468 research outputs found
Ocular sequelae of congenital toxoplasmosis in Brazil compared with Europe
Toxoplasmic retinochoroiditis appears to be more severe in Brazil, where it is a leading cause of blindness, than in Europe, but direct comparisons are lacking. Evidence is accumulating that more virulent genotypes of Toxoplasma gondii predominate in South America
Can mothers rely on the Brazilian health system for their deliveries? An assessment of use of the public system and out-of-pocket expenditure in the 2004 Pelotas Birth Cohort Study, Brazil
<p>Abstract</p> <p>Background</p> <p>In a country where comprehensive free health care is provided via a public health system (SUS), an unexpected high frequency of catastrophic out-of-pocket expenditure has been described. We studied how deliveries were financed among mothers of a birth cohort and whether they were an important source of household out-of-pocket expenditure.</p> <p>Methods</p> <p>All deliveries occurring in the city of Pelotas, Brazil, during 2004, were recruited for a birth cohort study. All mothers were interviewed just after birth and three months later. Comprehensive data on the pregnancy, delivery, birth conditions and newborn health were collected, along with detailed information on expenses related to the delivery.</p> <p>Results</p> <p>The majority of the deliveries (81%) were financed by the public health system, a proportion that increased to more than 95% among the 40% poorest mothers. Less than 1% of these mothers reported some out-of-pocket expenditure. Even among those mothers covered by a private health plan, nearly 50% of births were financed by the SUS. Among the 20% richest, a third of the deliveries were paid by the SUS, 50% by private health plans and 17% by direct payment.</p> <p>Conclusion</p> <p>The public health system offered services in quantity and quality enough to attract even beneficiaries of private health plans and spared mothers from the poorest strata of the population of practically any expense.</p
The endothelium in the metabolic syndrome
The endothelium is responsible for the maintenance of vascular homeostasis. In physiological conditions it acts keeping vascular tonus, laminar blood flow, plasmatic membrane fluidity, the balance between coagulation and fibrinolysis and the inhibition of cellular proliferation, migration and the inflammatory response. Endothelial dysfunction is defined as an alteration of vascular relaxation induced by reduction of endothelium-derived relaxing factors (ERRFs), mainly nitric oxide. These abnormal vasomotor responses occur in the presence of various risk factors for atherosclerosis. The metabolic syndrome is considered a state of chronic inflammation accompanied of endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. This revision will encompass the physiological process of vascular function regulation, methods for in vivo assessment of endothelial dysfunction and therapies capable to improve vascular function and consequently minimize the cardiovascular risk due to metabolic syndrome.O endotélio é responsável pela manutenção da homeostase vascular. Em condições fisiológicas, mantém o tônus vascular, o fluxo sangüíneo laminar, a fluidez da membrana plasmática, o equilíbrio entre coagulação e fibrinólise, a inibição da proliferação e da migração celulares e o controle da resposta inflamatória. A disfunção endotelial é definida como uma alteração do relaxamento vascular por diminuição da biodisponibilidade de fatores de relaxamento derivados do endotélio, principalmente o óxido nítrico (NO). Estas respostas vasomotoras anormais ocorrem na presença de inúmeros fatores de risco para a aterosclerose. A síndrome metabólica é considerada um estado de inflamação crônica que se acompanha de disfunção endotelial e ocasiona aumento na incidência de eventos isquêmicos cardiovasculares e elevada mortalidade. Essa revisão abordará o processo fisiológico de regulação da função vascular pelo endotélio, os métodos disponíveis para avaliação in vivo da disfunção endotelial e as terapias capazes de melhorar a função vascular e conseqüentemente minimizar o risco cardiovascular dessa síndrome tão prevalente no nosso meio.29130
Target repurposing for neglected diseases
Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Future Science for personal use, not for redistribution. The definitive version was published in Future Medicinal Chemistry 3 (2011): 1307-1315, doi:10.4155/fmc.11.92.Infectious diseases are an enormous burden to global health, and since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal chemistry, structural biology, and biochemistry knowledge around these human targets can be directly repurposed to launch and accelerate new drug discovery efforts against the pathogen targets. This article describes the overarching strategy of target repurposing as a tool for initiating and prosecuting neglected disease drug discovery programs, highlighting this approach with three case studies.Support from the National Institutes of Health (R01 AI082577) is gratefully acknowledged.2012-08-0
Development of microsatelllte markers for the genetic analysis of Crinipellis perniciosa.
Witches' broom disease of cacao (Theobroma cacao L.), caused by Crinipellis perniciosa (Stahel) Singer, is the most importam disease of cacao in the cacao growing areas of South America and Caribbean Tslands. Very little is known about the genetic biology of the pathogen population, and this infonnation is very importam to the host improvement programs and deployment of resistant planting material. A collaborative America Countries intemational program was initiated to identify and describe the genetic diversity of Crinipellis perniciosa in South America. Microsatellites (SSR) constitute highly infonnative genetic markers for popuJation genetic studies due to their co-dominant and multiallelic nature and distribution in the genome. SSR primers were searched in the C.perniciosa genome data base and designed as potential candidates to define an efficient, standardized, molecular fingerprinting protocol for this pathogen. These primers have been evaluated for reliability, widespread disttibution across the C.perniciosa genome and their ability to discriminate isolates ofthis fungus. The final objective here is to study the diversity structure ofthe C. perniciosa population from the main cacao growing area in South America countries. Preliminary results are reported
Eukaryotic Protein Kinases (ePKs) of the Helminth Parasite Schistosoma mansoni
<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The <it>Schistosoma mansoni </it>genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the <it>S. mansoni </it>predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets.</p> <p>Results</p> <p>We have identified 252 ePKs, which corresponds to 1.9% of the <it>S. mansoni </it>predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that <it>S. mansoni </it>has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in <it>S. mansoni </it>or belong to an expanded family in this parasite. Only 16 <it>S. mansoni </it>ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite.</p> <p>Conclusions</p> <p>Our approach has improved the functional annotation of 40% of <it>S. mansoni </it>ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of <it>S. mansoni </it>in response to diverse environments during the parasite development, vector interaction, and host infection.</p
Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
Studies of micronuclei and other nuclear abnormalities in red blood cells of Colossoma macropomum exposed to methylmercury
The frequencies of micronuclei (MN) and morphological nuclear abnormalities (NA) in erythrocytes in the peripheral blood of tambaqui (Colossoma macropomum), treated with 2 mg.L−1 methylmercury (MeHg), were analyzed. Two groups (nine specimens in each) were exposed to MeHg for different periods (group A - 24 h; group B - 120 h). A third group served as negative control (group C, untreated; n = 9). Although, when compared to the control group there were no significant differences in MN frequency in the treated groups, for NA, the differences between the frequencies of group B (treated for 120 h) and the control group were extremely significant (p < 0.02), thus demonstrating the potentially adverse effects of MeHg on C. macropomum erythrocytes after prolonged exposure
Grazing, motives to eat palatable foods, and fat and sugar consumption: an exploratory investigation
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