RESUMO
Chytridiomycosis is affecting amphibians worldwide, causing the decline and extinction of several amphibian populations. The disease is caused by the fungus Batrachochytrium dendrobatidis (Bd), a multihost pathogen living in freshwater habitats. While several environmental factors have been associated with the prevalence of Bd and its virulence, the effects of water quality on the pathogen are not clear yet. Some evidence suggests that water pollution may reduce amphibians' immune response and increase prevalence of Bd. To explore this hypothesis, we analyzed the relationship between water quality and the presence of Bd by using spatial data mining of 150 geolocations of Bd in amphibians from 9 families where Bd positive specimens have been previously reported, and water quality in 4,202 lentic and lotic water bodies in Mexico from 2010 to 2021. Our model showed that in the 3 main families where Bd was recorded, its presence is high in locations with low water quality, i.e., water polluted likely contaminated with urban and industrial waste. Using this model, we inferred areas suitable for Bd in Mexico; mainly in poorly studied areas along the gulf and on the pacific slope. We further argue that actions to reduce water pollution should become an integral part of public policies to prevent the spread of Bd and protect amphibians from this deadly pathogen.
Assuntos
Quitridiomicetos , Micoses , Humanos , Animais , México/epidemiologia , Ecossistema , Batrachochytrium , Micoses/epidemiologia , Micoses/veterinária , Micoses/microbiologia , Anfíbios/microbiologia , Poluição da Água/efeitos adversosRESUMO
Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.
Assuntos
Amidinas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Parasitemia/tratamento farmacológico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Amidinas/química , Animais , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Masculino , Camundongos , Parasitemia/mortalidade , Parasitemia/parasitologia , Testes de Sensibilidade Parasitária , Tripanossomicidas/químicaRESUMO
We extend a recently developed method for constructing ecological networks to infer potential biotic interactions between species and to also include environmental factors, in particular land cover, thus permitting a simultaneous analysis of the interaction between environment and species distribution as well as inter-species interactions. We apply the method to the transmission and dispersal of leishmaniasis in Mexico. We find that the most important potential vectors and reservoirs can be classified into assemblages associated with different types of habitat. This in turn can be used to understand and map potential transmission risk, as well as to construct risk scenarios for the dispersal of disease from one geographical region to another.
Assuntos
Reservatórios de Doenças/veterinária , Ecossistema , Leishmaniose/epidemiologia , Leishmaniose/transmissão , Modelos Biológicos , Zoonoses/epidemiologia , Animais , Vetores Artrópodes/fisiologia , Demografia , Humanos , Mamíferos , México/epidemiologia , Especificidade da EspécieRESUMO
Due to limited efficacy and considerable toxicity, the therapy for Chagas' disease is far from being ideal, and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829), eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one guanylhydrazone (DB1080) were assayed in thermal denaturation (T(m)) and circular dichroism (CD) studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative of minor groove binding. Our findings showed that some of the compounds that exhibited the highest trypanocidal activities (e.g., DB766) caused low or no change in the T(m) measurements. However, while some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like DB1831, although effective, did not result in altered T(m) and CD measurements. Our data suggest that the strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final evaluation of the mechanisms of action of these compounds.
Assuntos
Amidinas/metabolismo , Amidinas/farmacologia , DNA de Cinetoplasto/metabolismo , Tripanossomicidas/metabolismo , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Amidinas/química , Sequência Conservada , DNA de Cinetoplasto/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Termodinâmica , Tripanossomicidas/químicaRESUMO
Aromatic diamidines represent a class of DNA minor groove-binding ligands that exhibit high levels of antiparasitic activity. Since the chemotherapy for Chagas' disease is still an unsolved problem and previous reports on diamidines and related analogues show that they have high levels of activity against Trypanosoma cruzi infection both in vitro and in vivo, our present aim was to evaluate the cellular effects in vitro of three reversed amidines (DB889, DB702, and DB786) and one diguanidine (DB711) against both amastigotes and bloodstream trypomastigotes of T. cruzi, the etiological agent of Chagas' disease. Our data show that the reversed amidines have higher levels of activity than the diguanidine, with the order of trypanocidal activities being as follows: DB889 > DB702 > DB786 > DB711. Transmission electron microscopy analysis showed that the reversed amidines induced many alterations in the nuclear morphology, swelling of the endoplasmic reticulum and Golgi structures, and consistent damage in the mitochondria and kinetoplasts of the parasites. Interestingly, in trypomastigotes treated with the reversed amidine DB889, multiple axoneme structures (flagellar microtubules) were noted. Flow cytometry analysis confirmed that the treated parasites presented an important loss of the mitochondrial membrane potential, as revealed by a decrease in rhodamine 123 fluorescence. Our results show that the reversed amidines have promising activities against the relevant mammalian forms of T. cruzi and display high trypanocidal effects at very low doses. This is especially the case for DB889, which merits further in vivo evaluation.
Assuntos
Amidinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/ultraestrutura , Amidinas/química , Animais , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Furanos/farmacologia , Guanidina/análogos & derivados , Guanidina/farmacologia , Concentração Inibidora 50 , Microscopia Eletrônica de Transmissão , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/química , Células VeroRESUMO
Parasitic infections are widespread in developing countries and frequently associated with immunocompromised patients in developed countries. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need for the development of new antiparasitic compounds, mostly due to the large number of drug-resistant parasites and the fact that currently available drugs are expensive, highly toxic, require long treatment regimens and frequently exhibit significantly reduced activity towards certain parasite strains and evolutive stages. In this context, the activity of aromatic diamidines has been explored against a widespread range of micro-organisms, and the authors' present aim is to review the current status of chemotherapy with these compounds against human parasitic infections.
Assuntos
Antiparasitários/uso terapêutico , Drogas em Investigação/uso terapêutico , Doenças Parasitárias/tratamento farmacológico , Pentamidina/análogos & derivados , Pentamidina/uso terapêutico , Animais , Antiparasitários/química , Drogas em Investigação/química , Humanos , Doenças Parasitárias/parasitologiaRESUMO
OBJECTIVE: Investigate the environmental conditions in and the state of health of women who live in rural communities surrounded by oil wells and oil production stations in the Amazon region of Ecuador. METHOD: We used a comparative cross-sectional design, classifying exposure according to the location of the communities with respect to the oil wells and production stations. Water samples from the local rivers were analyzed to determine total petroleum hydrocarbons, and a structured questionnaire was used with the head of each family in the study. The study was performed in rural communities in northeastern Ecuador from November 1998 through April 1999. The study included 9 communities in the exposed area (368 participants) and 14 communities in the unexposed area (291 participants). RESULTS: The rivers of the exposed communities showed contamination levels much above the limits acceptable for human use. Statistically significant differences between the exposed communities and the unexposed communities were found for the prevalence of skin fungi for the two weeks prior to the study (odds ratio (OR) = 1.37; 95% confidence interval (CI) = 1.01-1.86) as well as for nasal irritation (OR = 2.18, 95% CI = 1.64-2.91) and for throat irritation (OR = 1.68, 95% CI = 1.02-2.75) in the preceding 12 months. Also associated with exposure in the two preceding weeks were fatigue and the category of "other symptoms"; similarly associated with exposure in the preceding 12 months were headaches, eye irritation, earaches, diarrhea, and gastritis. CONCLUSIONS: The symptoms found among the participants in the exposed communities match the toxicity symptoms caused by oil. There is an urgent need to establish an adequate environmental control and remediation program in order to prevent unnecessary and unacceptable health hazards for these populations.
Assuntos
Indústria Química , Exposição Ambiental/efeitos adversos , Nível de Saúde , Petróleo , Saúde da População Rural , Adolescente , Adulto , Estudos Transversais , Equador , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Poluição da Água/análiseRESUMO
OBJECTIVES: To examine environmental exposure and incidence and mortality of cancer in the village of San Carlos surrounded by oil fields in the Amazon basin of Ecuador. METHODS: Water samples of the local streams were analyzed for total petroleum hydrocarbons (TPHs). A preliminary list of potential cancer cases from 1989 to 1998 was prepared. Cases were compared with expected numbers of cancer morbidity and mortality registrations from a Quito reference population. RESULTS: Water analysis showed severe exposure to TPHs by the residents. Ten patients with cancer were diagnosed while resident in the village of San Carlos. An overall excess for all types of cancer was found in the male population (8 observed v 3.5 expected) with a risk 2.26 times higher than expected (95% confidence interval (95% CI) 0.97 to 4.46). There was an overall excess of deaths for all types of cancer (6 v 1.6 expected) among the male population 3.6 times higher than the reference population (95% CI 1.31 to 7.81). CONCLUSIONS: The observed excess of cancer might be associated with the pollution of the environment by toxic contaminants coming from the oil production.
Assuntos
Exposição Ambiental/efeitos adversos , Indústrias Extrativas e de Processamento , Hidrocarbonetos/efeitos adversos , Neoplasias/epidemiologia , Poluição Química da Água/efeitos adversos , Adulto , Idoso , Pré-Escolar , Equador/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Hidrocarbonetos/análise , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Petróleo/efeitos adversos , Poluição Química da Água/análiseRESUMO
We argue that an induced breaking of the genetic synonym symmetry due to the action of genetic operators such as mutation can enhance the adaptability of a species to changes in the environment. In the case of a virus, the claim is that the codon bias in the neutralization epitope improves the virus' ability to generate mutants that evade the induced immune response. We support our claim with a simple 'toy model' of a viral epitope evolving in competition with the immune system. The effective selective advantage of a higher mutability leads to a dominance of codons that favor non-synonymous mutations. As further evidence we present a simple model for a genetic regulatory network that leads to adaptive evolution in a population of giraffes by means of an induced symmetry breaking rather than through any direct selective advantage.
Assuntos
Cromossomos/genética , Evolução Molecular , Modelos Genéticos , Mutação/genética , Vírus/genética , Adaptação Fisiológica , Aminoácidos/genética , Animais , Códon/genética , Simulação por Computador , Fractais , Expressão Gênica , Variação Genética , Genótipo , Humanos , Sistema Imunitário/fisiologia , Modelos Teóricos , Fenótipo , Vírus/imunologiaRESUMO
PIP: This paper presents the research methodology that applied existing data to the study of environmental and health inequalities in Accra, Ghana, and Sao Paulo, Brazil. After an introductory section, the paper considers why more research in this area is necessary and the reasons why information on cities in the South is lacking. The third section describes the aims and methods of the study by 1) looking at the development of the methodology, a form of descriptive epidemiology that uses existing data on morbidity and mortality rates to explore and describe the intra-urban distribution of health and environmental conditions in each location; 2) discussing the creation of an index of socioenvironmental deprivation based on judgements about the validity and quality of data on various socioeconomic and environmental indicators made by working groups in each location; and 3) reviewing data collection techniques and problems with data quality. Section 4 summarizes the results of the study by first noting that the study proved that existing data can be used to identify the extent of intra-urban differentials in environmental and health conditions and then presenting the results of the data analysis that exposed the myth of urban benefits by revealing the unequal distribution of socioeconomic conditions and exposed the myth of urban health by revealing the inequalities in life chances between groups in each setting. The concluding section explores the relevance of these results in environmental and health terms. A main achievement of the study was to introduce a method that allowed planners and policy-makers to work together to devise complex definitions of deprivation using existing data and to use the resulting information for actual decision-making to reduce inequalities.^ieng
Assuntos
Fatores Etários , Meio Ambiente , Saúde , Formulação de Políticas , Pesquisa , Fatores de Risco , Fatores Socioeconômicos , População Urbana , Urbanização , África , África Subsaariana , África Ocidental , América , Biologia , Brasil , Demografia , Países em Desenvolvimento , Economia , Geografia , Gana , Planejamento em Saúde , América Latina , Organização e Administração , População , Características da População , América do SulRESUMO
This article addresses the development of data linkage methods for the analysis of urban environmental health problems and the development of appropriate policies and discusses, based on existing experience of data linkage in São Paulo (Brazil), the potential for routine environmental health monitoring and management in a major developing country industrial centre. The article looks briefly at two major environmental health problems in São Paulo: first, air pollution which has potential impacts on health of the whole population; and second, environmental differentials in conditions between groups within cities, which have substantial health effects on the economically deprived. The article argues that the health impact of environmental differentials in São Paulo is large, but unmonitored as a serious environmental health threat. In contrast, air pollution is monitored routinely, although its health effects are relatively small at present. The paper concludes with a discussion of policy implications of environmental health monitoring--which potentially require a substantial shift in attitudes of the urban wealthy.
Assuntos
Países em Desenvolvimento , Exposição Ambiental/estatística & dados numéricos , Monitoramento Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Morbidade , Formulação de Políticas , Saúde da População Urbana/estatística & dados numéricos , Poluição do Ar/prevenção & controle , Poluição do Ar/estatística & dados numéricos , Viés , Brasil/epidemiologia , Coleta de Dados , Interpretação Estatística de Dados , Exposição Ambiental/prevenção & controle , Poluição Ambiental/prevenção & controle , Monitoramento Epidemiológico , Humanos , Fatores SocioeconômicosRESUMO
A project concerned with the study of intra-urban health differentials in S. Paulo city, Brazil, is described. A brief outline of urban problems in the city is presented, followed by a review of the locally published literature on the subject of geographical differentials (stratification by socioeconomic status and environment). Two topics are introduced: geographical subdivision of the area studied and the methods used to choose the socio-environmental indicators for the construction of a deprivation index with to stratify the city. Suggestions are made as to possible applications of results achieved by the project.