Cholera toxin

霍乱毒素
  • 文章类型: Journal Article
    霍乱是一种急性,由霍乱弧菌O1或139引起的腹泻病与高全球负担有关。
    我们从现有的已发表的研究中分析了霍乱感染后免疫的估计持续时间。我们搜索了PubMed和WebofScience,以研究霍乱感染后的长期免疫力。我们确定了22项符合条件的研究,并将其归类为观察性,挑战,或血清学。
    我们在观察和攻击研究中发现了感染后3年保护的有力证据。然而,血清学研究表明,体液标记物的潜在保护作用在1年内恢复到基线水平.此外,亚临床霍乱感染可能比临床霍乱提供更低的保护,正如3项研究表明的那样,尽管样本量很小,大多数因霍乱初次攻击而出现亚临床感染的参与者在接受同源生物型再次攻击时出现有症状的感染.
    这篇综述强调了阐明临床和亚临床霍乱感染所提供保护的潜在差异的必要性。Further,有必要进行更多的研究来弥合保护和霍乱免疫之间的差距.了解霍乱自然免疫的持续时间可以帮助指导控制策略和政策。
    Cholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden.
    We analyzed the estimated duration of immunity following cholera infection from available published studies. We searched PubMed and Web of Science for studies of the long-term immunity following cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological.
    We found strong evidence of protection at 3 years after infection in observational and challenge studies. However, serological studies show that elevated humoral markers of potential correlates of protection returned to baseline within 1 year. Additionally, a subclinical cholera infection may confer lower protection than a clinical one, as suggested by 3 studies that found that, albeit with small sample sizes, most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype.
    This review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.
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  • 文章类型: Journal Article
    OBJECTIVE: The oral rehydration solution is the most efficient method to treat cholera; however, it does not interfere in the action mechanism of the main virulence factor produced by Vibrio cholerae, the cholera toxin (CT), and this disease still stands out as a problem for human health worldwide. This review aimed to describe therapeutic alternatives available in the literature, especially those related to the search for molecules acting upon the physiopathology of cholera.
    RESULTS: New molecules have offered a protection effect against diarrhoea induced by CT or even by infection from V. cholerae. The receptor regulator cystic fibrosis channel transmembrane (CFTR), monosialoganglioside (GM1), enkephalinase, AMP-activated protein kinase (AMPK), inhibitors of expression of virulence factors and activators of ADP-ribosylarginine hydrolase are the main therapeutic targets studied. Many of these molecules or extracts still present unclear action mechanisms.
    CONCLUSIONS: Knowing therapeutic alternatives and their molecular mechanisms for the treatment of cholera could guide us to develop a new drug that could be used in combination with the rehydration solution.
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  • 文章类型: Journal Article
    Genetic engineering revolutionized the concept of traditional vaccines since subunit vaccines became reality. Additionally, over the past two decades plant-derived antigens have been studied as potential vaccines with several advantages, including low cost and convenient administration. More specifically, genetic fusions allowed the expression of fusion proteins carrying two or more components with the aim to elicit immune responses against different targets, including antigens from distinct pathogens or strains. This review aims to provide an update in the field of the production of plant-based vaccine, focusing on those approaches based on the production of chimeric proteins comprising antigens from human pathogens, emphasizing the case of cholera toxin/E. coli enterotoxin fusions, chimeric viruses like particles approaches as well as the possible use of adjuvant-producing plants as expression hosts. Challenges for the near future in this field are also discussed.
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  • 文章类型: Journal Article
    Cholera toxin (Ctx) from Vibrio cholerae and its closely related homologue, heat-labile enterotoxin (Etx) from Escherichia coli have become superb tools for illuminating pathways of cellular trafficking and immune cell function. These bacterial protein toxins should be viewed as conglomerates of highly evolved, multi-functional elements equipped to engage the trafficking and signalling machineries of cells. Ctx and Etx are members of a larger family of A-B toxins of bacterial (and plant) origin that are comprised of structurally and functionally distinct enzymatically active A and receptor-binding B sub-units or domains. Intoxication of mammalian cells by Ctx and Etx involves B pentamer-mediated receptor binding and entry into a vesicular pathway, followed by translocation of the enzymatic A1 domain of the A sub-unit into the target cell cytosol, where covalent modification of intracellular targets leads to activation of adenylate cyclase and a sequence of events culminating in life-threatening diarrhoeal disease. Importantly, Ctx and Etx also have the capacity to induce a wide spectrum of remarkable immunological processes. With respect to the latter, it has been found that these toxins activate signalling pathways that modulate the immune system. This review explores the complexities of the cellular interactions that are engaged by these bacterial protein toxins, and highlights some of the new insights to have recently emerged.
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  • 文章类型: Journal Article
    OBJECTIVE: To analyze the distribution of thyroid goiters into the mediastinum and/or behind or along the sides of the pharynx, and to review the anatomy of the spaces in the neck that explains these extensions.
    METHODS: We used a 28-month period, to retrospectively identify 190 cases of neck goiters that underwent computed tomographic imaging. The maximal size of a normal thyroid gland and the limits of the normal thyroid bed were defined on the basis of established anatomic measurements. Standard definitions of the mediastinum and its compartments were also used. Each case was reviewed by 3 radiologists, and extension of the thyroid gland into the mediastinum or cranially behind or along the sides of the pharynx was noted. All cases were correlated with clinical observations.
    RESULTS: Of the 190 goiters, 106 (55.8%) were confined to the thyroid bed, 70 (36.8%) extended into the mediastinum, and 14 (7.4%) extended behind or along the sides of the pharynx. All 70 cases that extended into the mediastinum involved the anterior mediastinum, and 5 (7.1%) of these extended into the posterior mediastinum.
    CONCLUSIONS: Goiterous extension outside of the thyroid bed occurred in 84 (44.2%) of cases. Although extension cranially behind the pharynx is uncommon, the physician should be aware of this diagnosis and the fascial anatomy that explains its occurrence. All of the goiters that were in the posterior mediastinum also had a component in the anterior mediastinum.
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  • 文章类型: Case Reports
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    文章类型: Journal Article
    Much progress has been made in developing vaccines against the most important enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin, each conferred 50-53% protection over three years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in less developed countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. In experimental challenge studies in volunteers, a single dose of CVD 103-HgR confers significant protection against challenge with wild-type V. cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa serotype. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. A multivalent rotavirus vaccine (rhesus reassortant vaccine) is undergoing extensive field testing in developed and less developed countries.
    The development of safe, effective vaccines to prevent diseases due to rotavirus, enterotoxigenic Escherichia coli, enteropathogenic E. coli, Shigella, and Vibrio cholerae O1 would markedly reduce the burden of diarrheal diseases in Third World countries. This review concentrates on vaccines that have already been licensed, that have been evaluated in controlled trials of efficacy, or that have entered clinical trials to assess their safety and immunogenicity. Two new vaccines against typhoid fever have been licensed. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Inactivated oral cholera vaccines consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin conferred 50-53% protection in a field trial in Bangladesh. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated and highly immunogenic after a single oral dose. In experimental challenge studies, a single dose of CVD 103-HgR conferred significant protection against challenge with wild-type V. cholerae O1. Several candidate vaccines against Shigella and enterotoxigenic E. coli are in clinical trials. Finally, a multivalent rotavirus vaccine (rhesus reassortant) is undergoing extensive field testing.
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    文章类型: Journal Article
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    文章类型: Journal Article
    This report reviews the work of other investigators regarding Aeromonas toxins and describes work conducted in our laboratory relating to the biochemical characterization of a cytolytic factor with an antigenic moiety that cross-reacts with cholera toxin (referred to as CTC-cytolysin), as well as the purification and partial characterization of a non-CTC enterotoxin. These two toxins were produced by Aeromonas hydrophila, isolate SSU, and are capable of causing fluid accumulation in animal models.
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