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Showing papers by "Oswaldo Cruz Foundation published in 2007"


Journal ArticleDOI
TL;DR: This review summarizes current studies that have been regarding the production of ROS and the general redox-sensitive targets of cell signalling cascades.

1,121 citations


Journal ArticleDOI
TL;DR: The results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology.
Abstract: Background At least 75% of head and neck cancers are attributable to a combination of cigarette smoking and alcohol drinking. A precise understanding of the independent association of each of these factors in the absence of the other with the risk of head and neck cancer is needed to elucidate mechanisms of head and neck carcinogenesis and to assess the efficacy of interventions aimed at controlling either risk factor. Methods We examined the extent to which head and neck cancer is associated with cigarette smoking among never drinkers and with alcohol drinking among never users of tobacco. We pooled individual-level data from 15 case – control studies that included 10 244 head and neck cancer case subjects and 15 227 control subjects, of whom 1072 case subjects and 5775 control subjects were never users of tobacco and 1598 case subjects and 4051 control subjects were never drinkers of alcohol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. All statistical tests were two-sided. Results Among never drinkers, cigarette smoking was associated with an increased risk of head and neck cancer (OR for ever versus never smoking = 2.13, 95% CI = 1.52 to 2.98), and there were clear dose – response relationships for the frequency, duration, and number of pack-years of cigarette smoking. Approximately 24% (95% CI = 16% to 31%) of head and neck cancer cases among nondrinkers in this study would have been prevented if these individuals had not smoked cigarettes. Among never users of tobacco, alcohol consumption was associated with an increased risk of head and neck cancer only when alcohol was consumed at high frequency (OR for three or more drinks per day versus never drinking = 2.04, 95% CI = 1.29 to 3.21). The association with high-frequency alcohol intake was limited to cancers of the oropharynx/hypopharynx and larynx. Conclusions Our results represent the most precise estimates available of the independent association of each of the two main risk factors of head and neck cancer, and they exemplify the strengths of large-scale consortia in cancer epidemiology. J Natl Cancer Inst 2007;99: 777 – 89

849 citations


Journal ArticleDOI
TL;DR: In this article, the authors used a multiplex system for simultaneous detection of 17 cytokines (IL-1β, IL-2, IL 4, IL 5, IL 6, IL 7, IL 8, IL 9, IL 10, IL 11, IL 12, IL 13, interferon-γ, MCP-1, macrophage inflammatory protein-1 and tumour necrosis factor-α).
Abstract: The current shortage of accurate and readily available, validated biomarkers of disease severity in sepsis is an important limitation when attempting to stratify patients into homogeneous groups, in order to study pathogenesis or develop therapeutic interventions. The aim of the present study was to determine the cytokine profile in plasma of patients with severe sepsis by using a multiplex system for simultaneous detection of 17 cytokines. This was a prospective cohort study conducted in four tertiary hospitals. A total of 60 patients with a recent diagnosis of severe sepsis were included. Plasma samples were collected for measurement of cytokine concentrations. A multiplex analysis was performed to evaluate levels of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-γ, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein-1 and tumour necrosis factor-α). Cytokine concentrations were related to the presence of severe sepsis or septic shock, the severity and evolution of organ failure, and early and late mortality. Concentrations of IL-1β, IL-6, IL-7, IL-8, IL-10, IL-13, interferon-γ, MCP-1 and tumour necrosis factor-α were significantly higher in septic shock patients than in those with severe sepsis. Cytokine concentrations were associated with severity and evolution of organ dysfunction. With regard to the severity of organ dysfunction on day 1, IL-8 and MCP-1 exhibited the best correlation with Sequential Organ Failure Assessment score. In addition, IL-6, IL-8 and G-CSF concentrations during the first 24 hours were predictive of worsening organ dysfunction or failure of organ dysfunction to improve on day three. In terms of predicting mortality, the cytokines IL-1β, IL-4, IL-6, IL-8, MCP-1 and G-CSF had good accuracy for predicting early mortality (< 48 hours), and IL-8 and MCP-1 had the best accuracy for predicting mortality at 28 days. In multivariate analysis, only MCP-1 was independently associated with prognosis. In this exploratory analysis we demonstrated that use of a multiple cytokine assay platform allowed identification of distinct cytokine profiles associated with sepsis severity, evolution of organ failure and death.

651 citations


Journal ArticleDOI
01 Apr 2007
TL;DR: In this article, an artigo busca analisar as relacoes entre saude and seus determinantes sociais de saude, apresentando inicialmente o conceito de determinantes Sociais of saude (DSS) and uma breve evolucao history of the processo saude/doenca no âmbito das sociedades, desde meados do seculo XIX.
Abstract: RESUMO Este artigo busca analisar as relacoes entre saude e seus determinantes sociais, apresentando inicialmente o conceito de determinantes sociais de saude (DSS) e uma breve evolucao historica dos diversos paradigmas explicativos do processo saude/doenca no âmbito das sociedades, desde meados do seculo XIX. Em seguida sao discutidos os principais avancos e desafios no estudo dos DSS, com enfase em novos enfoques e marcos de referencia explicativos das relacoes ente os diversos niveis de DSS e a situacao de saude. Com base nesses estudos e marcos explicativos, discutese, em seguida, uma serie de possibilidades de intervencoes de politicas e programas voltados para o combate as iniquidades de saude geradas pelos DSS. Finalmente, sao apresentados os objetivos, linhas de atuacao e principais atividades da Comissao Nacional sobre Determinantes Sociais da Saude, criada em marco de 2006, com o objetivo de promover estudos sobre os DSS, recomendar politicas para a promocao da equidade em saude e mobilizar setores da sociedade para o debate e posicionamento em torno dos DSS e do enfrentamento das iniquidades de saude.

615 citations


Journal ArticleDOI
TL;DR: In patients with few remaining treatment options, raltegravir at all doses studied provided better viral suppression than placebo when added to an optimised background regimen.

559 citations


Journal ArticleDOI
TL;DR: It is demonstrated that a new serotype may exist within an established and well-characterized serogroup or serotype, with 90 pneumococcal serotypes having previously been recognized.
Abstract: Using two monoclonal antibodies, we found subtypes among pneumococcal isolates that are typed as serotype 6A by the quellung reaction. The prevalent subtype bound to both monoclonal antibodies and was labeled here 6Aα, whereas the minor subtype bound to only one monoclonal antibody and was labeled 6Aβ. To determine the biochemical nature of the two serologically defined subtypes, we purified capsular polysaccharides (PSs) from the two subtypes and examined their chemical structures with gas-liquid chromatography and mass spectrometry. The study results for 6Aα PS are consistent with the previously published structure of 6A PS, which is →2) galactose (1→3) glucose (1→3) rhamnose (1→3) ribitol (5→phosphate. In contrast, the 6Aβ PS study results show that its repeating unit is →2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→3) ribitol (5→phosphate. We propose to continue referring to 6Aα as serotype 6A but to refer to 6Aβ as serotype 6C. Serotype 6C would thus represent the 91st pneumococcal serotype, with 90 pneumococcal serotypes having previously been recognized. This study also demonstrates that a new serotype may exist within an established and well-characterized serogroup or serotype.

459 citations


Journal ArticleDOI
TL;DR: The social imagination by which men are viewed as invulnerable leads them to take less care of their own health and expose themselves to greater risk.
Abstract: O estudo tem como objetivo analisar as explicacoes presentes em discursos masculinos para a pouca procura dos homens por servicos de saude. O metodo do estudo baseia-se numa abordagem de pesquisa qualitativa. A representacao do cuidar como tarefa feminina, as questoes relacionadas ao trabalho, a dificuldade de acesso aos servicos e a falta de unidades especificamente voltadas para a saude do homem sao os principais motivos expressos pelos sujeitos para a pouca procura pelos servicos de saude. Conclui-se, dentre outros aspectos, que o imaginario social que ve o homem como ser invulneravel acaba contribuindo para que ele menos se cuide e mais se exponha a situacoes de risco.

363 citations


Journal ArticleDOI
TL;DR: The results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.
Abstract: Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.

344 citations


Journal ArticleDOI
TL;DR: Because there is no vaccine available against RMSF, avoidance of tick-infested areas is still the best way to prevent the infection.
Abstract: Rocky Mountain spotted fever (RMSF) is a life-threatening disease caused by Rickettsia rickettsii, an obligately intracellular bacterium that is spread to human beings by ticks. More than a century after its first clinical description, this disease is still among the most virulent human infections identified, being potentially fatal even in previously healthy young people. The diagnosis of RMSF is based on the patient's history and a physical examination, and often presents a dilemma for clinicians because of the non-specific presentation of the disease in its early course. Early empirical treatment is essential to prevent severe complications or a fatal outcome, and treatment should be initiated even in unconfirmed cases. Because there is no vaccine available against RMSF, avoidance of tick-infested areas is still the best way to prevent the infection.

335 citations


Journal ArticleDOI
TL;DR: Both TLR2 and TLR4 receptors may participate in the host defense against T. gondii infection through their activation by the GPIs and could work together with other MyD88-dependent receptors, like other TLRs or even IL-18R or IL-1R, to obtain an effective host response against the parasite.
Abstract: GPIs isolated from Toxoplasma gondii , as well as a chemically synthesized GPI lacking the lipid moiety, activated a reporter gene in Chinese hamster ovary cells expressing TLR4, while the core glycan and lipid moieties cleaved from the GPIs activated both TLR4- and TLR2-expressing cells. MyD88, but not TLR2, TLR4, or CD14, is absolutely needed to trigger TNF-α production by macrophages exposed to T. gondii GPIs. Importantly, TNF-α response to GPIs was completely abrogated in macrophages from TLR2/4-double-deficient mice. MyD88 −/− mice were more susceptible to death than wild-type (WT), TLR2 −/− , TLR4 −/− , TLR2/4 −/− , and CD14 −/− mice infected with the ME-49 strain of T. gondii . The cyst number was higher in the brain of TLR2/4 −/− , but not TLR2 −/− , TLR4 −/− , and CD14 −/− , mice, as compared with WT mice. Upon infection with the ME-49 strain of T. gondii , we observed no decrease of IL-12 and IFN-γ production in TLR2-, TLR4-, or CD14-deficient mice. Indeed, splenocytes from T. gondii -infected TLR2 −/− and TLR2/4 −/− mice produced more IFN-γ than cells from WT mice in response to in vitro stimulation with parasite extracts enriched in GPI-linked surface proteins. Together, our results suggest that both TLR2 and TLR4 receptors may participate in the host defense against T. gondii infection through their activation by the GPIs and could work together with other MyD88-dependent receptors, like other TLRs or even IL-18R or IL-1R, to obtain an effective host response against T. gondii infection.

298 citations


Journal ArticleDOI
TL;DR: This article presents the ten top Chagas disease needs for the near future, characterized by an acute phase with or without symptoms, and with entry point signs (inoculation chagoma or Romaña's sign), fever, adenomegaly, hepatosplenomeGaly, and evident parasitemia.
Abstract: Chagas disease began millions of years ago as an enzootic disease of wild animals and started to be transmitted to man accidentally in the form of an anthropozoonosis when man invaded wild ecotopes. Endemic Chagas disease became established as a zoonosis over the last 200-300 years through forest clearance for agriculture and livestock rearing and adaptation of triatomines to domestic environments and to man and domestic animals as a food source. It is estimated that 15 to 16 million people are infected with Trypanosoma cruzi in Latin America and 75 to 90 million people are exposed to infection. When T. cruzi is transmitted to man through the feces of triatomines, at bite sites or in mucosa, through blood transfusion or orally through contaminated food, it invades the bloodstream and lymphatic system and becomes established in the muscle and cardiac tissue, the digestive system and phagocytic cells. This causes inflammatory lesions and immune responses, particularly mediated by CD4+, CD8+, interleukin-2 (IL) and IL-4, with cell and neuron destruction and fibrosis, and leads to blockage of the cardiac conduction system, arrhythmia, cardiac insufficiency, aperistalsis, and dilatation of hollow viscera, particularly the esophagus and colon. T. cruzi may also be transmitted from mother to child across the placenta and through the birth canal, thus causing abortion, prematurity, and organic lesions in the fetus. In immunosuppressed individuals, T. cruzi infection may become reactivated such that it spreads as a severe disease causing diffuse myocarditis and lesions of the central nervous system. Chagas disease is characterized by an acute phase with or without symptoms, and with entry point signs (inoculation chagoma or Romana's sign), fever, adenomegaly, hepatosplenomegaly, and evident parasitemia, and an indeterminate chronic phase (asymptomatic, with normal results from electrocardiogram and x-ray of the heart, esophagus, and colon) or with a cardiac, digestive or cardiac-digestive form. There is great regional variation in the morbidity due to Chagas disease, and severe cardiac or digestive forms may occur in 10 to 50% of the cases, or the indeterminate form in the other asymptomatic cases, but with positive serology. Several acute cases have been reported from Amazon region most of them by T. cruzi I, Z3, and a hybrid ZI/Z3. We conclude this article presenting the ten top Chagas disease needs for the near future.

Journal ArticleDOI
TL;DR: The main focus of this study was the effect of chronic disease on the functional status (activities of daily living - ADL, instrumental activities of dailyLiving - IADL) among the elderly, controlling for age, gender, living arrangements, education, and comorbidity.
Abstract: The main focus of this study was the effect of chronic disease (hypertension, diabetes mellitus, heart disease, lung disease, cancer, and arthropathy) on the functional status (activities of daily living - ADL, instrumental activities of daily living - IADL) among the elderly, controlling for age, gender, living arrangements, education, and comorbidity. The analysis was based on information provided by the SABE Project, from the city of Sao Paulo, Brazil, including individuals 60 years of age and over (n = 1,769), from January 2000 to March 2001. A multinomial logistic regression model was used. Compared to the absence of dependency category, heart disease (OR = 1.82), arthropathy (OR = 1.59), lung disease (OR = 1.50), and hypertension (OR = 1.39) were the main diseases that affected the IADL dependency category. Lung disease (OR = 2.58), arthropathy (OR = 2.27), hypertension (OR = 2.13), and heart disease (OR = 2.10) had important impact on the IADL and ADL dependency categories. The results were statistically significant (p < 0.05).

Journal ArticleDOI
TL;DR: A trend toward incremental change in the primary care model in Brazil is confirmed, and the expansion of the FHP in large urban areas faces several obstacles to guaranteeing all individuals access to comprehensive care with adequate clinical and collective health services, including secondary and tertiary care.
Abstract: As part of the implementation of the country's Unified Health System (Sistema Unico de Saude), the Brazilian Government created, in the second half of the 1990s, the Family Health Program (FHP) (Programa de Saude da Familia), based on community-oriented, multidisciplinary care serving people organized into small groups. For this study, we evaluated the implementation of the FHP, based on three criteria: (1) the construction of the program as an entry point for most health needs and for access to specialized care, (2) the program's linkages with a comprehensive network of health services, and (3) the incorporation of new care practices into the health system. We found that the implementation of the FHP was far from uniform. In some municipalities the FHP is a focused program that runs in parallel with other primary care efforts. However, in other municipalities the FHP is viewed as a strategy aimed at changing the primary care model, and it partially or completely replaces preexisting primary care health units. Our research confirms a trend toward incremental change in the primary care model in Brazil. However, the expansion of the FHP in large urban areas faces several obstacles to guaranteeing all individuals access to comprehensive care with adequate clinical and collective health services, including secondary and tertiary care. The positive results that we found with some of the experiences with the FHP indicate that, in addition to increased federal financial incentives, the success of the FHP depends on creative local strategies to deal with Brazil's diversity.

Journal ArticleDOI
TL;DR: Insightful insights derived from recent research indicate that not dogs but humans are probably the most important domestic reservoirs of L. (L.) infantum and L. braziliensis, and the role of dogs as reservoirs of Leishmania parasites is reviewed.

Journal ArticleDOI
TL;DR: Observations made in one slum community of 58,000 people in Salvador, the third largest city in Brazil, are discussed to highlight the existence of a spectrum and burden of chronic illnesses not likely to be detected by the formal sector health services until they result in complications or death.
Abstract: Urban slums, like refugee communities, comprise a social cluster that engenders a distinct set of health problems. With 1 billion people currently estimated to live in such communities, this neglected population has become a major reservoir for a wide spectrum of health conditions that the formal health sector must deal with. Unlike what occurs with refugee populations, the formal health sector becomes aware of the health problems of slum populations relatively late in the course of their illnesses. As such, the formal health sector inevitably deals with the severe and end-stage complications of these diseases at a substantially greater cost than what it costs to manage non-slum community populations. Because of the informal nature of slum settlements, and cultural, social, and behavioral factors unique to the slum populations, little is known about the spectrum, burden, and determinants of illnesses in these communities that give rise to these complications, especially of those diseases that are chronic but preventable. In this article, we discuss observations made in one slum community of 58,000 people in Salvador, the third largest city in Brazil, to highlight the existence of a spectrum and burden of chronic illnesses not likely to be detected by the formal sector health services until they result in complications or death. Lack of health-related data from slums could lead to inappropriate and unrealistic allocation of health care resources by the public and private providers. Similar misassumptions and misallocations are likely to exist in other nations with large urban slum populations. Continued neglect of ever-expanding urban slum populations in the world could inevitably lead to greater expenditure and diversion of health care resources to the management of end-stage complications of diseases that are preventable. A new approach to health assessment and characterization of social-cluster determinants of health in urban slums is urgently needed.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated the evolution in smoking indicators in the adult Brazilian population between 1989 and 2003 and found that there was a substantial decrease in the prevalence of smoking (from 34.8% to 22.4% and a modest reduction in the mean number of cigarettes consumed per day (from 13.3 to 11.6).
Abstract: Objective To evaluate the evolution in smoking indicators in the adult Brazilian population between 1989 and 2003. Methods We compared age-adjusted prevalence ratios and means for smoking indicators, stratified by age, sex and sociodemographic variables, obtained from two comparable household surveys that used probabilistic sampling of the Brazilian population aged > 18 years (n = 34 808 in 1989 and n = 5000 in 2003). Findings Between 1989 and 2003, there was a substantial decrease in the prevalence of smoking (from 34.8% to 22.4%; ageadjusted prevalence ratio, 0.65; 95% confidence interval, CI, 0.60–0.70) and a modest reduction in the mean number of cigarettes smoked per day (from 13.3 to 11.6; age-adjusted difference, –1.8; 95% CI, –2.6 – –1.0). Reductions in the prevalence and intensity of smoking were greater among males, younger age groups and higher socioeconomic strata. Conclusion The prevalence of smoking in the adult Brazilian population declined by 35% between 1989 and 2003, or an average of 2.5% per year. This exceptional reduction surpasses those seen in other countries that implemented wide-ranging and rigorous policies for controlling smoking during the same period. The more intense decline in smoking in younger age groups was consistent with the concentration of efforts of the Brazilian tobacco control programme to prevent the onset of smoking among youths and the total prohibition of cigarette advertising. We recommend the intensification of programme initiatives targeting women and less economically favoured population strata.

Journal ArticleDOI
11 Oct 2007-Arkivoc
TL;DR: Nicotinic and isoniazid derivatives, most of them containing nitro groups were synthesized by this group, and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in mg/mL.
Abstract: Several nicotinic and isoniazid derivatives, most of them containing nitro groups were synthesized by our group, and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in mg/mL. The compound 11d exhibited the best result (1.2 µg/mL) when compared with first line drugs such as isoniazid (INH) and rifampicin (RIP). Therefore this class of compounds could be a good starting point to develop new lead compounds in the treatment of multi-drug resistant tuberculosis.

Journal ArticleDOI
TL;DR: Loa22 is necessary for virulence of L. interrogans in the animal model and represents the first genetically defined virulence factor in Leptospira species, according to predicted OmpA domain based on sequence identity.
Abstract: Pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetic manipulations of pathogenic species. In this study, we characterized a mutant obtained by insertion of the transposon Himar1 into a gene encoding a putative lipoprotein, Loa22, which has a predicted OmpA domain based on sequence identity. The resulting mutant did not express Loa22 and was attenuated in virulence in the guinea pig and hamster models of leptospirosis, whereas the genetically complemented strain was restored in Loa22 expression and virulence. Our results show that Loa22 was expressed during host infection and exposed on the cell surface. Loa22 is therefore necessary for virulence of L. interrogans in the animal model and represents, to our knowledge, the first genetically defined virulence factor in Leptospira species.

Journal ArticleDOI
TL;DR: The Copaiba Oil from Copaifera multijuga Hayne (100 mg/kg) was the most potent, inhibiting both NO production and the pleurisy induced by zymosan, and the oleoresins from CopAifera cearensis Huber ex Ducke and Copaifiera reticulata Ducke were also able to inhibit NOProduction and the Pleurisy but with less intensity.

Journal ArticleDOI
TL;DR: The text shows the advance of technical and operative activities of the Southern Cone Initiative, emphasizing some factors for the initiative success, as well as some difficulties and constraints.
Abstract: Created in 1991 by the governments of Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay, the Southern Cone Initiative (SCI) has been extremely important for Chagas disease control in this region. Its basic objective was to reach the interruption of this disease, chiefly by means of the elimination of the principal vector Triatoma infestans and by the selection of safe donors in the regional blood banks. After a summarized historic of SCI, the text shows the advance of technical and operative activities, emphasizing some factors for the initiative success, as well as some difficulties and constraints. The future of SCI will depend of the continuity of the actions and of political priority. Scientific community has been highly responsible for this initiative and its maintenance. At the side of this, national and international efforts must be involved and reinforced to assure the accomplishment of the final targets of SCI. Very specially, the Pan American Health Organization has cooperated with the Initiative in all its moments and activities,being the most important catalytic and technical factor for SCI success.

Journal ArticleDOI
TL;DR: The data reveal a critical role for WASP in nTreg cell function and implicate nT Reg cell dysfunction in the autoimmunity associated with WASP deficiency and reveal significant impaired homing to both mucosal and peripheral sites upon adoptive transfer into WT recipient mice.
Abstract: The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4+CD25+Foxp3+ naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development/function of nTreg cells. We show that WKO mice have decreased numbers of CD4+CD25+Foxp3+ nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RBhi T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor–mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor–mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency.

Journal ArticleDOI
TL;DR: In Brazil, Aedes aegypti resistance to temephos, used since 1967, was detected in several municipalities in 2000, and Gluthathione-S-transferase alteration was encountered only in the northeast region in 2001, spreading the entire country thereafter.
Abstract: In Brazil, Aedes aegypti resistance to temephos, used since 1967, was detected in several municipalities in 2000. Organophosphates were substituted by pyrethroids against adults and, in some localities, by Bti against larvae. However, high temephos resistance ratios were still detected between 2001 and 2004. Field-simulated assays confirmed a low temephos residual effect. Acethylcholinesterase and Mixed Function Oxidase profiles were not altered. In contrast, higher Esterase activity, studied with three substrates, was found in all examined populations collected in 2001. From 2001 to 2004, a slight reduction in α-Esterase (EST) and β-EST activity together with a gradual increase of p-nitrophenyl acetate (PNPA)-EST was noted. Gluthathione-S-transferase alteration was encountered only in the northeast region in 2001, spreading the entire country thereafter. In general, except for α-EST and β-EST, only one enzyme class was altered in each mosquito specimen. Data are discussed in the context of historic application of insecticides in Brazil.

Book
01 Jan 2007
TL;DR: Hess as mentioned in this paper proposes a theory of scientific and technological change that considers the roles that both industry and grassroots consumers play in setting the research agenda in science and technology, and identifies "alternative pathways" by which social movements can influence scientific innovation.
Abstract: In Alternative Pathways in Science and Industry, David Hess examines how social movements and other forms of activism affect innovation in science, technology, and industry. Synthesizing and extending work in social studies of science and technology, social movements, and globalization, Hess explores the interaction of grassroots environmental action and mainstream industry and offers a conceptual framework for understanding it.Hess proposes a theory of scientific and technological change that considers the roles that both industry and grassroots consumers play in setting the research agenda in science and technology, and he identifies "alternative pathways" by which social movements can influence scientific and technological innovation. He analyzes four of these pathways: industrial opposition movements, organized against targeted technologies (as in the campaign against nuclear energy); technology- and product-oriented movements, which press for alternatives (as does the organic food movement); localism, which promotes local ownership (as in "buy-local" campaigns); and access pathways, which support a more equitable distribution of resources. Within each pathway, Hess examines reforms in five different areas: agriculture, energy, waste and manufacturing, infrastructure, and finance. The book's theoretical argument and empirical evidence demonstrate the complex pattern of incorporation (of grassroots innovations) and transformation (of alternative ownership structures and the alternative products themselves) that has characterized the relationship of industry and activism. Hess's analysis of alternative pathways to change suggests ways economic organizations could shift to a more just and sustainable course in the twenty-first century.

Journal ArticleDOI
TL;DR: In this paper, the authors describe the application of a protocol for biological assessment of water quality at first to third order streams at Serra dos Orgaos, an area covered by Atlantic Forest in Rio de Janeiro State, Brazil.
Abstract: This study describes the application of a protocol for biological assessment of water quality at first to third order streams at Serra dos Orgaos, an area covered by Atlantic Forest in Rio de Janeiro State, Brazil. Major impacts in the region are domestic effluents and deforestation. Our main objective is to establish biocriteria for the establishment of the Serra dos Orgaos Multimetric Index (SOMI) based on benthic macroinvertebrates. We used data from previous studies, sampled by experienced biologists, from 1999 through 2002. The benthic macroinvertebrate community was sampled in 12 reference sites and seven impaired sites in three river basins: Guapimirim, Macae and Grande, all from the same bioregion. From the 22 tested metrics, 6 were included in the SOMI (% Diptera, % Coleoptera, Family Taxa, EPT Taxa, BMWP-CETEC and % Shredders). Scores (5, 3 or 1) were developed for these metrics to allow for aggregation into the index. Seven intermediately impaired sites were used for evaluating the applicability of the multimetric index. We concluded that the SOMI is a robust easy-to-apply tool for biomonitoring programs in the Serra dos Orgaos region, south-east Brazil.

Journal ArticleDOI
TL;DR: The term "global health diplomacy" aims to capture these multi-level and multi-actor negotiation processes that shape and manage the global policy environment for health.
Abstract: Introduction "In the past"--said Robert Cooper, one of Europe's pre-eminent diplomats--"it was enough for a nation to look after itself. Today it is no longer sufficient." (1) This is particularly true in the health arena, There is an increasing range of health issues that transcend national boundaries and require action on the global forces that determine the health of people. The broad political, social and economic implications of health issues have brought more diplomats into the health arena and more public health experts into the world of diplomacy. Simple classifications of policy and politics--domestic and foreign, hard and soft, or high and low--no longer apply. (2) Diplomacy is frequently referred to as the art and practice of conducting negotiations. (3) It is usually still understood to mean the conduct of international relations through the intervention of professional diplomats from ministries of foreign affairs with regard to issues of "hard power", initially war and peace, and--as countries compete economically--economics and trade. But in recent years there has also been an increase in the number of international agreements on "soft issues", such as the environment and health; it is now recognized that some of these issues have significant "hard" ramifications on national economies. The term "global health diplomacy" aims to capture these multi-level and multi-actor negotiation processes that shape and manage the global policy environment for health. Global health diplomacy is at the coal-face of global health governance --it is where the compromises are found and the agreements are reached, in multilateral venues, new alliances and in bilateral agreements. It is a world to which outsiders find it difficult to relate, where the art of diplomacy juggles with the science of public health and concrete national interest balances with the abstract collective concern of the larger international community in the face of intensive lobbying and advocacy. No longer do diplomats just talk to other diplomats--they need to interact with the private sector, nongovernmental organizations, scientists, activists and the media, to name but a few, since all these actors are part and parcel of the negotiating process. Global health diplomacy is gaining in importance and its negotiators should be well prepared. Some countries have added a full-time health attache to their diplomatic staff in recognition of the importance and complexity of global health deliberations; others have added diplomats to the staff of international health departments. Their common challenge is to navigate a complex system in which issues in domestic and foreign policy intertwine the lines of power and constantly influence change, and where increasingly rapid decisions and skilful negotiations are required in the face of outbreaks of disease, security threats or other issues. Missions to the United Nations and international organizations--for example, in New York and Geneva--increasingly need to deal with health issues, as do the classical bilateral embassies. An important part of global health diplomacy still takes place within the World Health Organization; indeed it has recently gained new momentum through the negotiation during the past five years of the Framework Convention on Tobacco Control and the International Health Regulations. But the venue of global health diplomacy has shifted to include other spaces of negotiation and influence, and the number of organizations dealing with health has increased exponentially. At all levels we are witnessing a diversification of actors, the most illustrative development being the growth of public--private partnerships and platforms around a multitude of health issues, all clamouring for attention and funds. It is clear that the profound change underway requires new mechanisms and new skills for global health diplomacy. Yet an informal survey by the authors of staff of the international departments of health in countries that belong to the Organisation for Economic Co-operation and Development (OECD), in Latin America and of health attaches in Geneva has confirmed that many do not feel well prepared for the challenges that confront them. …

Journal ArticleDOI
TL;DR: The action of the main classes of compounds traditionally employed in Public Health is described, as well as the resistance mechanisms selected by vector populations.
Abstract: In Brazil, dengue is transmitted by Aedes aegypti. Aedes albopictus, a potential dengue vector, is spreading all over the country. The use of chemical insecticides is yet the main vector control component. The action of the main classes of compounds traditionally employed in Public Health is described, as well as the resistance mechanisms selected by vector populations. Alternative products, with potential to be used in the control of A. aegypti, including the biolarvicide Bti and some insect growth regulators, are also discussed. The authors aim at contributing with the rational insecticide use, taking into account the different components of the integrated control


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TL;DR: The presence of "full PTSD" was associated with evidences of considerable morbidity and may contribute to the development of effective policies aimed at the prevention and treatment of PTSD in law enforcement agents.

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TL;DR: PBDEs have been shown to reduce T4 concentrations in several studies, but this is the first study demonstrating endocrine disruption at low doses and the adipose tissue concentration of PBDE-99 measured in this study was close to those reported in non-occupationally exposed humans.

Journal ArticleDOI
TL;DR: This work presents a brief historic of the disease in Brazil, emphasizing the political strategies and programs for Aedes aegypti control since the urban yellow fever epidemics in the early 1900´s.
Abstract: A dengue tem se destacado como uma das mais importantes doencas reermegentes no mundo. No Brasil, a partir da decada de 1980, iniciou-se um processo de intensa circulacao viral, com epidemias explosivas que atingiram todas as regioes brasileiras. Atualmente, cerca de 70 por cento dos municipios brasileiros estao infestados pelo mosquito Aedes aegypti, vetor da doenca no Pais, onde circulam tres sorotipos do virus (DEN-1, DEN-2 e DEN-3). Este trabalho faz um breve relato do historico da dengue no Brasil, com enfase nas politicas e programas de controle do Aedes aegypti, desde as epidemias de febre amarela urbana do inicio do seculo XX. Os aspectos fundamentais do atual Programa Nacional de Controle da Dengue tambem sao mencionados.(AU) Dengue is presently one of the most important reemerging diseases in the world. In Brazil, since the 1980’s, there is an intense virus circulation with epidemic bursts affecting all the regions of the country. Nowadays, roughly 70% of the Brazilian municipalities are infested with the dengue vector, Aedes aegypti, and the serotypes DEN-1, DEN-2 and DEN-3 are circulating in the country. This work presents a brief historic of the disease in Brazil, emphasizing the political strategies and programs for Aedes aegypti control since the urban yellow fever epidemics in the early 1900´s. The basic aspects of the present Brazilian Dengue Control Program are also mentioned.(AU)