Página 1 dos resultados de 437 itens digitais encontrados em 0.004 segundos

Resistance of schistosomes to hycanthone and oxamniquine

Cioli,Donato; Pica-Mattoccia,Livia; Archer,Sydney
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/1989 EN
Relevância na Pesquisa
37.57%
Genetic crosses between phenotypically resistant and sensitive schistosomes demonstrated that resistance to hycanthone and oxamniquine behaves like a recessive trait, thus suggesting that resistance is due to the lack of some factor. We hypothesized that, in order to kill schistosomes, hycanthone and oxamniquine need to be converted into an active metabolite by some parasite enzyme wich, if inactive, results in drug resistance. Esterification of the drugs seemed to be the most likely event as it would lead to the production of an alkylating agent upon dissociation of the ester. An artificial ester of hycanthone was indeed active even in resistant worms, thus indirectly supporting our hypothesis. In addition, several lines of evidence demonstrated that exposure to hycanthone and oxamniquine results in alkylation of worm macromolecules. Thus, radioactive drugs formed covalent bonds with the DNA of sensitive (but not of resistant) schistosomes; an antiserum raised against hycanthone detected the presence of the drug in the purified DNA fraction of sensitive (but not of resistant) schistosomes; a drug-DNA adduct was isolated from hycanthone-treated worms and fully characterized as hycanthone-deoxyguanosine.

The p53 gene expression and its developmental regulation in schistosomes

Tanaka,Manami; Matsu-Ura,Tadashi; Hirai,Hirohisa
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/1992 EN
Relevância na Pesquisa
37.37%
We have studied the gene expression, especially of the oncoproteins, and its regulation in schistosomes. Schistosomes have a complex life cycle with defined dimorphic lifestyle. The parasite are so far unique in biology in expressing oncogene products in their adult stage. In order to characterize the expression and developmental regulation, a lambda gt 11 cDNA library and lambda EMBL4 genomic DNA library of each growth stage of Schistosoma mansoni and S. japonicum was constructed, and was screened with various monoclonal antibodies against ongogene products. One positive plaque reacted to anti-p53 antibody (Ab-2, Oncogene Science, Inc.) was further analyzed. This fusion protein was about 120 KDa in molecular weights, and expressed as 1.4 Kb RNA in the adult stage. P53 gene is well-known as the negative regulator of the cell cicle, and the mutations in the gene are turning out to be the most common genetic alterations in human cancers. The comparison of the gene structure among species and stages were being conducted. Chromosome structures, C-band formation, and the results of in situ hybridization using the phage probe would be discussed.

DNA polymorphism of schistosomes and their snail hosts

Simpson,Andrew J. G.; Dias Neto,Emmanuel; Vidigal,Teofania H. D. A.; Pena,Heloísa B.; Carvalho,Omar S.; Pena,Sergio D. J.
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/1995 EN
Relevância na Pesquisa
37.2%
Analysis of the genomes of schistosomes and one of their intermediate hosts, Biomphalaria glabrata, using Random Amplified Polymorphic DNA (RAPD) demonstrated that intraspecific genetic polymorphism in the parasite is limited but in the snail is highly pronounced. This suggests an important role for the snail in the determination of the epidemiology of the disease. In addition to their intraspecific stability, schistosome derived RAPDs exhibit a high level of interspecific polymorphism and are thus ideal for the construction of phylogenetic trees. For the detection of intraspecific polymorphisms extensive variation in the mitochondrial DNA is being exploited for the development of a PCR based test for Schistosoma mansoni. Gene level polymorphisms are being analyzed by Low Stringency Single Specific Primer PCR.

Chromatin regulation in schistosomes and histone modifying enzymes as drug targets

Pierce,Raymond John; Dubois-Abdesselem,Florence; Caby,Stéphanie; Trolet,Jacques; Lancelot,Julien; Oger,Frédérik; Bertheaume,Nicolas; Roger,Emmanuel
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2011 EN
Relevância na Pesquisa
27.2%
Only one drug is currently available for the treatment and control of schistosomiasis and the increasing risk of selecting strains of schistosome that are resistant to praziquantel means that the development of new drugs is urgent. With this objective we have chosen to target the enzymes modifying histones and in particular the histone acetyltransferases and histone deacetylases (HDAC). Inhibitors of HDACs (HDACi) are under intense study as potential anti-cancer drugs and act via the induction of cell cycle arrest and/or apoptosis. Schistosomes like other parasites can be considered as similar to tumours in that they maintain an intense metabolic activity and rate of cell division that is outside the control of the host. We have shown that HDACi can induce apoptosis and death of schistosomes maintained in culture and have set up a consortium (Schistosome Epigenetics: Targets, Regulation, New Drugs) funded by the European Commission with the aim of developing inhibitors specific for schistosome histone modifying enzymes as novel lead compounds for drug development.

Towards an understanding of the epigenetics of schistosomes: a comparative epigenomic study

Lepesant,Julie Mireille Joé; Grunau,Christoph; Cosseau,Céline
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2011 EN
Relevância na Pesquisa
27.2%
As in perhaps all eukaryotes, schistosomes use a supplementary information transmitting system, the epigenetic inheritance system, to shape genetic information and to produce different phenotypes. In contrast to other important parasites, the study of epigenetic phenomena in schistosomes is still in its infancy. Nevertheless, we are beginning to grasp what goes on behind the epigenetic scene in this parasite. We have developed techniques of native chromatin immunoprecipitation (N-ChIP) and associated the necessary bioinformatics tools that allow us to run genome-wide comparative chromatin studies on Schistosoma mansoni at different stages of its life cycle, on different strains and on different sexes. We present here an application of such an approach to study the genetic and epigenetic basis for a phenotypic trait, the compatibility of S. mansoni with its invertebrate host Biomphalaria glabrata. We have applied the ChIP procedure to two strains that are either compatible or incompatible with their intermediate host. The precipitated DNA was sequenced and aligned to a reference genome and this information was used to determine regions in which both strands differ in their genomic sequence and/or chromatin structure. This procedure allowed us to identify candidate genes that display either genetic or epigenetic difference between the two strains.

5-Octadecenoic acid: evidence for a novel type of fatty acid modification in schistosomes.

Brouwers, J F; Versluis, C; van Golde, L M; Tielens, A G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/09/1998 EN
Relevância na Pesquisa
27.37%
The lipid metabolism of schistosomes is characterized by several intriguing adaptations to a parasitic way of living. The surface of the parasite consists of two closely apposed phospholipid bilayers, a structure unique to blood flukes. Schistosomes do not synthesize fatty acids de novo, but are able to modify fatty acids, which they obtain from the host, by chain elongation. Here we present evidence that schistosomes are capable of another type of fatty acid modification, resulting in the formation of 5-octadecenoic acid [C18:1(5)]. This highly unusual fatty acid, which is absent in the blood of the host, was shown to be almost exclusively located in the outer membrane complex of the schistosome. Within these membranes, it was almost exclusively present in one molecular phospholipid species, 1-palmitoyl-2,5-octadecenoyl phosphatidylcholine [C16:0-18:1(5)PtdCho]. Apart from dipalmitoyl phosphatidylcholine, this was the most abundant phosphatidylcholine species in the outer membrane complex. The specific synthesis by the schistosome of C18:1(5) and the highly specific localization of this fatty acid to the tegumental membranes suggest an important tegument-mediated role for this lipid.

Two Isoforms of a Divalent Metal Transporter (DMT1) in Schistosoma mansoni Suggest a Surface-associated Pathway for Iron Absorption in Schistosomes*

Smyth, Danielle J.; Glanfield, Amber; McManus, Donald P.; Hacker, Elke; Blair, David; Anderson, Greg J.; Jones, Malcolm K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.2%
We describe two homologues of the mammalian divalent metal transporter (DMT1) for Schistosoma mansoni, a pathogenic intravascular parasite of humans. Schistosomes have a high nutritional and metabolic demand for iron. Nucleotide sequences of the parasite homologues, designated SmDMT1A and -B, are identical in all but the 5′-regions. The predicted amino acid sequences share at least 60% identity with DMT1 (=Nramp2) of humans, mice, and rats, and at least 55% identity with Nramp1 from mice, humans and Caenorhabditis elegans. SmDMT1A is expressed in differentiating eggs, miracidia, cercariae, schistosomula, and adults, whereas SmDMT1B is expressed in all but the miracidium and occurs at lower levels than SmDMT1A in differentiating eggs and cercariae. An iron-responsive element, present at the 3′-untranslated region of many DMT1 molecules, is not present in schistosome mRNAs studied here. A Western blot analysis of adult worm preparations using a homologous rabbit serum raised against a schistosome DMT1 peptide and a heterologous serum raised against mammalian DMT1, revealed a band approximating 115 kDa. By immunofluorescence microscopy, the schistosome DMT1s localize primarily to the tegument. Iron uptake assays demonstrated that SmDMT1s were able to rescue yeast growth in ferrous iron-transport deficient yeast (fet3fet4). The results suggest that schistosomes express molecules for ferrous iron transport in their tegument...

Protocols for Gene Silencing in Schistosomes

Ndegwa, David; Krautz-Peterson, Greice; Skelly, Patrick J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.2%
Schistosomes are parasitic platyhelminths that infect over 200 million people globally. In recent years there have been many advances in schistosome genomics and proteomics and in the development of molecular tools for use with these parasites. Among the more promising methodologies is RNA interference (RNAi) which is a mechanism by which gene-specific double-stranded RNA (dsRNA) triggers degradation of homologous mRNA transcripts. We aim to develop effective protocols utilizing RNAi for use in the intra-mammalian life stages of Schistosoma mansoni. In this work, the gene encoding alkaline phosphatase (SmAP) was targeted by exposing the parasites to dsRNA encoding part of the SmAP coding region. SmAP is known to be expressed in a variety of parasite tissues. We report that both long dsRNAs as well as synthetic short inhibitory RNAs (siRNAs) are effective at eliciting SmAP gene suppression in cultured schistosomula and in adult males and females. Electroporation as a mode of dsRNA delivery is more efficient than simply soaking the parasites in an equivalent dose. Relative SmAP RNA levels >90% lower than controls were routinely detected, when measured 2 days after treatment by electroporation, using quantitative real time PCR. Commensurate with this decline in SmAP RNA...

Imaging schistosomes in vivo

Krautz-Peterson, Greice; Ndegwa, David; Vasquez, Kristine; Korideck, Houari; Zhang, Jun; Peterson, Jeffrey D.; Skelly, Patrick J.
Fonte: The Federation of American Societies for Experimental Biology Publicador: The Federation of American Societies for Experimental Biology
Tipo: Artigo de Revista Científica
Publicado em /08/2009 EN
Relevância na Pesquisa
27.37%
Schistosomes are intravascular, parasitic helminths that cause a chronic, often debilitating disease afflicting over 200 million people in over 70 countries. Here we describe novel imaging methods that, for the first time, permit visualization of live schistosomes within their living hosts. The technology centers on fluorescent agent uptake and activation in the parasite’s gut, and subsequent detection and signal quantitation using fluorescence molecular tomography (FMT). There is a strong positive correlation between the signal detected and parasite number. Schistosoma mansoni parasites of both sexes recovered from infected experimental animals exhibit vivid fluorescence throughout their intestines. Likewise, the remaining important human schistosome parasites, S. japonicum and S. hematobium, also exhibit gut fluorescence when recovered from infected animals. Imaging has been used to efficiently document the decline in parasite numbers in infected mice treated with the antischistosome drug praziquantel. This technology will provide a unique opportunity both to help rapidly identify much-needed, novel antischistosome therapies and to gain direct visual insight into the intravascular lives of the major schistosome parasites of humans.—Krautz-Peterson...

RNA interference in schistosomes: machinery and methodology

KRAUTZ-PETERSON, GREICE; BHARDWAJ, RITA; FAGHIRI, ZAHRA; TARARAM, CIBELE A.; SKELLY, PATRICK J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.37%
RNA interference (RNAi) is a potent gene silencing process that is playing an increasingly important role in investigations of gene function in schistosomes. Here we review what is known about the process in these parasites and provide an update on the methodology and machinery of RNAi. Data are presented to demonstrate that: (1) not all schistosome genes can be suppressed to the same extent, using the methods employed here; (2) while there is variation in the level of suppression achieved for one target gene (SmAP) in adult parasites, all individuals exhibit robust (>80%) suppression; (3) short interfering RNAs (siRNAs) can effect suppression when delivered by soaking (and not just via electroporation, as reported previously); (4) Male/female adult pairs need not be separated prior to siRNA delivery by electroporation for effective gene suppression in both genders and (5) electroporation of siRNAs in medium is as efficient as in commercial electroporation buffer. Regarding the machinery of RNAi in schistosomes, a homologue of the C. elegans multi-membrane spanning, RNA importing protein SID-1 is identified in silico. The gene encoding this protein contains 21 exons and spans over 50 kb to potentially encode a 115,556 Mr protein (SmSID-1). These analyses...

SCHISTOSOMES IN THE SOUTHWEST UNITED STATES AND THEIR POTENTIAL FOR CAUSING CERCARIAL DERMATITIS OR “SWIMMER’S ITCH”

Brant, Sara V.; Loker, Eric S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.37%
Cercarial dermatitis or swimmer’s itch results when cercariae of schistosomes penetrate human skin and initiate inflammatory responses. The parasites typically die in the skin but in some cases may persist and infect other organs. Cercarial dermatitis is caused by a complex and poorly known assemblage of schistosome species, and can occur anywhere where people come in contact with water bodies harboring schistosome-infected snails. In North America, most cases are reported from the upper Midwest. In the southwest U.S., this phenomenon has not been well studied, and it is not known which schistosome species are present, or if cercarial dermatitis occurs with any regularity. As part of our ongoing studies of schistosome diversity, using morphological traits and sequence data to differentiate species, we have thus far identified eight schistosome genetic lineages from snails from New Mexico and Colorado. We have investigated two cercarial dermatitis outbreaks, one occurring in Stubblefield Lake in northern New Mexico, and one in Prospect Lake in the heart of Colorado Springs, Colorado. The New Mexico outbreak likely involved two different avian schistosome species, both transmitted by physid snails. The Colorado outbreak was due to Trichobilharzia brantae...

Indian Schistosomes: A Need for Further Investigations

Agrawal, M. C.; Rao, V. G.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.49%
India is uniquely positioned with regard to schistosomes and schistosomiasis—discovering seven new mammalian species with the existence of three more schistosome species: Orientobilharzia turkestanicum, O. harinasutai, and Schistosoma haematobium(?). An endemic focus of urinary schistosomiasis was reported from Gimvi village of Ratnagiri, Maharashtra with infrequent occurrence of schistosome eggs in human stools. Cercarial dermatitis has been reported to be more abundant in rural population using ponds, tanks, and so forth, for their domestic purposes. Few dermatitis cases were tested positive by CHR. Schistosome antigen was also detected in urine of five cases suggesting existence of active schistosomiasis in India. Nevertheless, human kind does not appear to be the usual host for Indian schistosomes in contrast to S. haematobium, S. mansoni, or S. japonicum. Various reasons for this phenomenon are discussed including evolution of Indian schistosomes, immune mechanisms, and environmental conditions. These and other aspects such as seasonal effect on the prevalence, snail infectivity, heterologous mating, existence of hybrids, and number of schistosomes in heterologous infections need further investigations with application of molecular techniques. Joint efforts by the national as well as international scientific community would be much more rewarding for better understanding of the parasite and the infection.

Schistosomes Induce Regulatory Features in Human and Mouse CD1dhi B Cells: Inhibition of Allergic Inflammation by IL-10 and Regulatory T Cells

van der Vlugt, Luciën E. P. M.; Labuda, Lucja A.; Ozir-Fazalalikhan, Arifa; Lievers, Ellen; Gloudemans, Anouk K.; Liu, Kit-Yeng; Barr, Tom A.; Sparwasser, Tim; Boon, Louis; Ngoa, Ulysse Ateba; Feugap, Eliane Ngoune; Adegnika, Ayola A.; Kremsner, Peter G.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 08/02/2012 EN
Relevância na Pesquisa
27.2%
Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3+ regulatory T cells, in vivo ablation of FoxP3+ T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d+ B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3+ T cells in vitro. Indeed, transfer of CD1d+ MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1dhi B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly...

The use of imaging to detect schistosomes and diagnose schistosomiasis

Skelly, Patrick
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/2013 EN
Relevância na Pesquisa
27.57%
Several imaging modalities have been employed to examine schistosomes and monitor schistosome-induced pathology. Ultrasound is a non-invasive imaging method that has long been used in the laboratory and in the field to evaluate pathological changes, notably fibrosis, that arise as a consequence of the host response to schistosome eggs lodging in a variety of tissues. Ultrasonography has been widely used to monitor changes in the extent of fibrosis and in spleen/liver enlargement following chemotherapeutic treatment for schistosomiasis. Imaging methods to monitor schistosomes themselves in vivo (as opposed to detecting schistosome-induced pathology) include positron emission tomography (PET) and fluorescence molecular tomography (FMT). Both approaches rely on schistosome uptake of tracers that are introduced into infected animals and that can be detected externally. These methods have been used to successfully detect schistosomes in vivo and to monitor their elimination following chemotherapeutic treatment. Direct monitoring of live schistosomes in vivo has been achieved using intravital microscopy (IVM), when the infected tissues of anaesthetized animals are exposed. Finally, schistosome eggs have been visualized by confocal laser scanning microscopy in infected mice as well as in a human patient with schistosomiasis hematobium. Further advances in imaging technologies seem likely to provide greater insight into disease progression and into the biology of schistosomes in the most relevant setting – within a live animal.

Transduction of Schistosoma japonicum schistosomules with vesicular stomatitis virus glycoprotein pseudotyped murine leukemia retrovirus and expression of reporter human telomerase reverse transcriptase in the transgenic schistosomes

Yang, Sheng-Hui; Brindley, Paul J.; Zeng, Qing-Ren; Li, Yue-Sheng; Zhou, Jun; Liu, Yan; Liu, Bi-Yuan; Cai, Li-Ting; Zeng, Tie-Bing; Wei, Qi; Lan, Lin-Mei; McManus, Donald P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.57%
Although draft genome sequences of two of the major human schistosomes, Schistosoma japonicum and S. mansoni are available, the structures and characteristics of most genes and the influence of exogenous genes on the metabolism of schistosomes remain uncharacterized. Furthermore, which functional genomics approaches will be tractable for schistosomes are not yet apparent. Here, the vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped pantropic retroviral vector pBABE-puro was modified to incorporate the human telomerase reverse transcriptase gene (hTERT) as a reporter, under the control of the retroviral long terminal repeat (LTR). Pseudotyped virions were employed to transduce S. japonicum to investigate the utility of retrovirus-mediated transgenesis of S. japonicum and the activity of human telomerase reverse transcriptase as a reporter transgene in schistosomes. Schistosomules perfused from experimentally infected rabbits were cultured for six days after exposure to the virions after which genomic DNAs from virus-exposed and control worms were extracted. Analysis of RNA from transduced parasites and immunohistochemistry of thin parasite sections revealed expression of hTERT in the transduced worms. Expression of hTERT was also confirmed by immunoblot analysis. These findings indicated that S. japonicum could be effectively transduced by VSVG pseudotyped retrovirus carrying the hTERT gene. Given the potential of hTERT to aid in derivation of immortalized cells...

Revisiting glucose uptake and metabolism in schistosomes: new molecular insights for improved schistosomiasis therapies

You, Hong; Stephenson, Rachel J.; Gobert, Geoffrey N.; McManus, Donald P.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 11/06/2014 EN
Relevância na Pesquisa
27.49%
A better understanding of the molecular mechanisms required for schistosomes to take up glucose, the major nutritional source exploited by these blood flukes from their mammalian hosts and the subsequent metabolism required to fuel growth and fecundity, can provide new avenues for developing novel interventions for the control of schistosomiasis. This aspect of parasitism is particularly important to paired adult schistosomes, due to their considerable requirements for the energy needed to produce the extensive numbers of eggs laid daily by the female worm. This review describes recent advances in characterizing glucose metabolism in adult schistosomes. Potential intervention targets are discussed within the insulin signaling and glycolysis pathways, both of which play critical roles in the carbohydrate and energy requirements of schistosomes.

Schistosomes and snails: a molecular encounter

Knight, Matty; Arican-Goktas, Halime D.; Ittiprasert, Wannaporn; Odoemelam, Edwin C.; Miller, André N.; Bridger, Joanna M.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 21/07/2014 EN
Relevância na Pesquisa
27.37%
Biomphalaria glabrata snails play an integral role in the transmission of Schistosoma mansoni, the causative agent for human schistosomiasis in the Western hemisphere. For the past two decades, tremendous advances have been made in research aimed at elucidating the molecular basis of the snail/parasite interaction. The growing concern that there is no vaccine to prevent schistosomiasis and only one effective drug in existence provides the impetus to develop new control strategies based on eliminating schistosomes at the snail-stage of the life cycle. To elucidate why a given snail is not always compatible to each and every schistosome it encounters, B. glabrata that are either resistant or susceptible to a given strain of S. mansoni have been employed to track molecular mechanisms governing the snail/schistosome relationship. With such snails, genetic markers for resistance and susceptibility were identified. Additionally, differential gene expression studies have led to the identification of genes that underlie these phenotypes. Lately, the role of schistosomes in mediating non-random relocation of gene loci has been identified for the first time, making B. glabrata a model organism where chromatin regulation by changes in nuclear architecture...

Inhibition or Knockdown of ABC Transporters Enhances Susceptibility of Adult and Juvenile Schistosomes to Praziquantel

Kasinathan, Ravi S.; Sharma, Lalit Kumar; Cunningham, Charles; Webb, Thomas R.; Greenberg, Robert M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 16/10/2014 EN
Relevância na Pesquisa
27.57%
Parasitic flatworms of the genus Schistosoma cause schistosomiasis, a neglected tropical disease that affects hundreds of millions. Treatment of schistosomiasis depends almost entirely on the drug praziquantel (PZQ). Though essential to treating and controlling schistosomiasis, a major limitation of PZQ is that it is not active against immature mammalian-stage schistosomes. Furthermore, there are reports of field isolates with heritable reductions in PZQ susceptibility, and researchers have selected for PZQ-resistant schistosomes in the laboratory. P-glycoprotein (Pgp; ABCB1) and other ATP binding cassette (ABC) transporters remove a wide variety of toxins and xenobiotics from cells, and have been implicated in multidrug resistance (MDR). Changes in ABC transporter structure or expression levels are also associated with reduced drug susceptibility in parasitic helminths, including schistosomes. Here, we show that the activity of PZQ against schistosome adults and juveniles ex vivo is potentiated by co-administration of either the highly potent Pgp inhibitor tariquidar or combinations of inhibitors targeting multiple ABC multidrug transporters. Adult worms exposed to sublethal PZQ concentrations remain active, but co-administration of ABC transporter inhibitors results in complete loss of motility and disruption of the tegument. Notably...

From allergy to schistosomes: role of Fc receptors and adhesion molecules in eosinophil effector function

Nutten,Sophie; Trottein,François; Gounni,Abdelillah Soussi; Papin,Jean-Paul; Capron,André; Capron,Monique
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/1997 EN
Relevância na Pesquisa
37.37%
The dual function of eosinophils has been evidenced in protective immunity against parasites as well as in pathological manifestations during allergic disorders. We have demonstrated that a new class of IgE receptors, FcepsilonRII/CD23, was involved in the functional duality of eosinophils and other proinflammatory cells. More recently, we have shown that FcepsilonRI, the high affinity IgE receptor thought to be only expressed by basophils and mast cells, was involved in eosinophil-mediated cytotoxicity against schistosomes as well as in mediator release. These results favour the view that both IgE and its receptors have been primarily associated to a protective immune response, rather than to pathology. Not only IgE receptors but also members belonging to the family of adhesion molecules can participate as co-receptors in eosinophil effector function. The inhibitory role of monoclonal antibodies to LewisX (LeX, CD15) or to selectins in eosinophil-mediated cytotoxicity towards schistosomes and the detection of LeX and 'selectin-like' molecules on schistosomula surface indicate a double interaction mediated by selectins and their carbohydrate ligands between eosinophils and schistosomula. These results suggest new functions for these adhesion molecules...

Interference with the Host Haemostatic System by Schistosomes

Mebius, Mirjam M.; van Genderen, Perry J. J.; Urbanus, Rolf T.; Tielens, Aloysius G. M.; de Groot, Philip G.; van Hellemond, Jaap J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
27.37%
Schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, are still a threat. They are responsible for 200 million infections worldwide and an estimated 280,000 deaths annually in sub-Saharan Africa alone. The adult parasites reside as pairs in the mesenteric or perivesicular veins of their human host, where they can survive for up to 30 years. The parasite is a potential activator of blood coagulation according to Virchow's triad, because it is expected to alter blood flow and endothelial function, leading to hypercoagulability. In contrast, hepatosplenic schistosomiasis patients are in a hypocoagulable and hyperfibrinolytic state, indicating that schistosomes interfere with the haemostatic system of their host. In this review, the interactions of schistosomes with primary haemostasis, secondary haemostasis, fibrinolysis, and the vascular tone will be discussed to provide insight into the reduction in coagulation observed in schistosomiasis patients.