análise do impacto da disciplina nas taxas de reprovação e evasão.The aim of this paper is to present the stages of development of the module Theoretical Physics I for online presentation. In previous face-to-face presentations, the module has had a failure rate of about 40%, constituting one of the main reasons for attrition in engineering courses during the first two study years. Our experience has been that failure occurs due to gaps in students’ previous knowledge of Mathematics and Physics. In face-to-face mode there is no sufficient time to both remedy these deficiencies and deliver the main module content. This has motivated development of the module in a Virtual Learning Environment including access for students enrolled in the traditional mode. The online module has been designed to allow for flexible pathways that include the option to learn or revise pre-requisite topics. Thus, it is intended to allow students to fill in knowledge gaps that exist as a consequence of deficient schooling. It is hoped that the module will give students the opportunity of restructuring their knowledge, reducing the failure rate and consequent attrition. The new scheme was implemented in the first academic semester of 2013, and, so far, student response has been positively and very encouraging. Further work is underway to examine the impact of the module on repetition and dropout rates.Universidade Aberta; Pavilhão do Conhecimento; LEA

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of TMC/EVER Alterations

Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs).; To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC.; We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25).; Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs.; To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary