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Search Results: 1 - 10 of 185 matches for " Coura "
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The state of the art of adeno-associated virus-based vectors in gene therapy
Renata Coura, Nance Nardi
Virology Journal , 2007, DOI: 10.1186/1743-422x-4-99
Abstract: The adeno-associated virus (AAV) is a small, icosaedral and nonenveloped virus that belongs to the parvovirus family, specifically the Dependovirus genus. The members of this genus require a helper virus, such as adenovirus or herpes simplex virus, to facilitate productive infection and replication. In the absence of a helper virus, AAVs establish a latent infection within the cell, either by site-specific integration into the host genome or by persisting in episomal forms. The wild AAV capsid has approximately 22 nm and encapsidates a linear single-stranded DNA genome of about 4.7 kb of either plus or minus polarity [1,2]. The AAV2 DNA termini consists of a 145 nucleotide-long inverted terminal repeat (ITR) that forms a characteristic T-shaped hairpin structure, due to the multipalindromic nature of its terminal 125 bases, which allows its fold on itself via complementary base pairing [3], forming a secondary structure that provides a free 3' hydroxyl group for the initiation of viral DNA replication [4]. This viral replication process relies on host cell polymerase activities, since AAV does not encode its own polymerase [5]. These ITRs are the only cis-acting elements required for genome replication and packaging, and flank the two large open reading frames (ORFs) of the virus genome. The left ORF, Rep (replication), encodes four replication proteins (Rep 78, Rep 68, Rep 52, and Rep 48), through the use of two different promoters and alternative splicing, responsible for site-specific integration, nicking, and helicase activity, as well as regulation of promoters within the AAV genome. The right ORF, Cap (capsid), encodes, through alternative mRNA splicing and alternative start codon usage, the three viral structural proteins (VP1, VP2 and VP3) that assemble at a ratio of approximately 1:1:10, respectively, to form a mature AAV particle [6].Following the establishment of the first infectious clone of AAV serotype 2 (AAV2) in 1982 [7] and the pioneering work on th
Epidemiological and control aspects of schistosomiasis in Brazilian endemic areas
Coura, JR;Amaral, RS;
Memórias do Instituto Oswaldo Cruz , 2004, DOI: 10.1590/S0074-02762004000900003
Abstract: the present work analyzes the epidemiology of schistosomiasis in brazil, its expansion, the attempts to control the disease, and the overall difficulties. the authors present the distribution of schistosomiasis intermediary hosts in brazil, the migration routes of the human population, and disease distribution in highly and lowly endemic areas and isolated foci. they also analyze the controlling programs developed from 1977 to 2002, indicating the prevalence evolution and the reduction of disease morbi-mortality. in addition, the authors also evaluate controlling methods and conclude that: (a) no isolated method is able to control schistosomiasis, and every controlling program should consider the need of a multidisciplinary application of existing methods; (b) in long term, basic sanitation, potable water supply, as well as sanitary education, and community effective participation are important for infection control; (c) in short term, specific treatment at endemic areas, associated with control of intermediary hosts at epidemiologically important foci, are extremely relevant for controlling disease morbidity, although not enough for interrupting infection transmission.
Chagas disease: what is known and what is needed - A background article
Coura, José Rodrigues;
Memórias do Instituto Oswaldo Cruz , 2007, DOI: 10.1590/S0074-02762007000900018
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 roma?a'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 car
Present situation and new strategies for Chagas disease chemotherapy: a proposal
Coura, José Rodrigues;
Memórias do Instituto Oswaldo Cruz , 2009, DOI: 10.1590/S0074-02762009000400002
Abstract: treatments for chagas disease have been administered since the first attempts by mayer & rocha lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. several diseases such as tuberculosis, leprosy and aids only came under control after they were treated with associations of drugs with different mechanisms of action. this not only boosts the action of the different compounds, but also may avoid the development of parasite resistance .to this end, over the short term, we propose experimental studies on laboratory animals and clinical trials with the following associations: (i) nifurtimox (8 mg/kg/day) + benznidazole (5 mg/kg/day) x 60 consecutive days; (ii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + allopurinol (8-10 mg/kg/day) x 60 days and (iii) nifurtimox (8 mg/kg/day) or benznidazole (5 mg/kg/day) + ketoconazole, fluconazole or itraconazole (5-6 mg/kg/day) x 60 consecutive days. the doses of the drugs and the treatment schedules for the clinical trials must be adapted according to the side effects. from these, other double or triple associations could be made, using drugs with different mechanisms of action. this proposal does not exclude investigations on new drugs over the median and long terms, targeting other aspects of the metabolism of trypanosoma cruzi. until such time as the ideal drug for specific treatment of chagas disease might be discovered, we need to develop new strategies for achieving greater efficacy with the old drugs in associations and to develop rational experimentation with new drugs.
Control of schistosomiasis in Brazil: perspectives and proposals
Coura, José Rodrigues;
Memórias do Instituto Oswaldo Cruz , 1995, DOI: 10.1590/S0074-02761995000200023
Abstract: attempts to control schistosomiasis have hitherto involved the use of one or more of the following methods, either in isolation or in combination: (1) control of the intermediate host using molluscicides or biological methods; (2) basic sanitation and clean water supply; (3) health education; (4) individual or mass treatment; (5) protection of individuals in such a way as to prevent cercariae from penetrating the skin; (6) vaccine-based strategies against schistosomiasis. none of these methods is capable, on its own, of bringing about effective control of schistosomiasis, except in populations of a very limited size or under very special conditions. molluscicides, besides expensive and toxic, have only a temporary effect. as for biological control, there is no effective method yet. basic sanitation and clean water supply combined with health education potentially constitute the most effective approach, but only in the mid-to-long term. mass treatment reduces morbidity, but does not control transmission. protection of individuals has proved to be impracticable on a large scale. vaccine-based strategies against schistosomiasis are still in the experimental stage. experiments carried out in brazil in the last 20 years have shown that mass treatment with single doses of oxamniquine or praziquantel can rapidly reduce levels of shistosoma mansoni infection and morbidity in endemic areas. they have also shown that subsequent transmission and reinfection frequently occur in defined foci or "clusters", due to human contact with water, and in inverse proportion to the number and frequency of treatments carried out. on the basis of these experiments, the author suggests a multidisciplinary strategy for schistosomiasis control.
Uso do paradigma de risco para a esquistossomose em áreas endêmicas no Brasil
Coura-Filho, Pedro;
Cadernos de Saúde Pública , 1994, DOI: 10.1590/S0102-311X1994000400006
Abstract: this study shows the results of risk factor determination for infection with schistosoma mansoni in endemic areas in brazil. an association was observed between infection with s. mansoni and a number of general conditions: absence of drinking water in the home, low individual income, illiteracy, and residence in an endemic area for more than five years. in addition to these conditions there was also association with a number of habits (risk factors): agricultural and domestic activities in open water supplies, swimming, and fishing. analysis of the general conditions that may determine these risk factors indicated that provision of drinking water in the home and access to treatment are basic measures that could be adopted in many cases in order to prevent or control the morbidity of the disease. the efficacy of the use of risk factor determination for indication of control measures for this disease is questioned.
O falso dilema sobre a luta antivetorial e as perspectivas de controle da doen?a de Chagas no Brasil: BHC ou BNH?
Coura, José R.;
Cadernos de Saúde Pública , 1993, DOI: 10.1590/S0102-311X1993000400013
Abstract: the technical basis for the control of chagas' disease in brazil was established with the creation of the oswaldo cruz institute's research center in bambuí, in western minas gerais, at the beginning of the 1940's, under the leadership of emmanuel dias. however, only with the creation of the national department for rural endemic diseases, in march 1956, did control of rural endemic diseases become systematic in brazil. from the 1960's onwards, the chagas' disease control program in brazil started to suffer from postponements and lack of systematic action: first because the priority ascribed to the malaria control program, since this was an acute, "explosive" disease that was hampering land settlement and development in the interior; second the "new ecologists" began calling for "bnh" (referring to the initials for the national low-cost housing program) and not "bhc" (insecticides program) for chagas' disease control, ignoring a number of issues and difficulties; and third, other priorites given to the special program for schistosomiasis control and the meningococcal meningitis epidemic in the 1970's and the dengue epidemic in the 1980's. in 1983, however, a new phase in chagas' disease control began, with the allocation of ten billion cruzeiros from finsocial for this program which covered two thousand municipalities, in 19 brazilian states, to the benefit of 47 million people potentially at risk. finally it was concluded that in the short term, insecticide spraying is the most effective and manageable control measure against natural transmission of chagas' infection. other methods of control and urbanization of chagas' disease are also discussed.
Endemias e meio ambiente no século XXI
Coura, José R.;
Cadernos de Saúde Pública , 1992, DOI: 10.1590/S0102-311X1992000300012
Abstract: in the introduction the autor defines health as the "adaptation of man to environment, preserving his physical, functional, mental and social integrity". he extends the concept of development to "good living conditions, including food, housing, education, health care, social welfare, security, recreation, safety, and freedom". the relationship between development and health is associated with natural and artificial resources and environments and with human behaviours such as population growth, crowding and migrations. man is "nature's host and his own victim". although the 1978 alma-ata conference predicted "health for all by the year 2000", the world's health deteriorated in the last decade because of the economic crisis and a population increase of about one billion persons that could not be matched by sendees such as health, education, transportation, food, housing and social security. infectious diseases are responsible for 34% of deaths in the developing world and only 1% in developed countries. yearly, 15 million children die from infectious diseases and/or malnutrition and 93% of avoidable deaths occur in the developing countries. there is no direct correlation between economic development and health quality; it depends on health and social organization.
Abordagens alternativas no controle da esquistossomose: buscando incluir o subjetivo na epidemiologia
Coura-Filho, Pedro;
Cadernos de Saúde Pública , 1996, DOI: 10.1590/S0102-311X1996000100021
Abstract: this study discusses the possibility of integrating the "subjective" in epidemiological research. alternative approaches are presented for programs to provide health and educational services, as well as others which are the right of citizens to receive and the responsibility of the government to provide. the characteristics of participatory research, community-based epidemiology, and popular education programs are described, with the purpose of constructing a model for the control of schistosomiasis using alternative methodologies, including in the model the perceptions and life styles of populations exposed to schistosoma mansoni. the federal government is indicated as the institution to provide the material conditions necessary to form a citizenry with the collective will to control schistosomiasis.
Distribui??o da esquistossomose no espa?o urbano. 2. Aproxima??o teórica sobre a acumula??o, concentra??o, centraliza??o do capital e a produ??o de doen?as
Coura-Filho, Pedro;
Cadernos de Saúde Pública , 1997, DOI: 10.1590/S0102-311X1997000300017
Abstract: this study discusses the urbanization of schistosomiasis in the greater metropolitan area of belo horizonte, minas gerais, brazil. the observation that schistosomiasis has become endemic in an urban area is discussed using the concept of social organization of space as an exercise in providing an operational basis for the social and environmental paradigms of collective health. elements from the new world economic order are discussed: the concept of socially constructed space, the internationalization of capital, the periphery, and the resulting collective disease generation process. due to the deterioration of state health services and the logic of the new world economic order, the need for local schistosomiasis control solutions is stressed.
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