Induction of metallothionein in human skin by routine exposure to sunlight: Evidence for a systemic response and enhanced induction at certain body sites

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo . Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

Early pregnancy factor treatment suppresses the inflammatory response and adhesion molecule expression in the spinal cord of SJL/J mice with experimental autoimmune encephalomyelitis and the delayed-type hypersensitivity reaction to trinitrochlorobenzene in normal BALB/c mice

Early pregnancy factor (EPF) is a secreted protein, present in serum during early pregnancy and essential for maintaining viability of the embryo. It is a homologue of chaperonin 10 (Cpn10) but, unlike Cpn10, it has an extracellular role. EPF has immunosuppressive and growth regulatory properties. Previously we have reported the preparation of recombinant EPF (rEPF) and shown that treatment with rEPF will suppress clinical signs of MBP-EAE in Lewis rats and PLP-EAE in SJL/J mice. In the present study, these findings have been extended to investigate possible mechanisms involved in the action of EPF. Following treatment of mice with rEPF from the day of inoculation, there were fewer infiltrating CD3+ and CD4+ cells in the parenchyma of the spinal cord during the onset of disease and after the initial episode, compared with mice treated with vehicle. Expression of the integrins LFA-1, VLA-4 and Mac-1 and of members of the immunoglobulin superfamily of adhesion molecules ICAM-1 and VCAM-1 was suppressed in the central nervous system (CNS) following rEPF treatment. The expression of PECAM-1 was not affected. To determine if rEPF suppressed T cell activation in the periphery, the delayed-type hypersensitivity (DTH) reaction of normal BALB/c mice to trinitrochlorobenzene (TNCB) following treatment with rEPF was studied. The results showed that treatment with rEPF suppressed the DTH reaction, demonstrating the ability of EPF to downregulate the cell-mediated immune response. These results indicate that suppression of immunological mechanisms by rEPF plays a major role in the reduction of clinical signs of disease in experimental autoimmune encephalomyelitis (EAE). (C) 2003 Elsevier Science B.V. All rights reserved.

Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis

Background/Aims: The role of cytokines in hepatic injury has been examined for many liver diseases however little is known of the cytokine involvement in haemochromatosis. The aim of the current study was to examine the hepatic gene expression of potential proinflammatory and profibrogenic cytokines in haemochromatosis. Methods: Interferon-gamma, interleukin-10, transforming growth factor-beta(1) and tumor necrosis factor-alpha mRNA expression was assessed in liver tissue from 20 haemochromatosis patients, eight controls and eight chronic hepatitis C patients. To assess the immunophenotype of the inflammatory infiltrate in haemochromatosis, liver sections were subjected to immunohistochemistry using markers for macrophages (CD68, HAM56, MAC387) or T cells (CD3 and CD45RO). Results: Interferon-gamma mRNA was increased in both haemochromatosis (0.29+/-0.08%, P=0.01) and hepatitis C patients (1.02+/-0.32%, P=0.03) compared to controls (0.04+/-0.01%). Interleukin-10 mRNA was significantly decreased in both haemochromatosis and hepatitis C patients (0.01+/-0.003%, P=0.008 and 0.03+/-0.015%, P=0.02, respectively) compared to controls (0.12+/-0.01%). CD3 positive T-cell number was significantly correlated with increasing hepatic iron concentration (r=0.56, P=0.03). Conclusions: This study has demonstrated a distinct pattern of cytokine gene expression in haemochromatosis, which resembles that of inflammatory conditions such as chronic hepatitis C. These factors may play a role in the development of iron-induced hepatic fibrosis in haemochromatosis. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

χ-conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter

The interactions of chi-conopeptide MrIA with the human norepinephrine transporter (hNET) were investigated by determining the effects of hNET point mutations on the inhibitory potency of MrIA. The mutants were produced by site-directed mutagenesis and expressed in COS-7 cells. The potency of MrIA was greater for inhibition of uptake by hNET of [H-3] norepinephrine (K-i 1.89 muM) than [H-3] dopamine (K-i 4.33 muM), and the human dopamine transporter and serotonin transporter were not inhibited by MrIA ( to 7 muM). Of 18 mutations where hNET amino acid residues were exchanged with those of the human dopamine transporter, MrIA had increased potency for inhibition of [H-3] norepinephrine uptake for three mutations ( in predicted extracellular loops 3 and 4 and transmembrane domain (TMD) 8) and decreased potency for one mutation (in TMD6 and intracellular loop (IL) 3). Of the 12 additional mutations in TMDs 2, 4, 5, and 11 and IL1, three mutations (in TMD2 and IL1) had reduced MrIA inhibitory potency. All of the other mutations tested had no influence on MrIA potency. A comparison of the results with previous data for desipramine and cocaine inhibition of norepinephrine uptake by the mutant hNETs reveals that MrIA binding to hNET occurs at a site that is distinct from but overlaps with the binding sites for tricyclic antidepressants and cocaine.

Balancing the number and size of sites: An economic approach to the optimal design of cluster samples

The design of randomized controlled trials entails decisions that have economic as well as statistical implications. In particular, the choice of an individual or cluster randomization design may affect the cost of achieving the desired level of power, other things being equal. Furthermore, if cluster randomization is chosen, the researcher must decide how to balance the number of clusters, or sites, and the size of each site. This article investigates these interrelated statistical and economic issues. Its principal purpose is to elucidate the statistical and economic trade-offs to assist researchers to employ randomized controlled trials that have desired economic, as well as statistical, properties. (C) 2003 Elsevier Inc. All rights reserved.

Portaria n?? 173, de 25 de setembro de 2012: institui o Comit?? Gestor para os sites da ENAP e o Grupo de Administradores de Conte??do dos sites da ENAP

O Comit?? Gestor para os sites da ENAP, inst??ncia institu??da pela Portaria n?? 173, de 25 de setembro de 2012, cujas atribui????es est??o relacionadas aos sites da ENAP, teve participa????o ativa durante os anos de 2012 e 2013, per??odo em que estiveram envolvidos no processo de constru????o da proposta do novo Portal da ENAP, atualmente em desenvolvimento.

Avaliação das informações sobre rinite alérgica em sites brasileiros na rede mundial de computadores (Internet)

A rede mundial de computadores (Internet) é, atualmente, fonte de informação sobre saúde para leigos e profissionais da área médica. A Rinite Alérgica é uma doença muito prevalente que chega a atingir mais de 10% da população geral, causando queda da qualidade de vida. OBJETIVO: Avaliar os princípios éticos de sites brasileiros que divulgam informações a respeito do tema "rinite alérgica". FORMA DE ESTUDO: revisional. MATERIAL E MÉTODO: Foi feita avaliação de 173 sites brasileiros encontrados através de quatro mecanismos de busca (Google, Yahoo, Altavista e Radar Uol). Os sites foram avaliados de acordo com o Manual de Princípios Éticos para Sites de Medicina e Saúde do CREMESP (Conselho Regional de Medicina do Estado de São Paulo), de acordo com os itens transparência, honestidade, qualidade, consentimento livre e esclarecido, privacidade, ética médica, responsabilidade e procedência. RESULTADOS: Entre os sites analisados, 149 (86,1%) não estavam de acordo como Manual de Princípios Éticos para Sites de Medicina e Saúde do CREMESP. As proporções de irregularidades entre os itens avaliados foram: qualidade (84,4%), privacidade (46,2%) honestidade (18,5%), consentimento livre e esclarecido (15,6%), responsabilidade (13,9%), transparência (12,1%), ética médica (2,3%). Havia informações inexatas em 24,3% dos sites analisados. CONCLUSÕES: A maioria dos sites estudados contendo informações sobre rinite alérgica fere os princípios éticos para sites do CREMESP. Tanto a qualidade em geral de grande parte dos sites brasileiros que abordam o tema "rinite alérgica", quanto à qualidade das informações por eles divulgadas, são insuficientes para satisfazer a médicos e pacientes.

Os sites dos ministérios de relações exteriores no mundo e a História

A Internet é aqui considerada uma fonte alternativa do estudo da história, sobretudo história das relações diplomáticas. São analisados os sites dos ministérios das relações exteriores pelo mundo: alguns atribuem grande importância à história, com detalhada visão retrospectiva (Brasil, França, México, Rússia, Alemanha, Estados Unidos), outros têm abordagem seletiva ou restrita a determinados períodos (Espanha, Argentina, Itália, Bélgica, Portugal, China, Japão), uns se voltam para o passado, somente com informações históricas que sejam indispensáveis à imagem nacional (Suíça) e outros mostram sua história voltada para o futuro (Grã-Bretanha).

The perceived potential of business social networking sites

Business social networking is a facilitator of several business activities, such as market studies, communication with clients, and identification of business partners. This paper traduces the results of a study undertaken with the purpose of getting to know how the potential of networking is perceived in the promotion of business by participants of the LinkedIn network, and presents two main contributions: (1) to disseminate within the business community which is the relevance given to social networking; and (2) which are the social networks best suitable to the promotion of business, to support the definition of strategies and approaches accordingly. The results confirm that LinkedIn is the most suitable network to answer the needs of those that look for professional contacts and for the promotion of business, while innovation is the most recognized factor in the promotion of business through social networking. This study contributes to a better understanding of the potential of different business social networking sites, to support organizations and professionals to align their strategies with the perceived potential of each network.

Uma análise dos sites de governos eletrônicos no Brasil sob a ótica dos usuários dos serviços e sua satisfação

Os sites de governo eletrônico (e-gov) têm sido muito analisados do ponto de vista dos aspectos técnicos, existindo poucos estudos que os avaliem do ponto de vista dos usuários dos serviços oferecidos por estes sites. Este estudo propôs um modelo de análise dos serviços de sites de e-gov avaliados com a técnica de análise de conteúdo e identificados os níveis de atendimento dos atributos do modelo. As principais contribuições do estudo são: uma crítica das deficiências verificadas nos principais sites analisados e uma proposição de um modelo abrangente que facilite a orientação para o atendimento das principais dimensões a serem analisadas, quais sejam: eficiência, realização, disponibilidade do sistema, privacidade, site e sinergia. Do ponto de vista gerencial, o estudo contribuiu com um modelo de fácil aplicação que pode auxiliar a identificar os aspectos mais importantes dos serviços de e-gov.

A acessibilidade nos sites do Poder Executivo estadual à luz dos direitos fundamentais das pessoas com deficiência

Este artigo investiga se a acessibilidade, analisada à luz dos direitos das pessoas com deficiência, é valorizada no desenvolvimento do governo eletrônico e se reflete na estrutura dos portais governamentais, contribuindo para a concretização do direito de participação política deste grupo social. Para tanto, com apoio do método dedutivo e da técnica de observação direta, sistemática e não participante, verificou-se a acessibilidade nos portais do Poder Executivo estadual de oito unidades da federação, contrastando-se a realidade destes sites com as determinações de cartilhas governamentais que preveem padrões mínimos sobre o tema. Concluiu-se que a acessibilidade nos sites pesquisados é mínima, dificultando assim o exercício de uma cidadania mais ativa por parte das pessoas com deficiência, uma vez que o acesso é a primeira condição de possibilidade para a participação.

Proportional cancer incidence according to selected sites: comparison between residents in the City of S. Paulo, Brazil: Japanese and Brazilian/Portuguese descent

The percentual distributions of selected sites of cancer cases according to origin, sex and age are compared. Data were obtained from the Registry of Cancer of S. Paulo (School of Public Health of the University of S. Paulo, Brazil). The reference period for inhabitants of Japanese descent was 1969/78 and for those of Brazilian descent, the period was 1969/75. Standardized Proportionate Incidence Ratios (SPIR) with approximate 95% Confidence Intervals (CI) were evaluated using age specific Incidence Ratios of S. Paulo, 1973, as standards. The results agree with findings of previous works on mortality, but show different patterns according to origin. The well known fact that some sub-groups of a population may be different from the overall group is once again brought to the fore. Attention should be drawn to the differences detected for stomach, skin and prostate, in males, and for stomach, skin, cervix and uterus in females.

Populations of larvae of Anopheles spp. in natural breeding sites in Western Venezuela, an area of refractory malaria

Studies have been un dertaken into on the diversity and relative abundance of larvae of Anopheles (Nyssorhynchus) spp. in 22 permanent or temporary pools in an area of 70 km² in the eastern piedmont of the Venezuela Andes, between the mountains and the plains, an area in which malaria is refractory and A. nuñeztovari is present. Twelve species were identified, the most frequent, abundant and sympatric being A. triannulatus, A. albitarsis, A. nuñeztovari, A. oswaldoi and A. strodei. The samples from the permanent pools showed greater diversity of species and greater numbers of larvae than the samples from the temporary pools. The existence of the same larval associations in pools of other localities in the eastern piedmont of the Venezuelan Andes suggests the possibility of the making an ecological map of the breeding sites of A. nuñeztovari and for these anophelines in a region extending for 430 km.

Equilibrium self-assembly of colloids with distinct interaction sites: Thermodynamics, percolation, and cluster distribution functions

We calculate the equilibrium thermodynamic properties, percolation threshold, and cluster distribution functions for a model of associating colloids, which consists of hard spherical particles having on their surfaces three short-ranged attractive sites (sticky spots) of two different types, A and B. The thermodynamic properties are calculated using Wertheim's perturbation theory of associating fluids. This also allows us to find the onset of self-assembly, which can be quantified by the maxima of the specific heat at constant volume. The percolation threshold is derived, under the no-loop assumption, for the correlated bond model: In all cases it is two percolated phases that become identical at a critical point, when one exists. Finally, the cluster size distributions are calculated by mapping the model onto an effective model, characterized by a-state-dependent-functionality (f) over bar and unique bonding probability (p) over bar. The mapping is based on the asymptotic limit of the cluster distributions functions of the generic model and the effective parameters are defined through the requirement that the equilibrium cluster distributions of the true and effective models have the same number-averaged and weight-averaged sizes at all densities and temperatures. We also study the model numerically in the case where BB interactions are missing. In this limit, AB bonds either provide branching between A-chains (Y-junctions) if epsilon(AB)/epsilon(AA) is small, or drive the formation of a hyperbranched polymer if epsilon(AB)/epsilon(AA) is large. We find that the theoretical predictions describe quite accurately the numerical data, especially in the region where Y-junctions are present. There is fairly good agreement between theoretical and numerical results both for the thermodynamic (number of bonds and phase coexistence) and the connectivity properties of the model (cluster size distributions and percolation locus).