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1

Isozyme electrophoresis patterns of the liver fluke, Clonorchis sinensis from Kimhae, Korea and from Shenyang, China  

Microsoft Academic Search

An enzyme analysis of the liver fluke, Clonorchis sinensis from Kimhae, Korea and from Shenyang, China was conducted using a horizontal starch gel electrophoresis in order to elucidate their genetic relationships. A total of eight enzymes was employed from two different kinds of buffer systems. Two loci from each enzyme of aconitase and esterase (? -Na and ?-Na); and only

Gab-Man Park; Tai-Soon Yong; Kyung-il Im; Kyu-Je Lee

2000-01-01

2

The zoonotic, fish-borne liver flukes Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini.  

PubMed

Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini are the three most important liver flukes involved in human health, infecting more than 45 million people worldwide. Both C. sinensis and O. viverrini, and possibly O. felineus, can induce human cholangiocarcinoma as well as inducing other hepatobiliary pathology. Although the life cycles of all three species are similar, only that of O. felineus in Europe remains predominantly zoonotic, while O. felineus in Asia and C. sinensis have a stronger mixture of zoonotic and anthroponotic components in their life cycles. Opisthorchis viverrini from the Mekong area of southeastern Asia is predominantly anthroponotic. Here we discuss the comparative epidemiology of these three taxa comparing in detail the use of first, second and final animal hosts, and consider the potential role of humans in spreading these pathogens. In addition we discuss the genetic structure of all three species in relation to potentially cryptic species complexes. PMID:23978669

Petney, Trevor N; Andrews, Ross H; Saijuntha, Weerachai; Wenz-Mücke, Alexandra; Sithithaworn, Paiboon

2013-11-01

3

Genetic diversity of the Chinese liver fluke Clonorchis sinensis from Russia and Vietnam.  

PubMed

Clonorchiasis is a parasitic disease of high public health importance in many countries in southeastern Asia and is caused by the Chinese liver fluke Clonorchis sinensis. However, the genetic structure and demographic history of its populations has not been sufficiently studied throughout the geographic range of the species and available data are based mainly on partial gene sequencing. In this study, we explored the genetic diversity of the complete 1560 bp cytochrome c oxidase subunit 1 (cox1) gene sequence for geographically isolated C. sinensis populations in Russia and Vietnam, to our knowledge for the first time. The results demonstrated low nucleotide and high haplotype differentiation within and between the two compared regions and a clear geographical vector for the distribution of genetic diversity patterns among the studied populations. These results suggest a deep local adaptation of the parasite to its environment including intermediate hosts and the existence of gene flow across the species' range. Additionally, we have predicted an amino acid substitution in the functional site of the COX1 protein among the Vietnamese populations, which were reported to be difficult to treat with praziquantel. The haplotype networks consisted of several region-specific phylogenetic lineages, the formation of which could have occurred during the most extensive penultimate glaciations in the Pleistocene Epoch. The patterns of genetic diversity and demographics are consistent with population growth of the liver fluke in the late Pleistocene following the Last Glacial Maximum, indicating the lack of a population bottleneck during the recent past in the species' history. The data obtained have important implications for understanding the phylogeography of C. sinensis, its host-parasite interactions, the ability of this parasite to evolve drug resistance, and the epidemiology of clonorchiasis under global climate change. PMID:25123068

Chelomina, Galina N; Tatonova, Yulia V; Hung, Nguyen Manh; Ngo, Ha Duy

2014-10-01

4

An EF-handed Ca(2+)-binding protein of Chinese liver fluke Clonorchis sinensis.  

PubMed

A cDNA clone encoding 8 kDa protein was retrieved from an EST pool of Chinese liver fluke Clonorchis sinensis. A deduced polypeptide of the cDNA clone was similar to 8 kDa Ca(2+)-binding proteins from other parasitic trematodes, and, thus, named as CsCa8, containing two EF-hand Ca(2+)-binding sites. Homology models predicted CsCa8 to be a single globular structure having four helices and molecular folds similar to Ca(2+)-binding state of other small Ca(2+)-binding proteins. Recombinant CsCa8 protein showed specific Ca(2+)-binding affinity and shifting in native gel mobility assay. Mouse immune sera raised against recombinant CsCa8 protein recognized native CsCa8 from adult C. sinensis worm extract. CsCa8 was localized in oral and ventral suckers, vitelline follicles and subtegumental tissues. These findings suggest that CsCa8 might be involved in cellular Ca(2+) signal transduction for muscle contraction and egg production. PMID:24018708

Chung, Eun Joo; Kim, Tae Yun; Hong, Sung-Jong; Yong, Tai-Soon

2013-12-01

5

Adult Opisthorchis felineus major protein fractions deduced from transcripts: comparison with liver flukes Opisthorchis viverrini and Clonorchis sinensis.  

PubMed

The epidemiologically important liver flukes Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis are of interest to health professionals, epidemiologists, pharmacologists, and molecular biologists. Recently the transcriptomes of the latter two species were intensively investigated. However our knowledge on molecular biology of O. felineus is scarce. We report the first results of the O. felineus transcriptome analysis. We isolated and annotated a total of 2560 expressed sequence tag (EST) sequences from adult O. felineus (deposited within the database of expressed sequence tags (dbEST), under accession numbers GenBank: JK624271-JK626790, JK006511-JK006547, JK649790-JK649792). Clustering and analysis resulted in the detection of 267 contigs. Of the protein sequences deduced from these, 82% had homologs in the NCBI (nr) protein database and 63% contained conserved domains, allowing the functions to be interpreted using the Gene Ontology terms. Comprehensive analysis of Opisthorchiidae- and Trematoda-specific substitutions within amino acid sequences deduced for the proteins myoglobin, vitelline precursor protein, cathepsin F, and 28kDa glutathione transferase was carried out. The gene set of the 32 ribosomal proteins for the three Opisthorchiidae species with the addition of available Schistosoma and Fasciola orthologs was created and is provided in the supplementary. The orthologous gene set created was used for inferring phylogeny within the Trematoda with special attention to interrelations within the Opisthorchiidae. The phylogenetic analysis revealed a closer relationship between C. sinensis and O. viverrini and some divergence of O. felineus from either O. viverrini or C. sinensis. PMID:23891942

Pomaznoy, Mikhail; Tatkov, Sergey; Katokhin, Alexey; Afonnikov, Dmitry; Babenko, Vladimir; Furman, Dagmara; Brusentsov, Ilya; Belavin, Pavel; Najakshin, Alexandr; Guselnikov, Sergey; Vasiliev, Gennady; Sivkov, Anton; Prokhortchouk, Egor; Skryabin, Konstantin; Mordvinov, Viatcheslav

2013-10-01

6

Expressed sequence tag analysis of adult Clonorchis sinensis , the Chinese liver fluke  

Microsoft Academic Search

Expressed sequence tag (EST) pools represent partial profiles of the gene expressions of organisms. In an effort to construct a Clonorchis sinensis EST pool, 2,387 ESTs were collected from an adult C. sinensis cDNA library and assembled into 1,573 clusters. Of these clusters, 1,225 ESTs (51%) were singletons and 348 clusters consisted of more than two ESTs. There were 848

Pyo Yun Cho; Mi Jung Lee; Tae Im Kim; Shin-Yong Kang; Sung-Jong Hong

2006-01-01

7

Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.  

PubMed

Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P?

Chen, Wenjun; Wang, Xiaoyun; Lv, Xiaoli; Tian, Yanli; Xu, Yanquan; Mao, Qiang; Shang, Mei; Li, Xuerong; Huang, Yan; Yu, Xinbing

2014-09-01

8

Taxonomy and biology of liver flukes  

Microsoft Academic Search

Opisthorchis viverrini is a human liver fluke endemic in Thailand, Lao PDR and Cambodia. Three subspecies of Bithynia siamensis and 18 species of cyprinoid fish are susceptible first and second intermediate hosts, respectively. The differentiation between the adult worm of O. viverrini and that of the closely related species, Opisthorchis felineus and Clonorchis sinensis, is mainly based on the shape

Sasithorn Kaewkes

2003-01-01

9

Sequences and gene organization of the mitochondrial genomes of the liver flukes Opisthorchis viverrini and Clonorchis sinensis (Trematoda)  

Microsoft Academic Search

Opisthorchis viverrini and Clonorchis sinensis are important trematodes infecting humans and animals, belonging to the family Opisthorchiidae. In the present study, we\\u000a sequenced the nearly complete mitochondrial (mt) DNA (mtDNA) sequences of O. viverrini from Laos, obtained the complete mtDNA sequences of C. sinensis from China and Korea, and revealed their gene annotations and genome organizations. The mtDNA sequences of

X. Q. Cai; G. H. Liu; H. Q. Song; C. Y. Wu; F. C. Zou; H. K. Yan; Z. G. Yuan; R. Q. Lin; X. Q. Zhu

10

Taxonomy and biology of liver flukes.  

PubMed

Opisthorchis viverrini is a human liver fluke endemic in Thailand, Lao PDR and Cambodia. Three subspecies of Bithynia siamensis and 18 species of cyprinoid fish are susceptible first and second intermediate hosts, respectively. The differentiation between the adult worm of O. viverrini and that of the closely related species, Opisthorchis felineus and Clonorchis sinensis, is mainly based on the shape and position of the testes and the arrangement of the vitellaria. Eggs of these flukes are morphologically similar and problematic in identification. However, the differentiation between opisthorchid and lecithodendrid eggs is possible. Morphology and biology of each stage are comparatively reviewed. Biological aspects of snail and fish hosts are also included. PMID:14611872

Kaewkes, Sasithorn

2003-11-01

11

Roles of liver fluke infection as risk factor for cholangiocarcinoma.  

PubMed

Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O. viverrini, and its role as a carcinogenic parasite are presented. The trends of age-specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O. viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer. PMID:24408775

Sithithaworn, Paiboon; Yongvanit, Puangrat; Duenngai, Kunyarat; Kiatsopit, Nadda; Pairojkul, Chawalit

2014-05-01

12

Is Opisthorchis viverrini an avian liver fluke?  

PubMed

Recently, in the Journal of Helminthology (May 2013), Dao et al. reported that Opisthorchis viverrini-like flukes were found in the bile duct of domestic ducks in Vietnam. They stated that this is the first record of Opisthorchis sp. in birds in Vietnam. However, three Opisthorchis species - O. cheelis, O. longissimus and O. parageminus - in birds in Vietnam were described by Le in 2000. Amongst these, O. parageminus was first reported, by Oshmarin in 1970, as a new Opisthorchis species found in domestic ducks (Anas platyrhynchos) in Vietnam. Morphologially O. viverrini-like flukes described by Dao et al. are much more similar to O. parageminus than to O. viverrini. The phylogenetic trees of internal transcribed spacer 2 (ITS2) and cytochrome oxidase 1 (CO1) gene sequences also showed that the O. viverrini-like liver flukes from domestic ducks were closer to O. lobatus than to O. viverrini. Therefore, O. viverrini-like liver flukes reported by Dao et al. (2013) are most likely to be O. parageminus. PMID:24160690

Nawa, Y; Doanh, P N; Thaenkham, U

2015-03-01

13

Opisthorchis viverrini: The carcinogenic human liver fluke  

PubMed Central

Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas. PMID:18205254

Kaewpitoon, Natthawut; Kaewpitoon, Soraya J; Pengsaa, Prasit; Sripa, Banchob

2008-01-01

14

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini  

Microsoft Academic Search

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labeled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20ms of 125V in the presence of 50?g\\/ml of Cy3-siRNA. The parasites tolerated

Jittiyawadee Sripa; Porntip Pinlaor; Paul J. Brindley; Banchob Sripa; Sasithorn Kaewkes; Mark W. Robinson; Neil D. Young; Robin B. Gasser; Alex Loukas; Thewarach Laha

2011-01-01

15

Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.  

PubMed

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture. PMID:25566326

Correia da Costa, José M; Vale, Nuno; Gouveia, Maria J; Botelho, Mónica C; Sripa, Banchob; Santos, Lúcio L; Santos, Júlio H; Rinaldi, Gabriel; Brindley, Paul J

2014-01-01

16

Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers  

PubMed Central

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture. PMID:25566326

Correia da Costa, José M.; Vale, Nuno; Gouveia, Maria J.; Botelho, Mónica C.; Sripa, Banchob; Santos, Lúcio L.; Santos, Júlio H.; Rinaldi, Gabriel; Brindley, Paul J.

2014-01-01

17

Liver fluke infection in horses and ponies.  

PubMed

Thirty eight cases of Fasciola hepatica infection in horses with associated clinical signs are reported. A method of examining large amounts of faeces for fluke is described. A safe method of treatment for infected horses is given which involves oral medication with oxyclozanide at a dose rate of 15 ml/50 kg body weight. PMID:837900

Owen, J M

1977-01-01

18

Cathepsin F Cysteine Protease of the Human Liver Fluke, Opisthorchis viverrini  

PubMed Central

Background The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct, the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities. Methodology/Principal Findings Here, we describe the cDNA, gene organization, phylogenetic relationships, immunolocalization, and functional characterization of the cathepsin F cysteine protease gene, here termed Ov-cf-1, from O. viverrini. The full length mRNA of 1020 nucleotides (nt) encoded a 326 amino acid zymogen consisting of a predicted signal peptide (18 amino acids, aa), prosegment (95 aa), and mature protease (213 aa). BLAST analysis using the Ov-CF-1 protein as the query revealed that the protease shared identity with cathepsin F-like cysteine proteases of other trematodes, including Clonorchis sinensis (81%), Paragonimus westermani (58%), Schistosoma mansoni and S. japonicum (52%), and with vertebrate cathepsin F (51%). Transcripts encoding the protease were detected in all developmental stages that parasitize the mammalian host. The Ov-cf-1 gene, of ?3 kb in length, included seven exons interrupted by six introns; the exons ranged from 69 to 267 bp in length, the introns from 43 to 1,060 bp. The six intron/exon boundaries of Ov-cf-1 were conserved with intron/exon boundaries in the human cathepsin F gene, although the gene structure of human cathepsin F is more complex. Unlike Ov-CF-1, human cathepsin F zymogen includes a cystatin domain in the prosegment region. Phylogenetic analysis revealed that the fluke, human, and other cathepsin Fs branched together in a clade discrete from the cathepsin L cysteine proteases. A recombinant Ov-CF-1 zymogen that displayed low-level activity was expressed in the yeast Pichia pastoris. Although the recombinant protease did not autocatalytically process and activate to a mature enzyme, trans-processing by Fasciola hepatica cathepsin L cleaved the prosegment of Ov-CF-1, releasing a mature cathepsin F with activity against the peptide Z-Phe-Arg-NHMec >50 times that of the zymogen. Immunocytochemistry using antibodies raised against the recombinant enzyme showed that Ov-CF-1 is expressed in the gut of the mature hermaphroditic fluke and also in the reproductive structures, including vitelline glands, egg, and testis. Ov-CF-1 was detected in bile duct epithelial cells surrounding the flukes several weeks after infection of hamsters with O. viverrini and, in addition, had accumulated in the secondary (small) bile ducts where flukes cannot reach due to their large size. Conclusions/Significance A cathepsin F cysteine protease of the human liver fluke O. viverrini has been characterized at the gene and protein level. Secretion of this protease may contribute to the hepatobiliary abnormalities, including cholangiocarcinogenesis, observed in individuals infected with this parasite. PMID:19308250

Laha, Thewarach; Sripa, Banchob; Kaewkes, Sasithorn; Morales, Maria E.; Mann, Victoria H.; Parriott, Sandi K.; Suttiprapa, Sutas; Robinson, Mark W.; To, Joyce; Dalton, John P.; Loukas, Alex; Brindley, Paul J.

2009-01-01

19

Experimental infection of bighorn sheep with liver flukes (Fasciola hepatica).  

PubMed

Nine Rocky Mountain bighorn sheep (Ovis canadensis canadensis) were each inoculated orally with 250 metacercariae of Fasciola hepatica. Blood and fecal samples were collected at the time of inoculation and at 5, 10, 14, and 20 wk after inoculation. Numbers of fluke eggs in feces, hemoglobin, packed cell volume, and eosinophil values were determined. Five of the bighorn sheep were treated with triclabendazole at 40 mg/kg of body weight 14 wk after inoculation. Based on fecal evaluations, all bighorns developed patent infections. Six weeks after treatment, fluke eggs were not detected in feces from the five treated animals but were present in two of four untreated animals. One untreated bighorn sheep was euthanized 20 wk after inoculation, and 57 adult F. hepatica were recovered from the liver. Results from this experiment indicated that bighorn sheep are efficient hosts for F. hepatica. Triclabendazole at 40 mg/kg of body weight was safe and, based on fluke egg recovery in feces, apparently an effective treatment. To my knowledge, this is the first published report of F. hepatica in bighorn sheep. PMID:19901401

Foreyt, William J

2009-10-01

20

The detection of snail host habitats in liver fluke infected farms by use of plant indicators  

Microsoft Academic Search

Field investigations in 361 liver fluke infected cattle- or sheep-breeding farms on acid soil were carried out during thirty years in March and April to record indicator plants in relation to the category of site colonized by the intermediate host of liver fluke, the snail Galba truncatula. Seven types of snail zones and six species of indicator plants were recorded

Daniel Rondelaud; Philippe Hourdin; Philippe Vignoles; Gilles Dreyfuss; Jacques Cabaret

2011-01-01

21

Delineation of the Structural Elements of Oriental Liver Fluke PLA2 Isoforms for Potent Drug Designing.  

PubMed

Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A2, an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a ?-wing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidine-aspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA2 described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis. PMID:25298624

Hariprasad, Gururao; Kota, Divya; Baskar Singh, Sundararajan; Srinivasan, Alagiri; Adhikary, Souparno

2014-10-01

22

Liver fluke vaccines in ruminants: strategies, progress and future opportunities.  

PubMed

The development of a vaccine for Fasciola spp. in livestock is a challenge and would be advanced by harnessing our knowledge of acquired immune mechanisms expressed by resistant livestock against fluke infection. Antibody-dependent cell-mediated cytotoxicity directed to the surface tegument of juvenile/immature flukes is a host immune effector mechanism, suggesting that antigens on the surface of young flukes may represent prime candidates for a fluke vaccine. A Type 1 immune response shortly after fluke infection is associated with resistance to infection in resistant sheep, indicating that vaccine formulations should attempt to induce Type 1 responses to enhance vaccine efficacy. In cattle or sheep, an optimal fluke vaccine would need to reduce mean fluke burdens in a herd below the threshold of 30-54 flukes to ensure sustainable production benefits. Fluke infection intensity data suggest that vaccine efficacy of approximately 80% is required to reduce fluke burdens below this threshold in most countries. With the increased global prevalence of triclabendazole-resistant Fasciolahepatica, it may be commercially feasible in the short term to introduce a fluke vaccine of reasonable efficacy that will provide economic benefits for producers in regions where chemical control of new drug-resistant fluke infections is not viable. Commercial partnerships will be needed to fast-track new candidate vaccines using acceptable adjuvants in relevant production animals, obviating the need to evaluate vaccine antigens in rodent models. PMID:25200351

Toet, Hayley; Piedrafita, David M; Spithill, Terry W

2014-10-15

23

Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini: potential target for DNA-based diagnosis.  

PubMed

Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3330 bp in length, encoded 1101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as 5 fg of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes. PMID:24394447

Thi Phung, Luyen; Loukas, Alex; Brindley, Paul J; Sripa, Banchob; Laha, Thewarach

2014-01-01

24

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini  

PubMed Central

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labelled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125 volts in the presence of 50 ?g/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 hours after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen. PMID:21565281

Sripa, Jittiyawadee; Pinlaor, Porntip; Brindley, Paul J.; Sripa, Banchob; Kaewkes, Sasithorn; Robinson, Mark W.; Young, Neil D.; Gasser, Robin B.; Loukas, Alex; Laha, Thewarach

2011-01-01

25

RNA interference targeting cathepsin B of the carcinogenic liver fluke, Opisthorchis viverrini.  

PubMed

Functional genomics have not been reported for Opisthorchis viverrini or the related fish-borne fluke, Clonorchis sinensis. Here we describe the introduction by square wave electroporation of Cy3-labeled small RNA into adult O. viverrini worms. Adult flukes were subjected to square wave electroporation employing a single pulse for 20 ms of 125V in the presence of 50 ?g/ml of Cy3-siRNA. The parasites tolerated this manipulation and, at 24 and 48 h after electroporation, fluorescence from the Cy3-siRNA was evident throughout the parenchyma of the worms, with strong fluorescence evident in the guts and reproductive organs of the adult worms. Second, other worms were treated using the same electroporation settings with double stranded RNA targeting an endogenous papain-like cysteine protease, cathepsin B. This manipulation resulted in a significant reduction in specific mRNA levels encoding cathepsin B, and a significant reduction in cathepsin B activity against the diagnostic peptide, Z-Arg-Arg-AMC. This appears to be the first report of introduction of reporter genes into O. viverrini and the first report of experimental RNA interference (RNAi) in this fluke. The findings indicated the presence of an intact RNAi pathway in these parasites which, in turn, provides an opportunity to probe gene functions in this neglected tropical disease pathogen. PMID:21565281

Sripa, Jittiyawadee; Pinlaor, Porntip; Brindley, Paul J; Sripa, Banchob; Kaewkes, Sasithorn; Robinson, Mark W; Young, Neil D; Gasser, Robin B; Loukas, Alex; Laha, Thewarach

2011-09-01

26

Infection status of Clonorchis sinensis in residents of Hamyang-gun, Gyeongsangnam-do, Korea  

Microsoft Academic Search

Oriental liver fluke (Clonorchis sinensis) infection was surveyed among residents of Hamyang-gun, Gyeongsangnam-do, Korea during the period of January 2001 to March 2002. Total 1,041 stool samples were collected from residents who visited Public Health Center and its branches in Hamyang-gun and examined using formalin-ether sedimentation method. The overall egg positive rate was 16%, male showing higher positive rate (21%)

Bong Jin Kim; Mee-Sun Ock; Ik Su Kim; Un Bo Yeo

2002-01-01

27

High prevalence of liver and intestinal fluke infections among residents of Savannakhet Province in Laos  

PubMed Central

The prevalence of liver and intestinal fluke infections was surveyed on residents of Savannakhet Province, Laos. Fecal specimens were collected from a total of 981 residents in 4 Mekong riverside villages and examined by the Kato-Katz thick smear technique. The results revealed that the overall helminth egg positive rate was 84.2%, and the positive rate for small trematode eggs, including Opisthorchis viverrini, heterophyids, or lecithodendriids, was 67.1%. To obtain adult flukes, 38 small trematode egg positive cases were treated with a 20-30 mg/kg single dose of praziquantel and purged. Diarrheic stools were then collected from 29 people and searched for helminth parasites using stereomicroscopes. Mixed infections with O. viverrini and 6 kinds of intestinal flukes were found, namely, Haplorchis taichui, Haplorchis pumilio, Haplorchis yokogawai, Prosthodendrium molenkampi, Phaneropsolus bonnei, and echinostomes. The total number of flukes collected was 7,693 specimens (av. no. per treated person; 265.3). The most common species was O. viverrini, followed by H. taichui, P. molenkampi, echinostomes, H. pumilio, P. bonnei, and H. yokogawai. The results indicate that foodborne liver and intestinal fluke infections are prevalent among residents of Savannakhet Province, Laos. PMID:17876167

Han, Eun-Taek; Guk, Sang-Mee; Shin, Eun-Hee; Sohn, Woon-Mok; Yong, Tai-Soon; Eom, Keeseon S.; Lee, Keon-Hoon; Jeong, Hoo-Gn; Ryang, Yong-Sang; Hoang, Eui-Hyug; Phommasack, Bounlay; Insisiengmay, Bounnaloth; Lee, Soon-Hyung; Rim, Han-Jong

2007-01-01

28

Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica  

Microsoft Academic Search

BACKGROUND: The common liver fluke Fasciola hepatica is the agent of a zoonosis with significant economic consequences in livestock production worldwide, and increasing relevance to human health in developing countries. Although flukicidal drugs are available, re-infection and emerging resistance are demanding new efficient and inexpensive control strategies. Understanding the molecular mechanisms underlying the host-parasite interaction provide relevant clues in this

Martín Cancela; Natalia Ruétalo; Nicolás Dell'Oca; Edileuza da Silva; Pablo Smircich; Gabriel Rinaldi; Leda Roche; Carlos Carmona; Fernando Alvarez-Valín; Arnaldo Zaha; José F. Tort

2010-01-01

29

Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic human liver fluke, Opisthorchis viverrini  

Microsoft Academic Search

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for many years. The mechanisms by which it avoids oxidative damage are unknown. In this study, thioredoxin peroxidase (TPx), a member of the peroxiredoxin superfamily, was cloned from an O. viverrini cDNA library.

Sutas Suttiprapa; Alex Loukas; Thewarach Laha; Sopit Wongkham; Sasithorn Kaewkes; Soraya Gaze; Paul J. Brindley; Banchob Sripa

2008-01-01

30

Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini  

Microsoft Academic Search

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and\\/or thioredoxin utilizing systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini

Sutas Suttiprapa; Pitchaya Matchimakul; Alex Loukas; Thewarach Laha; Sopit Wongkham; Sasithorn Kaewkes; Paul J. Brindley; Banchob Sripa

31

CsCF-6, a novel cathepsin F-like cysteine protease for nutrient uptake of Clonorchis sinensis  

Microsoft Academic Search

Clonorchis sinensis, the Chinese liver fluke, is a trematode parasite that causes clonorchiasis in humans. In this study, we identified a novel gene encoding a cathepsin F-like cysteine protease of C. sinensis (CsCF-6) and characterised its role in nutrient uptake by the parasite. Sequence and phylogeny analyses showed that CsCF-6 was clearly different from all presently known C. sinensis cysteine

Byoung-Kuk Na; Jung-Mi Kang; Woon-Mok Sohn

2008-01-01

32

Effects of the injectable contraceptive depot medroxyprogesterone acetate in Thai women with liver fluke infestation: results after six months  

PubMed Central

The effect of the three-monthly injectable contraceptive depot medroxyprogesterone acetate (DMPA) on liver and lipid function was assessed in Thai women with liver fluke (Opisthorchis viverrini) infestation, DMPA administration being started in the immediate postpartum period. Immediate postpartum IUD and sterilization acceptors with fluke infestation were recruited as a comparison (control) group for the fluke-positiv DMPA acceptors. Comparable groups of fluke-negative acceptors were recruited in an area of Thailand free of liver fluke transmission. Results are presented for the first 6 follow-up months for 170 DMPA and 177 control fluke-positive subjects and for 153 DMPA and 150 control fluke-negative subjects. Small and similar increases occurred in each of the four groups for alanine amino transferase, isocitrate dehydrogenase, and total bilirubin levels while aspartate amino transferase levels changed less in the DMPA groups than in their respective control groups. None of the subjects in either DMPA group had clearly abnormal results in these tests at 6 months. Alkaline phosphatase, cholesterol, and triglycerides levels were markedly lower in each group at 6 months than in the puerperal specimens. There was a greater decrease in triglycerides levels in both DMPA groups than in their respective control groups. However, the decrease in the alkaline phosphatase and cholesterol levels was greater only in the fluke-positive DMPA group than in the fluke-positive control group. None of these biochemical results were related to differences in age, parity, or lactation status between the groups. The results indicate that DMPA did not cause any early deleterious effects in the metabolic factors studied in women with liver fluke infestation. PMID:302157

Grossman, Richard A.; Assawasena, Vinich; Chalpati, Sopon; Taewtong, Dilok

1977-01-01

33

Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome  

PubMed Central

Opisthorchis viverrini is a fish-borne trematode endemic in East Asia. Following ingestion, the flukes locate to the biliary tre? where chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whole O. viverrini were examined in this model of fluke-induced CCA. Microbial communities were characterized by high-throughput sequencing of variable regions 7–9 of prokaryotic 16S ribosomal DNA. Of ?1 million sequences, 536,009 with useable reads were assignable to 29,776 operational taxonomy units (OTUs) and, in turn, to 20 phyla and 273 genera of Bacteria or Archaea. Microbial community analyses revealed that fluke infection perturbed the gastrointestinal tract microbiome, increasing Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae, while decreasing Porphyromonadaceae, Erysipelotrichaceae, and Eubacteriaceae (P?0.05). More than 60 OTUs were detected in the biliary system, which confirmed bacteriobilia and a noteworthy community of microbes associated with the parasites. The fluke-associated microorganisms included potential pathogens from the Enterobacteriaceae and Listeriaceae and others, including Cyanobacteria and Deinococci, usually found in external environments. Given that opisthorchiasis is distinguished from other helminth infections by a robust inflammatory phenotype with conspicuously elevated IL-6, and that inflammation of the biliary system leads to periductal fibrosis, which is a precursor of CCA, the flukes and their microbiota may together drive this distinctive immune response.—Plieskatt, J. L., Raksawan, D., Mulvenna, J. P., Krause, L., Sripa, B., Bethony, J. M., Brindley, P. J. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. PMID:23925654

Plieskatt, Jordan L.; Deenonpoe, Raksawan; Mulvenna, Jason P.; Krause, Lutz; Sripa, Banchob; Bethony, Jeffrey M.; Brindley, Paul J.

2013-01-01

34

Cathepsin F Cysteine Protease of the Human Liver Fluke, Opisthorchis viverrini  

Microsoft Academic Search

Background: The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct,the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities. Methodology\\/Principal Findings: Here, we describe the cDNA, gene organization,

Porntip Pinlaor; Natthawut Kaewpitoon; Thewarach Laha; Banchob Sripa; Sasithorn Kaewkes; Maria E. Morales; Victoria H. Mann; Sandi K. Parriott; Sutas Suttiprapa; Mark W. Robinson; Joyce To; John P. Dalton; Alex Loukas; Paul J. Brindley

2009-01-01

35

Cathepsin F Cysteine Protease of the Human Liver Fluke, Opisthorchis viverrini  

Microsoft Academic Search

BackgroundThe liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct, the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities.Methodology\\/Principal FindingsHere, we describe the cDNA, gene organization, phylogenetic relationships,

Porntip Pinlaor; Natthawut Kaewpitoon; Thewarach Laha; Banchob Sripa; Sasithorn Kaewkes; Maria E. Morales; Victoria H. Mann; Sandi K. Parriott; Sutas Suttiprapa; Mark W. Robinson; Joyce To; John P. Dalton; Alex Loukas; Paul J. Brindley

2009-01-01

36

Evaluation of liver fluke recombinant cathepsin B1 protease as a serodiagnostic antigen for human opisthorchiasis  

Microsoft Academic Search

A cathepsin B-like cysteine protease belonging to family C1 is abundantly expressed in the transcriptome and proteome of the carcinogenic liver fluke of humans, Opisthorchis viverrini. This enzyme is present in excretory\\/secretory (ES) products released by parasites cultured in vitro. This study evaluated the performance of recombinant O. viverrini cathepsin B1 (rOv-CB-1) as an antigen for immunodiagnosis of opisthorchiasis. The

Jittiyawadee Sripa; Paul J. Brindley; Banchob Sripa; Alex Loukas; Sasithorn Kaewkes; Thewarach Laha

37

Suppression of aquaporin, a mediator of water channel control in the carcinogenic liver fluke, Opisthorchis viverrini  

PubMed Central

Background Opisthorchiasis and Opisthorchis viverrini-associated bile duct cancer represent major public health threats in Thailand and Laos. The tegument of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis and osmoregulation. Excretory/secretory products also pass from the fluke to the biliary environment, products that likely underlie pathogenesis of liver fluke infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily of integral plasma membrane channel proteins that selectively transport water across cell membranes. AQPs play key roles as water and ion transport channels through the tegument of helminth parasites. Methods Here, two forms of AQP mRNAs from the adult developmental stage of O. viverrini, termed O. viverrini aquaporin-1 and -2 (Ov-aqp-1 and -2) were investigated. Roles of Ov-aqp-1 and -2 in the movement of water across the tegument of this carcinogenic liver fluke were investigated using RNA interference. Results Ov-AQP-1 and Ov-AQP-2 contain unique characteristic asparagine-proline-alanine (NPA) motifs of AQP transmembrane proteins. Phylogenetic analysis indicated that Ov-AQPs belong to an expanding group of aquaglyceroporin-like water channel proteins characterized from helminth and protozoan parasites, which is pivotal to the specialized requirements of water and solute control during parasitism. Elevated transcription of Ov-aqp-1 was evident in the egg, cercaria, metacercaria and adult stages of O. viverrini, whereas Ov-aqp-2 transcripts were detected at higher level in egg, metacercaria, cercaria and adult stage, respectively. RNA interference using electroporated dsRNA suppressed transcript levels of Ov-aqp-1 and Ov-aqp-2 in adult worms by 58-99% over periods of up to 16 days in vitro. Suppression of Ov-aqp-1 and Ov-aqp-2 in vitro disabled water transport in adult flukes. Conclusion The apparently pivotal roles of Ov-AQP in solute homeostasis at the fluke surface suggest that deeper investigation will be informative for the pathophysiology of O. viverrini, and may uncover intervention targets, particularly in view of the singularly notable predilection of this pathogen for residence within ducts of the biliary tree. PMID:24885060

2014-01-01

38

RNAi Dynamics in Juvenile Fasciola spp. Liver Flukes Reveals the Persistence of Gene Silencing In Vitro  

PubMed Central

Background Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a ?-class glutathione transferase (Fhe?GST). Methodology/Principal Findings Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200–320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ?25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; Fhe?GST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively. Conclusions/Significance In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to infection. PMID:25254508

McVeigh, Paul; McCammick, Erin M.; McCusker, Paul; Morphew, Russell M.; Mousley, Angela; Abidi, Abbas; Saifullah, Khalid M.; Muthusamy, Raman; Gopalakrishnan, Ravikumar; Spithill, Terry W.; Dalton, John P.; Brophy, Peter M.; Marks, Nikki J.; Maule, Aaron G.

2014-01-01

39

Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic human liver fluke, Opisthorchis viverrini.  

PubMed

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for many years. The mechanisms by which it avoids oxidative damage are unknown. In this study, thioredoxin peroxidase (TPx), a member of the peroxiredoxin superfamily, was cloned from an O. viverrini cDNA library. O. viverrini TPx cDNA encoded a polypeptide of 212 amino acid residues, of molecular mass 23.57kDa. The putative amino acid sequence shared 60-70% identity with TPXs from other helminths and from mammals, and phylogenetic analysis revealed a close relationship between TPxs from O. viverrini and other trematodes. Recombinant O. viverrini TPx was expressed as soluble protein in Escherichia coli. The recombinant protein dimerized, and its antioxidant activity was deduced by observing protection of nicking of supercoiled plasmid DNA by hydroxyl radicals. Antiserum raised against O. viverrini TPx recognized native proteins from egg, metacercaria and adult developmental stages of the liver fluke and excretory-secretory products released by adult O. viverrini. Immunolocalization studies revealed ubiquitous expression of TPx in O. viverrini organs and tissues. TPx was also detected in bile fluid and bile duct epithelial cells surrounding the flukes 2 weeks after infection of hamsters with O. viverrini. In addition, TPx was observed in the secondary (small) bile ducts where flukes cannot reach due to their large size. These results suggested that O. viverrini TPx plays a significant role in protecting the parasite against damage induced by reactive oxygen species from inflammation. PMID:18538872

Suttiprapa, Sutas; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Gaze, Soraya; Brindley, Paul J; Sripa, Banchob

2008-08-01

40

Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic human liver fluke, Opisthorchis viverrini  

PubMed Central

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for many years. The mechanisms by which it avoids oxidative damage are unknown. In this study, thioredoxin peroxidase (TPx), a member of the peroxiredoxin superfamily, was cloned from an O. viverrini cDNA library. O. viverrini TPx cDNA encoded a polypeptide of 212 amino acid residues, of molecular mass 23.57 kDa. The putative amino acid sequence shared 60-70% identity with TPXs from other helminths and from mammals, and phylogenetic analysis revealed a close relationship between TPxs from O. viverrini and other trematodes. Recombinant O. viverrini TPx was expressed as soluble protein in Escherichia coli. The recombinant protein dimerized, and its antioxidant activity was deduced by observing protection of nicking of supercoiled plasmid DNA by hydroxyl radicals. Antiserum raised against O. viverrini TPx recognized native proteins from egg, metacercaria and adult developmental stages of the liver fluke and excretory-secretory products released by adult O. viverrini. Immunolocalization studies revealed ubiquitous expression of TPx in O. viverrini organs and tissues. TPx was also detected in bile fluid and bile duct epithelial cells surrounding the flukes two weeks after infection of hamsters with O. viverrini. In addition, TPx was observed in the secondary (small) bile ducts where flukes cannot reach due to their large size. These results suggested that O. viverrini TPx plays a significant role in protecting the parasite against damage induced by reactive oxygen species from inflammation. PMID:18538872

Suttiprapa, Sutas; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Gaze, Soraya; Brindley, Paul J.; Sripa, Banchob

2013-01-01

41

Raw fish consumption in liver fluke endemic areas in rural southern Laos.  

PubMed

Consumption of raw or insufficiently cooked fish is a major public health concern in Southeast Asia, and in Lao People's Democratic Republic (Lao PDR), in particular. We aimed to assess the knowledge, attitudes, perceptions and practices of villagers in liver fluke endemic areas related to raw fish preparation, consumption and its health consequences. In February 2010, eight focus group discussions (FGDs, 35 men and 37 women total) and direct observations were conducted in four randomly selected villages in Saravane District, Saravane Province (Lao PDR). FGDs distilled the knowledge, attitudes, perceptions and practices of adult community members on raw fish preparation, consumption and its consequences for health. Conversations were transcribed from notes and tape-recorders. MaxQDA software was used for content analysis. Knowledge regarding the health effects of raw fish consumption was heterogeneous. Some participants did not associate liver fluke infection with any ill health, while others linked it to digestive problems. Participants also associated vegetables and tree leave consumption with liver fluke infection. The majority of FGD participants considered fish flesh that had been prepared with weaver ant extract to be safe for consumption. Visual appearance, taste, smell and personal preference were given as reasons for consuming raw fish dishes. Moreover, participants considered it a traditional way of food preparation, practiced for generations in Laos. Ten different fish dishes that use raw or fermented fish were identified. All FGD participants reported consuming dishes with raw fish. This study reveals a low degree of knowledge among local people on the health risks related to frequent consumption of raw or insufficiently cooked fish. Fish dishes were considered to be 'well-prepared' (that is, 'cooked') even though the fish had not been heated. In future, successful health education campaigns will have to address the specific knowledge, attitudes, perceptions and practices of the concerned population. PMID:23567553

Xayaseng, Vilavanh; Phongluxa, Khampheng; van Eeuwijk, Peter; Akkhavong, Kongsap; Odermatt, Peter

2013-08-01

42

The effect of liver flukes on nutrient utilization in beef cattle  

E-print Network

from the jugular vein in sterile vacuum tubes containing anticoagulant. The blood was prepared for blood urea analysis by adding one milliliter of sulfosalicylic acid (50 percent w/v) to four milli liters of blood. After cooling for one hour at 4 C... December 1978 Major Subject: Animal Nutrition THE EFFECT OF LIVER FLUKES ON NUTRIFNT UTILIZATION IN BEEF CATTLE A Thesis by RICHARD ARNOLD CRAIN Approued as to style and content by: p Chairman of Committee a CC~ laced of o /t. ti Member :", ;6...

Crain, Richard Arnold

2012-06-07

43

The detection of snail host habitats in liver fluke infected farms by use of plant indicators.  

PubMed

Field investigations in 361 liver fluke infected cattle- or sheep-breeding farms on acid soil were carried out during thirty years in March and April to record indicator plants in relation to the category of site colonized by the intermediate host of liver fluke, the snail Galba truncatula. Seven types of snail zones and six species of indicator plants were recorded in the 7709 positive sites studied. The most frequent habitats were located at the peripheral extremities of open drainage furrows. Juncus acutiflorus, Juncus effusus, Glyceria fluitans, and Agrostis stolonifera were the indicator plants. Plant indicators were highly efficient (38-80% of variance explained) when used with the size of site area within a hydrographical zone. The identification of positive sites for G. truncatula is a key for controlling the intermediate host on pastures through biological control with predatory molluscs. The positive sites may be detected using a two-step method including first categorization of hydrographical zones and then, within a zone, use of one or several indicator plants (frequently J. acutiflorus). PMID:21524858

Rondelaud, Daniel; Hourdin, Philippe; Vignoles, Philippe; Dreyfuss, Gilles; Cabaret, Jacques

2011-09-27

44

Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini  

PubMed Central

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilising systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular mass 11.63 kDa. The predicted protein has similarity to previously characterized thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was expressed as soluble protein in E. coli. The recombinant protein showed insulin reduction activity and supported the enzymatic function of O. viverrini thioredoxin peroxidase. Expression of Ov-Trx-1at mRNA and protein levels were observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was also detected in excretory-secretory products released by adult O. viverrini. Immunohistochemsitry, Ov-Trx-1 was expressed in nearly all parasite tissue excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the infected biliary epithelium but not normal bile ducts. These results suggest that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in protecting the parasite against damage induced by reactive oxygen species from inflammation. PMID:21740981

Suttiprapa, Sutas; Matchimakul, Pitchaya; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Brindley, Paul J.; Sripa, Banchob

2013-01-01

45

Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini.  

PubMed

The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilizing systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular mass 11.63 kDa. The predicted protein has similarity to previously characterized thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was expressed as soluble protein in E. coli. The recombinant protein showed insulin reduction activity and supported the enzymatic function of O. viverrini thioredoxin peroxidase. Expression of Ov-Trx-1 at mRNA and protein levels was observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was also detected in excretory-secretory products released by adult O. viverrini. Immunohistochemistry, Ov-Trx-1 was expressed in nearly all parasite tissue excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the infected biliary epithelium but not in normal bile ducts. These results suggest that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in protecting the parasite against damage induced by reactive oxygen species from inflammation. PMID:21740981

Suttiprapa, Sutas; Matchimakul, Pitchaya; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Brindley, Paul J; Sripa, Banchob

2012-03-01

46

MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma  

PubMed Central

AIM: To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma (ICC). Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS: The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS: Fifty-two patients (60%) exhibited both MUC1 and MUC5AC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation with tumor progression as reflected by vascular invasion (P<0.001), whereas high expression of MUC5AC significantly correlated with neural invasion (P = 0.022) and advanced ICC stage (P = 0.008). Patients with high expression of MUC1 had a significantly shorter survival (P = 0.0002). According to multivariate analyses, MUC1 reactivity (P = 0.026), histological grading and stage of tumor represented the least probability of survival. CONCLUSION: MUC1 is overexpressed in liver fluke-associated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients. PMID:16124042

Boonla, Chanchai; Sripa, Banchob; Thuwajit, Peti; Cha-On, Ubon; Puapairoj, Anucha; Miwa, Masanao; Wongkham, Sopit

2005-01-01

47

The effect of the hydrogen ionophore closantel upon the pharmacology and ultrastructure of the adult liver fluke Fasciola hepatica  

Microsoft Academic Search

The present study describes the effects of the H+ ionophore and anthelmintic closantel upon the in vitro motility and in vivo ultrastructure of the liver fluke,Fasciola hepatica. At a concentration of 50 µg\\/ml, closantel caused an initial stimulation, then suppression of activity, which was accompanied by an increase in muscle tone and led to a spastic paralysis within 2 h.

P. J. Skuce; I. Fairweather

1990-01-01

48

Multiple origins of European populations of the giant liver fluke Fascioloides magna (Trematoda: Fasciolidae), a liver parasite of ruminants.  

PubMed

The giant liver fluke, Fascioloides magna, a liver parasite of free-living and domestic ruminants of Europe and North America, was analysed in order to determine the origin of European populations and to reveal the biogeography of this originally North American parasite on the European continent. The variable fragments of the mitochondrial cytochrome c oxidase subunit I (cox1; 384bp) and nicotinamide dehydrogenase subunit I (nad1; 405bp) were used. Phylogenetic trees and haplotype networks were constructed and the level of genetic structuring was evaluated using population genetic tools. In F. magna individuals originating from all European foci of infection (Italy, Czech Republic and Danube floodplain forests involving the territories of Slovakia, Hungary and Croatia) and from four of five major North American enzootic areas, 16 cox1 and 18 nad1 haplotypes were determined. The concatenated sequence set produced 22 distinct haplotypes. The European fluke populations were less diverse than those from North America in that they contained proportionately fewer haplotypes (eight), while a more substantial level of genetic diversity and a greater number of haplotypes (15) were recorded in North America. Only one haplotype was shared between the European (Italy) and North American (USA/Oregon and Canada/Alberta) flukes, supporting a western North American origin of the Italian F. magna population. Haplotypes found in Italy were distinct from those determined in the remaining European localities which indicates that introduction of F. magna to the European continent occurred more than once. In the Czech focus of infection, a south-eastern USA origin was revealed. Identical haplotypes, common to parasites from the Czech Republic and from an expanding focus in Danube floodplain forests, implies that the introduction of F. magna to the Danube region came from an already established Czech focus of infection. PMID:21172350

Králová-Hromadová, Ivica; Bazsalovicsová, Eva; Stefka, Jan; Spakulová, Marta; Vávrová, Silvia; Szemes, Tomáš; Tkach, Vasyl; Trudgett, Alan; Pybus, Margo

2011-03-01

49

Asparaginyl endopeptidase from the carcinogenic liver fluke, Opisthorchis viverrini, and its potential for serodiagnosis  

PubMed Central

Summary Objectives To isolate and characterize an asparaginyl endopeptidase from the carcinogenic liver fluke, Opisthorchis viverrini, and evaluate its expression profile, biochemical activity, and potential as an immunodiagnostic antigen. Methods The full length mRNA encoding an asparaginyl endopeptidase (family C13), Ov-aep-1, was isolated by immunoscreening of a cDNA bacteriophage library of adult O. viverrini using sera from patients infected with O. viverrini. Investigation of Ov-aep-1 transcripts in developmental stages of the parasite, and phylogenetic analysis, immunohistochemical localization, and recombinant protein expression and enzymology were employed to characterize the Ov-AEP-1 protein. Immunoblotting was used to assess the potential of this enzyme for immunodiagnosis of human opisthorchiasis. Results Ov-AEP-1 is characteristic of the C13 cysteine protease family. Ov-aep-1 transcripts were detected in adult and juvenile worms, eggs, and metacercariae. Phylogenetic analysis indicated that Ov-AEP-1 is closely related to homologous proteins in other trematodes. Recombinant Ov-AEP-1 was expressed in bacteria in inclusion bodies and refolded to a soluble form. Excretory–secretory (ES) products derived from adult O. viverrini and refolded recombinant Ov-AEP-1 both displayed catalytic activity against the diagnostic tripeptide substrate, Ala–Ala–Asn-aminomethylcoumarin. Rabbit antiserum raised to recombinant Ov-AEP-1 identified the native AEP-1 protease in both somatic extract and ES products of adult worms. Anti-Ov-AEP-1 IgG immunolocalized the anatomical site of expression to the gut of the fluke, implying a physiological role in digestion of food or activation of other digestive enzymes. Recombinant Ov-AEP-1 was recognized by serum antibodies from patients with opisthorchiasis but not other helminth infections, with a sensitivity and specificity of 85% and 100%, respectively. The positive and negative predictive values are 100% and 67%, respectively. Conclusions The liver fluke, O. viverrini, has a gut-localized asparaginyl endopeptidase. Refolded recombinant Ov-AEP-1 is catalytically active and has potential for immunodiagnosis of human opisthorchiasis. PMID:18619888

Laha, Thewarach; Sripa, Jittiyawadee; Sripa, Banchob; Pearson, Mark; Tribolet, Leon; Kaewkes, Sasithorn; Sithithaworn, Paiboon; Brindley, Paul J.; Loukas, Alex

2008-01-01

50

Acute cholecystitis associated with Clonorchis sinensis infection  

PubMed Central

Clonorchis sinensis is one of the most common causes of trematodiasis that is caused by the ingestion of raw fish contaminated with infective cysts. The adult flukes are predominantly present in the intrahepatic bile ducts, but occasionally they may be found in the pancreatic duct and extrahepatic bile ducts. The clinical manifestations depend on the number of flukes, the period of infestation, and complications such as pericholangitic abscess, cholangitis, bile duct stones, and cholangiocarcinoma. However, primary acute cholecystitis associated with C. sinensis infection is extremely rare. Herein, we report on a case of primary acute cholecystitis associated with C. sinensis infection. PMID:25114891

Oh, Jung Taek; Jo, Hyang Jeong

2014-01-01

51

Acute cholecystitis associated with Clonorchis sinensis infection.  

PubMed

Clonorchis sinensis is one of the most common causes of trematodiasis that is caused by the ingestion of raw fish contaminated with infective cysts. The adult flukes are predominantly present in the intrahepatic bile ducts, but occasionally they may be found in the pancreatic duct and extrahepatic bile ducts. The clinical manifestations depend on the number of flukes, the period of infestation, and complications such as pericholangitic abscess, cholangitis, bile duct stones, and cholangiocarcinoma. However, primary acute cholecystitis associated with C. sinensis infection is extremely rare. Herein, we report on a case of primary acute cholecystitis associated with C. sinensis infection. PMID:25114891

Oh, Jung Taek; Kang, Dong Baek; Jo, Hyang Jeong

2014-08-01

52

Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: Functional expression, immunolocalization and subsite specificity  

Microsoft Academic Search

The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS

Sutas Suttiprapa; Jason Mulvenna; Ngo Thi Huong; Mark S. Pearson; Paul J. Brindley; Thewarach Laha; Sopit Wongkham; Sasithorn Kaewkes; Banchob Sripa; Alex Loukas

2009-01-01

53

Stage-specific expression and antigenicity of glycoprotein glycans isolated from the human liver fluke, Opisthorchis viverrini.  

PubMed

Infection by Opisthorchis viverrini (liver fluke) is a major public health problem in southeastern Asia, resulting in hepatobiliary disease and cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to the host, thereby constituting a crucial immunological interface that can determine the parasite's success in establishing infection. Therefore, N- and O-linked glycoprotein glycan profiles of the infective metacercarial stage and of the mature adult were investigated by nanospray ionisation-linear ion trap mass spectrometry (NSI-MS(n)). Glycan immunogenicity was investigated by immunoblotting with serum from infected humans. Metacercariae and adult parasites exhibit similar glycan diversity, although the prevalence of individual glycans and glycan classes varies by stage. The N-glycans of the metacercaria are mostly high mannose and monofucosylated, truncated-type oligosaccharides (62.7%), with the remainder processed to complex and hybrid type glycans (37.3%). The N-linked glycan profile of the adult is also dominated by high mannose and monofucosylated, truncated-type oligosaccharides (80.0%), with a smaller contribution from complex and hybrid type glycans (20.0%). At both stages, complex and hybrid type glycans are detected as mono-, bi-, tri-, or tetra-antennary structures. In metacercariae and adults, O-linked glycans are detected as mono- to pentasaccharides. The mucin type core 1 structure, Gal?1-3GalNAc, predominates in both stages but is less prevalent in the adult than in the metacercaria. Immunogenic recognition of liver fluke glycoproteins is reduced after deglycosylation but infected human serum was unable to recognise glycans released from peptides. Therefore, the most potent liver fluke antigenic epitopes are mixed determinants, comprised of glycan and polypeptide elements. PMID:23174105

Talabnin, Krajang; Aoki, Kazuhiro; Saichua, Prasert; Wongkham, Sopit; Kaewkes, Sasithorn; Boons, Geert-Jan; Sripa, Banchob; Tiemeyer, Michael

2013-01-01

54

Stage-specific expression and antigenicity of glycoprotein glycans isolated from the human liver fluke, Opisthorchis viverrini  

PubMed Central

Infection by Opisthorchis viverrini (liver fluke) is a major public health problem in southeastern Asia, resulting in hepatobiliary disease and cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to the host, thereby constituting a crucial immunological interface that can determine the parasite’s success in establishing infection. Therefore, N- and O-linked glycoprotein glycan profiles of the infective metacercarial stage and of the mature adult were investigated by nanospray ionization-linear ion trap mass spectrometry (NSI-MSn). Glycan immunogenicity was investigated by immunobloting with serum from infected humans. Metacercariae and adult parasites exhibit similar glycan diversity, although the prevalence of individual glycans and glycan classes varies by stage. The N-glycans of the metacercaria are mostly high mannose and monofucosylated, truncated-type oligosaccharides (62.7%), with the remainder processed to complex and hybrid type glycans (37.3%). The N-linked glycan profile of the adult is also dominated by high mannose and monofucosylated, truncated-type oligosaccharides (80.0%), with a smaller contribution from complex and hybrid type glycans (20.0%). At both stages, complex and hybrid type glycans are detected as mono-, bi-, tri-, or tetra-antennary structures. In metacercariae and adults, O-linked glycans are detected as mono- to pentasaccharides. The mucin type core 1 structure, Gal?1-3GalNAc, predominates in both stages but is less prevalent in the adult than in the metacercaria. Immunogenic recognition of liver fluke glycoproteins is reduced after deglycosylation but infected human serum was unable to recognize glycans released from peptides. Therefore, the most potent liver fluke antigenic epitopes are mixed determinants, comprised of glycan and polypeptide elements. PMID:23174105

Talabnin, Krajang; Aoki, Kazuhiro; Saichua, Prasert; Wongkham, Sopit; Kaewkes, Sasithorn; Boons, Geert-Jan; Sripa, Banchob; Tiemeyer, Michael

2013-01-01

55

Differential expression of liver fluke ?-tubulin isotypes at selected life cycle stages.  

PubMed

We have shown that Fasciola hepatica expresses at least six ?-tubulins in the adult stage of its life cycle, designated F.hep-?-tub1-6 (Ryan et al., 2008). Here we show that different complements of tubulin isotypes are expressed in different tissues and at different life cycle stages; this information may inform the search for novel anthelmintics. The predominant (as judged by quantitative PCR) isotype transcribed at the adult stage was F.hep-?-tub1 and immunolocalisation studies revealed that this isotype occurred mainly in mature spermatozoa and vitelline follicles. Quantitative PCR indicated that changes occurred in the transcription levels of ?-tubulin isotypes at certain life cycle stages and may be of importance in the efficacy of benzimidazole-based anthelmintic drugs, but there were no significant differences between the triclabendazole-susceptible Leon isolate and the triclabendazole-resistant Oberon isolate in the transcription levels of each of the isotypes. When three well-characterised isolates with differing susceptibilities to triclabendazole were compared, only one amino acid change resulting from a homozygous coding sequence difference (Gly269Ser) in isotype 4 was observed. However, this change was not predicted to alter the overall structure of the protein. In conclusion, these findings indicate that there is tissue-specific expression of tubulin isotypes in the liver fluke but the development of resistance to triclabendazole is not associated with changes in its presumed target molecule. PMID:24162076

Fuchs, Marc-Aurel; Ryan, Louise A; Chambers, Emma L; Moore, Catherine M; Fairweather, Ian; Trudgett, Alan; Timson, David J; Brennan, Gerry P; Hoey, Elizabeth M

2013-12-01

56

Evaluation of liver fluke recombinant cathepsin B-1 protease as a serodiagnostic antigen for human opisthorchiasis  

PubMed Central

A cathepsin B-like cysteine protease belonging to family C1 is abundantly expressed in the transcriptome and proteome of the carcinogenic liver fluke of humans, Opisthorchis viverrini. This enzyme is present in excretory/secretory (ES) products released by parasites cultured in vitro. This study evaluated the performance of recombinant O. viverrini cathepsin B1 (rOv-CB-1) as an antigen for immunodiagnosis of opisthorchiasis. The full length Ov-CB-1 cDNA was cloned and recombinant protein was produced in catalytically active form in Pichia pastoris. The recombinant Ov-CB-1 (rOv-CB-1) was affinity purified via nickel-NTA chromatography and tested in enzyme-linked immunosorbent assays (ELISA) with human sera from an opisthorchiasis endemic area. Sera from egg-positive O. viverrini infections produced a strong IgG antibody response to rOv-CB-1 both in ELISA and immunoblot analysis. The sensitivity and specificity of the ELISA test was 67% and 81%, respectively. These findings support the feasibility of using recombinant Ov-CB-1 in ELISA for the serodiagnosis of human opisthorchiasis. PMID:21704728

Sripa, Jittiyawadee; Brindley, Paul J.; Sripa, Banchob; Loukas, Alex; Kaewkes, Sasithorn; Laha, Thewarach

2011-01-01

57

Evaluation of liver fluke recombinant cathepsin B-1 protease as a serodiagnostic antigen for human opisthorchiasis.  

PubMed

A cathepsin B-like cysteine protease belonging to family C1 is abundantly expressed in the transcriptome and proteome of the carcinogenic liver fluke of humans, Opisthorchis viverrini. This enzyme is present in excretory/secretory (ES) products released by parasites cultured in vitro. This study evaluated the performance of recombinant O. viverrini cathepsin B1 (rOv-CB-1) as an antigen for immunodiagnosis of opisthorchiasis. The full length Ov-CB-1 cDNA was cloned and recombinant protein was produced in catalytically active form in Pichia pastoris. The recombinant Ov-CB-1 (rOv-CB-1) was affinity purified via nickel-NTA chromatography and tested in enzyme-linked immunosorbent assays (ELISA) with human sera from an opisthorchiasis endemic area. Sera from egg-positive O. viverrini infections produced a strong IgG antibody response to rOv-CB-1 both in ELISA and immunoblot analysis. The sensitivity and specificity of the ELISA test was 67% and 81%, respectively. These findings support the feasibility of using recombinant Ov-CB-1 in ELISA for the serodiagnosis of human opisthorchiasis. PMID:21704728

Sripa, Jittiyawadee; Brindley, Paul J; Sripa, Banchob; Loukas, Alex; Kaewkes, Sasithorn; Laha, Thewarach

2012-03-01

58

Biochemical characterisation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) from the liver fluke, Fasciola hepatica.  

PubMed

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyses one of the two steps in glycolysis which generate the reduced coenzyme NADH. This reaction precedes the two ATP generating steps. Thus, inhibition of GAPDH will lead to substantially reduced energy generation. Consequently, there has been considerable interest in developing GAPDH inhibitors as anti-cancer and anti-parasitic agents. Here, we describe the biochemical characterisation of GAPDH from the common liver fluke Fasciola hepatica (FhGAPDH). The primary sequence of FhGAPDH is similar to that from other trematodes and the predicted structure shows high similarity to those from other animals including the mammalian hosts. FhGAPDH lacks a binding pocket which has been exploited in the design of novel antitrypanosomal compounds. The protein can be expressed in, and purified from Escherichia coli; the recombinant protein was active and showed no cooperativity towards glyceraldehyde 3-phosphate as a substrate. In the absence of ligands, FhGAPDH was a mixture of homodimers and tetramers, as judged by protein-protein crosslinking and analytical gel filtration. The addition of either NAD? or glyceraldehyde 3-phosphate shifted this equilibrium towards a compact dimer. Thermal scanning fluorimetry demonstrated that this form was considerably more stable than the unliganded one. These responses to ligand binding differ from those seen in mammalian enzymes. These differences could be exploited in the discovery of reagents which selectively disrupt the function of FhGAPDH. PMID:24566472

Zinsser, Veronika L; Hoey, Elizabeth M; Trudgett, Alan; Timson, David J

2014-04-01

59

Hepatobiliary/Pancreas Pathology: SY11-2 LIVER FLUKE AND CHOLANGIOCARCINOMA IN THAILAND.  

PubMed

In northeastern Thailand, prevalent risks for cholangiocarcinoma (CC) include infestation with liver fluke O. viverrini (OV), infection with HBV and HCV, and consumption of nitrosamine-rich foods. The ASR for intrahepatic cholangiocarcinoma (ICC) is the highest in the world (44 and 16 per 100,000 males and females). ICC accounts for 58% of cases, exceeding that of hepatoma (42%). As per the AJCC-2009, the spectrum of CC among the 221 patients operated at Khon Kaen University Hospital included: perihilar CC (52.9%); ICC (37.1%); distal extrahepatic CC (4.1%) and combined ICC and extrahepatic CC (5.8%). Peak age incidence was in the sixth decade, about 5-10 years younger than sporadic CC. Chronic inflammation associated with OV infestation may be a contributing factor for the spectrum of CC vs HBV or HVC, since ICC with cirrhosis is rare and the phenotypes related to chronic hepatitis (CC and cholangio-hepatoma) account for <3%. Studies comparing OV-associated CC and sporadic CC shared similar pathological features, precursor lesions, growth factors and molecular alterations (like pancreatic ductal carcinoma). PMID:25188107

Pairojkul, Chawalit

2014-10-01

60

Liver fluke (Opisthorchiidae) findings in red foxes ( Vulpes vulpes ) in the eastern part of the Federal State Brandenburg, Germany – a contribution to the epidemiology of opisthorchiidosis  

Microsoft Academic Search

Parasitological examination of 677 livers from red foxes shot in connection with a rabies control programme were carried\\u000a out in the eastern districts of the Federal State Brandenburg\\/Germany in 1996. Of the foxes, 32.5% were positive for opisthorchiid\\u000a flukes. Metorchis bilis, the most frequently occurring fluke was found in 28.1% of foxes with numbers between 1 and 185. Opisthorchis felineus

Rolf Schuster; Jörg Bonin; Christoph Staubach; Rolf Heidrich

1999-01-01

61

Molecular characterization of Clonorchis sinensis tetraspanin 2 extracellular loop 2.  

PubMed

In the course of examining EST of the liver fluke Clonorchis sinensis, a cDNA encoding the protein similar to tetraspanin 2 (TSP-2) of blood fluke schistosome was identified as CsTSP2. TSPs are a family of eukaryotic cell membrane-spanning proteins thought to anchor multiple proteins to one area of the cell membrane. Multiple sequence alignment of CsTSP2 revealed over 40% of identities with those of schistosomes. The CCC, PXSC, and CG motives characteristic to extracellular loop 2 (EC2) region of TSP-2 were well conserved. PCR-amplified EC2 of CsTSP2 (CsTSP2EC2) was subcloned into pEXP5 NT/TOPO bacterial expression plasmid vector. Recombinant CsTSP2EC2 protein (rCsTSP2EC2) fused with 6X His tag was overexpressed bacterially and purified by using Ni-NTA affinity chromatography under denaturing condition. The purified rCsTSP2EC2 was recognized specifically by the sera from human infected with C. sinensis. Considering biological role and specific immunity of TSPs, rCsTSP2EC2 might be a probable vaccine candidate against clonorchiasis. Protective effects of immunizing rCsTSP2EC2 should be further studied. PMID:21842393

Kim, Tae Yun; Chung, Eun Joo; Sohn, Woon-Mok; Hong, Sung-Hong; Yong, Tai-Soon

2012-02-01

62

High prevalence of human liver infection by Amphimerus spp. flukes, Ecuador.  

PubMed

Amphimerus spp. flukes are known to infect mammals, but human infections have not been confirmed. Microscopy of fecal samples from 397 persons from Ecuador revealed Opisthorchiidae eggs in 71 (24%) persons. Light microscopy of adult worms and scanning electron microscopy of eggs were compatible with descriptions of Amphimerus spp. This pathogen was only observed in communities that consumed undercooked fish. PMID:22172165

Calvopiña, Manuel; Cevallos, William; Kumazawa, Hideo; Eisenberg, Joseph

2011-12-01

63

The effects of farm management practices on liver fluke prevalence and the current internal parasite control measures employed on Irish dairy farms.  

PubMed

Fasciolosis caused by Fasciola hepatica is responsible for major production losses in cattle farms. The objectives of this study were to assess the effect of farm management practices on liver fluke prevalence on Irish dairy farms and to document the current control measures against parasitic diseases. In total, 369 dairy farms throughout Ireland were sampled from October to December 2013, each providing a single bulk tank milk (BTM) sample for liver fluke antibody-detection ELISA testing and completing a questionnaire on their farm management. The analysis of samples showed that cows on 78% (n=288) of dairy farms had been exposed to liver fluke. There was a difference (P<0.05) between farms where cows were positive or negative for liver fluke antibodies in (a) the total number of adult dairy cows in herds, (b) the number of adult dairy cows contributing to BTM samples, and (c) the size of the total area of grassland, with positive farms having larger numbers in each case. There was no difference (P>0.05) between positive and negative farms in (a) the grazing of dry cows together with replacement cows, (b) whether or not grazed grassland was mowed for conservation, (c) the type of drinking water provision system, (d) spreading of cattle manure on grassland or (e) for grazing season length (GSL; mean=262.5 days). Also, there were differences (P<0.001) between drainage statuses for GSL with farms on good drainage having longer GSL than moderately drained farms. The GSL for dairy cows on farms with good drainage was 11 days longer than for those with moderate drainage (P<0.001). The percentage of farmers that used an active ingredient during the non-lactating period against liver fluke, gastrointestinal nematodes, lungworm, and rumen fluke was 96%, 85%, 77% and 90%, respectively. Albendazole was the most frequently used active ingredient for treatment against gastrointestinal nematodes (57%), liver fluke (40%) and lungworm (47%), respectively. There was a difference (P<0.05) in the use of triclabendazole and albendazole between positive and negative farms, with triclabendazole use being more common in positive farms. This study highlighted differences in dairy management practices between Irish farms with dairy herds exposed or not exposed to liver fluke and stressed the need of fine-scale mapping of the disease patterns even at farm level to increase the accuracy of risk models. Also, comprehensive advice and professional support services to farmers on appropriate farm management practices are very important for an effective anthelmintic control strategy. PMID:25591405

Selemetas, Nikolaos; Phelan, Paul; O'Kiely, Padraig; de Waal, Theo

2015-01-30

64

Low Genetic Diversity in Wide-Spread Eurasian Liver Fluke Opisthorchis felineus Suggests Special Demographic History of This Trematode Species  

PubMed Central

Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species. PMID:23634228

Brusentsov, Ilja I.; Katokhin, Alexey V.; Brusentsova, Irina V.; Shekhovtsov, Sergei V.; Borovikov, Sergei N.; Goncharenko, Grigoriy G.; Lider, Lyudmila A.; Romashov, Boris V.; Rusinek, Olga T.; Shibitov, Samat K.; Suleymanov, Marat M.; Yevtushenko, Andrey V.; Mordvinov, Viatcheslav A.

2013-01-01

65

Low genetic diversity in wide-spread Eurasian liver fluke Opisthorchis felineus suggests special demographic history of this trematode species.  

PubMed

Opisthorchis felineus or Siberian liver fluke is a trematode parasite (Opisthorchiidae) that infects the hepato-biliary system of humans and other mammals. Despite its public health significance, this wide-spread Eurasian species is one of the most poorly studied human liver flukes and nothing is known about its population genetic structure and demographic history. In this paper, we attempt to fill this gap for the first time and to explore the genetic diversity in O. felineus populations from Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Analysis of marker DNA fragments from O. felineus mitochondrial cytochrome c oxidase subunit 1 and 3 (cox1, cox3) and nuclear rDNA internal transcribed spacer 1 (ITS1) sequences revealed that genetic diversity is very low across the large geographic range of this species. Microevolutionary processes in populations of trematodes may well be influenced by their peculiar biology. Nevertheless, we suggest that lack of population genetics structure observed in O. felineus can be primarily explained by the Pleistocene glacial events and subsequent sudden population growth from a very limited group of founders. Rapid range expansion of O. felineus through Asian and European territories after severe bottleneck points to a high dispersal potential of this trematode species. PMID:23634228

Brusentsov, Ilja I; Katokhin, Alexey V; Brusentsova, Irina V; Shekhovtsov, Sergei V; Borovikov, Sergei N; Goncharenko, Grigoriy G; Lider, Lyudmila A; Romashov, Boris V; Rusinek, Olga T; Shibitov, Samat K; Suleymanov, Marat M; Yevtushenko, Andrey V; Mordvinov, Viatcheslav A

2013-01-01

66

Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: functional expression, immunolocalization and subsite specificity.  

PubMed

The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS classification. Ov-APR-1 is expressed in the gut of the mature hermaphroditic parasite, in the reproductive tissues including the testis and immature spermatids, and the developing miracidium within the eggshell. The enzyme was also detected in the excretory/secretory products of cultured adult flukes, indicating a role in host-parasite relationships. A recombinant form of the enzyme expressed in Escherichia coli and refolded from denatured inclusion bodies underwent autocatalytic activation and demonstrated hydrolytic activity against the peptide substrate 7-methoxycoumarin-4-acetyl-GKPILFFRLK(DNP)-D-Arg-amide with a k(cat)/K(m)=1.7 x 10(4)M(-1)s(-1) and a pH optimum around pH 2.5-3.0. The recombinant enzyme digested hemoglobin and bovine serum albumin. Forty-six serum albumin peptides were detected after digestion with recombinant Ov-APR-1 and sequenced. Like many other aspartic proteases, Ov-APR-1 displayed promiscuous preferences for residues accommodated at the key subsites of the binding pocket although hydrophobic (Leu, Ala, Ile), positively charged (Lys) and bulky aromatic (Phe) residues, in that order, were preferred at P1. Similar residues were accommodated at P1' although even less selectivity was exerted at this position. PMID:18996218

Suttiprapa, Sutas; Mulvenna, Jason; Huong, Ngo Thi; Pearson, Mark S; Brindley, Paul J; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Sripa, Banchob; Loukas, Alex

2009-05-01

67

Ov-APR-1, an aspartic protease from the carcinogenic liver fluke, Opisthorchis viverrini: functional expression, immunolocalization and subsite specificity  

PubMed Central

The human liver fluke Opisthorchis viverrini is endemic in Thailand, Laos and Cambodia where long standing infection is associated with cancer of the bile ducts, cholangiocarcinoma. Here we describe a cathepsin D-like aspartic protease from the gut and other tissues in O. viverrini. Phylogenetic analysis indicated that Ov-APR-1 is cathepsin D-like, conforming with Clan AA, Family A1 of the MEROPS classification. Ov-APR-1 is expressed in the gut of the mature hermaphroditic parasite, in the reproductive tissues including the testis and immature spermatids, and the developing miracidium within the eggshell. The enzyme was also detected in the excretory/secretory products of cultured adult flukes, indicating a role in host-parasite relationships. A recombinant form of the enzyme expressed in Escherichia coli and refolded from denatured inclusion bodies underwent autocatalytic activation and demonstrated hydrolytic activity against the peptide substrate 7-methoxycoumarin-4-acetyl-GKPILFFRLK(DNP)-D-Arg-amide with a kcat/Km = 1.7 × 104 M?1s?1 and a pH optimum around pH 2.5–3.0. The recombinant enzyme digested hemoglobin and bovine serum albumin. Forty-six serum albumin peptides were detected after digestion with recombinant Ov-APR-1 and sequenced. Like many other aspartic proteases, Ov-APR-1 displayed promiscuous preferences for residues accommodated at the key subsites of the binding pocket although hydrophobic (Leu, Ala, Ile), positively charged (Lys) and bulky aromatic (Phe) residues, in that order, were preferred at P1. Similar residues were accommodated at P1? although even less selectivity was exerted at this position. PMID:18996218

Suttiprapa, Sutas; Mulvenna, Jason; Huong, Ngo Thi; Pearson, Mark S.; Brindley, Paul J.; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Sripa, Banchob; Loukas, Alex

2009-01-01

68

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells  

PubMed Central

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma. PMID:19816559

Smout, Michael J.; Laha, Thewarach; Mulvenna, Jason; Sripa, Banchob; Suttiprapa, Sutas; Jones, Alun; Brindley, Paul J.; Loukas, Alex

2009-01-01

69

Rapid Detection and Differentiation of Clonorchis sinensis and Opisthorchis viverrini Using Real-Time PCR and High Resolution Melting Analysis  

PubMed Central

Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini. PMID:25386621

Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

2014-01-01

70

Rapid detection and differentiation of Clonorchis sinensis and Opisthorchis viverrini using real-time PCR and high resolution melting analysis.  

PubMed

Clonorchis sinensis and Opisthorchis viverrini are both important fish-borne pathogens, causing serious public health problem in Asia. The present study developed an assay integrating real-time PCR and high resolution melting (HRM) analysis for the specific detection and rapid identification of C. sinensis and O. viverrini. Primers targeting COX1 gene were highly specific for these liver flukes, as evidenced by the negative amplification of closely related trematodes. Assays using genomic DNA extracted from the two flukes yielded specific amplification and their identity was confirmed by sequencing, having the accuracy of 100% in reference to conventional methods. The assay was proved to be highly sensitive with a detection limit below 1 pg of purified genomic DNA, 5 EPG, or 1 metacercaria of C. sinensis. Moreover, C. sinensis and O. viverrini were able to be differentiated by their HRM profiles. The method can reduce labor of microscopic examination and the contamination of agarose electrophoresis. Moreover, it can differentiate these two flukes which are difficult to be distinguished using other methods. The established method provides an alternative tool for rapid, simple, and duplex detection of C. sinensis and O. viverrini. PMID:25386621

Cai, Xian-Quan; Yu, Hai-Qiong; Li, Rong; Yue, Qiao-Yun; Liu, Guo-Hua; Bai, Jian-Shan; Deng, Yan; Qiu, De-Yi; Zhu, Xing-Quan

2014-01-01

71

A New PCR-Based Approach Indicates the Range of Clonorchis sinensis Now Extends to Central Thailand  

PubMed Central

Differentiation of the fish-borne trematodes belonging to the Opisthorchiidae, Heterophyidae and Lecithodendriidae is important from a clinical and epidemiological perspective, yet it is impossible to do using conventional coprological techniques, as the eggs are morphologically similar. Epidemiological investigation therefore currently relies on morphological examination of adult worms following expulsion chemotherapy. A PCR test capable of amplifying a segment of the internal transcribed spacer region of ribosomal DNA for the opisthorchiid and heterophyid flukes eggs taken directly from faeces was developed and evaluated in a rural community in central Thailand. The lowest quantity of DNA that could be amplified from individual adults of Opisthorchis viverrini, Clonorchis sinensis and Haplorchis taichui was estimated at 0.6 pg, 0.8 pg and 3 pg, respectively. The PCR was capable of detecting mixed infection with the aforementioned species of flukes under experimental conditions. A total of 11.6% of individuals in rural communities in Sanamchaikaet district, central Thailand, were positive for ‘Opisthorchis-like’ eggs in their faeces using conventional parasitological detection techniques. In comparison to microscopy, the PCR yielded a sensitivity and specificity of 71.0% and 76.7%, respectively. Analysis of the microscopy-positive PCR products revealed 64% and 23% of individuals to be infected with O. viverrini and C. sinensis, respectively. The remaining 13% (three individuals) were identified as eggs of Didymozoidae, presumably being passed mechanically in the faeces following the ingestion of infected fishes. An immediate finding of this study is the identification and first report of a C. sinensis–endemic community in central Thailand. This extends the known range of this liver fluke in Southeast Asia. The PCR developed herein provides an important tool for the specific identification of liver and intestinal fluke species for future epidemiological surveys. PMID:19156191

Traub, Rebecca J.; Macaranas, Julie; Mungthin, Mathirut; Leelayoova, Saovanee; Cribb, Thomas; Murrell, K. Darwin; Thompson, R. C. Andrew

2009-01-01

72

Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica.  

PubMed

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member. PMID:23167294

Morphew, Russell M; Eccleston, Neil; Wilkinson, Toby J; McGarry, John; Perally, Samirah; Prescott, Mark; Ward, Deborah; Williams, Diana; Paterson, Steve; Raman, M; Ravikumar, G; Khalid Saifullah, M; Abbas Abidi, S M; McVeigh, Paul; Maule, Aaron G; Brophy, Peter M; LaCourse, E James

2012-12-01

73

Stage-specific differences in fecundity over the life-cycle of two characterized isolates of the liver fluke, Fasciola hepatica.  

PubMed

The variability inherent in different isolates of Fasciola hepatica has been evident from reports in the literature but to date there has been no systematic examination of the relationship between these differences and the fecundity of the parasite. In this study we have attempted to remedy this situation by comparing the relative efficiencies with which 2 well-characterized isolates of the liver fluke (Oberon and Fairhurst) progress through both their definitive and intermediate hosts. We did not observe a reduction in fitness in the Oberon isolate which has been reported to be triclabendazole-resistant, compared to the triclabendazole-susceptible Fairhurst isolate, but considerable inter- and intra-isolate variability at different life-cycle stages was recorded. Thus the Oberon isolate gave 4-fold the number of cercariae when 100 snails were each challenged with a single miracidium and was more successful in establishing productive infections in rats. Fairhurst metacercariae excysted at a higher rate than those from the Oberon isolate and Fairhurst flukes produced 4-fold more eggs. The extent of the intra- and inter-isolate variability revealed in this work will provide a basis for the development of models of population dynamics aimed at predicting the response of the liver fluke to changing environmental conditions such as the use of anthelmintics or climatic change. PMID:16597358

Walker, S M; Hoey, E; Fletcher, H; Brennan, G; Fairweather, I; Trudgett, A

2006-08-01

74

Advanced periductal fibrosis from infection with the carcinogenic human liver fluke Opisthorchis viverrini correlates with elevated levels of IL-6  

PubMed Central

More than 750 million people are at risk of infection with food-borne liver flukes. Opisthorchis viverrini is considered among the most important of these parasites, due to its strong association with cholangiocarcinoma (CCA). O. viverrini infection results in a chronic inflammatory challenge to the host, which can lead to advanced, pathogen-specific disease sequelae including obstructive jaundice, hepatomegaly, cholecystitis, as well as CCA. However, before disease sequelae are apparent, important inflammatory changes to the liver can be detected early during O. viverrini infection. In a case-control study involving 328 men and women with O. viverrini infection, we determined the presence of advanced periductal fibrosis in asymptomatic, O. viverrini-infected individuals and then measured cytokine responses to O. viverrini excretory/secretory products (ES). In the 200 participants with advanced periductal fibrosis (cases), levels of Interleukin (IL)-6 to O. viverrini ES were 8 times higher than levels of the 128 O. viverrini-infected individuals without advanced periductal fibrosis (controls). Moreover, elevated IL-6 to parasite ES was associated with increased risk of advanced periductal fibrosis by 63% in a model adjusted for sex and age. The risk of advanced periductal fibrosis was also found to increase with higher levels of IL-6: individuals in the third quartile of IL-6-ES production had a 127% higher risk of developing advanced periductal fibrosis than individuals in the first quartile of IL-6 production. O. viverrini-infected individuals with advanced periductal fibrosis showed other hepatobiliary abnormalities, including reduced gallbladder contractility and the presence of gallbladder sludge. Conclusion These data strongly implicate a role for parasite specific IL-6 in the pathogenesis of advanced periductal fibrosis in opisthorchiasis, with possible links to other hepatobiliary abnormalities, including cholangiocarcinoma. PMID:19676135

Sripa, Banchob; Mairiang, Eimorn; Thinkhamrop, Bandit; Laha, Thewarach; Kaewkes, Sasithorn; Sithithaworn, Paiboon; Tessana, Smarn; Loukas, Alex; Brindley, Paul J.

2009-01-01

75

Opisthorchis viverrini-like liver fluke in birds from Vietnam: morphological variability and rDNA/mtDNA sequence confirmation.  

PubMed

Flukes were found in the bile ducts of domestic ducks (Anas platyrhynchos), necropsied in the Binh Dinh province of Central Vietnam. Following staining, morphological characteristics of the bird flukes were compatible with Opisthorchis viverrini, although some characteristics differed from those described in specimens collected from mammal hosts. Computation of the phylogenetic trees on the partial sequences of the second internal ribosomal spacer (ITS2) of the ribosomal DNA and cytochrome c oxidase subunit I (COI) markers of the mitochondrial DNA showed close similarity of the 'bird' Opisthorchis sp. with O. viverrini. We speculate that these bird flukes are O. viverrini that show intraspecies morphological and molecular variability compared to isolates from mammals. This demonstrates the complex epidemiological situation of opisthorchiasis in Vietnam and urges investigations on the potential of birds as a reservoir host of this zoonotic fluke. PMID:23721954

Dao, T H; Nguyen, T G; Victor, B; Gabriël, S; Dorny, P

2014-12-01

76

UDP-galactose 4'-epimerase from the liver fluke, Fasciola hepatica: biochemical characterization of the enzyme and identification of inhibitors.  

PubMed

SUMMARY The Leloir pathway enzyme uridine diphosphate (UDP)-galactose 4'-epimerase from the common liver fluke Fasciola hepatica (FhGALE) was identified and characterized. The enzyme can be expressed in, and purified from, Escherichia coli. The recombinant enzyme is active: the K m (470 ? m) is higher than the corresponding human enzyme (HsGALE), whereas the k cat (2·3 s-1) is substantially lower. FhGALE binds NAD+ and has  shown to be dimeric by analytical gel filtration. Like the human and yeast GALEs, FhGALE is stabilized by the substrate UDP-galactose. Molecular modelling predicted that FhGALE adopts a similar overall fold to HsGALE and that tyrosine 155 is likely to be the catalytically critical residue in the active site. In silico screening of the National Cancer Institute Developmental Therapeutics Program library identified 40 potential inhibitors of FhGALE which were tested in vitro. Of these, 6 showed concentration-dependent inhibition of FhGALE, some with nanomolar IC50 values. Two inhibitors (5-fluoroorotate and N-[(benzyloxy)carbonyl]leucyltryptophan) demonstrated selectivity for FhGALE over HsGALE. These compounds also thermally destabilized FhGALE in a concentration-dependent manner. Interestingly, the selectivity of 5-fluoroorotate was not shown by orotic acid, which differs in structure by 1 fluorine atom. These results demonstrate that, despite the structural and biochemical similarities of FhGALE and HsGALE, it is possible to discover compounds which preferentially inhibit FhGALE. PMID:25124392

Zinsser, Veronika L; Lindert, Steffen; Banford, Samantha; Hoey, Elizabeth M; Trudgett, Alan; Timson, David J

2014-08-15

77

Induction of cancer-related microRNA expression profiling using excretory-secretory products of Clonorchis sinensis.  

PubMed

Clonorchis sinensis is a carcinogenic human liver fluke by which chronic infection is strongly associated with the development of cholangiocarcinoma. Although this cholangiocarcinoma is caused by both physical and chemical irritation from direct contact with adult worms and their excretory-secretory products (ESPs), the precise molecular events of the host-pathogen interactions remain to be elucidated. To better understand the effect of C. sinensis infection on cholangiocarcinogenesis, we profiled the kinetics of changes in cancer-related microRNAs (miRNAs) in human cholangiocarcinoma cells (HuCCT1) treated with C. sinensis ESPs for different periods. Using miRNA microarray chips containing 135 cancer-related miRNAs, we identified 16 miRNAs showing differentially altered expression following ESP exposure. Of these miRNAs, 13 were upregulated and 3 were downregulated in a time-dependent manner compared with untreated controls. Functional clustering of these dysregulated miRNAs revealed involvement in cell proliferation, inflammation, oncogene activation/suppression, migration/invasion/metastasis, and DNA methylation. In particular, decreased expression of let-7i, a tumor suppressor miRNA, was found to be associated with the ESP-induced upregulation of TLR4 mRNA and protein, which contribute to host immune responses against liver fluke infection. Further real-time quantitative PCR analysis using ESP-treated normal cholangiocytes (H69) revealed that the expressions of nine miRNAs (miR-16-2, miR-93, miR-95, miR-153, miR-195, miR-199-3P, let7a, let7i, and miR-124a) were similarly regulated, indicating that the cell proliferation and inhibition of tumor suppression mediated by these miRNAs is common to both cancerous and non-cancerous cells. These findings constitute further our understanding of the multiple cholangiocarcinogenic pathways triggered by liver fluke infection. PMID:25217977

Pak, Jhang Ho; Kim, In Ki; Kim, Seon Min; Maeng, Sejung; Song, Kyoung Ju; Na, Byoung-Kuk; Kim, Tong-Soo

2014-12-01

78

Heterogeneity of the “oval-cell” response in the hamster liver during cholangiocarcinogenesis following Clonorchis sinensis infection and dimmethylnitrosamine treatment  

Microsoft Academic Search

Background: Small intraportal “oval” cells which appear in the livers of humans and experimental animals after liver injury, are suspected to be early progenitor cells for both hepatocytes and bile duct cells, as well as cells of origin of hepatocellular and cholangiocellular carcinomas.Methods: The origin and fate of small “oval” cells expressing different immunohistologic phenotypes and ultrastructural appearance were examined

Jae-Hyun Lee; Han-Jong Rim; Stewart Sell

1997-01-01

79

Evidence for high genetic diversity of NAD1 and COX1 mitochondrial haplotypes among triclabendazole resistant and susceptible populations and field isolates of Fasciola hepatica (liver fluke) in Australia.  

PubMed

In recent years, the global incidence of Fasciola hepatica (liver fluke) infections exhibiting resistance to triclabendazole (TCBZ) has increased, resulting in increased economic losses for livestock producers and threatening future control. The development of TCBZ resistance and the worldwide discovery of F. hepatica population diversity has emphasized the need to further understand the genetic structure of drug susceptible and resistant Fasciola populations within Australia. In this study, the genetic diversity of liver flukes was estimated by sequencing mitochondrial DNA (mtDNA) encoding the NAD1 (530 bp) and COX1 (420 bp) genes of 208 liver flukes (F. hepatica) collected from three populations: field isolates obtained from abattoirs from New South Wales (NSW) and Victoria (Vic); three TCBZ-resistant fluke populations from NSW and Victoria; and the well-established TCBZ-susceptible Sunny Corner laboratory isolate. Overall nucleotide diversity for all flukes analysed of 0.00516 and 0.00336 was estimated for the NAD1 and COX1 genes respectively. Eighteen distinct haplotypes were established for the NAD1 gene and six haplotypes for the COX1 gene, resulting in haplotype diversity levels of 0.832 and 0.482, respectively. One field isolate showed a similar low level of haplotype diversity as seen in the Sunny Corner laboratory isolate. Analysis of TCBZ-resistant infrapopulations from 3 individual cattle grazing one property revealed considerable sequence parasite diversity between cattle. Analysis of parasite TCBZ-resistant infrapopulations from sheep and cattle revealed haplotypes unique to each host, but no significant difference between parasite populations. Fst analysis of fluke populations revealed little differentiation between the resistant and field populations. This study has revealed a high level of diversity in field and drug resistant flukes in South-Eastern Australia. PMID:24360656

Elliott, T; Muller, A; Brockwell, Y; Murphy, N; Grillo, V; Toet, H M; Anderson, G; Sangster, N; Spithill, T W

2014-02-24

80

In vitro evaluation of anthelmintic property of ethno-veterinary plant extracts against the liver fluke Fasciola gigantica  

Microsoft Academic Search

The present study was envisaged to evaluate the efficacy of ethno-medicinal plant aqueous extracts such as Allium sativum, Lawsonia inermis, and Opuntia ficus indica in vitro in comparison with the chemotherapeutic agent, Oxyclozanide on Fasciola gigantica adults. The efficacy was evaluated by gross visual motility and mortality of F. gigantica with score index, light microscopic examination of carmine stained flukes

N. Jeyathilakan; K. Murali; A. Anandaraj; S. Abdul Basith

81

A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica  

Microsoft Academic Search

Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 µg\\/ml).

M. Meaney; S. Haughey; G. P. Brennan; I. Fairweather

2005-01-01

82

Liver Fluke Infection and Fish Consumption in Khon Kaen, Thailand: A Case Study on Negotiating the Middle Ground between Western Science and Eastern Culture  

NASA Astrophysics Data System (ADS)

This research investigates why typical strategies for promoting health, prolonging life, and preventing disease do not work in many communities. I use the liver fluke infection endemic in Khon Kaen, Thailand to explore the middle ground between Western science and Eastern culture. Prior work on the O.viverrini infection in Khon Kaen, Thailand has focused almost exclusively on developing effective medical treatment for the liver fluke infection. This dissertation employs a case study designed to explore the conditions that created and perpetuate the problem in the first place. In concrete terms, I analyze how the worldviews of local villagers shape their attitudes toward life (and death), which in turn determine if they engage in the high-risk behavior -- eating undercooked fish -- that makes them vulnerable to the infection. My research focuses on these people in-situ over a three-month period, and includes data from participant-observation, interviews, and video-recordings. This work seeks to illuminate how people's thinking and reasoning skills, and personal/cultural identities affect their abilities to learn and act on new health concepts. This potentially provides a window into future educational strategies in a complex world.

Samiphak, Sara

83

Liver Fluke Induces Cholangiocarcinoma  

Microsoft Academic Search

The authors discuss the molecular pathogenesis of opisthorchiasis and associated cholangiocarcinogenesis, particularly nitrative and oxidative DNA damage and the clinical manifestations of cholangiocarcinoma.

Banchob Sripa; Sasithorn Kaewkes; Paiboon Sithithaworn; Eimorn Mairiang; Thewarach Laha; Michael Smout; Chawalit Pairojkul; Vajaraphongsa Bhudhisawasdi; Smarn Tesana; Bandit Thinkamrop; Jeffrey M Bethony; Alex Loukas; Paul J Brindley

2007-01-01

84

In vitro evaluation of anthelmintic property of ethno-veterinary plant extracts against the liver fluke Fasciola gigantica.  

PubMed

The present study was envisaged to evaluate the efficacy of ethno-medicinal plant aqueous extracts such as Allium sativum, Lawsonia inermis, and Opuntia ficus indica in vitro in comparison with the chemotherapeutic agent, Oxyclozanide on Fasciola gigantica adults. The efficacy was evaluated by gross visual motility and mortality of F. gigantica with score index, light microscopic examination of carmine stained flukes and histopathology of treated flukes. Based on the in vitro trials conducted using above plant extracts at 1 percent, 2.5 percent and 5 percent concentration, the extracts of O. ficus indica showed flukicidal effect at 2.5 and 5% concentration. However A. sativum and L. inermis were effective at 5% concentration only. The study indicated the potential for developing herbal-based anthelmintics to control F. gigantica in livestock. PMID:23543611

Jeyathilakan, N; Murali, K; Anandaraj, A; Abdul Basith, S

2012-04-01

85

Cytokine/Chemokine Secretion and Proteomic Identification of Upregulated Annexin A1 from Peripheral Blood Mononuclear Cells Cocultured with the Liver Fluke Opisthorchis viverrini  

PubMed Central

We investigated the cytokine/chemokine secretions and alteration of protein expression from peripheral blood mononuclear cells (PBMCs) cocultured with adult liver flukes (Opisthorchis viverrini) for 6 to 24 h. PBMC-derived proteins were identified by two-dimensional electrophoresis and mass spectrometry, and the cytokines/chemokines in the supernatant were assessed using a cytokine array. Exposure to O. viverrini induced increases in secretion of proinflammatory cytokines, costimulating protein, adhesion molecules, and chemotactic chemokines relative to untreated controls. In contrast, secretion of the CD40 ligand, interleukin 16, and macrophage inflammatory protein 1? decreased. Proteomic analysis revealed that expression of 48 proteins was significantly altered in PBMCs stimulated with O. viverrini. Annexin A1 (ANXA1) was selected for further study, and immunoblotting showed upregulation of ANXA1 expression in PBMCs after 12 and 24 h coculture with liver flukes. In an in vivo study, transcription and translation of ANXA1 significantly increased in livers of hamsters infected with O. viverrini at 21 days and from 3 months onwards compared to normal controls. Interestingly, immunohistochemistry revealed that ANXA1 was present not only in the cytoplasm of inflammatory cells but also in the cytoplasm of cholangiocytes, which are in close contact with the parasite and its excretory/secretory products in the biliary system. Expression of ANXA1 increased with time concomitant with bile duct enlargement, bile duct formation, and epithelial cell proliferation. In conclusion, several cytokines/chemokines secreted by PBMCs and upregulation of ANXA1 in PBMCs and biliary epithelial cells might have a role in host defense against O. viverrini infection and tissue resolution of inflammation. PMID:24614660

Hongsrichan, Nuttanan; Intuyod, Kitti; Pinlaor, Porntip; Khoontawad, Jarinya; Yongvanit, Puangrat; Wongkham, Chaisiri; Roytrakul, Sittiruk

2014-01-01

86

High Prevalence of the Liver Fluke Amphimerus sp. in Domestic Cats and Dogs in an Area for Human Amphimeriasis in Ecuador  

PubMed Central

Background Amphimerus sp. is a liver fluke which recently has been shown to have a high prevalence of infection among an indigenous group, Chachi, who reside in a tropical rainforest in the northwestern region of Ecuador. Since it is unknown which animals can act as a reservoir and/or definitive hosts for Amphimerus sp. in this endemic area, a study was done to determine the prevalence of infection in domestic cats and dogs. This information is important to understand the epidemiology, life cycle and control of this parasite. Methodology/Findings In July 2012, three Chachi communities located on Rio Cayapas, province of Esmeraldas, were surveyed. A total of 89 of the 109 registered households participated in the study. Of the 27 cats and 43 dogs found residing in the communities, stool samples were collected from 14 cats and 31 dogs (total of 45 animals) and examined microscopically for the presence of Amphimerus eggs. The prevalence of infection was 71.4% in cats and 38.7% in dogs, with similar rates of infection in all three communities. Significantly more cats were infected than dogs (p = 0.042). Conclusions/Significance The data show a high rate of Amphimerus sp. infection in domestic cats and dogs residing in Chachi communities. It can be concluded that these animals act as definitive and reservoir hosts for this liver fluke and that amphimeriasis is a zoonotic disease. These findings provide important epidemiological data which will aid in the development and implementation of control strategies against the transmission of Amphimerus. PMID:25647171

Calvopiña, Manuel; Cevallos, William; Atherton, Richard; Saunders, Matthew; Small, Alexander; Kumazawa, Hideo; Sugiyama, Hiromu

2015-01-01

87

ClonorESTdb: a comprehensive database for Clonorchis sinensis EST sequences  

PubMed Central

Background Clonorchiasis, which is primarily caused by liver fluke (Platyhelminthes), is a fatal infectious disease that is mainly associated with bile duct malignancy and the subsequent development of cholangiocarcinoma. Thus, a genomic approach now represents an important step to further our knowledge of biology and the pathology of these parasites. The results of expressed sequence tags (ESTs) sequencing need to be well organized into databases to provide an integrated set of tools and functional information. Findings Here, the ClonorESTdb database represents a collection of Clonorchis sinensis ESTs that is intended as a resource for parasite functional genomics. A total of 55,736 successful EST sequences, which are cleaned and clustered into non-redundant 13,305 C. sinensis assembled EST sequences (6,497 clusters and 6,808 singletons), were obtained from three in-house prepared cDNA libraries of C. sinensis at different developmental stages. The assembled consensus sequences were annotated using the BLAST algorithm or/and hmm against NCBI NR, UniProt, KEGG and InterProScan. The ClonorESTdb database provides functional annotation, their expression profiles, tandem repeats and putative single nucleotide polymorphisms with utility tools such as local BLAST search and text retrieval. Conclusions This resource enables the researcher to identify and compare expression signatures under different biological stages and promotes ongoing parasite drug and vaccine development and biological research. Database URL: http://pathod.cdc.go.kr/clonorestdb/ PMID:24957044

2014-01-01

88

Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B  

PubMed Central

Summary Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that auto-catalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot auto-catalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma. PMID:20070308

Sripa, Jittiyawadee; Laha, Thewarach; To, Joyce; Brindley, Paul J.; Sripa, Banchob; Kaewkes, Sasithorn; Dalton, John P.; Robinson, Mark W.

2010-01-01

89

Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.  

PubMed

Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot autocatalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma. PMID:20070308

Sripa, Jittiyawadee; Laha, Thewarach; To, Joyce; Brindley, Paul J; Sripa, Banchob; Kaewkes, Sasithorn; Dalton, John P; Robinson, Mark W

2010-06-01

90

Regulation of anti-inflammatory cytokines IL-10 and TGF-? in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen  

PubMed Central

Dendritic cells (DCs), which are regarded as the most potent antigen-presenting cells, are involved in innate and adaptive immunity. Upon uptake of pathogens, DCs express cell surface markers and secrete cytokines. In this study, we analyzed production of cytokines and found that interleukin (IL)-10 and transforming growth factor (TGF)-? production significantly increased in bone marrow-derived DCs and a mouse DC line, DC2.4, after treatment with crude antigen (CA) from liver fluke, Clonorchis sinensis. However, expression patterns of several activation molecules did not change. In addition, following treatment of DC2.4 cells with antigen from the lung fluke, Paragonimus westermani, production of IL-10 and TGF-? significantly increased compared with groups treated with other parasite antigens, Spirometra erinacei plerocercoid CA and Echinococcus granulosus hydatid cystic fluid. We also found that treatment of DC2.4 cells with C. sinensis CA resulted in rapid and significant phosphorylation of extracellular signal-regulated kinase 1/2, a mitogen-activated protein kinase. Following treatment of DC2.4 cells with C. sinensis CA, treatment with an inhibitor specific to an extracellular signal-regulated kinase inhibited production of IL-10 and TGF-?. Our results suggest that CA from C. sinensis has a role in the anti-inflammatory function of DC cells by inducing IL-10 and TGF-? through activation of extracellular signal-regulated kinase 1/2. PMID:24480801

Jin, Yan; Wi, Hae Joo; Choi, Min-Ho; Hong, Sung-Tae; Bae, Young Mee

2014-01-01

91

Regulation of anti-inflammatory cytokines IL-10 and TGF-? in mouse dendritic cells through treatment with Clonorchis sinensis crude antigen.  

PubMed

Dendritic cells (DCs), which are regarded as the most potent antigen-presenting cells, are involved in innate and adaptive immunity. Upon uptake of pathogens, DCs express cell surface markers and secrete cytokines. In this study, we analyzed production of cytokines and found that interleukin (IL)-10 and transforming growth factor (TGF)-? production significantly increased in bone marrow-derived DCs and a mouse DC line, DC2.4, after treatment with crude antigen (CA) from liver fluke, Clonorchis sinensis. However, expression patterns of several activation molecules did not change. In addition, following treatment of DC2.4 cells with antigen from the lung fluke, Paragonimus westermani, production of IL-10 and TGF-? significantly increased compared with groups treated with other parasite antigens, Spirometra erinacei plerocercoid CA and Echinococcus granulosus hydatid cystic fluid. We also found that treatment of DC2.4 cells with C. sinensis CA resulted in rapid and significant phosphorylation of extracellular signal-regulated kinase 1/2, a mitogen-activated protein kinase. Following treatment of DC2.4 cells with C. sinensis CA, treatment with an inhibitor specific to an extracellular signal-regulated kinase inhibited production of IL-10 and TGF-?. Our results suggest that CA from C. sinensis has a role in the anti-inflammatory function of DC cells by inducing IL-10 and TGF-? through activation of extracellular signal-regulated kinase 1/2. PMID:24480801

Jin, Yan; Wi, Hae Joo; Choi, Min-Ho; Hong, Sung-Tae; Bae, Young Mee

2014-01-01

92

Genetic differentiation in eastern European and western Asian populations of the liver fluke, Fasciola hepatica, as revealed by mitochondrial nad1 and cox1 genes.  

PubMed

Partial sequences of mitochondrial genes nad1 (316 bp) and cox1 (429 bp) were analyzed to estimate the variability of the liver fluke samples collected in 20 localities in Russia, Belarus, Ukraine, Bulgaria, Armenia, Azerbaijan, Georgia, Turkey, Turkmenistan, and China. The sequences had 4.1% (nad1) and 2.3% (cox1) of variable sites, and 13 and 10 haplotypes were identified among nad1 and cox1 genes, respectively. Spatial analysis of genetic and nucleotide diversity indicated little or no structuring of genetic variation between hosts or regions. The analysis of distribution of both separate and combined (nad1 + cox1) haplotypes revealed the existence of 2 well-defined lineages with 2 main haplotypes and a number of shared divergent haplotypes. Our study showed that the first lineage included the main N1-C1 haplotype, which was found in Australia, China, Georgia, Turkey, Armenia, Azerbaijan, and in all European populations (from Russia, Belarus, Ukraine, Bulgaria). The second lineage was found in all European populations and in populations from Armenia and Azerbaijan. It was suggested that one of the lineages (I) has an Asian origin. The possible source of mtDNA variability and associations between lineage divergence of parasite and its definitive hosts (cattle and sheep) are discussed. PMID:16883995

Semyenova, Seraphima K; Morozova, Elena V; Chrisanfova, Galina G; Gorokhov, Vladimir V; Arkhipov, Ivan A; Moskvin, Alexander S; Movsessyan, Sergey O; Ryskov, Alexei P

2006-06-01

93

Molecular differentiation of Opisthorchis viverrini and Clonorchis sinensis eggs by multiplex real-time PCR with high resolution melting analysis.  

PubMed

Opisthorchis viverrini and Clonorchis sinensis are parasites known to be carcinogenic and causative agents of cholangiocarcinoma in Asia. The standard method for diagnosis for those parasite infections is stool examination to detect parasite eggs. However, the method has low sensitivity, and eggs of O. viverrini and C. sinensis are difficult to distinguish from each other and from those of some other trematodes. Here, we report a multiplex real-time PCR coupled with high resolution melting (HRM) analysis for the differentiation of O. viverrini and C. sinensis eggs in fecal samples. Using 2 pairs of species-specific primers, DNA sequences from a portion of the mitochondrial NADH dehydrogenase subunit 2 (nad 2) gene, were amplified to generate 209 and 165 bp products for O. viverrini and C. sinensis, respectively. The distinct characteristics of HRM patterns were analyzed, and the melting temperatures peaked at 82.4±0.09? and 85.9±0.08? for O. viverrini and C. sinensis, respectively. This technique was able to detect as few as 1 egg of O. viverrini and 2 eggs of C. sinensis in a 150 mg fecal sample, which is equivalent to 7 and 14 eggs per gram of feces, respectively. The method is species-specific, rapid, simple, and does not require fluorescent probes or post-PCR processing for discrimination of eggs of the 2 species. It offers a new tool for differentiation and detection of Asian liver fluke infections in stool specimens. PMID:24516275

Kaewkong, Worasak; Intapan, Pewpan M; Sanpool, Oranuch; Janwan, Penchom; Thanchomnang, Tongjit; Laummaunwai, Porntip; Lulitanond, Viraphong; Doanh, Pham Ngoc; Maleewong, Wanchai

2013-12-01

94

Fasciola hepatica - monitoring the milky way? The use of tank milk for liver fluke monitoring in dairy herds as base for treatment strategies.  

PubMed

In this study 595 lactating cows originating from 31 carinthian farms were investigated in accordance of liver fluke infection using individual and tank milk as well as individual blood and faecal samples. Two commercial ELISAs were used to test the milk and blood serum, and the results were compared with coproscopy and a commercial copro-antigen ELISA. Receiver operating characteristics (ROC) and two-graph operating characteristics (TG ROC) of tank milk results were conducted based on the individual milk to determine the minimum reliable in-herd antibody prevalence for the predominant condition in the investigation area. In 17.8% of the examined individuals located in 64.5% of the farms eggs were detected by coproscopy. The copro-antigen ELISA delivered 13.4% positive individuals from 54.8% of the farms. The milk ELISAs showed 42.7% (Euroclone) and 44.2% (Pourquier) positive cows on 90.3% of the farms. The blood samples were positive in 43% (Euroclone) and 45.2% (Pourquier) of the individuals from 90.3% to 96.8% of the herds, respectively. Based on the milk and the blood an average in-herd prevalence of 30-45% can be assumed. The serum and milk samples delivered correlating results with kappa values between 0.94 and 0.97, whereas the coproscopy and copro-antigen ELISA did not correlate well with the ELISA results. The two different ELISA tests highly correlated on individual and on herd level. Both showed a reliable minimum in-herd prevalence of ?20%, meaning that one fifth of the individuals in a herd have to be positive to obtain a positive bulk tank milk result. In the investigated area a higher in-herd prevalence is expected, therefore the tank milk is useful as a monitoring tool and can be used as a basis for intervention strategies. PMID:21334811

Duscher, Ruth; Duscher, Georg; Hofer, Johannes; Tichy, Alexander; Prosl, Heinrich; Joachim, Anja

2011-06-10

95

A tegument-specific venom allergen-like protein of Clonorchis sinensis.  

PubMed

Venom allergen-like (VAL) proteins, members of the SCP/TAPS (sperm coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, have been reported from several parasitic helminths. As little is known about their biological functions, a VAL protein of the Chinese liver fluke Clonorchis sinensis was cloned and characterized. A complementary DNA (cDNA) encoding a 25-kDa protein was identified from an EST database of C. sinensis. A BLAST search revealed that the protein shares 46 % sequence identity with Schistosoma mansoni VAL 13 protein, and thus, the protein was named CsVAL13. Multiple sequence alignment indicated that the SCP/TAPS domain of CsVAL13 shares 39-46 % sequence identity with VAL proteins from parasitic helminths. His and Tyr, which help to stabilize protein structure, were highly conserved across the VAL protein sequences. Phylogenetic analysis showed that the SCP/TAPS domain of the CsVAL13 sequence clusters together with other group 2 VAL protein sequences. In the homology-modeled structure of CsVAL13, an ?-?-? sandwich and residues for a putative active site were highly conserved. Immune sera were obtained from BALB/c mice immunized with the recombinant CsVAL13 protein. Immunohistochemical localization using the immune sera revealed that CsVAL13 was distributed mainly in the tegument and intrauterine eggs of adult C. sinensis. These findings suggest that CsVAL13 may be involved in host-parasite interactions and immune stimulation on the surrounding host environments. PMID:25403376

Woo, Hea Sun; Kim, Tae Yun; Sohn, Woon-Mok; Yong, Tai-Soon

2015-01-01

96

Proteomic identification of potential Clonorchis sinensis excretory/secretory products capable of binding and activating human hepatic stellate cells.  

PubMed

Epidemiological and experimental evidence demonstrated that Clonorchis sinensis is an important risk factor of hepatic fibrosis and cholangiocarcinoma. C. sinensis excretory/secretory products (CsESPs) are protein complex including proteases, antioxidant enzymes, and metabolic enzymes, which may contribute to pathogenesis of liver fluke-associated hepatobiliary diseases. However, potential CsESP candidates involved into hepatic fibrosis and cholangiocarcinoma still remain to be elucidated. In the present study, we performed proteomic identification of CsESP candidates capable of binding and activating human hepatic stellate cell line LX-2. Immunofluorescence analysis confirmed the interaction of CsESPs with LX-2 cell membrane. LX-2 cells could be stimulated by CsESPs from 24 h post incubation (p?

Wang, Xiaoyun; Hu, Fengyu; Hu, Xuchu; Chen, Wenjun; Huang, Yan; Yu, Xinbing

2014-08-01

97

Immunization and challenge shown by hamsters infected with Opisthorchis viverrini following exposure to gamma-irradiated metacercariae of this carcinogenic liver fluke.  

PubMed

Here we report findings to optimize and standardize conditions to attenuate metacercariae of Opisthorchis viverrini by ionizing radiation to elicit protective immune responses to challenge infection. Metacercariae were gamma-irradiated and the ability of irradiated metacercariae to prevent patent infection of challenge metacercariae in hamsters was determined, as well as their ability to induce a host antibody response. Metacercariae irradiated in a dose-dependent manner, with 3, 5, 10, 12, 20, 25 and 50 Gray, were used to infect Syrian golden hamsters by stomach gavage to ascertain the effect of irradiation on ability of the worms to establish infection. In addition, other hamsters were infected with metacercariae irradiated with 20-50 Gray, followed by challenge with intact/wild-type (non-irradiated) metacercariae to determine the protective effect as established by the numbers of adult flukes, eggs of O. viverrini in hamster faeces and anti-O. viverrini antibody titres. Significantly fewer worms were recovered from hamsters immunized with metacercariae irradiated at 20, 25 and 50 Gray than from control hamsters infected with intact metacercariae or 0 Gray, and the worms showed damaged reproductive organs. Faecal egg numbers were decreased significantly in hamsters immunized with 25 and 50 Gray metacercariae of O. viverrini. Moreover, hamsters administered metacercariae that were protected elicited a robust, specific anti-fluke immunoglobulin G response compared to control hamsters, suggesting a role for antibody in protection elicited by radiation-attenuated metacercariae. PMID:25315797

Papatpremsiri, A; Junpue, P; Loukas, A; Brindley, P J; Bethony, J M; Sripa, B; Laha, T

2014-10-15

98

Expression profiles of glyceraldehyde-3-phosphate dehydrogenase from Clonorchis sinensis: a glycolytic enzyme with plasminogen binding capacity.  

PubMed

Globally, 15-20 million people are infected with Clonorchis sinensis (C. sinensis) which results in clonorchiasis. In China, clonorchiasis is considered to be one of the fastest-growing food-borne parasitic diseases. That more key molecules of C. sinensis are characterized will be helpful to understand biology and pathogenesis of the carcinogenic liver fluke. Glyceraldehyde-3-phosphate dehydrogenases (GAPDHs) from many species have functions other than their catalytic role in glycolysis. In the present study, we analyzed the sequence and structure of GAPDH from C. sinensis (CsGAPDH) by using bioinformatics tools and obtained its recombinant protein by prokaryotic expression system, to learn its expression profiles and molecular property. CsGAPDH could bind to human intrahepatic biliary epithelial cell in vivo and in vitro by the method of immunofluorescence assays. CsGAPDH also disturbed in lumen of biliary tract near to the parasite in the liver of infected rat. Western blotting analysis together with immunofluorescence assay indicated that CsGAPDH was a component of excretory/secretory proteins (CsESPs) and a surface-localized protein of C. sinensis. Quantitative real-time PCR (Q-PCR) and Western blotting demonstrated that CsGAPDHs are expressed at the life stages of adult worm, metacercaria, and egg, but the expression levels were different from each other. Recombinant CsGAPDH (rCsGAPDH) was confirmed to have the capacity to catalyze the conversion of glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate which was inhibited by AMP in a dose-dependent manner. In addition, rCsGAPDH was able to interact with human plasminogen in a dose-dependent manner by ELISA. The interaction could be inhibited by lysine. The plasminogen binding capacity of rCsGAPDH along with the distribution of CsGAPDH in vivo and in the liver of C. sinensis-infected rat hinted that surface-localized CsGAPDH might play an important role in host invasion of the worm besides its glycolytic activity. Our work will be a cornerstone for getting more messages about CsGAPDH and its role in biology and parasitism of C. sinensis. PMID:25300416

Hu, Yue; Zhang, Erhong; Huang, Lisi; Li, Wenfang; Liang, Pei; Wang, Xiaoyun; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-12-01

99

Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions  

SciTech Connect

Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection.

Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)] [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of)] [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

2011-04-22

100

Unchanged triclabendazole kinetics after co-administration with ivermectin and methimazole: failure of its therapeutic activity against triclabendazole-resistant liver flukes  

PubMed Central

Background The reduced drug accumulation based on enhanced drug efflux and metabolic capacity, identified in triclabendazole (TCBZ)-resistant Fasciola hepatica may contribute to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics and clinical efficacy of TCBZ administered alone or co-administered with ivermectin (IVM, efflux modulator) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica-parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica (Sligo isolate) were divided into three groups (n = 4): untreated control, TCBZ-treated (i.r. at 10 mg/kg) and TCBZ+IVM+MTZ treated sheep (10 i.r., 0.2 s.c. and 1.5 i.m. mg/kg, respectively). Plasma samples were collected and analysed by HPLC. In the clinical efficacy study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. Results The presence of IVM and MTZ did not affect the plasma disposition kinetics of TCBZ metabolites after the i.r. administration of TCBZ. The AUC value of TCBZ.SO obtained after TCBZ administration (653.9 ± 140.6 ?g.h/ml) was similar to that obtained after TCBZ co-administered with IVM and MTZ (650.7 ± 122.8 ?g.h/ml). Efficacy values of 56 and 38% were observed for TCBZ alone and for the combined treatment, respectively. No statistical differences (P > 0.05) were observed in fluke counts between treated groups and untreated control, which confirm the resistant status of the Sligo isolate. Conclusions The presence of IVM and MTZ did not affect the disposition kinetics of TCBZ and its metabolites. Thus, the combined drug treatment did not reverse the poor efficacy of TCBZ against TCBZ-resistant F. hepatica. PMID:20128898

2010-01-01

101

Epidemiological Survey on the Infection of Intestinal Flukes in Residents of Muan-gun, Jeollanam-do, the Republic of Korea  

PubMed Central

Infection status of intestinal flukes was investigated in residents of Muan-gun, Jeollanam-do, the Republic of Korea. Total 1,257 fecal samples of residents were examined by formalin-ether sedimentation technique and Kato-Katz thick smear method. Helminth eggs were detected from 95 (7.6%) residents, and eggs of heterophyid flukes and Clonorchis sinensis were found from 62 (4.9%) and 40 (3.2%) cases, respectively. The larger heterophyid eggs, somewhat dark-brown in color and 37.7 × 21.5 µm in average size, and found in 32 (2.6%) out of 62 egg positive cases of heterophyid flukes. To confirm the adult flukes, we performed worm recovery from 12 cases after praziquantel treatment and purgation with MgSO4. A total of 1,281 adult flukes, assigned to 7 species, were recovered from 9 cooperative cases. Heterophyes nocens (total 981 specimens) was collected from 9 cases, Stictodora fuscata (80) from 7, Gymnophalloides seoi (75) from 5, Pygidiopsis summa (140) from 3, Stellantchasmus falcatus (3) from 2, and Stictodora lari and Acanthotrema felis (each 1 worm) from 1 case each. The intrauterine eggs of S. fuscata collected from the recovered worm were identical with the larger heterophyid eggs detected in the stool examination. By the present study, it was confirmed that A. felis is a new intestinal fluke infecting humans, and residents in Muan-gun, Jeollanam-do are infected with variable species of intestinal trematodes. PMID:20585529

Cho, Shin-Hyeong; Cho, Pyo-Yun; Lee, Dong-Min; Kim, Tong-Soo; Kim, In-Sang; Hwang, Eun-Jung; Na, Byoung-Kuk

2010-01-01

102

Artemether, artesunate, praziquantel and tribendimidine administered singly at different dosages against Clonorchis sinensis: A comparative in vivo study  

Microsoft Academic Search

We comparatively assessed the in vivo efficacy of artemether, artesunate, praziquantel and tribendimidine against different stages of Clonorchis sinensis. Rats were infected with 40–50 C. sinensis metacercariae, and drugs were administered singly by the oral route at different dosages. Rats were dissected 2–4 weeks post-treatment and C. sinensis trematodes were removed from the liver and bile ducts and counted. We

Shu-Hua Xiao; Xue Jian; Marcel Tanner; Zhang Yong-Nian; Jennifer Keiser; Jürg Utzinger; Qiang Hui-Qiang

2008-01-01

103

A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites  

PubMed Central

The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs just prior to invasion into the wall of the gut of the host, rendering it an important target for drug development. The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. Here we characterize one of the cathepsin B enzymes (recombinant FhcatB1) from NEJ flukes. FhcatB1 has biochemical properties distinct from mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or Arg residues at the P2 substrate position and an inability to act as an exopeptidase. FhcatB1 was active across a broad pH range (optimal activity at pH 5.5–7.0) and resistant to inhibition by cystatin family inhibitors from sheep and humans, suggesting that this enzyme would be able to function in extracellular environments in its mammalian hosts. It appears, however, that the FhcatB1 protease functions largely as a digestive enzyme in the gut of the parasite, due to the localization of a specific, fluorescently labeled inhibitor with an Ile at the P2 position. Molecular modelling and dynamics were used to predict the basis for the unusual substrate specificity: a P2 Ile residue positions the substrate optimally for interaction with catalytic residues of the enzyme, and the enzyme lacks an occluding loop His residue crucial for exopeptidase activity. The unique features of the enzyme, particularly with regard to its specificity and likely importance to a vital stage of the parasite’s life cycle, make it an excellent target for therapeutic inhibitors or vaccination. PMID:19401154

Beckham, Simone A.; Piedrafita, David; Phillips, Carolyn I.; Samarawickrema, Nirma; Law, Ruby H.P.; Smooker, Peter M.; Quinsey, Noelene S.; Irving, James A.; Greenwood, Deanne; Verhelst, Steven H. L.; Bogyo, Matthew; Turk, Boris; Coetzer, Theresa H.; Wijeyewickrema, Lakshmi C.; Spithill, Terry W.; Pike, Robert N.

2012-01-01

104

Microscopic examination of gallbladder stones improves rate of detection of Clonorchis sinensis infection.  

PubMed

To improve the rate of detection of Clonorchis sinensis infection, we compared different specimens from patients with cholecystolithiasis. Feces, gallbladder bile, and gallbladder stones collected from 179 consecutive patients with cholecystolithiasis underwent microscopic examination, and according to the results, 30 egg-positive and 30 egg-negative fecal, gallbladder bile, and gallbladder stone specimens, respectively, underwent real-time fluorescent PCR. The detection rates of eggs in feces, bile, and gallbladder stones were 30.7%, 44.7%, and 69.8%, respectively, and the differences were statistically significant (P<0.01). The PCR results confirmed that the eggs in the specimens were C. sinensis eggs. Eggs in the feces were "fresh" and in the gallbladder stones were "old." Microscopic examination of gallbladder stones may improve the detection rates of C. sinensis infection, which is important for developing individualized treatments to prevent the recurrence of gallbladder stones and to prevent the occurrence of severe liver damage and cholangiocarcinoma. PMID:23698535

Qiao, Tie; Ma, Rui-hong; Luo, Xiao-bing; Zheng, Pei-ming; Luo, Zhen-liang; Yang, Liu-qing

2013-08-01

105

Fasciola hepatica: comparative effects of host resistance and parasite intra-specific interactions on size and reproductive histology in flukes from rats infected with isolates differing in triclabendazole sensitivity.  

PubMed

The efficacies of putative fasciolicides and vaccines against Fasciola hepatica are frequently monitored in clinical and field trials by determination of fluke egg output in host faeces and by worm counts in the host liver at autopsy. Less often used are parameters based on fluke size and histology, yet these can provide important indications of specific effects on the development of particular germ-line or somatic tissues, especially in relation to the timing and profligacy of egg production. In this study, F. hepatica metacercariae of two distinct isolates, the triclabendazole (TCBZ)-sensitive Cullompton isolate and the TCBZ-resistant Oberon isolate, were administered to rats as single-isolate or mixed-isolate infections. At autopsy 16 weeks later individual adult flukes were counted, measured and the reproductive organs were examined histologically. The degree of development of the testis tubules in each fluke was represented by a numerical score, based on the proportion of the histological section profiles occupied by testis tissue. The level of anti-F. hepatica antibody in the serum of each rat was determined by ELISA. It was found that Cullompton flukes were significantly larger than Oberon flukes, and that significantly more Cullompton metacercariae developed to adults than Oberon metacercariae. The Cullompton flukes showed histological evidence of aspermy and spermatogenic arrest, which was reflected in quantitatively reduced testicular development, as compared with the Oberon isolate. In Cullompton flukes, parthenogenetic egg development is implied. The size of Cullompton and Oberon flukes was significantly related to the number of adult flukes recovered, to the number of metacercariae administered, and to the percentage success of infection. The testis development score in both isolates was significantly related to the number of adult flukes recovered but not to the number of metacercariae administered, or to the percentage success of infection. Fluke size was positively related to testis score for both isolates, and a significant negative relationship was found between percentage success of infection and metacercarial dose. The results are interpreted in terms of differing interactions between various numbers of young flukes and host immunity during invasion of and migration in the hepatic parenchyma, and of fluke intra-specific (possibly pheromonal) stimulatory effects in the final stages of development, within the host bile ducts. No significant relationships were found between host antibody levels and fluke size or testis score. False positive serological reactions were found in some rats that had been infected, but found to harbour no flukes at autopsy. Clearly the act of eliminating the flukes involved generation of an immune response. PMID:21333449

Hanna, R E B; Gordon, A W; Moffett, D; Edgar, H W J; Oliver, L F; McConnell, S; Shaw, L; Brennan, G P; Fairweather, I

2011-06-10

106

Structural analysis of secretory phospholipase A2 from Clonorchis sinensis: therapeutic implications for hepatic fibrosis.  

PubMed

Hepatic fibrosis is a common complication of the infection by the parasite, Clonorchis sinensis. There is a high incidence of this disease in the Asian countries with an increased risk of conversion to cancer. A secretory phospholipase A(2) (PLA(2)) enzyme from the parasite is implicated in the pathology. This is an attractive drug target in the light of extensive structural characterization of this class of enzyme. In this study, the structure of the enzyme was modeled based on its sequence homology to the group III bee venom PLA(2). On analysis, the overall structure essentially is comprised of three helices, two sets of ?-wings and an elongated C-terminal extension. The structure is stabilized by four disulfide bonds. The structure is comprised of a calcium binding loop, active site and a substrate binding hydrophobic channel. The active site of the enzyme shows the classical features of PLA(2) with the participation of the three residues: histidine-aspartic acid-tyrosine in hydrogen bond formation. This is an interesting variation from the house keeping group III PLA(2) enzyme of human which has a histidine-aspartic acid and phenylalanine arrangement at the active site. This difference is therefore an important structural parameter that can be exploited to design specific inhibitor molecules against the pathogen PLA(2). Likewise, there are certain unique structural features in the hydrophobic channel and the putative membrane binding surface of the PLA(2) from Clonorchis sinensis that not only help understand the mechanism of action but also provide knowledge for a targeted therapy of liver fibrosis caused by the parasite. PMID:22215060

Hariprasad, Gururao; Kaur, Punit; Srinivasan, Alagiri; Singh, Tej Pal; Kumar, Manoj

2012-07-01

107

Cytokine responses in mice infected with Clonorchis sinensis  

Microsoft Academic Search

FVB and BALB\\/c mice show different morbidity, development of Clonorchis sinensis, and pathological changes following C. sinensis infection. FVB mice are susceptible and BALB\\/c mice are relatively more resistant to C. sinensis infection. To investigate the relationship between cytokine reaction and susceptibility to C. sinensis infection in FVB and BALB\\/c mice, we described both the patterns and kinetics of Th1

Yang Kyu Choi; Byung Il Yoon; Young Suk Won; Chul Ho Lee; Byung Hwa Hyun; Hyoung Chin Kim; Goo Taeg Oh; Dae Yong Kim

2003-01-01

108

Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.  

PubMed

Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. PMID:24958325

Chu, K-B; Kim, S-S; Lee, S-H; Lee, H-S; Joo, K-H; Lee, J-H; Lee, Y-S; Zheng, S; Quan, F-S

2014-10-01

109

Foodborne Intestinal Flukes in Southeast Asia  

PubMed Central

In Southeast Asia, a total of 59 species of foodborne intestinal flukes have been known to occur in humans. The largest group is the family Heterophyidae, which constitutes 22 species belonging to 9 genera (Centrocestus, Haplorchis, Heterophyes, Heterophyopsis, Metagonimus, Procerovum, Pygidiopsis, Stellantchasmus, and Stictodora). The next is the family Echinostomatidae, which includes 20 species in 8 genera (Artyfechinostomum, Acanthoparyphium, Echinochasmus, Echinoparyphium, Echinostoma, Episthmium, Euparyphium, and Hypoderaeum). The family Plagiorchiidae follows the next containing 5 species in 1 genus (Plagiorchis). The family Lecithodendriidae includes 3 species in 2 genera (Phaneropsolus and Prosthodendrium). In 9 other families, 1 species in 1 genus each is involved; Cathaemaciidae (Cathaemacia), Fasciolidae (Fasciolopsis), Gastrodiscidae (Gastrodiscoides), Gymnophallidae (Gymnophalloides), Microphallidae (Spelotrema), Neodiplostomidae (Neodiplostomum), Paramphistomatidae (Fischoederius), Psilostomidae (Psilorchis), and Strigeidae (Cotylurus). Various types of foods are sources of human infections. They include freshwater fish, brackish water fish, fresh water snails, brackish water snails (including the oyster), amphibians, terrestrial snakes, aquatic insects, and aquatic plants. The reservoir hosts include various species of mammals or birds.The host-parasite relationships have been studied in Metagonimus yokogawai, Echinostoma hortense, Fasciolopsis buski, Neodiplostomum seoulense, and Gymnophalloides seoi; however, the pathogenicity of each parasite species and host mucosal defense mechanisms are yet poorly understood. Clinical aspects of each parasite infection need more clarification. Differential diagnosis by fecal examination is difficult because of morphological similarity of eggs. Praziquantel is effective for most intestinal fluke infections. Continued efforts to understand epidemiological significance of intestinal fluke infections, with detection of further human cases, are required. PMID:19885337

Shin, Eun-Hee; Lee, Soon-Hyung; Rim, Han-Jong

2009-01-01

110

Evaluation of Clonorchis sinensis Recombinant 7-Kilodalton Antigen for Serodiagnosis of Clonorchiasis  

Microsoft Academic Search

The diagnostic applicability of the Clonorchis sinensis recombinant 7-kDa protein was evaluated. In enzyme- linked immunosorbent assays and immunoblots, the protein showed high sensitivities (81.3 and 71.9%, respectively) and specificities (92.6 and 89.7%, respectively) for sera obtained from various helminthic infec- tions. Some paragonimiasis sera showed cross-reactions. The antigen might be valuable in the serodiagnosis of human clonorchiasis. Clonorchis sinensis,

Qin-Ping Zhao; Sung-Ung Moon; Hyeong-Woo Lee; Byoung-Kuk Na; Seung-Yull Cho; Yoon Kong; Ming-Sen Jiang; Ai-Hua Li; Tong-Soo Kim

2004-01-01

111

Liver  

E-print Network

Lipids in liver wet and dry matter, liver moist and dry matter and their relationships were investigated based on species, sex and age in cows, buffaloes, sheep and goats. Mean percentage of lipids in liver wet and dry matter and liver dry matter in cows were 3.60%, 1.10%, 29.70%, and for buffaloes were 5.30%, 1.55%, 29.20%, sheep 3.00%, 0.83%, 27.90%, and goats 2.910%, 1.55 % and 28.40%, respectively. The highest and lowest percentage of lipids in liver wet and dry matter was observed in buffaloes and sheep, and for the liver dry matter was recorded in cows and sheep, respectively. Analyses showed significant differences in liver parameters among ruminants (p liver parameters. In overall 15.00 % of buffaloes and 3.50 % of cows showed over 10.00 % lipids in liver, while none of small ruminants appeared to have over 6.00 % lipids in liver. There was no correlation between liver lipid and liver dry matter. In conclusion mean percentage of lipid in liver dry matter in small ruminants was less than large ruminants. Liver dry matter was high in cows and low in sheep. Mean differences in liver parameters was significant, while the age and sex of the

Aligholi Ramin; Shahram Nozad; Babak Jelodari; Ghazaleh Ashtab; Zohreh Eftekhari; Sina Ramin; Key Words

2011-01-01

112

Human consumption of rumen flukes of cattle in India.  

PubMed

The practice of eating rumen flukes of cattle by a section of people living in Meghalaya, a north eastern State of India, is reported in this communication. Economically backward, some rural people belonging to Khasi, Jaintia, Garo, and Karbi tribes of Christian and Nepali communities who eat beef are accustomed to consuming cooked flukes during breakfast, meals, and also along with rice beer or alcohol. Inspection of the rumens of cattle during slaughter indicated a prevalence of flukes belonging to Cotylophoron, Paramphistomum, Calicophoron, Gastrothylax, and Fischoederius genera in 74% cases, and their collection from rumen ranged approximately from 50 g to 600 g. Biochemical analysis of flukes found 12.60% total protein, 0.78% fat, and 0.87% ash on fresh weight basis. High prevalence of flukes, easy visualization in rumen, their bulk collection, presence of nutritive value, absence of any ill effect, and lack of imminent danger of transmissibility are believed to be the rationales influencing their consumption by people. It is suggested that dietary benefits obtained from flukes might contribute to the energy transfer and inclusion in the food web. PMID:24964650

Sarmah, P C; Laha, R; Bhattacharjee, K; Goswami, A; Raquib, M; Kakati, P

2014-01-01

113

Biochemical characterization and functional analysis of fructose-1,6-bisphosphatase from Clonorchis sinensis.  

PubMed

Fructose-1,6-bisphosphatase (FBPase), a key regulatory enzyme of gluconeogenesis, plays an essential role in metabolism and development of most organisms. To the wealth of available knowledge about FBPase from Clonorchis sinensis (CsFBPase), in this study, the characteristics of CsFBPase and its potential role in pathogenesis of clonorchiasis were investigated. The Km value of CsFBPase was calculated to be 41.9 uM. The optimal temperature and pH of CsFBPase were 37 °C and pH 7.5-8.0, respectively. In addition, Mg(2+) or K(+) played a regulatory role in enzyme activity of CsFBPase. Both transcriptional and translational level of CsFBPase were higher in metacercariae (one of larva stages) than those in adult worm (P < 0.05). CsFBPase were observed to extensively express in the intestine, vitellaria and tegument of adult worms and ubiquitously in metacercariae. Moreover, CsFBPase was confirmed as a component of excretory/secretory products. Consequently, the translocation of CsFBPase could be detected on epithelial cells of bile duct in liver of C. sinensis infected rat. Recombinant CsFBPase can specifically bind to the membrane of human hepatic stellate cell line LX-2 by immunofluorescence analysis and stimulated proliferation and activation of LX-2 which demonstrated by Cell Counting Kit-8 and upregulation of key fibrosis-related factors, such as ?-smooth muscle actin, collagen I and collagen III using qRT-PCR. Thus, we predicated that CsFBPase might be a multifunctional enzyme which played as both regulatory enzyme and virulence factor in pathogenesis of C. sinensis infection. PMID:23652997

Liang, Pei; Sun, Jiufeng; Huang, Yan; Zhang, Fan; Zhou, Juanjuan; Hu, Yue; Wang, Xiaoyun; Liang, Chi; Zheng, Minghui; Xu, Yanquan; Mao, Qiang; Hu, Xuchu; Li, Xuerong; Xu, Jin; Lu, Gang; Yu, Xinbing

2013-07-01

114

Clonorchis sinensis: Molecular Cloning and Characterization of 28-kDa Glutathione S-Transferase  

Microsoft Academic Search

Kang, S-Y., Ahn, I.-Y., Park, C-Y., Chung, Y-B., Hong, S.-T., Kong, Y., Cho, S-Y., and Hong, S-J. 2001. Clonorchis sinensis: Molecular cloning and characterization of 28-kDa glutathione S-transferase. Experimental Parasitology97, 186–195. A 28-kDa glutathione S-transferase (Cs28GST) was purified from a Clonorchis sinensis cytosolic fraction through anion-exchange and glutathione-affinity column chromatographies. A monoclonal antibody raised against Cs28GST reacted specifically to the

Shin-Yong Kang; Il-Young Ahn; Chi-Young Park; Young-Bae Chung; Sung-Tae Hong; Yoon Kong; Seung-Yull Cho; Sung-Jong Hong

2001-01-01

115

Fatal multi-organ Clonorchis sinensis infection in dog: a case report.  

PubMed

We describe here a fatal case of a dog with extensive Clonorchis sinensis (C. sinensis) infection. C. sinensis were detected in organs including the abdomen, bladder and heart. The infection was very heavy with a total number of 155,183 worms. These worms were in different developmental stages, but the majority of them were adult. PMID:23643359

Ye, Chun-Yang; Yang, Zhi-Dong; Zheng, Hong-Lin

2013-07-01

116

Clonorchis sinensis: Development and evaluation of a nested polymerase chain reaction (PCR) assay  

Microsoft Academic Search

Clonorchis sinensis is a fish-borne trematode endemic to East Asia, which infects over 35 million people globally. In the study described here, we developed a nested polymerase chain reaction (PCR) method for the specific and reliable detection of C. sinensis. The primers designed from the nucleotide sequence data derived in this study were evaluated for their specificity and sensitivity for

Ammini Parvathi; H. Sanath Kumar; B. Kenchanna Prakasha; Jieyuan Lu; Xuenian Xu; Wei Hu; Zheng Feng; Indrani Karunasagar; Iddya Karunasagar

2007-01-01

117

Intraductal papillary neoplasm of the bile duct associated with Clonorchis sinensis infection  

Microsoft Academic Search

Intraductal papillary neoplasm of bile duct (IPNB) is one of the precursor lesions of cholangiocarcinoma. Although hepatolithiasis\\u000a has been extensively studied in its association with IPNBs, there had been no comprehensive study of IPNBs with Clonorchis sinensis infection. Twelve IPNBs were selected from 20 surgically resected cholangiocarcinomas, positive for C. sinensis tests (60%) and compared with eight IPNBs, selected from

Kee-Taek Jang; Seung-Mo Hong; Kyu Taek Lee; Jong Gyun Lee; Seoung Ho Choi; Jin Seok Heo; Dong Wook Choi; Dongil Choi; Jae Hoon Lim

2008-01-01

118

Analysis of the genes expressed in Clonorchis sinensis adults using the expressed sequence tag approach  

Microsoft Academic Search

Clonorchis sinensis is a biliary tract parasite, which infects over 30 million people in China, Korea and Southeast Asia through the ingestion of undercooked freshwater fish that harbour the infective metacercariae. The genes expressed in C. sinensis adults were identified in order to develop novel drugs, better diagnostics and vaccines for the parasite. The C. sinensis cDNA library was constructed and

Ji-Sook Lee; Jongweon Lee; Soon-Jung Park; Tai-Soon Yong

2003-01-01

119

Molecular cloning and immunological characterization of phosphoglycerate kinase from Clonorchis sinensis  

Microsoft Academic Search

The parasite Clonorchis sinensis was determined to utilize a large amount of external glucose to carry its energy metabolism. Phosphoglycerate kinase (PGK), a glycolytic enzyme, found in many parasites, has been identified as one of the candidate molecules distinguished from human counterparts for vaccine and drug developments. A cDNA clone purified by screening a C. sinensis cDNA library using a

Sung-Jong Hong; Kee-Young Seong; Woon-Mok Sohn; Kye-Yong Song

2000-01-01

120

Effect of artesunate and artemether against Clonorchis sinensis and Opisthorchis viverrini in rodent models  

Microsoft Academic Search

Food-borne trematodiasis is an emerging public health problem and there is a need to develop novel treatment options. We examined the in vivo efficacy of single oral doses of artesunate and artemether administered to rodents experimentally infected with either Clonorchis sinensis or Opisthorchis viverrini. Rats infected with adult C. sinensis were administered artesunate or artemether at doses of 75, 150

Jennifer Keiser; Xiao Shu-Hua; Xue Jian; Chang Zhen-San; Peter Odermatt; Smarn Tesana; Marcel Tanner; Jürg Utzinger

2006-01-01

121

Sensitive and species-specific detection of Clonorchis sinensis by PCR in infected snails and fishes  

Microsoft Academic Search

In the present study, PCR procedures have been established for a rapid and easy preparation of DNA of parasite stages from\\u000a the intermediate hosts, i.e. sporocysts and rediae in snails and metacercariae in fishes. Primers have been developed, which\\u000a enable a highly sensitive and species-specific detection of Clonorchis sinensis.

Boris Müller; Jürgen Schmidt; Heinz Mehlhorn

2007-01-01

122

Expression pattern and substrate specificity of Clonorchis sinensis tyrosinases.  

PubMed

Tyrosinase (TYR) is a copper-containing glycoenzyme that mediates hydroxylation of tyrosine into dihydroxyphenylalanine and oxidation of dihydroxyphenylalanine into dihydroxyphenylalanine quinone. TYRs play pivotal roles in eggshell sclerotisation of trematode parasites, while their comprehensive biochemical properties remain elusive. We characterised genes encoding four TYRs (CsTYR1-4) of Clonorchis sinensis, a causative agent of human hepatobiliary disease. These genes shared tightly conserved amino acid residues, two copper binding catalytic motifs and a cysteine-rich epidermal growth factor-like domain. The native and recombinant CsTYRs showed high reactivity against diphenol compounds, especially those with hydroxyl groups in ortho-positions (catechol and l-dihydroxyphenylalanine), but showed minimal activity toward monophenol compounds. Diphenolase activity was enhanced by increased pH of the reaction buffer from 5.0 to 7.0. The temporal induction of CsTYR expression coordinated with the sexual maturation of the worm; enzyme activity was mainly in the vitelline glands and intrauterine immature eggs proximal to the ovary. The primary structures and functional domains of CsTYRs showed significant similarities to those of the vertebrate orthologs, whereas the amino acids shared with the nematode and insect proteins were largely restricted in the bicopper active center. Unlike highly diverged TYR homologs in vertebrates, multiple paralogs have not yet evolved into the separate lineages in trematode genomes, suggesting that duplication of TYR genes might relate to increased genic dosage/redundancy in trematodes. In vitro treatment of copper chelator, diethyldithiocarbamic acid, inhibited generation of phenotypically normal egg. TYR proteins are essential for C. sinensis reproduction, thus might be targeted for therapeutic and vaccine strategies against clonorchiasis, which is prevalent in several Asian countries and is one of the most important predisposing factors for human cholangiocarcinoma. The close phylogenetic relationships between trematode and vertebrate homologs also provide a molecular clue to understand the multifaceted evolutionary pathway of TYR homologs across animal taxa. PMID:23770035

Bae, Young-An; Cai, Guo-Bin; Kim, Seon-Hee; Sohn, Woon-Mok; Kong, Yoon

2013-10-01

123

Biliary parasitic diseases including clonorchiasis, opisthorchiasis and fascioliasis  

Microsoft Academic Search

Parasitic infection of the biliary tree is caused by liver flukes, namely Clonorchis sinensis and Opisthorchis viverrini. These flukes reside in the peripheral small bile ducts of the liver and produce chronic inflammation of the bile duct, bile\\u000a duct dilatation, mechanical obstruction, and bile duct wall thickening. On imaging,\\u000a peripheral small intrahepatic bile ducts are dilated, but the large bile

Jae Hoon Lim; Eimorn Mairiang; Geung Hwan Ahn

2008-01-01

124

Biliary parasitic diseases including clonorchiasis, opisthorchiasis and fascioliasis  

Microsoft Academic Search

Parasitic infection of the biliary tree is caused by liver flukes, namely Clonorchis sinensis and Opisthorchis viverrini. These flukes reside in the peripheral small bile ducts of the liver and produce chronic inflammation of the bile duct, bile\\u000a duct dilatation, mechanical obstruction, and bile duct wall thickening. On imaging, peripheral small intrahepatic bile ducts\\u000a are dilated, but the large bile

Jae Hoon Lim; Eimorn Mairiang; Geung Hwan Ahn

125

Identification and characterization of microRNAs in Clonorchis sinensis of human health significance  

PubMed Central

Background Clonorchis sinensis is a zoonotic parasite causing clonorchiasis-associated human disease such as biliary calculi, cholecystitis, liver cirrhosis, and it is currently classified as carcinogenic to humans for cholangiocarcinoma. MicroRNAs (miRNAs) are non-coding, regulating small RNA molecules which are essential for the complex life cycles of parasites and are involved in parasitic infections. To identify and characterize miRNAs expressed in adult C. sinensis residing chronically in the biliary tract, we developed an integrative approach combining deep sequencing and bioinformatic predictions with stem-loop real-time PCR analysis. Results Here we report the use of this approach to identify and clone 6 new and 62,512 conserved C. sinensis miRNAs which belonged to 284 families. There was strong bias on families, family members and sequence nucleotides in C. sinensis. Uracil was the dominant nucleotide, particularly at positions 1, 14 and 22, which were located approximately at the beginning, middle and end of conserved miRNAs. There was no significant "seed region" at the first and ninth positions which were commonly found in human, animals and plants. Categorization of conserved miRNAs indicated that miRNAs of C. sinensis were still innovated and concentrated along three branches of the phylogenetic tree leading to bilaterians, insects and coelomates. There were two miRNA strategies in C. sinensis for its parasitic life: keeping a large category of miRNA families of different animals and keeping stringent conserved seed regions with high active innovation in other places of miRNAs mainly in the middle and the end, which were perfect for the parasite to perform its complex life style and for host changes. Conclusions The present study represented the first large scale characterization of C. sinensis miRNAs, which have implications for understanding the complex biology of this zoonotic parasite, as well as miRNA studies of other related species such as Opisthorchis viverrini and Opisthorchis felineus of human and animal health significance. PMID:20920166

2010-01-01

126

Fluke abundance versus host age for an invasive trematode (Dicrocoelium dendriticum) of sympatric elk and beef cattle in southeastern Alberta, Canada  

PubMed Central

Epidemiological parameters such as transmission rate, rate of parasite-induced host mortality, and rate of development of host defenses can be assessed indirectly by characterizing the manner in which parasite burdens change with host age. For parasites that are host generalists, estimates of these important parameters may be host-species dependent. In a cross-sectional study, we determined age–abundance profiles of infection in samples of sympatric free-ranging elk and domestic cattle infected with the lancet liver fluke, Dicrocoelium dendriticum. This parasite was introduced into Cypress Hills Provincial Park in southeastern Alberta, Canada in the mid 1990s, and now occurs in 60–90% of co-grazing elk and beef cattle examined at necropsy. The livers of 173 elk were made available by hunters during the 1997–2011 hunting seasons and livers from 35 cattle were purchased from ranchers. In elk, median worm abundance peaked in 6–24 month-olds (median?=?72, range?=?0–1006) then significantly declined to <10 worms/host in 10–16?year olds. The decline in fluke burden with age is not consistent with an age-related decline in exposure to metacercariae in intermediate hosts and high rates of fluke-induced host mortality are unlikely. Rather, the pattern of peak fluke burdens in elk calves and juveniles, followed by a decline in older animals is consistent with the development of a protective immune response in older hosts. There was no pattern of worm accumulation or decline in sympatric cattle, although statistical power to detect a significant effect was low. These results highlight the complexity and context-dependent nature of epidemiological processes in multi-host systems. PMID:25426422

Beck, Melissa A.; Goater, Cameron P.; Colwell, Douglas D.; van Paridon, Bradley J.

2014-01-01

127

Fluke abundance versus host age for an invasive trematode (Dicrocoelium dendriticum) of sympatric elk and beef cattle in southeastern Alberta, Canada.  

PubMed

Epidemiological parameters such as transmission rate, rate of parasite-induced host mortality, and rate of development of host defenses can be assessed indirectly by characterizing the manner in which parasite burdens change with host age. For parasites that are host generalists, estimates of these important parameters may be host-species dependent. In a cross-sectional study, we determined age-abundance profiles of infection in samples of sympatric free-ranging elk and domestic cattle infected with the lancet liver fluke, Dicrocoelium dendriticum. This parasite was introduced into Cypress Hills Provincial Park in southeastern Alberta, Canada in the mid 1990s, and now occurs in 60-90% of co-grazing elk and beef cattle examined at necropsy. The livers of 173 elk were made available by hunters during the 1997-2011 hunting seasons and livers from 35 cattle were purchased from ranchers. In elk, median worm abundance peaked in 6-24 month-olds (median?=?72, range?=?0-1006) then significantly declined to <10 worms/host in 10-16?year olds. The decline in fluke burden with age is not consistent with an age-related decline in exposure to metacercariae in intermediate hosts and high rates of fluke-induced host mortality are unlikely. Rather, the pattern of peak fluke burdens in elk calves and juveniles, followed by a decline in older animals is consistent with the development of a protective immune response in older hosts. There was no pattern of worm accumulation or decline in sympatric cattle, although statistical power to detect a significant effect was low. These results highlight the complexity and context-dependent nature of epidemiological processes in multi-host systems. PMID:25426422

Beck, Melissa A; Goater, Cameron P; Colwell, Douglas D; van Paridon, Bradley J

2014-12-01

128

Clonorchis sinensis: molecular cloning and functional expression of novel cytosolic malate dehydrogenase  

Microsoft Academic Search

The NAD-dependent cytosolic malate dehydrogenase (cMDH, EC 1.1.1.37) plays a pivotal role in the malate–aspartate shuttle pathway that operates in a metabolic coordination between cytosol and mitochondria, and thus is crucial for the survival and pathogenicity of the parasite. In the high throughput sequencing of the cDNA library constructed from the adult stage of Clonorchis sinensis, a cDNA clone containing

Nancai Zheng; Jin Xu; Zhongdao Wu; Jinzhong Chen; Xuchu Hu; Linxia Song; Guang Yang; Chaoneng Ji; Shouyi Chen; Shaohua Gu; Kang Ying; Xinbing Yu

2005-01-01

129

Viability of metacercariae of Clonorchis sinensis in frozen or salted freshwater fish  

Microsoft Academic Search

Metacercariae of Clonorchis sinensis were collected from freshwater fish (Pseudorasbora parva) after storage in a freezer at ?12°C for 10–20 days, in a freezer at ?20°C for 3–7 days, or treating with heavy salt (fish\\/salt = 10 gm\\/3 gm) at 26°C for 5–15 days. The metacercariae from the frozen fish were inoculated into 30 rats and eight rabbits, and those

P. C. Fan

1998-01-01

130

Epidemiological study on Clonorchis sinensis infection in Shenzhen area of Zhujiang delta in China  

Microsoft Academic Search

To study the transmission route and epidemiological features of Clonorchis sinensis infection in Shenzhen area, which is the biggest immigration city in the south of China, we examined 1,473 individuals (710\\u000a males and 763 females) to assess the current status of C. sinensis infection among the people in a village of Shenzhen in Zhujiang delta of Guangdong province, China. Freshwater

Renli Zhang; Shitong Gao; Yijie Geng; Dana Huang; Lei Yu; Shunxiang Zhang; Jingquan Cheng; Yucai Fu

2007-01-01

131

Variation of nuclear and mitochondrial DNAs in Korean and Chinese isolates of Clonorchis sinensis  

Microsoft Academic Search

We compared the DNA sequence difference of isolates of Clonorchis sinensis from one Korean (Kimhae) and two Chinese areas (Guangxi and Shenyang). The sequences of nuclear rDNA (18S, internal transcribed spacer 1 and 2: ITS1 and ITS2) and mitochondrial DNA (cytochrome c oxidase subunit 1: cox1) were compared. A very few intraspecific nucleotide substitution of the 18S, ITS1, ITS2 and

Soo-Ung Lee; Sun Huh

2004-01-01

132

Molecular cloning and characterization of a mu-class glutathione S-transferase from Clonorchis sinensis  

Microsoft Academic Search

In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high

Sung-Jong Hong; Ji-Yun Lee; Dong-Hwa Lee; Woon-Mok Sohn; Seung-Yull Cho

2001-01-01

133

The involvement of the cysteine proteases of Clonorchis sinensis metacercariae in excystment  

Microsoft Academic Search

The effects of trypsin, bile, trypsin-bile, pepsin, dithiothreitol (DTT) and metacercarial excretory-secretory product (ESP) on the in vitro excystment of Clonorchis sinensis metacercariae were investigated. The majority of metacercariae excysted immediately in trypsin-bile in PBS solution, a process which was complete after 30 min of incubation. When incubated in metacercarial ESP in PBS, excystment was potentiated in the presence of 5 mM

Shunyu Li; Young-Bae Chung; Byung-Suk Chung; Min-Ho Choi; Jae-Ran Yu; Sung-Tae Hong

2004-01-01

134

Characterization of partially purified 8 kDa antigenic protein of Clonorchis sinensis  

Microsoft Academic Search

The 8 kDa antigenic protein of Clonorchis sinensis was partially purified by ammonium sulfate precipitation and subsequently by a column chromatographic steps. The purified protein was separated into 7 and 8 kDa protein bands through SDS-tricine gel electrophoresis, while the protein was found to migrate to a 8 kDa band in 7.5-15% SDS-PAGE. The molecular weight of the antigen was

Young-Bae Chung; Mejeong Lee; Hyun-Jong Yang; Byung-Suk Chung; Shun-Yu Lee; Min-Ho Choi; Sung-Tae Hong

2002-01-01

135

Epidemiological investigation of Clonorchis sinensis infection in freshwater fishes in the Pearl River Delta  

Microsoft Academic Search

Pearl River Delta region is a high clonorchiasis-endemic area in China. However, no complete epidemiological data exist regarding\\u000a its infection in freshwater fishes, an important epidemic factor for Clonorchis sinensis. The present study collected freshwater fishes and shrimps from 32 sites of nine cities in the Pearl River Delta, and the\\u000a encysted metacercariae of C. sinensis were detected by digesting

Daixiong Chen; Jieyun Chen; Ji Huang; Xueying Chen; Dana Feng; Baofang Liang; Yuchuan Che; Xiaodan Liu; Cuihua Zhu; Xiaomin Li; Haoxian Shen

2010-01-01

136

The inability of tapeworm Hymenolepis diminuta and fluke Dicrocoelium dendriticum to metabolize praziquantel.  

PubMed

Biotransformation enzymes can, to a certain extent, protect parasitic worms against the toxic effects of anthelmintics and can contribute to drug-resistance development. The objective of our work was (1) to find and identify phase I and II metabolites of the anthelmintic praziquantel (PZQ) formed by the lancet fluke (Dicrocoelium dendriticum) and the rat tapeworm (Hymenolepis diminuta) and (2) to compare PZQ metabolites in helminths with PZQ biotransformation in rat as host species. Ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was used for this purpose. During in vitro incubations, mitochondria-like and microsomes-like fractions (prepared from homogenates of adult worms or from rat liver homogenate) were incubated with 10 and 100 ?M PZQ. Liquid/liquid extraction was used for samples during in vitro experiments. In the ex vivo study, living D. dendriticum and H. diminuta adults were incubated in RPMI-1640 medium in the presence of 50 nM or 100 nM PZQ for 24h. After incubation, the worms were removed from the medium and homogenized. Homogenates of worms, medium from the incubation of worms or rat hepatocytes and rat urine (collected during 24h after oral PZQ administration) were separately extracted using solid-phase extraction. The results showed that both D. dendriticum and H. diminuta enzymatic systems are not able to metabolize PZQ. On the other hand, thirty one different phase I and four phase II PZQ metabolites were detected in rat samples using UHPLC/MS/MS analyses. These results show that our experimental helminths, as the members of tapeworm and fluke groups of parasites, are not able to deactivate PZQ, and that the biotransformation enzymes of the studied helminths do not contribute to PZQ-resistance. PMID:21996005

Vok?ál, Ivan; Jirásko, Robert; Jedli?ková, Veronika; Bártíková, Hana; Skálová, Lenka; Lamka, Ji?í; Hol?apek, Michal; Szotáková, Barbora

2012-04-30

137

Genomic linkage map of the human blood fluke Schistosoma mansoni  

Microsoft Academic Search

Background  \\u000a Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained\\u000a in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals\\u000a heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance.\\u000a However, there is a

Charles D Criscione; Claudia LL Valentim; Hirohisa Hirai; Philip T LoVerde; Timothy JC Anderson

2009-01-01

138

Clonorchis sinensis ferritin heavy chain triggers free radicals and mediates inflammation signaling in human hepatic stellate cells.  

PubMed

Clonorchiasis, caused by direct and continuous contact with Clonorchis sinensis, is associated with hepatobiliary damage, inflammation, periductal fibrosis, and the development of cholangiocarcinoma. Hepatic stellate cells respond to liver injury through production of proinflammatory mediators which drive fibrogenesis; however, their endogenous sources and pathophysiological roles in host cells were not determined. C. sinensis ferritin heavy chain (CsFHC) was previously confirmed as a component of excretory/secretory products and exhibited a number of extrahepatic immunomodulatory properties in various diseases. In this study, we investigated the expression pattern and biological role of CsFHC in C. sinensis. CsFHC was expressed throughout life stages of C. sinensis. More importantly, we found that treatment of human hepatic stellate cell line LX-2 with CsFHC triggered the production of free radicals via time-dependent activation of NADPH oxidase, xanthine oxidase, and inducible nitric oxide synthase. The increase in free radicals substantially promoted the degradation of cytosolic I?B? and nuclear translocation of NF-?B subunits (p65 and p50). CsFHC-induced NF-?B activation was markedly attenuated by preincubation with specific inhibitors of corresponding free radical-producing enzyme or the antioxidant. In addition, CsFHC induced an increased expression level of proinflammatory cytokines, IL-1? and IL-6, in NF-?B-dependent manner. Our results indicate that CsFHC-triggered free radical-mediated NF-?B signaling is an important factor in the chronic inflammation caused by C. sinensis infection. PMID:25413629

Mao, Qiang; Xie, Zhizhi; Wang, Xiaoyun; Chen, Wenjun; Ren, Mengyu; Shang, Mei; Lei, Huali; Tian, Yanli; Li, Shan; Liang, Pei; Chen, Tingjin; Liang, Chi; Xu, Jin; Li, Xuerong; Huang, Yan; Yu, Xinbing

2015-02-01

139

Examination of the Three-Dimensional Geometry of Cetacean Flukes Using  

E-print Network

: Hydrodynamic Implications FRANK E. FISH,1 * JOHN T. BENESKI,1 AND DARLENE R. KETTEN2 1 Department of Biology Institution, Woods Hole, Massachusetts ABSTRACT The flukes of cetaceans function in the hydrodynamic, which were superior to engineered foils by 12­19%. Variation in the structure of ceta- cean flukes

140

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni  

E-print Network

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni Jan Dvora´k1 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH, Braschi S, Delcroix M, et al. (2009) SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke

Craik, Charles S.

141

Molecular cloning and characterization of WD40-repeat protein from Clonorchis sinensis.  

PubMed

WD40-repeat proteins have four to eight repeating units flanked by Gly-His (GH) and Trp-Asp (WD) at both termini and folds into a beta-propeller. A polypeptide deduced from a Clonorchis sinensis cDNA clone analyzed to have seven WD40-repeats and predicted to form a beta-propeller (CsWD1). The CsWD1 protein was expressed stage-specifically in the metacercariae and localized in the tegumental syncytium. The CsWD1 protein is suggested to serve as a platform for interacting partner proteins in the tegumental syncytium of C. sinensis metacercariae. PMID:17721710

Cho, Pyo Yun; Kim, Tea Im; Yoo, Won Gi; Li, Shunyu; Hong, Sung-Jong; Kim, Tae Yun; Park, Young Soon; Song, Kye-Yong; Choi, Min-Ho; Hong, Sung-Tae; Chung, Yong Je; LoVerde, Philip T; Osman, Ahmed

2007-12-01

142

Molecular cloning and characterization of WD40-repeat protein from Clonorchis sinensis  

Microsoft Academic Search

WD40-repeat proteins have four to eight repeating units flanked by Gly-His (GH) and Trp-Asp (WD) at both termini and folds\\u000a into a ?-propeller. A polypeptide deduced from a Clonorchis sinensis cDNA clone analyzed to have seven WD40-repeats and predicted to form a ?-propeller (CsWD1). The CsWD1 protein was expressed\\u000a stage-specifically in the metacercariae and localized in the tegumental syncytium. The

Pyo Yun Cho; Tea Im Kim; Won Gi Yoo; Shunyu Li; Sung-Jong Hong; Tae Yun Kim; Young Soon Park; Kye-Yong Song; Min-Ho Choi; Sung-Tae Hong; Yong Je Chung; Philip T. LoVerde; Ahmed Osman

2007-01-01

143

Enhanced liver cell mutations in trematode-infected Big Blue ® transgenic mice  

Microsoft Academic Search

Parasite infections in humans have long been associated with specific types of cancers. Schistosoma hematobium is a known inducer of urinary bladder cancer, Helicobacter pylori is a gastric carcinogen, and hepatitis B virus and Opisthorchis viverrini are causative agents of liver cell cancers. Another liver fluke, Fasciola hepatica, has also been identified as a neoplastic risk agent, primarily in animals.

James M. Gentile; Glenda J. Gentile; Bonnie Nannenga; Michelle Johnson; Harvey Blankespoor; Regina Montero

1998-01-01

144

Prevalence of cattle flukes infection at Andassa Livestock Research Center in north-west of Ethiopia  

PubMed Central

A cross sectional study was carried out from October 2010 to March 2011 at Andassa Livestock Research Center, North-West Ethiopia. The objective was to determine the prevalence of cattle flukes infection. Faecal samples were collected from a total of 384 cattle, cross breed (n= 39) and Fogera breed (n=345) of all age groups and sex. Sedimentation technique was employed for the recovery of fluke eggs from freshly collected fecal sample. The results indicated that the overall prevalence of bovine flukes infection was 60.42%. In this study, the highest prevalence was recorded from Paramphistomosis (45.83%) followed by Fasciolosis (23.96%), and Schistosomosis (9.89%). The prevalence of flukes infection was higher in age group 1- 2 years old. There was significant difference in case of Paramphistomosis among age groups. No significant association was found between crossed breeds and sex groups for fluke’s infection. The prevalence of Paramphistomosis was high in cross breed (58.97%) than Fogera breed (44.35%). However, in both cases, there was no significant difference. The result of the present study revealed that the prevalence of major bovine fluke infection in the study area was relatively low and is the definite proof of active infection.

Yeneneh, Asressa; Kebede, Hassen; Fentahun, Tewodros; Chanie, Mersha

2012-01-01

145

Karyological studies of bovine pancreatic flukes (Eurytrema sp.) and their phenotypes.  

PubMed

Chromosomes of gonadal tissues from pancreatic flukes of bovines were examined using air-drying techniques. Detailed karyological analyses on somatic cells with 26 chromosomes demonstrated the existence of two different karyotypes in these flukes. In conventional Giemsa preparations, two (Nos. 5 and 7) of 13 pairs of homologs showed a significant variance of morphology between flukes designated Types I and II by size. Additional differences were demonstrated by the C-banding method. The C-banded pattern in Nos. 3 and 8 of each karyotype was different, thereby indicating a different distribution of constitutive heterochromatin on these chromosomes. Among flukes recovered from seven cattle, 76.7% of the flukes were Type I (smaller) and 23.3% were Type II (larger). Obvious phenotypic variance between Types I and II was seen in the taxonomic characteristics such as body size, comparative size of the ventral to the oral sucker, and the egg size. Considering the variance of both types, as based on the statistical data of these characteristics and on comparable published data, at least two species of flukes can be found in the Japanese bovine pancreas. These were Eurytrema coelomaticum for Type I and E. pancreaticum for Type II, respectively. PMID:7131195

Moriyama, N

1982-10-01

146

Clonorchis sinensis infestation promotes three-dimensional aggregation and invasion of cholangiocarcinoma cells.  

PubMed

Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA). However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs). Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM). Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs) gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM. PMID:25340585

Won, Jihee; Ju, Jung-Won; Kim, Sun Min; Shin, Yoojin; Chung, Seok; Pak, Jhang Ho

2014-01-01

147

Clonorchis sinensis Infestation Promotes Three-Dimensional Aggregation and Invasion of Cholangiocarcinoma Cells  

PubMed Central

Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA). However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs). Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM). Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs) gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM. PMID:25340585

Won, Jihee; Ju, Jung-Won; Kim, Sun Min; Shin, Yoojin; Chung, Seok; Pak, Jhang Ho

2014-01-01

148

In vitro effects of various neuropharmacological agents on the motility of adult Clonorchis sinensis.  

PubMed

Stimulatory effects were observed in vitro when 5-HT was applied to whole worm preparations of Clonorchis sinensis. The stimulatory action of 5-HT was antagonized by tryptophol, clomipramine and imipramine. Strychnine remarkably stimulated motility. The action of strychnine was enhanced by 5-HT but inhibited by tryptophol. GABA, Phenylephrine, isoproterenol, dibenamine and phentolamine showed little influence on motility. Inhibitory effects were caused by eserine, arecoline, carbachol, DMPP and hemicholinium-3, but not by ACh, pilocarpine and McN-A-343. The inhibitory actions of eserine or carbachol were not antagonized by d-tubocurarine, hexamethonium or atropine. These results suggest that in regulating the motility of C. sinensis ACh may function as an inhibitory neurotransmitter and 5-HT as an excitatory transmitter in a manner similar to that already established for other trematodes such as Fasciola hepatica and Schistosoma mansoni. PMID:9780596

Shyu, L Y; Terada, M; Lee, H H

1998-08-01

149

[Prevalence of metacercariae of Clonorchis sinensis in wild freshwater fishes from Nenjiang River around Qiqihaer City].  

PubMed

From May to November 2013, a total of 1175 wild freshwater fishes were collected from the rivers of Chuoer, Yalu, Wuyuer, Alun, and Yin in Nenjiang River basin Qiqihaer City, and examined for metacercariae by direct compression method. The metacercariae were collected by artificial digestion method. Forty Kunming mice were infected with 30-40 metacercariae of Clonorchis sinensis. The mice were sacrificed 36 days after infection, and the adult worms were collected from bile duct, and observed under microscope. The results showed that a total of 1 175 fishes, belonging to nine species were taken from the Nenjiang basin of Qiqihaer region. The infection rate of Clonorchis sinensis metacercariae was 51.2% (602/1 175). All the species were infected besides Silurus asotus, and the highest prevalence (82.7%, 91/149) was found in Longnose gudgeon and the lowest (7.1%, 6/84) in Perccottus glenii. Among the rivers, the highest prevalence of metacercariae was in Wuyuer River. (65.7%, 218/332), and the lowest was in Alun River and Yin River (24.1%, 67/278) (P<0.05). Each part of the body in the Carassius auratus and Pseudorasbora parva were susceptible for metacercariae. The main infection site in Longnose gudgeon was the fish scales, and C. sinensis metacercaria was first discovered in the brain tissue of Phoxinus lagowskii. The experimental results showed that the adult worms of C. sinensis were found in the hepatic bile duct of the mice, with an infection rate of 85.0% (34/40). The suckers, digestive system and reproductive system of C. sinensis were visible clearly. PMID:25518594

Liu, Ji-xin; Sun, Yan-hong; Zhang, Hao; Li, Chao-pin

2014-08-01

150

Novel insights into the pathogenic importance, diagnosis and treatment of the rumen fluke (Calicophoron daubneyi) in cattle.  

PubMed

Recently, sharp increases in the prevalence of rumen fluke infections have been recorded throughout Western Europe. However, scarce information is available on the diagnosis, pathogenic importance and control of this parasite. We undertook 3 pilot studies to gain more insights into these aspects of rumen fluke biology in cattle. First, we evaluated the diagnostic performance of mini-FLOTAC to detect adult rumen fluke infections based on faecal egg count in an abattoir survey and found high sensitivity (0.94) and specificity (0.98). Moreover, there was an association between ruminal fluke burden (assessed by visual scoring) and faecal egg count and a cut-off of 200 eggs per gram is proposed to detect highly infected animals (>200 flukes present in the rumen and/or reticulum). There was also a significant association between ruminal fluke burden and faecal consistency. However, in a second study, we performed a case-control field survey to investigate the association between rumen fluke infection and herd-level problems with diarrhoea and no association was found. Finally, we evaluated the use of closantel (Flukiver(®), Elanco Animal Health, subcutaneous administration at 10mg/kg) to treat rumen fluke infection on 3 herds, but no significant reduction in egg output post-treatment was found. Because this result is in contrast with a previous study using an oral dose of closantel, more research is required into the effect of administration route on the efficacy of closantel on rumen fluke. PMID:25466618

Malrait, Karen; Verschave, Sien; Skuce, Philip; Van Loo, Hans; Vercruysse, Jozef; Charlier, Johannes

2015-01-15

151

Evaluation of the In Vivo Activity of Tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini  

Microsoft Academic Search

We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg\\/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg\\/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica. One-quarter of a billion people are infected with parasitic

Jennifer Keiser; Xiao Shu-Hua; Jacques Chollet; Marcel Tanner; Jurg Utzinger

2007-01-01

152

Clonorchis sinensis: glutathione S-transferase as a serodiagnostic antigen for detecting IgG and IgE antibodies  

Microsoft Academic Search

Human Clonorchis sinensis infection is endemic in East Asian countries. Glutathione S-transferases (GSTs) are anti-oxidant enzymes found in all living creatures as well as in trematodes. In this study, we examined the recombinant 26kDa GST protein of C. sinensis (Cs26GST) for its serodiagnostic antigenicity toward IgG and IgE antibodies by ELISA and immuno-enhanced chemiluminescence, respectively. In IgG ELISA, recombinant Cs26GST

Sung-Jong Hong; Tae Yun Kim; Xiao-Xian Gan; Li-Ying Shen; Kom Sukontason; Kabkaew Sukontason; Shin-Yong Kang

2002-01-01

153

Clonorchis sinensis and Opisthorchis viverrini: Development of a mitochondrial-based multiplex PCR for their identification and discrimination  

Microsoft Academic Search

We report a single, one-step PCR approach for detection and discrimination of Clonorchis sinensis and Opisthorchis viverrini in different life-stage forms (adults, metacercariae, and eggs) from fish intermediate hosts and from infected patients. Primers designed for species-specific PCR, amplifying portions of the mitochondrial (mt) genome, were also suitable for a multiplex PCR. The latter was a single, one-step reaction under

Thanh Hoa Le; Nguyen Van De; David Blair; Paiboon Sithithaworn; Donald P. McManus

2006-01-01

154

Molecular cloning and characterization of cDNA encoding a ubiquitin-conjugating enzyme from Clonorchis sinensis  

Microsoft Academic Search

The ubiquitin–proteasome system is an essential mechanism for protein degradation in eukaryotes. Protein ubiquitination is composed of a series of enzymatic reactions. The ubiquitin-conjugating enzyme (E2) is one of the important enzymes involved in the process. A cDNA encoding an E2 enzyme was cloned from a Clonorchis sinensis cDNA library by large-scale sequencing. This new cDNA contains 862 bp with a

Linxia Song; Shouyi Chen; Xinbing Yu; Zhongdao Wu; Jin Xu; Guang Yang; Nancai Zheng; Xuchu Hu; Lingchen Guo; Jianfeng Dai; Jian Xu; Chaoneng Ji; Shaohua Gu; Kang Ying

2004-01-01

155

HOST SPECIFICITY OF A PARASITIC FLUKE: IS POSTHODIPLOSTOMUM MINIMUM A CENTRARCHID-INFECTING GENERALIST OR SPECIALIST?  

PubMed

Abstract Parasite host specificity has important implications for species diversity estimates, food web dynamics, and host shifts. "White grub" is the metacercaria stage of a fluke (Posthodiplostomum minimum) that occurs in many fish species, but no attempt has been made to quantify variation in host use by this worm. Here, we used two approaches to evaluate host specificity within the strain that infects centrarchids (P. m. centrarchi). First, we measured parasite loads in two centrarchid hosts, bluegill (Lepomis macrochirus) and white crappie (Pomoxis annularis), from Spring Lake in McDonough County, Illinois. We found that infection levels differed significantly between these hosts. Prevalence in bluegill was 100% and the median intensity was 940 metacercariae, but only 57% of white crappie were infected (median intensity = 4). Site specificity of white grub also differed significantly between the two hosts. In bluegills, kidneys were most heavily infected, while in white crappies, livers harbored the most worms. We also performed a literature survey of P. minimum prevalence estimates from 14 centrarchid species from other localities. We calculated the mean white grub prevalence for each host species, and used this to calculate STD*, a quantitative index of host specificity. STD* was 1.33, significantly closer to the value for a specialist (STD* = 1.00) than a generalist (STD* = 2.00). This reflects the fact that P. minimum prevalence is higher in Lepomis species than it is in centrarchids outside this genus. These data show that P. minimum centrarchi specializes on Lepomis species, but the causes of this specialization are unknown. This worm may be a single species that differs in host use due to ecological or physiological host differences, or it may be a complex of species that vary in host use for similar reasons. Genetic data are required to evaluate these possibilities. PMID:25260116

Lane, Beth; Spier, Timothy; Weiderholt, Julia; Meagher, Shawn

2014-09-26

156

Fasciola hepatica: A comparative survey of adult fluke resistance to triclabendazole, nitroxynil and closantel on selected upland and lowland sheep farms in Northern Ireland using faecal egg counting, coproantigen ELISA testing and fluke histology.  

PubMed

In order to investigate the incidence and distribution of adult fluke resistance to the fasciolicide tricalbendazole (TCBZ) amongst populations of Fasciola hepatica in sheep flocks in Northern Ireland (NI), individual rectal faeces samples were collected from 3 groups of 20 sheep, before (pre-dose), and 21 days after (post-dose) treatment of the animals with TCBZ, nitroxynil or closantel, on each of 13 well-managed sheep farms distributed across the province. The efficacy of each flukicide was determined for each farm, using faecal egg count reduction (FECRT) and F. hepatica coproantigen ELISA testing. In certain flocks, 2 sheep with high pre-dose faecal egg counts (FEC) were killed 3 days and 21 days respectively after TCBZ treatment, and the histology of the fluke reproductive organs was compared with that of flukes from untreated sheep, and from sheep treated with nitroxynil or closantel 2 days prior to death, using haematoxylin and eosin (H&E) staining and an in situ hybridisation method (TdT-mediated dUDP nick end labelling [TUNEL]) to demonstrate apoptosis. Results from FECRT revealed that in all flocks with a high fluke burden, TCBZ was ineffective in treating chronic fasciolosis, and this finding was generally supported by the results of the coproantigen reduction test (CRT). The histology of reproductive organs of flukes from TCBZ-treated sheep in these flocks was normal, when compared with untreated flukes, and this, together with the FECRT and CRT findings, indicated a likely diagnosis of TCBZ resistance in all the flocks with a high fluke burden. In contrast, nitroxynil and closantel were found to be fully effective against TCBZ-resistant flukes in each of the flocks bearing a high chronic fluke burden. All of the flocks with a high fluke burden and TCBZ resistance were managed on lowland in the South and East of NI. Upland flocks, in the North and West, had low fluke burdens, or were clear of infection; and FECs were too low to allow valid resistance testing. The study highlights the high level of penetration of TCBZ resistance throughout F. hepatica populations in areas of intensively managed sheep production with a high level of fluke challenge. Further, it emphasises the importance of pre-emptive chemotherapeutic action against chronic fasciolosis, using flukicides effective against the egg-producing adult flukes to minimise pasture contamination for the next season's lamb crop. This study also exemplifies the use of several complementary methods (FECRT; CRT; fluke histology; comparative anthelmintic efficacy testing) for confirmation of a diagnosis of fluke drug resistance. PMID:25529143

Hanna, R E B; McMahon, C; Ellison, S; Edgar, H W; Kajugu, P-E; Gordon, A; Irwin, D; Barley, J P; Malone, F E; Brennan, G P; Fairweather, I

2015-01-15

157

The genome of the blood fluke Schistosoma mansoni.  

PubMed

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease. PMID:19606141

Berriman, Matthew; Haas, Brian J; LoVerde, Philip T; Wilson, R Alan; Dillon, Gary P; Cerqueira, Gustavo C; Mashiyama, Susan T; Al-Lazikani, Bissan; Andrade, Luiza F; Ashton, Peter D; Aslett, Martin A; Bartholomeu, Daniella C; Blandin, Gaelle; Caffrey, Conor R; Coghlan, Avril; Coulson, Richard; Day, Tim A; Delcher, Art; DeMarco, Ricardo; Djikeng, Appolinaire; Eyre, Tina; Gamble, John A; Ghedin, Elodie; Gu, Yong; Hertz-Fowler, Christiane; Hirai, Hirohisha; Hirai, Yuriko; Houston, Robin; Ivens, Alasdair; Johnston, David A; Lacerda, Daniela; Macedo, Camila D; McVeigh, Paul; Ning, Zemin; Oliveira, Guilherme; Overington, John P; Parkhill, Julian; Pertea, Mihaela; Pierce, Raymond J; Protasio, Anna V; Quail, Michael A; Rajandream, Marie-Adèle; Rogers, Jane; Sajid, Mohammed; Salzberg, Steven L; Stanke, Mario; Tivey, Adrian R; White, Owen; Williams, David L; Wortman, Jennifer; Wu, Wenjie; Zamanian, Mostafa; Zerlotini, Adhemar; Fraser-Liggett, Claire M; Barrell, Barclay G; El-Sayed, Najib M

2009-07-16

158

The genome of the blood fluke Schistosoma mansoni  

PubMed Central

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. We report here analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and novel families of micro-exon genes that undergo frequent alternate splicing. As the first sequenced flatworm, and a representative of the lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, while the identification of membrane receptors, ion channels and more than 300 proteases, provide new insights into the biology of the life cycle and novel targets. Bioinformatics approaches have identified metabolic chokepoints while a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease. PMID:19606141

Berriman, Matthew; Haas, Brian J.; LoVerde, Philip T.; Wilson, R. Alan; Dillon, Gary P.; Cerqueira, Gustavo C.; Mashiyama, Susan T.; Al-Lazikani, Bissan; Andrade, Luiza F.; Ashton, Peter D.; Aslett, Martin A.; Bartholomeu, Daniella C.; Blandin, Gaelle; Caffrey, Conor R.; Coghlan, Avril; Coulson, Richard; Day, Tim A.; Delcher, Art; DeMarco, Ricardo; Djikeng, Appoliniare; Eyre, Tina; Gamble, John A.; Ghedin, Elodie; Gu, Yong; Hertz-Fowler, Christiane; Hirai, Hirohisha; Hirai, Yuriko; Houston, Robin; Ivens, Alasdair; Johnston, David A.; Lacerda, Daniela; Macedo, Camila D.; McVeigh, Paul; Ning, Zemin; Oliveira, Guilherme; Overington, John P.; Parkhill, Julian; Pertea, Mihaela; Pierce, Raymond J.; Protasio, Anna V.; Quail, Michael A.; Rajandream, Marie-Adèle; Rogers, Jane; Sajid, Mohammed; Salzberg, Steven L.; Stanke, Mario; Tivey, Adrian R.; White, Owen; Williams, David L.; Wortman, Jennifer; Wu, Wenjie; Zamanian, Mostafa; Zerlotini, Adhemar; Fraser-Liggett, Claire M.; Barrell, Barclay G.; El-Sayed, Najib M.

2009-01-01

159

Human infection with the pancreas fluke, Eurytrema pancreaticum.  

PubMed

A 70-year-old Japanese woman with gastric cancer in Fukuoka Prefecture, Japan, was found at autopsy to have about 15 adult flukes, Eurytrema pancreaticum, in the dilated pancreatic ducts. The number of eosinophils in the blood was within normal limits. The two worms which were least damaged when removed from the gland were used for stained specimens, and another two were macerated to collect the eggs. The parasites (10 X 5, 11 X 7 mm in size) were broad, flattened, oval to fusiform. The suckers were large, the oral (2.1 X 2.0, 2.0 X 1.9 mm) being larger than the ventral (1.6 X 1.6, 1.4 X 1.5 mm). The eggs (47.06 +/- 3.88 X 30.35 +/- 2.74 microns) were embryonated in the uterus. These findings led to the identification of E. pancreaticum. This is the second documented case of eurytremiasis in man. PMID:6625056

Ishii, Y; Koga, M; Fujino, T; Higo, H; Ishibashi, J; Oka, K; Saito, S

1983-09-01

160

Fasciola hepatica: Histology of the testis in egg-producing adults of several laboratory-maintained isolates of flukes grown to maturity in cattle and sheep and in flukes from naturally infected hosts.  

PubMed

A total of 8 calves approximately 6 months old and 22 lambs of similar age were infected with metacercariae of Fasciola hepatica of various laboratory-maintained isolates including: Cullompton (sensitive to triclabendazole) and Sligo, Oberon and Leon (reported as resistant to triclabendazole). Ten to 16 weeks after infection, flukes were harvested from these experimental animals and the histology of the testis tissue was examined in a representative sample of flukes from each population. Adult wild-type flukes were also collected from 5 chronically infected cattle and 7 chronically infected sheep identified at post-mortem inspection. The testis tissue of these flukes was compared with that of the various laboratory-maintained isolates. Whilst the testes of the wild-type, Oberon and Leon flukes displayed all the usual cell types associated with spermatogenesis in Fasciola hepatica (spermatogonia, spermatocytes, spermatids and mature sperm), the Cullompton flukes from both cattle and sheep showed arrested spermatogenesis, with no stages later than primary spermatocytes represented in the testis profiles. The presence of numerous eosinophilic apoptotic bodies and nuclear fragments suggested that meiotic division was anomalous and incomplete. In contrast to the wild-type flukes, no mature spermatozoa were present in the testes or amongst the shelled eggs in the uterus. A high proportion of the eggs collected from these flukes hatched to release normal-appearing miracidia after an appropriate incubation period, as indeed was the case with all isolates examined and the wild-type flukes. It is concluded that the eggs of Cullompton flukes are capable of development without fertilization, i.e. are parthenogenetic. The implications of this for rapid evolution of resistant clones following an anthelmintic selection event are discussed. Amongst the Sligo flukes examined, two subtypes were recognised, namely, those flukes with all stages of spermatogenesis and mature spermatozoa present in the testes (type 1), and those flukes with all stages of spermatogenesis up to spermatids present, but no maturing spermatozoa in the testes (type 2). Each sheep infected with the Sligo isolate had both type 1 (approximately 60%) and type 2 (approximately 40%) flukes present in the population. Spermatozoa were found amongst the eggs in the uterus in 64% of flukes and this did not necessarily reflect the occurrence of spermatozoa in the testis profiles of particular flukes, suggesting that cross-fertilization had occurred. The apparent disruption of meiosis in the spermatocytes of the Cullompton flukes is consistent with reports that Cullompton flukes are triploid (3n=30), whereas the Sligo and wild-type flukes are diploid (2n=20). In the Sligo flukes the populations are apparently genetically heterogenous, with a proportion of the flukes unable to produce fully formed spermatozoa perhaps because of a failure in spermiogenesis involving elongation of the nucleus during morphogenesis. PMID:18774647

Hanna, R E B; Edgar, H; Moffett, D; McConnell, S; Fairweather, I; Brennan, G P; Trudgett, A; Hoey, E M; Cromie, L; Taylor, S M; Daniel, R

2008-11-01

161

9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...  

...transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms...transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms...shall be condemned. (b) In the case of sheep carcasses affected with tapeworm...

2014-01-01

162

9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...  

Code of Federal Regulations, 2013 CFR

...transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms...transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms...shall be condemned. (b) In the case of sheep carcasses affected with tapeworm...

2013-01-01

163

Exposure to N-nitroso compounds in a population of high liver cancer regions in Thailand: volatile nitrosamine (VNA) levels in Thai food  

Microsoft Academic Search

The recent case-control studies in Thailand indicate that a high incidence of liver cancer in Thailand has not been associated with common risk factors such as hepatitis B infection, aflatoxin intake and alcohol consumption. While the infestation by the liver fluke Opisthorchis viverrini (OV) accounted for the high risk in north-east Thailand, there was no such exposure in the other

E. J Mitacek; K. D Brunnemann; M Suttajit; N Martin; T Limsila; H Ohshima; L. S Caplan

1999-01-01

164

Experimental Final Hosts of Metagonimus hakubaensis (Trematoda: Heterophyidae) and Their Suitability to the Fluke.  

PubMed

Seven laboratory mammal and bird species were orally inoculated with 200-1,000 encysted Metagonimus hakubaensis metacercariae that had been isolated from naturally infected lampreys (Lethenteron reissneri) captured in Aomori Prefecture. At 8 and 15 days post-infection, adult flukes were recovered from all of the laboratory animals tested, and therefore, hamster, rat, mouse, dog, cat, chicken and quail were considered as final hosts of M. hakubaensis. Recovery rates of the fluke were higher in dogs and hamsters than in cats, rats, mice, chickens and quails. The flukes recovered from dogs and hamsters showed increased body length and higher fecundity than those recovered from the other hosts. These results indicate that the suitability of dogs and hamsters for M. hakubaensis infection is higher than that of the other laboratory animals. PMID:25187303

Kudo, Noboru; Ota, Chieko; Saka, Fumiko; Ikeda, Yae; Tomihisa, Yusuke; Itoi, Yasunaga; Oyamada, Takashi

2014-09-01

165

Experimental Final Hosts of Metagonimus Hakubaensis (Trematoda: Heterophyidae) and Their Suitability to the Fluke  

PubMed Central

Seven laboratory mammal and bird species were orally inoculated with 200–1,000 encysted Metagonimus hakubaensis metacercariae that had been isolated from naturally infected lampreys (Lethenteron reissneri) captured in Aomori Prefecture. At 8 and 15 days post-infection, adult flukes were recovered from all of the laboratory animals tested, and therefore, hamster, rat, mouse, dog, cat, chicken and quail were considered as final hosts of M. hakubaensis. Recovery rates of the fluke were higher in dogs and hamsters than in cats, rats, mice, chickens and quails. The flukes recovered from dogs and hamsters showed increased body length and higher fecundity than those recovered from the other hosts. These results indicate that the suitability of dogs and hamsters for M. hakubaensis infection is higher than that of the other laboratory animals. PMID:25649951

KUDO, Noboru; OTA, Chieko; SAKA, Fumiko; IKEDA, Yae; TOMIHISA, Yusuke; ITOI, Yasunaga; OYAMADA, Takashi

2014-01-01

166

Genomic linkage map of the human blood fluke Schistosoma mansoni  

PubMed Central

Background Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen. Results We genotyped grandparents, parents and 88 progeny to construct a 5.6 cM linkage map containing 243 microsatellites positioned on 203 of the largest scaffolds in the genome sequence. The map allows 70% of the estimated 300 Mb genome to be ordered on chromosomes, and highlights where scaffolds have been incorrectly assembled. The markers fall into eight main linkage groups, consistent with seven pairs of autosomes and one pair of sex chromosomes, and we were able to anchor linkage groups to chromosomes using fluorescent in situ hybridization. The genome measures 1,228.6 cM. Marker segregation reveals higher female recombination, confirms ZW inheritance patterns, and identifies recombination hotspots and regions of segregation distortion. Conclusions The genetic linkage map presented here is the first for S. mansoni and the first for a species in the phylum Platyhelminthes. The map provides the critical tool necessary for quantitative genetic analysis, aids genome assembly, and furnishes a framework for comparative flatworm genomics and field-based molecular epidemiological studies. PMID:19566921

Criscione, Charles D; Valentim, Claudia LL; Hirai, Hirohisa; LoVerde, Philip T; Anderson, Timothy JC

2009-01-01

167

Evaluation of medicinal plant extracts against ticks and fluke.  

PubMed

The present study was based on assessments of the antiparasitic activities to determine the efficacies of leaf hexane, chloroform, ethyl acetate, acetone and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb, Andrographis lineata Wallich ex Nees., Andrographis paniculata (Burm.f.) Wallich ex Nees., Cocculus hirsutus (L.) Diels, Eclipta prostrata L., and Tagetes erecta L. against the adult cattle tick Haemaphysalis bispinosa Neumann 1897 (Acarina: Ixodidae), the larvae of Rhipicephalus (Boophilus) microplus Canestrini 1887 (Acari: Ixodidae) and sheep fluke Paramphistomum cervi Zeder 1790 (Digenea: Paramphistomatidae). All plant extracts showed moderate toxic effect on parasites after 24 h of exposure; however, the highest parasitic activity was found in leaf ethyl acetate extract of A. lineata, methanol extract of A. marmelos, A. paniculata, and C. hirsutus against H. bispinosa (LC(50)?= 395.27, 358.45, 327.21 and 420.50 ppm); ethyl acetate extract of A. paniculata, C. hirsutus, methanol extracts of A. marmelos, A. lineata, and E. prostrata against the larvae of R. microplus (LC(50)?= 207.70, 258.61, 134.09, 206.00, and 274.33 ppm); hexane extract of A. lineata, ethyl acetate extract of A. paniculata, E. prostrata, acetone extracts of T. erecta, methanol extracts of A. marmelos and C. hirsutus against P. cervi (LC(50)?= 254.23, 451.17, 425.73, 253.60, 542.71, and 360.17 ppm), respectively. The present study is the first report on the veterinary parasitic activity of plant extracts from Southern India. PMID:20922419

Elango, Gandhi; Rahuman, Abdul Abdul

2011-03-01

168

Molecular characterization of voltage-gated calcium channel ?-subunits of Clonorchis sinensis.  

PubMed

The voltage-gated Ca(2+) channel ?-subunit is a member of the membrane-associated guanylate kinase family and modulates kinetic properties of the Ca(2+) channels, such as their voltage-dependent activation and inactivation rates. Two cDNA clones were identified to encode each ?-subunit isotype of the voltage-gated Ca(2+) channel of Clonorchis sinensis, CsCav?1 and CsCav?2, which consist of 606 and 887 amino acids, respectively. CsCav?1 was found to be similar to the ?-subunit containing two conserved serine residues that constitute the consensus protein kinase C phosphorylation site in the ?-interaction domain (BID). CsCav?2 had cysteine and alanine residues instead of the two serine residues conserved in BID and was homologous to variant ?-subunit of Schistosoma mansoni and Schistosoma japonicum. CsCav?1 and CsCav?2 were almost equally expressed in the adults and metacercariae, but were more expressed in adult C. sinensis than in metacercariae. Collectively, our findings suggest that substitution of the two serine residues in BID of CsCav?2 may render C. sinensis sensitive to praziquantel. PMID:24221884

Cho, Pyo Yun; Yoo, Won Gi; Kim, Tae Im; Ahn, Seong Kyu; Cho, Shin-Hyeong; Kim, Tong-Soo; Hong, Sung-Jong

2014-01-01

169

Coinfection with Clonorchis sinensis modulates murine host response against Trichinella spiralis infection.  

PubMed

Concomitant infections of different species of parasites are common in the field. Infection with one parasite species likely triggers host responses that may influence the subsequent infection of another species and alter disease outcomes. So far, the majority of studies have focused on single species parasite infection, and the mechanisms of protection induced by the first parasite infection against the secondary infection remain poorly defined. In this study, we assess the impact of trematode Clonorchis sinensis infection on the course of another tissue nematode Trichinella spiralis challenge. We observed that mice with preexisting C. sinensis infection had lower worm burden of intestinal T. spiralis than those infected with T. spiralis alone; mice with preexisting C. sinensis also had severe enteric histopathological changes and higher counts of intestinal Paneth cells in responses to T. spiralis challenge. The mRNA levels of interleukin (IL)-4, IL-10, IL-13, and tumor necrosis factor (TNF)-? from the small intestine and spleen of the different groups were analyzed using quantitative real-time polymerase chain reaction. Compared with that in mice infected with T. spiralis alone, the mRNA expression of IL-13 was significantly increased in the small intestine tissues and IL-4, IL-13, and TNF-? were significantly increased in the spleen tissues in the dually infected mice. Our findings suggest that a "preexisting" trematode infection of C. sinensis is a factor which contributes to reducing the establishment of T. spiralis adult worms in the small intestine. PMID:23846239

Chen, Ying; Huang, Bo; Huang, Shiguang; Yu, Xinbing; Li, Yonglong; Song, Wenjian; Li, Yongxiang; Lu, Fangli

2013-09-01

170

[From recognition to practice: The 140th anniversary of the discovery of Clonorchis sinensis].  

PubMed

It has been the 140th anniversary since the discovery of Clonorchis sinensis, of which adult worms were found by McConnell in an oversea Chinese in Calcutta, India, September of 1874. Then, Japanese scholar Kobayashi proved that freshwater fish served as the second intermediate hosts in 1910, while another Japanese parasitologist Muto found that the first intermediate hosts were freshwater snails in 1918. However, the perniciousness has not been recognized until recently. C. sinensis infection was classified as definite carcinogen (group 1) in cholangiocarcinoma in 2009 by the International Agency for Research on Cancer, WHO, and listed as one of the 17 diseases in WHO's first report on neglected tropical diseases in 2010, while its disease burden was published on line in an international journal in 2011. Nevertheless, our awareness on and practices in the control of clonorchiasis still lag behind the reality. Great efforts on research and control of clonorchiasis are especially required in China, since China takes the biggest share in global disease burden of clonorchiasis. PMID:25518585

Qian, Men-bao; Chen, Ying-dan; Zhou, Xiao-nong

2014-08-01

171

Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.  

PubMed

Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection. PMID:25138068

Liang, Pei; He, Lei; Xu, Yanquan; Chen, Xueqing; Huang, Yan; Ren, Mengyu; Liang, Chi; Li, Xuerong; Xu, Jin; Lu, Gang; Yu, Xinbing

2014-10-01

172

Identification and characterization of the second cysteine protease inhibitor of Clonorchis sinensis (CsStefin-2).  

PubMed

CsStefin-2, the second cysteine protease inhibitor of Clonorchis sinensis, was identified and characterized. CsStefin-2 is a cysteine protease inhibitor that belongs to family 1 stefins based on its phylogenetic and structural properties. However, CsStefin-2 had a QIVSG cystatin motif distinct from the common QVVAG cystatin motif that is well conserved in family 1 stefins. Mutagenesis analysis revealed that the two amino acid substitutions in the QIVSG cystatin motif of CsStefin-2 did not affect its inhibitory activity. Molecular modeling also indicated that no critical change was induced in the interaction between CsStefin-2 and its target enzyme. CsStefin-2 showed broad inhibitory activities against several cysteine proteases, including human cathepsins B and L, papain, and cathepsin Fs of C. sinensis (CsCFs), and effectively inhibited the autocatalytic maturation of CsCF-6. Native CsStefin-2 was assembled into a homo-tetramer, in which intermolecular disulfide bonds are not involved in the assembly of the tetramer. CsStefin-2 was expressed throughout the various developmental stages of the parasite and was localized in the intestinal epithelium, where CsCFs are actively synthesized. These results suggest that CsStefin-2 is the second active cysteine protease inhibitor of C. sinensis that shares functional redundancy with CsStefin-1 to modulate the activity and processing of CsCFs. PMID:24100605

Kang, Jung-Mi; Ju, Hye-Lim; Lee, Kon Ho; Kim, Tong-Soo; Pak, Jhang Ho; Sohn, Woon-Mok; Na, Byoung-Kuk

2014-01-01

173

Molecular characterization and expression of Rab7 from Clonorchis sinensis and its potential role in autophagy.  

PubMed

Accumulating evidences suggest that Rab7 GTPase is important for the normal progression of autophagy. However, the role of Rab7 GTPase in regulation of autophagy in Clonorchis sinensis is not known. In this study, a gene encoding Rab7 was isolated from C. sinensis adult cDNA. Recombinant CsRab7 was expressed and purified from Escherichia coli. CsRab7 transcripts were detected in the cDNA of adult worm, metacercaria, cercaria, and egg of C. sinensis, and were highly expressed in the metacercaria. Immunohistochemical localization results revealed that CsRab7 was specifically deposited on the vitellarium and eggs of adult worm. Furthermore, EGFP signal of CsRab7WT and the active mutant CsRab7Q67L were associated with autophagic vesicles in transiently transfected 293T cells. It is concluded from the present study that CsRab7 GTPase possibly contributes to the development of C. sinensis and that the autophagy pathway could be an important site of action with respect to the developmental role of CsRab7 in C. sinensis. PMID:23609597

Jia, Feifei; Li, Ye; Huang, Yan; Chen, Tingjin; Li, Shan; Xu, Yanquan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2013-07-01

174

RNAi-mediated silencing of enolase confirms its biological importance in Clonorchis sinensis.  

PubMed

Clonorchis sinensis (C. sinensis) infection is still a common public health problem in freshwater fish consumption areas in Asian countries. More molecular evidence are required to speed up the prevention strategies to control this kind of infectious disease. In the present study, to confirm the biological importance of Csenolase followed by our previous observations of the key metabolic enzyme, we explored the RNA silence effect of the Csenolase-derived RNA interference (RNAi) in C. sinensis. The extramembranous region aa105-226 was selected as the target sequence of RNA silence. Csenolase-derived double strand RNA (dsRNA-Csenolase, 366 bp) was synthetized and delivered into C. sinensis by soaking approach. The penetration of dsRNA into adult worms and metacercariae was tracked using fluorescently labeled RNA. Western blotting and qRT-PCR experiments were performed to determine dsRNA-Csenolase-silencing effect. Our results showed that, after incubating for 120 h, dsRNA-Csenolase could effectively target and downregulate the expression of Csenolase in both adult worms (P < 0.001) and metacercariae (P < 0.01), resulting in a remarkable killing effect on C. sinensis adult worms (P < 0.01). Fluorescent Cy3-labeled dsRNA was mostly deposited in the uterus and vitellarium of adult worm and in the cyst wall of metacercaria. The present study is the first report of RNAi trials in C. sinensis, allowing further applications in identifying functional genes in C. sinensis. PMID:24458653

Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Huang, Yan; Li, Xuerong; Yu, Xinbing

2014-04-01

175

The identification of a Clonorchis sinensis gene encoding an antigenic egg protein.  

PubMed

The cDNA library of Clonorchis sinensis was screened for genes encoding antigenic proteins by using sera from clonorchiasis patients. A gene of 888 bp encoding a 28-kDa protein (Cs28) was cloned and found to contain a high percentage of glycine (20%), tyrosine (11%), and lysine (11%). The amino acid sequence of Cs28 showed 60% homology with the vitelline B precursor protein of Opisthorchis viverrini and of 33% homology with the vitelline B1 and B2 proteins of Fasciola hepatica. A strong positive reaction was observed in the intrauterine eggs of adult C. sinensis by immunohistochemical analysis using specific immune sera against recombinant Cs28 protein (rCs28). By immunoblot analysis, rCs28 displayed an antigenic reaction with 73% of the serum samples from 115 cases of clonorchiasis. In addition, it cross-reacted with the sera of 77.5% of 40 opisthorchiasis cases, 90% of 20 schistosomiasis cases, and 50% of 10 paragonimiasis cases. However, no cross-reactions were observed with the sera of sparganosis or cysticercosis patients. In conclusion, the Cs28 protein was identified as an egg protein of C. sinensis and as an antigen common to the trematode species examined. PMID:15616856

Lee, Mejeong; Chung, Young-Bae; Lee, Suk-Keun; Chung, Byung-Suk; Li, Shunyu; Choi, Min-Ho; Hong, Sung-Tae

2005-02-01

176

Cloning, characterization, and expression of a novel secretory lipase-like gene from Clonorchis sinensis.  

PubMed

A secretory lipase-like gene was isolated from total cDNA of adult Clonorchis sinensis. The gene has an open reading frame of 1,218 bp long and encodes for a protein of 406 amino acids including a putative signal peptide of 20 amino acids. The deduced amino acid sequence including signal peptide has 42-45% identity with lipase of other species and two typical enzymic active sites that contain consensus sequence (Gly-X-Ser-X-Gly) of lipase. The cDNA encoding this protein was subcloned into pET-28a (+) expression vector and expressed in Escherichia coli. The expressed fusion protein has a molecular mass of about 45 kDa. Prediction of signal peptide and Western blot analysis indicated that the secretory lipase-like protein is an excretory-secretory product of C. sinensis. Immunostaining revealed that the secretory lipase-like protein was localized in the tegument of the adult worm and metacercaria. These results provide basis for further studies on the nutrition taking and invasion of C. sinensis mediated by the secretory lipase-like protein. PMID:19756752

Hu, Fengyu; Chen, Wanshan; Li, Linhua; Lu, Yecheng; Song, Weinan; Kuang, Yanling; Zhang, Fuchun

2009-11-01

177

Prevalence of Clonorchis sinensis infection in dogs and cats in subtropical southern China  

PubMed Central

Background Clonorchiasis, caused by Clonorchis sinensis, is one of the major parasitic zoonoses in China, particularly in China's southern Guangdong province where the prevalence of C. sinensis infection in humans is high. However, little is known of the prevalence of C. sinensis infection in its reservoir hosts dogs and cats. Hence, the prevalence of C. sinensis infection in dogs and cats was investigated in Guangdong province, China between October 2006 and March 2008. Results A total of 503 dogs and 194 cats from 13 administrative regions in Guangdong province were examined by post-mortem examination. The worms were examined, counted, and identified to species according to existing keys and descriptions. The average prevalences of C. sinensis infection in dogs and cats were 20.5% and 41.8%, respectively. The infection intensities in dogs were usually light, but in cats the infection intensities were more serious. The prevalences were higher in some of the cities located in the Pearl River Delta region which is the most important endemic area in Guangdong province, but the prevalences were relatively lower in seaside cities. Conclusions The present investigation revealed a high prevalence of C. sinensis infection in its reservoir hosts dogs and cats in China's subtropical Guangdong province, which provides relevant "base-line" data for conducting control strategies and measures against clonorchiasis in this region. PMID:21929783

2011-01-01

178

The Effects of Tail Flukes on the Swimming Pattern of Atlantic Bottlenose Dolphins  

Microsoft Academic Search

Atlantic bottlenose dolphins are top predators in the wild, due in part because they are excellent swimmers. When dolphins swim through the water, the tail flukes are moved in an up and down motion to propel the animal through the water. They use the pectoral fins for steering and braking, and the dorsal fin for stabilization as they swim. Using

Lauri Leach

2009-01-01

179

Eurytrema pancreaticum: the in vitro effect of praziquantel and triclabendazole on the adult fluke.  

PubMed

The efficacy and tolerance of the 80 microg/ml praziquantel (PZQ) and 40 microg/ml triclabendazole (TCZ) against adult stage Eurytrema pancreaticum in vitro were investigated at 3, 12, and 15 h incubation. Motility of the flukes and histopathological changes were studied. Sudden paralysis and death were observed after exposed to PZQ as early as 3h incubation. In contrast, the TCZ treated flukes showed active mobility at all intervals. By light microscopic examination, severe damages in various organs such as tegument, muscle, and testes were observed early at 12h incubation of these drugs. PZQ caused more severe damage to flukes than TCZ. There were vigorous contraction of musculature, progressive shrinkage of circular and longitudinal muscles, vacuolization and disintegration of the tegument disrupting the worms' outer surface including detachment of spines in the PZQ treatment. The cells in testes were slightly increased in size and followed by degeneration leaving several hollow spaces. The uterus and vitelline glands remained unaffected. The direct observation of the fluke motility and light microscopic study highly suggested that PZQ was more effective than TCZ treatment for the eurytremiasis infection. PMID:16125702

Jiraungkoorskul, Wannee; Sahaphong, Somphong; Tansatit, Tawewan; Kangwanrangsan, Niwat; Pipatshukiat, Siriporn

2005-11-01

180

Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini.  

PubMed

Protease activities in extracts of Opisthorchis viverrini were investigated using gelatin zymography and fluorogenic peptide substrates. Using gelatin-impregnated X-ray film, 2 microg of O. viverrini excretory-secretory products (Ov-ES) and adult somatic extract (Ov-SE) showed proteolytic activity. Zymography of both O. viverrini extracts revealed bands at approximately 30 kDa. Using fluorogenic peptide substrates, the majority of O. viverrini activity was determined to be cathepsin L-like cysteine protease (cleaved Z-Phe-Arg-aminomethylcoumarin (AMC)) whereas little or no activity was ascribable to other classes of proteases. The O. viverrini cysteine protease activity was greatest at pH 6.0 and the activity was inhibited by the class-specific inhibitors, E-64 and Z-Ala-CHN2. Chromatographic purification of O. viverrini cysteine proteases on thiol-sepharose enriched for protein(s) of approximately 30 kDa from Ov-ES and Ov-SE. The activity profile of the purified enzyme was similar to that of the cathepsin L-like activity characterized in Ov-SE and Ov-ES. Furthermore, determination of cysteine protease activity in several developmental stages of the parasite revealed the highest protease activity in metacercariae soluble extract, followed by Ov-ES, egg soluble extract, and Ov-SE. These findings demonstrated that O. viverrini has a cathepsin L-like cysteine protease(s) and suggested that abundant cysteine protease activity was present in metacercariae where the hydrolase might be involved in cyst excystation during mammalian infection. PMID:18092178

Kaewpitoon, Natthawut; Laha, Thewarach; Kaewkes, Sasithorn; Yongvanit, Puangrat; Brindley, Paul J; Loukas, Alex; Sripa, Banchob

2008-03-01

181

Characterization of cysteine proteases from the carcinogenic liver fluke, Opisthorchis viverrini  

Microsoft Academic Search

Protease activities in extracts of Opisthorchis viverrini were investigated using gelatin zymography and fluorogenic peptide substrates. Using gelatin-impregnated X-ray film, 2 ?g\\u000a of O. viverrini excretory–secretory products (Ov-ES) and adult somatic extract (Ov-SE) showed proteolytic activity. Zymography of both O. viverrini extracts revealed bands at ~30 kDa. Using fluorogenic peptide substrates, the majority of O. viverrini activity was determined to be cathepsin

Natthawut Kaewpitoon; Thewarach Laha; Sasithorn Kaewkes; Puangrat Yongvanit; Paul J. Brindley; Alex Loukas; Banchob Sripa

2008-01-01

182

Anti-inflammatory effect of prednisolone on the growth of human liver fluke in experimental opisthorchiasis.  

PubMed

Opisthorchis viverrini is one of the risk factors for cholangiocarcinoma (CCA) development and is endemic in Southeast Asia including Thailand. CCA is induced by chronic inflammation from a combination of mechanical damage, parasite secretions, and immunopathology. Chronic infection with O. viverrini has been associated with several hepatobiliary diseases which affect the development of hepatobiliary cancer and CCA. Therefore, reducing the pathogenesis from O. viverrini infection may be one of the choices to reduce the risk of cholangiocarcinoma development. Prednisolone is one of the steroidal anti-inflammatory drugs that suppress inflammation, and its use has risen continuously in recent years. We therefore investigated the effect of prednisolone on pathological changes in Syrian hamster opisthorchiasis, in terms of gross and histopathological changes, worm size, eggs per gram, eggs per worm, and immunohistochemical staining for COX2. Syrian hamsters were divided into three groups: uninfected control; O. viverrini-infected (OV); and O. viverrini-infected plus prednisolone administration (OVP). The results showed an anti-inflammatory effect in the OVP group by a reduction of the inflammatory cells surrounding the intrahepatic bile ducts. However, in addition, parasite sizes for all times of observation were larger than for other groups, which was also correlated with increased eggs per worm and eggs per gram of feces. This result suggests that prednisolone is useful in suppressing inflammation in Syrian hamster opisthorchiasis, whereas it was also beneficial for parasites by enhancing their reproductive development. To clarify the mechanism of this phenomenon, further studies are under investigation. PMID:22186974

Juasook, Amornrat; Boonmars, Thidarut; Kaewkes, Sasithorn; Loilome, Watcharin; Veteewuthacharn, Kulathida; Wu, Zhiliang; Yongvanit, Puangrat

2012-06-01

183

Aberrant Expression of NF-?B in Liver Fluke Associated Cholangiocarcinoma: Implications for Targeted Therapy  

PubMed Central

Background Up-regulation and association of nuclear factor kappa B (NF-?B) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-?B in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-?B as the therapeutic target of CCA was demonstrated. Methodology Expression of NF-?B in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-?B inhibitor, was used to inhibit NF-?B action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Principal Findings Normal bile duct epithelia rarely expressed NF-?B (subunits p50, p52 and p65), whereas all CCA patient tissues (n ?=? 48) over-expressed all NF-?B subunits. Inhibiting NF-?B action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions–Bcl-2, XIAP–and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. Conclusions NF-?B was over-expressed in CCA tissues. Inhibition of NF-?B action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-?B as a molecular target for CCA therapy. PMID:25170898

Seubwai, Wunchana; Wongkham, Chaisiri; Puapairoj, Anucha; Khuntikeo, Narong; Pugkhem, Ake; Hahnvajanawong, Chariya; Chaiyagool, Jariya; Umezawa, Kazuo; Okada, Seiji; Wongkham, Sopit

2014-01-01

184

Activity of luxabendazole against liver flukes, gastrointestinal roundworms, and lungworms in naturally infected sheep.  

PubMed

The anthelmintic potential of luxabendazole was investigated in sheep harboring mixed naturally acquired helminth infections. Results were assessed by comparing worm counts of the treated groups (seven animals each) on days 7-8 posttreatment with those of the nontreated control group, except for protostrongylid lungworms, for which the changes in pre- and posttreatment group mean larval counts/g feces were assessed for intensity effect. A single oral treatment at doses of 10.0 or 12.5 mg/kg body wt removed 97.6% of the adult Fasciola hepatica and 63.2%-83.8% of the Dicrocoelium dendriticum. Luxabendazole at 7.5, 10.0, and 12.5 mg/kg proved 100% effective in removing adult worms of the genera Haemonchus, Ostertagia, Trichostrongylus, Cooperia and Nematodirus as well as tissue-associated larval stages of gastrointestinal nematodes of the abomasal mucosa. The drug showed an intensity effect of 79.7%-87.6% against Strongyloides papillosus. Luxabendazole removed all Dictyocaulus filaria and reduced the fecal excretion of larvae of protostrongylid species (Protostrongylus rufescens, Neostrongylus linearis, Cystocaulus ocreatus, Muellerius capillaris) by 97.8%-99.6%. The efficacy of luxabendazole compared favorably with that of Diplin Kombi (oxyclozanide and levamisole), which was used as a reference drug. PMID:2974592

Kassai, T; Takáts, C; Fok, E; Redl, P

1988-01-01

185

Activity of luxabendazole against liver flukes, gastrointestinal roundworms, and lungworms in naturally infected sheep  

Microsoft Academic Search

The anthelmintic potential of luxabendazolc was investigated in sheep harboring mixed naturally acquired helminth infections. Results were assessed by comparing worm counts of the treated groups (seven animals each) on days 7–8 posttreatment with those of the nontreated control group, except for protostrongylid lungworms, for which the changes in pre-and posttreatment group mean larval counts\\/g feces were assessed for intensity

T. Kassai; Csilla Takfits; Éva Fok; P. Redl

1988-01-01

186

Molecular Expression of a Cysteine Proteinase of Clonorchis sinensis and Its Application to an Enzyme-Linked Immunosorbent Assay for Immunodiagnosis of Clonorchiasis  

Microsoft Academic Search

We produced a recombinant cysteine proteinase of Clonorchis sinensis and tested its value as an antigen for serologic diagnosis of C. sinensis infections. The predicted amino acid sequence of the cysteine proteinase of C. sinensis was 58, 48, and 40% identical to those of cathepsin L cysteine proteinases from Paragonimus westermani, Schistosoma japonicum, and Fasciola hepatica, respectively. Western blotting analysis

Isao Nagano; Fuquan Pei; Zhiliang Wu; Jun Wu; Huier Cui; Thidarut Boonmars; Yuzo Takahashi

2004-01-01

187

Clonorchis sinensis metacercarial infection in the pond smelt Hypomesus olidus and the minnow Zacco platypus collected from the Soyang and Daechung Lakes  

Microsoft Academic Search

The pond smelt Hypomesus olidus and minnow Zacco platypus were collected from the Soyang and Daechung Lakes in January 2003, and their metacercarial infections was examined by the muscle compression and artificial digestion techniques. In the Soyang Lake, 161 metacercariae of Clonorchis sinensis (0.35 per fish) were harvested from 459 pond smelts examined. Also, 13 metacercariae of C. sinensis (0.43

Jae-Hwan Park; Sang-Mee Guk; Tae-Yun Kim; Eun-Hee Shin; Aifen Lin; Ji-Yeon Park; Jae-Lip Kim; Sung-Tae Hong; Jong-Yil Chai

2004-01-01

188

CsRn1, a Novel Active Retrotransposon in a Parasitic Trematode, Clonorchis sinensis, Discloses a New Phylogenetic Clade of Ty3\\/gypsy-like LTR Retrotransposons  

Microsoft Academic Search

We screened the genome of a trematode, Clonorchis sinensis, in order to identify novel retrotransposons and thereby provide additional information on retrotransposons for comprehensive phylogenetic study. Considering the vast potential of retrotransposons to generate genetically variable regions among individual genomes, randomly amplified polymorphic DNAs (RAPDs) detected by arbitrarily primed polymerase chain reactions were selected as candidates for retrotransposon-related sequences. From

Young-An Bae; Seo-Yun Moon; Yoon Kong; Seung-Yull Cho; Mun-Gan Rhyu

2001-01-01

189

Liver Transplant  

MedlinePLUS

... Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

190

Low Divergence of Clonorchis sinensis in China Based on Multilocus Analysis.  

PubMed

Clonorchis sinensis, an ancient parasite that infects a number of piscivorous mammals, attracts significant public health interest due to zoonotic exposure risks in Asia. The available studies are insufficient to reflect the prevalence, geographic distribution, and intraspecific genetic diversity of C. sinensis in endemic areas. Here, a multilocus analysis based on eight genes (ITS1, act, tub, ef-1a, cox1, cox3, nad4 and nad5 [4.986 kb]) was employed to explore the intra-species genetic construction of C. sinensis in China. Two hundred and fifty-six C. sinensis isolates were obtained from environmental reservoirs from 17 provinces of China. A total of 254 recognized Multilocus Types (MSTs) showed high diversity among these isolates using multilocus analysis. The comparison analysis of nuclear and mitochondrial phylogeny supports separate clusters in a nuclear dendrogram. Genetic differentiation analysis of three clusters (A, B, and C) showed low divergence within populations. Most isolates from clusters B and C are geographically limited to central China, while cluster A is extraordinarily genetically diverse. Further genetic analyses between different geographic distributions, water bodies and hosts support the low population divergence. The latter haplotype analyses were consistent with the phylogenetic and genetic differentiation results. A recombination network based on concatenated sequences showed a concentrated linkage recombination population in cox1, cox3, nad4 and nad5, with spatial structuring in ITS1. Coupled with the history record and archaeological evidence of C. sinensis infection in mummified desiccated feces, these data point to an ancient origin of C. sinensis in China. In conclusion, we present a likely phylogenetic structure of the C. sinensis population in mainland China, highlighting its possible tendency for biogeographic expansion. Meanwhile, ITS1 was found to be an effective marker for tracking C. sinensis infection worldwide. Thus, the present study improves our understanding of the global epidemiology and evolution of C. sinensis. PMID:23825605

Sun, Jiufeng; Huang, Yan; Huang, Huaiqiu; Liang, Pei; Wang, Xiaoyun; Mao, Qiang; Men, Jingtao; Chen, Wenjun; Deng, Chuanhuan; Zhou, Chenhui; Lv, Xiaoli; Zhou, Juanjuan; Zhang, Fan; Li, Ran; Tian, Yanli; Lei, Huali; Liang, Chi; Hu, Xuchu; Xu, Jin; Li, Xuerong; Xinbingyu

2013-01-01

191

Biochemical and immunological characterization of annexin B30 from Clonorchis sinensis excretory/secretory products.  

PubMed

Clonorchis sinensis has been classified as group I biological carcinogen for cholangiocarcinoma by the World Health Organization. Biological studies on excretory/secretory products (ESPs) enabled us to understand the pathogenesis mechanism of C. sinensis and develop new strategies for the prevention of clonorchiasis. In this study, sequence analysis showed that annexin B30 from C. sinensis (CsANXB30) is composed of four annexin repeats which were characterized by type II and III Ca(2+)-binding sites or KGD motif with the capability of Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30 (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by CsESPs. Real-time PCR showed that its transcriptional level was the highest at the stage of metacercaria. Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in the tegument, intestine, and egg of adult worms, as well as the tegument and vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)-dependent manner and human plasminogen in a dose-dependent manner. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsANXB30 developed a strong IL-10 production in spleen cells and a high level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral and cellular immune response in rats. The present results implied that CsANXB30 might be involved in a host-parasite interaction and affected the immune response of the host during C. sinensis infection. PMID:24861011

He, Lei; Ren, Mengyu; Chen, Xueqing; Wang, Xiaoyun; Li, Shan; Lin, Jinsi; Liang, Chi; Liang, Pei; Hu, Yue; Lei, Huali; Bian, Meng; Huang, Yan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2014-07-01

192

Molecular characterization and serological reactivity of a vacuolar ATP synthase subunit ?-like protein from Clonorchis sinensis.  

PubMed

The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes, energized by hydrolysis of ATP. Extensive investigations on structural and biochemical features of these molecules have implied their importance in the physiological process. In this study, a full-length sequence encoding a vacuolar ATP synthase subunit ?-like protein of Clonorchis sinensis (CsATP-?) was isolated from our cDNA library. The hypothetical 226 amino acid sequence shared 76% identity with ATP-? proteins of Schistosoma japonicum and above 55% identity with ATP-? proteins from human and other eukaryotes. Characteristic Asp??? amino acid residues and seven B-cell epitopes were predicted in this sequence. The complete coding sequence of the gene was expressed in Escherichia coli. Recombinant CsATP-? (rCsATP-?) protein could be probed by anti-rCsATP-? rat serum and C.sinensis-infected human serum in Western blotting experiment, indicating that it is an antigen of strong antigenicity. The high level of antibody titers (1:204,800) showed that CsATP-? has a powerful immunogenicity. Both the increased level and the change trend of IgG1/IgG2a subtypes in serum showed that the rCsATP-? can induce strong combined Th1/Th2 immune responses in rats and stimulate the immune response changes to the dominant Th2 from Th1 along with long time infection. The results of immunoblot and immunolocalization demonstrated that CsATP-? was consecutively expressed at various developmental stages of the parasite, which was supported by real-time PCR analysis. In immunohistochemistry, CsATP-? was localized on the intestine, vitellarium, and testicle of an adult worm and excretory bladder of metacercaria, implying that CsATP-? may relate to energy intake and metabolism. This fundamental study would contribute to further researches that are related to growth and development and immunomodulation of C. sinensis. PMID:24535733

Lv, Xiaoli; Huang, Lisi; Chen, Wenjun; Wang, Xiaoyun; Huang, Yan; Deng, Chuanhuan; Sun, Jiufeng; Tian, Yanli; Mao, Qiang; Lei, Huali; Yu, Xinbing

2014-04-01

193

Identification, sequence analysis, and characterization of serine/threonine protein kinase 17A from Clonorchis sinensis.  

PubMed

This is the first report of a novel protein from Clonorchis sinensis (C. sinensis), serine/threonine protein kinase 17A (CsSTK17A), which belongs to a member of the death-associated protein kinase (DAPK) family known to regulate diverse biological processes. The full-length sequence encoding CsSTK17A was isolated from C. sinensis adult cDNA plasmid library. Two transcribed isoforms of the gene were identified from the genome of C. sinensis. CsSTK17A contains a kinase domain at the N-terminus that shares a degree of conservation with the DAPK families. Besides, the catalytic domain contains 11 subdomains conserved among STKs and shares the highest identity with STK from Schistosoma mansoni (55.9%). Three-dimensional structure of CsSTK17A displays the canonical STK fold, including the helix C, P-loop, and the activation loop. We obtained recombinant CsSTK17A (rCsSTK17A) and anti-rCsSTK17A IgG. The rCsSTK17A could be probed by anti-rCsSTK17A rat serum, C. sinensis-infected rat serum and the sera from rats immunized with C. sinensis excretory-secretory products, indicating that it is a circulating antigen possessing a strong immunocompetence. Moreover, quantitative RT-PCR and western blotting analyses revealed that CsSTK17A exhibited the highest mRNA and protein expression level in eggs, followed by metacercariae and adult worms. Intriguingly, in the immunolocalization assay, CsSTK17A was intensively localized to the operculum region of eggs in uterus, as well as the vitelline gland of both adult worm and metacercaria, implying that the protein was associated with the reproduction and development of C. sinensis. Overall, these fundamental studies might contribute to further researches on signaling systems of the parasite. PMID:24578258

Huang, Lisi; Lv, Xiaoli; Huang, Yan; Hu, Yue; Yan, Haiyan; Zheng, Minghui; Zeng, Hua; Li, Xuerong; Liang, Chi; Wu, Zhongdao; Yu, Xinbing

2014-05-01

194

Comparison of two serpins of Clonorchis sinensis by bioinformatics, expression, and localization in metacercaria.  

PubMed

Clonorchiasis, which has been an important public health problem in China, is caused by ingestion of raw or undercooked fish contaminated by live metacercaria. Therefore, preventing fish from infecting is of great significance for controlling the disease. SERPINs (serine protease inhibitors) are well known as negative regulators of hemostasis, thrombolysis, and innate immune responses. In the present study, two full-length sequences encoding SERPIN were identified from metacercaria cDNA library of Clonorchis sinensis (C. sinensis) and were denominated as CsSERPIN and CsSERPIN3, respectively. Bioinformatics analysis showed that the two sequences shares 35.9% identity to each other. Both of the sequences have SERPIN domain and the greatest difference between the two domains is the reactive centre loop. Transmembrane region was found in CsSERPIN3 while not in CsSERPIN. The expression of the two CsSERPINs was significantly higher at the life stage of metacercaria than that of adult. The transcription levels of CsSERPIN and CsSERPIN3 at metacercaria stage were 3.249- and 11.314-fold of that at adult stage, respectively. Furthermore, the expression of CsSERPIN was 4.32-fold of that of CsSERPIN3 at metacercaria stage. Immunobiochemistry revealed that CsERPIN was dispersed at subtegument and oral sucker of metacercaria, while CsSERPIN3 localized intensely in the tegument of metacercaria of C. sinensis inside of the cyst wall. All these indicated that the CsSERPINs play important roles at metacercaria stage of the parasite. CsSERPIN may take part in regulation of endogenous serine proteinase and CsSERPIN3 may be involved in immune evasion and be a potential candidate for vaccine and drug target for clonorchiasis. PMID:24831344

Yang, Yabo; Hu, Dong; Wang, Lexun; Liang, Chi; Hu, Xuchu; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-06-01

195

Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate.  

PubMed

Clonorchis sinensis (C. sinensis) infections remain the common public health problem in freshwater fish consumption areas. New effective prevention strategies are still the urgent challenges to control this kind of foodborne infectious disease. The biochemical importance and biological relevance render C. sinensis enolase (Csenolase) as a potential vaccine candidate. In the present study, we constructed Escherichia coli/Bacillus subtilis shuttle genetic engineering system and investigated the potential of Csenolase as an oral vaccine candidate for C. sinensis prevention in different immunization routes. Our results showed that, compared with control groups, both recombinant Csenolase protein and nucleic acid could induce a mixed IgG1/IgG2a immune response when administrated subcutaneously (P<0.001), intraperitoneally (P<0.01) and intramuscularly (P<0.001) with worm reduction rate of 56.29%, 15.38% and 37.42%, respectively. More importantly, Csenolase could be successfully expressed as a fusion protein (55kDa) on B. subtilis spore indicated by immunoblot and immunofluorescence assays. Killed spores triggered reactive Th1/Th2 immune response and exhibited protective efficacy against C. sinensis infection. Csenolase derived oral vaccine conferred worm reduction rate and egg reduction rate at 60.07% (P<0.001) and 80.67% (P<0.001), respectively. The shuttle genetic engineering system facilitated the development of oral vaccine with B. subtilis stably overexpressing target protein. Comparably vaccinal trails with Csenolase in different immunization routes potentialize Csenolase an oral vaccine candidate in C. sinensis prevention. PMID:24486347

Wang, Xiaoyun; Chen, Wenjun; Tian, Yanli; Mao, Qiang; Lv, Xiaoli; Shang, Mei; Li, Xuerong; Yu, Xinbing; Huang, Yan

2014-03-10

196

Prevalence of Clonorchis sinensis infection in freshwater fishes in northeastern China.  

PubMed

The prevalence of Clonorchis sinensis infection in freshwater fishes was surveyed in Heilongjiang Province, northeastern China, between August 2011 and September 2013. Thirteen species of freshwater fish (n=3221) and one species of shrimp (n=93) were collected from Songhua river, Nenjiang river and other lakes or ponds in 37 sites of 15 representative cities in Heilongjiang Province. They were individually examined by digestion technique, and the C. sinensis metacercariae were identified morphologically followed by confirmation using sequences of the second internal transcribed spacer of ribosomal DNA. Ten of the 13 examined species of freshwater fishes were infected with C. sinensis metacercariae, while all shrimps were negative. The overall prevalence of C. sinensis infection in 3221 examined freshwater fishes was 19.96%, with 42.57% (272/639) in Pseudorasbora parva, 22.55% (83/368) in Hemicculter leuciclus, 20.44% (121/592) in Carassius auratus, 17.71% (68/384) in Saurogobio dabryi, 10.85% (23/212) in Rhodeus ocellatus, 10.54% (48/455) in Phoxinus lagowskii, 8.20% (21/256) in Perccottus glehnii, 6.25% (5/80) in Misgurnus anguillicaudatus, 4.55% (1/22) in Xenocypris davidi, and 1.49% (1/67) in Cyprinus carpio. The average infection intensity in P. parva was 103.3 encysted metacercariae per gram of fish meat in Zhaoyuan city. The average prevalence of C. sinensis infection in Songhua river, Nenjiang river and lakes or ponds were 31.96% (503/1574), 11.30% (102/903) and 7.93% (59/744), respectively. The prevalence of C. sinensis infection in Zhaoyuan city (43.68%) was the highest among all sampling locations. These results revealed a high-prevalence of C. sinensis infection in freshwater fishes in Heilongjiang Province, northeastern China, posing significant public health concern. PMID:24880648

Zhang, Y; Chang, Q C; Zhang, Y; Na, L; Wang, W T; Xu, W W; Gao, D Z; Liu, Z X; Wang, C R; Zhu, X Q

2014-08-29

197

The biochemical and immunological characterization of two serpins from Clonorchis sinensis.  

PubMed

Serpins (serine proteinase inhibitors) are evidenced to regulate numerous biological processes such as immunoregulation in parasitic helminths. The functions of serpins from Clonorchis sinensis remain unclear to date. In this study, two serpin genes, respectively denominated as CsproSERPIN and CsSERPIN2, had been selected from metacercaria cDNA library of C. sinensis. The biochemical activities of both recombinant proteins (rCsproSERPIN and rCsSERPIN2) were analyzed by assays of inhibition on some serine or cysteine proteases, the results showed that rCsproSERPIN significantly inhibited trypsin, chymotrypsin and thrombin, while rCsSERPIN2 inhibited only chymotrypsin. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsproSERPIN and rCsSERPIN2 respectively developed a strong IFN-? production and IgG2a levers of sera were higher than IgG1. Besides, immunoblot assays revealed that the rCsproSERPIN and rCsSERPIN2 could be recognized by the sera of rats infected with C. sinensis and the sera of rabbits immunized by excretory/secretory products. Furthermore, immunofluorescence assays illuminated the two were similarly localized in the reproductive organs such as vitelline glands, testis and eggs in adult stage. In short, all the results collectively indicated that CsproSERPIN and CsSERPIN2 might play important role in the parasite development by preventing the parasite from digestion by exogenous serine proteases, as well as CsproSERPIN and CsSERPIN2 probably involved in immunoregulation of host by inducing Th1-biased type cytokines in rats. PMID:23275238

Lei, Huali; Tian, Yanli; Chen, Wenjun; Wang, Xiaoyun; Li, Xuerong; Mao, Qiang; Sun, Jiufeng; Li, Ran; Xu, Yanquan; Liang, Chi; Huang, Yan; Yu, Xinbing

2013-06-01

198

Epidemiological profile of Clonorchis sinensis infection in one community, Guangdong, People’s Republic of China  

PubMed Central

Background Clonorchiasis caused by ingesting improperly prepared fish ranks among the most important but still neglected food-borne parasitic diseases, especially in the People’s Republic of China (P.R. China). To promote the implementation of interventions efficiently, the demonstration of an epidemiological profile of Clonorchis sinensis infection is essential in hyper-epidemic areas. Methods In one community with higher levels of economic development in Guangdong province, P.R. China, villagers were motivated to provide stool samples for examining helminth eggs. Then, those infected with C. sinensis completed the structured questionnaire including demographical characteristics, knowledge and behavior. Results A total of 293 villagers infected with C. sinensis participated in questionnaire investigation. Among them, 94.54% were adult and 93.17% were indigenous. The geometric mean of C. sinensis eggs per gram of feces in the children, adult females and adult males was 58, 291 and 443, respectively. The divergence between knowledge and behavior in the adults, especially the adult males, was shown. Out of 228 persons eating raw fish, 160 did it more frequently at restaurants, the proportion of which varied in different populations, showing 25.00%, 54.88% and 80.28% in the children, adult females and adult males, respectively. Conclusions Different interventions need to be adopted in different populations. Chemotherapy should be prioritized in the adults, especially the adult males. In addition, health education targeting the children, is essential and may play a crucial role in controlling clonorchiasis in the long term. In order to successfully control clonorchiasis, intervention in the restaurant should not be overlooked in some endemic areas. PMID:23816055

2013-01-01

199

Molecular Cloning and Characterization of Growth Factor Receptor Bound-Protein in Clonorchis sinensis  

PubMed Central

Background Clonorchis sinensis causes clonorchiasis, a potentially serious disease. Growth factor receptor-bound protein 2 (Grb2) is a cytosolic protein conserved among animals and plays roles in cellular functions such as meiosis, organogenesis and energy metabolism. In the present study, we report first molecular characters of growth factor receptor bound-protein (CsGrb2) from C. sinensis as counter part of Grb2 from animals and its possible functions in development and organogenesis of C. sinensis. Methodology/Principal Findings A CsGrb2 cDNA clone retrieved from the C. sinensis transcriptome encoded a polypeptide with a SH3-SH2-SH3 structure. Recombinant CsGrb2 was bacterially produced and purified to homogeneity. Native CsGrb2 with estimated molecular weight was identified from C. sinensis adult extract by western blotting using a mouse immune serum to recombinant CsGrb2. CsGrb2 transcripts was more abundant in the metacercariae than in the adults. Immunohistochemical staining showed that CsGrb2 was localized to the suckers, mesenchymal tissues, sperms in seminal receptacle and ovary in the adults, and abundantly expressed in most organs of the metacercariae. Recombinant CsGrb2 was evaluated to be little useful as a serodiagnostic reagent for C. sinesis human infections. Conclusion Grb2 protein found in C. sinensis was conserved among animals and suggested to play a role in the organogenesis, energy metabolism and mitotic spermatogenesis of C. sinensis. These findings from C. sinensis provide wider understanding on diverse function of Grb2 in lower animals such as platyhelminths. PMID:24454892

Bai, Xuelian; Lee, Ji-Yun; Kim, Tae Im; Dai, Fuhong; Lee, Tae-Jin; Hong, Sung-Jong

2014-01-01

200

Liver Wellness  

MedlinePLUS

... Liver Foundation www.liverfoundation.org 1-800-GO-LIVER © 2009 American Liver Foundation. All rights reserved. Increasing Public Awareness of Liver Health Liver Wellness • The liver is the second ...

201

Mapping of the complement C9 binding domain in paramyosin of the blood fluke Schistosoma mansoni  

Microsoft Academic Search

Schistosomes are believed to evade complement-mediated damage by expression of complement inhibitory proteins. Our previous results [Deng, J., Gold, D., LoVerde, P.T., Fishelson, Z., 2003. Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infect. Immun. 71, 6402–6410.] have demonstrated that paramyosin (Pmy) of the blood fluke S. mansoni binds to the human complement proteins C8 and C9,

Jiusheng Deng; Daniel Gold; Philip T. LoVerde; Zvi Fishelson

2007-01-01

202

Molecular and biochemical characterizations of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis.  

PubMed

Fructose-1,6-bisphosphate aldolase (FbA) is a ubiquitous enzyme in glycolysis. In the present study, we screened out three distinct genes encoding FbA isozymes (CsFbAs, CsFbA-1/2/3) from Clonorchis sinensis (C. sinensis) and characterized their sequences and structures profiles as well as biochemical properties. The amino acid sequences of CsFbAs shared homology with those of Class I FbAs from other species. The putative quaternary structures revealed that CsFbA-2 and CsFbA-3 were tetramers, while CsFbA-1 was dimer. Recombinant CsFbA-2 and CsFbA-3 (rCsFbA-2/3) were confirmed to be Class I FbAs for their stable enzymatic activities in the presence of EDTA or metal ions. However, recombinant CsFbA-1 (rCsFbA-1) did not show the catalytic activity, which might be due to the inappropriate fold and interaction between its subunits. Both rCsFbA-2 and rCsFbA-3 showed similar enzymatic properties such as optimal temperatures and broad pH ranges that similar to human FbA isozymes. They showed relatively higher affinities for fructose-1,6-bisphosphate (FBP) than fructose-1-phosphate (F-1-P). Their kcat ratios of FBP to F-1-P were in accordance with those of human FbA-A or C. In addition, CsFbAs were differentially transcribed in the developmental stages of C. sinensis, suggesting their essential roles throughout the life stages. Extensive distribution of CsFbAs in adult worms indicated that ubiquitous activities of CsFbAs took place in these organs. Collectively, these results suggested that long-term parasitic environment might adapt these isozymes similar to host FbAs for metabolic requirement. Our study will provide new insight into CsFbAs in the glycometabolism of C. sinensis and relationship between the host and the parasite. PMID:24768689

Li, Shan; Bian, Meng; Wang, Xiaoyun; Chen, Xueqing; Xie, Zhizhi; Sun, Hengchang; Jia, Feifei; Liang, Pei; Zhou, Chenhui; He, Lei; Mao, Qiang; Huang, Bo; Liang, Chi; Wu, Zhongdao; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

2014-01-01

203

Molecular characterization of Clonorchis sinensis secretory myoglobin: Delineating its role in anti-oxidative survival  

PubMed Central

Background Clonorchiasis is a globally important, neglected food-borne disease caused by Clonorchis sinensis (C. sinensis), and it is highly related to cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has strongly suggested that the adult worm of C. sinensis continuously releases excretory-secretory proteins (ESPs), which play important roles in the parasite-host interactions, to establish successful infection and ensure its own survival. Myoglobin, a hemoprotein, is present in high concentrations in trematodes and ESPs. To further understand the biological function of CsMb and its putative roles in the interactions of C. sinensis with its host, we explored the molecular characterization of CsMb in this paper. Methods We expressed CsMb and its mutants in E. coli BL21 and identified its molecular characteristics using bioinformatics analysis and experimental approaches. Reverse transcription PCR analysis was used to measure myoglobin transcripts of C. sinensis with different culture conditions. The peroxidase activity of CsMb was confirmed by spectrophotometry. We co-cultured RAW264.7 cells with recombinant CsMb (rCsMb), and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu-Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated RAW264.7 cells. Results In the in vitro culture of adult worms, the transcripts of CsMb increased with the increase of oxygen content. Oxidative stress conditions induced by H2O2 increased the levels of CsMb transcripts in a dose-dependent manner. Furthermore, CsMb catalyzed oxidation reactions in the presence of H2O2, and amino acid 34 of CsMb played an essential role in its reaction with H2O2. In addition, CsMb significantly reduced H2O2 and NO levels in LPS-activated macrophages, and CsMb downregulated iNOS and SOD expression in activated macrophages. Conclusion The present study is the first to investigate the peroxidase activity of CsMb. This investigation suggested that C. sinensis may decrease the redox activation of macrophages by CsMb expression to evade host immune responses. These studies contribute to a better understanding of the role of CsMb in the molecular mechanisms involved in ROS detoxification by C. sinensis. PMID:24885788

2014-01-01

204

A novel nuclear marker, Pm-int9, for phylogenetic studies of Opisthorchis felineus , Opisthorchis viverrini , and Clonorchis sinensis (Opisthorchiidae, Trematoda)  

Microsoft Academic Search

Opisthorchis felineus, O. viverrini, and Clonorchis sinensis, the trematodes of the family Opisthorchiidae, are important human parasites. Two previous studies (Kang et al. Parasitol\\u000a Int 57:191–197, 2008; Katokhin et al. Dokl Biochem Biophys 421:214–217, 2008) have provided evidence using ribosomal and mitochondrial sequences that O. viverrini, O. felineus, and C. sinensis are closely related. We developed a novel nuclear marker,

Sergei V. Shekhovtsov; Alexei V. Katokhin; Konstantin V. Romanov; Vladimir V. Besprozvannykh; Konstantin P. Fedorov; Natalia I. Yurlova; Elena A. Serbina; Paiboon Sithithaworn; Nikolai A. Kolchanov; Viatcheslav A. Mordvinov

2009-01-01

205

A family of cathepsin F cysteine proteases of Clonorchis sinensis is the major secreted proteins that are expressed in the intestine of the parasite  

Microsoft Academic Search

Cysteine proteases of helminth parasites play essential roles in parasite physiology as well as in a variety of important pathobiological processes. In this study, we identified a multigene family of cathepsin F cysteine proteases in Clonorchis sinensis (CsCFs). We identified a total of 12 CsCF genes through cDNA cloning using degenerate PCR primers followed by RACE. Sequence and phylogenetic analysis

Jung-Mi Kang; Young-Yil Bahk; Pyo-Yun Cho; Sung-Jong Hong; Tong-Soo Kim; Woon-Mok Sohn; Byoung-Kuk Na

2010-01-01

206

Liver metastases  

MedlinePLUS

Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that can spread to the liver include: Breast cancer Colorectal cancer Esophageal ...

207

Liver Transplantation  

MedlinePLUS

... you on a waiting list for a liver transplant. Doctors do liver transplants when other treatment cannot keep a damaged liver ... and replaces it with a healthy one. Most transplant livers come from a donor who has died. ...

208

Pharmacological and autoradiographical characterization of serotonin transporter-like activity in sporocysts of the human blood fluke, Schistosoma mansoni  

Microsoft Academic Search

The present study focuses on the role of the biogenic monoamine serotonin (5-hydroxytryptamine) in the biology of sporocyst stages of the human blood fluke, Schistosoma mansoni, and its importance during obligate development within its snail host Biomphalaria glabrata. Based on previous work demonstrating that snails infected with S. mansoni have reduced levels of 5-hydroxytryptamine, we hypothesized that sporocysts actively transport

J. P. Boyle; J. F. Hillyer; T. P. Yoshino

2003-01-01

209

A retroposon-like short repetitive DNA element in the genome of the human blood fluke, Schistosoma mansoni  

Microsoft Academic Search

The genome of Schistosoma mansoni, a human blood fluke, contains a family of short repetitive DNA elements which we have named the SMa family. In this paper we report the sequences of two SMa family members which are derived from tandem arrangements and four family members which are dispersed copies. The two tandemly repeated copies are 331 and 335 bp,

Loretta D. Spotila; Hirohisa Hirai; David M. Rekosh; Philip T. LoVerde

1989-01-01

210

Development of a polymerase chain reaction applicable to rapid and sensitive detection of Clonorchis sinensis eggs in human stool samples.  

PubMed

Microscopic examination of eggs of parasitic helminths in stool samples has been the most widely used classical diagnostic method for infections, but tiny and low numbers of eggs in stool samples often hamper diagnosis of helminthic infections with classical microscopic examination. Moreover, it is also difficult to differentiate parasite eggs by the classical method, if they have similar morphological characteristics. In this study, we developed a rapid and sensitive polymerase chain reaction (PCR)-based molecular diagnostic method for detection of Clonorchis sinensis eggs in stool samples. Nine primers were designed based on the long-terminal repeat (LTR) of C. sinensis retrotransposon1 (CsRn1) gene, and seven PCR primer sets were paired. Polymerase chain reaction with each primer pair produced specific amplicons for C. sinensis, but not for other trematodes including Metagonimus yokogawai and Paragonimus westermani. Particularly, three primer sets were able to detect 10 C. sinensis eggs and were applicable to amplify specific amplicons from DNA samples purified from stool of C. sinensis-infected patients. This PCR method could be useful for diagnosis of C. sinensis infections in human stool samples with a high level of specificity and sensitivity. PMID:23916334

Cho, Pyo Yun; Na, Byoung-Kuk; Choi, Kyung Mi; Kim, Jin Su; Cho, Shin-Hyeong; Lee, Won-Ja; Lim, Sung-Bin; Cha, Seok Ho; Park, Yun-Kyu; Pak, Jhang Ho; Lee, Hyeong-Woo; Hong, Sung-Jong; Kim, Tong-Soo

2013-07-01

211

Characteristics and molecular phylogeny of Fasciola flukes from Bangladesh, determined based on spermatogenesis and nuclear and mitochondrial DNA analyses.  

PubMed

This study aimed to precisely discriminate Fasciola spp. based on DNA sequences of nuclear internal transcribed spacer 1 (ITS1) and mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (nad1) gene. We collected 150 adult flukes from the bile ducts of cattle, buffaloes, sheep, and goats from six different regions of Bangladesh. Spermatogenic status was determined by analyzing stained seminal vesicles. The ITS1 types were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The nad1 haplotypes were identified based on PCR and direct sequencing and analyzed phylogenetically by comparing with nad1 haplotypes of Fasciola spp. from other Asian countries. Of the 127 aspermic flukes, 98 were identified as Fg type in ITS1, whereas 29 were identified as Fh/Fg type, indicating a combination of ITS1 sequences of Fasciola hepatica and Fasciola gigantica. All the 127 aspermic flukes showed Fsp-NDI-Bd11 in nad1 haplotype with nucleotide sequences identical to aspermic Fasciola sp. from Asian countries. Further, 20 spermic flukes were identified as F. gigantica based on their spermatogenic status and Fg type in ITS1. F. gigantica population was thought to be introduced into Bangladesh considerably earlier than the aspermic Fasciola sp. because 11 haplotypes with high haplotype diversity were detected from the F. gigantica population. However, three flukes from Bangladesh could not be precisely identified, because their spermatogenic status, ITS1 types, and nad1 haplotypes were ambiguous. Therefore, developing a robust method to distinguish aspermic Fasciola sp. from other Fasciola species is necessary in the future. PMID:24781019

Mohanta, Uday Kumar; Ichikawa-Seki, Madoka; Shoriki, Takuya; Katakura, Ken; Itagaki, Tadashi

2014-07-01

212

Cellular and humoral responses in liver of cattle and buffaloes infected with a single dose of Fasciola gigantica.  

PubMed

The cellular components of the hepatic inflammatory infiltrate in cattle and buffaloes infected with a single dose of 1000 Fasciola gigantica were analysed by immunohistochemistry and histology. T and B lymphocytes, plasma cells, eosinophils and mast cells were present in the hepatic lesions. It is proposed that both cellular and humoral immune responses were induced in the liver of cattle and buffaloes during infection with F. gigantica probably by antigens released by the developing flukes and by damage caused by the flukes during their migration in the liver. The local T cell response differed between these animals, with the response decreasing after 3 weeks post-infection in cattle in contrast to a gradually increasing response in buffaloes. Difference in the T cell response between cattle and buffaloes may be related to their differences in resistance and resilience to infection with F. gigantica. PMID:15936148

Molina, Elizabeth C; Skerratt, Lee F

2005-07-15

213

Global status of fish-borne zoonotic trematodiasis in humans.  

PubMed

Fishborne zoonotic trematodes (FZT), infecting humans and mammals worldwide, are reviewed and options for control discussed. Fifty nine species belonging to 4 families, i.e. Opisthorchiidae (12 species), Echinostomatidae (10 species), Heterophyidae (36 species) and Nanophyetidae (1 species) are listed. Some trematodes, which are highly pathogenic for humans such as Clonorchis sinensis, Opisthorchis viverrini, O. felineus are discussed in detail, i.e. infection status in humans in endemic areas, clinical aspects, symptoms and pathology of disease caused by these flukes. Other liver fluke species of the Opisthorchiidae are briefly mentioned with information about their infection rate and geographical distribution. Intestinal flukes are reviewed at the family level. We also present information on the first and second intermediate hosts as well as on reservoir hosts and on habits of human eating raw or undercooked fish. PMID:23990419

Hung, Nguyen Manh; Madsen, Henry; Fried, Bernard

2013-09-01

214

Liver Facts  

MedlinePLUS

... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one of the largest and most complex ... a spongy mass of wedge-shaped lobes. The liver has numerous functions that are necessary for life. ...

215

Efficacy and Safety of Praziquantel, Tribendimidine and Mebendazole in Patients with Co-infection of Clonorchis sinensis and Other Helminths  

PubMed Central

Background Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. Method We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. Results 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. Conclusion Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. Trial Registration Controlled-Trials.com ISRCTN55086560 PMID:25122121

Xu, Li-Li; Jiang, Bin; Duan, Ji-Hui; Zhuang, Shi-Feng; Liu, Yong-Chun; Zhu, Shi-Qiao; Zhang, Li-Ping; Zhang, Hao-Bing; Xiao, Shu-Hua; Zhou, Xiao-Nong

2014-01-01

216

Liver biopsy  

MedlinePLUS

Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

217

Liver Biopsy  

MedlinePLUS

... 525 KB) Spanish Version Alternate Language URL Español Liver Biopsy Page Content DUE TO UNFORESEEN CIRCUMSTANCES, PUBLICATION ... Research For More Information Acknowledgments What is a liver biopsy? A liver biopsy is a procedure that ...

218

Intervention to Improve the Quality of Life of a Bottlenose Dolphin That Developed Necrosis on the Tail Flukes  

PubMed Central

[Purpose, Case, and Methods] A female bottlenose dolphin (Tursiops truncatus) in captivity developed necrosis of the tail flukes. Although the diseased site healed after surgical resection, the loss of approximately 75% of the tail greatly affected her swimming performance. To restore swimming ability, we developed artificial tail flukes as a prosthetic swimming aid and provided physical therapy that included swimming training from postoperative day 1 to day 1427. [Results] The prosthetic enabled the dolphin to recover swimming ability almost to the level prior to disease onset, but even acquire applied movement, and reestablish social relationships, thus greatly improving the animal's quality of life. [Conclusion] The results clearly demonstrate that, as in postoperative rehabilitation in humans, the use of prosthetic devices in physical therapy can be beneficial for marine animals such as dolphins. PMID:24259946

Ueda, Keiichi; Murakami, Masahito; Kato, Junichi; Miyahara, Hirokazu; Izumisawa, Yasuharu

2013-01-01

219

Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.  

PubMed

Cholangiocarcinoma is a relatively rare cancer; worldwide it accounts for an estimated 15% of liver cancers. In most areas, the etiology is rather obscure, and identified risk factors such as hepatolithiasis, inflammatory bowel disease, and exposure to Thorotrast can account for only a small proportion of cases. In certain areas of southeast and eastern Asia, however, incidence rates are very high, and here there is a strong association with infection with the liver flukes Clonorchis sinensis and Opisthorchis viverrini. The mechanisms of carcinogenesis in O. viverrini infection have been the subject of considerable research; it seems that the presence of parasites induces DNA damage and mutations as a consequence of the formation of carcinogens/free radicals and of cellular proliferation of the intrahepatic bile duct epithelium. Preventive strategies in areas endemic for liver flukes appear straightforward, but breaking the cycle of infection has proved difficult in practice. PMID:8268770

Parkin, D M; Ohshima, H; Srivatanakul, P; Vatanasapt, V

1993-01-01

220

The current status of opisthorchiasis and clonorchiasis in the Mekong Basin  

PubMed Central

This review highlights the current status and control of liver fluke infections in the Mekong Basin countries where Opisthorchis and Clonorchis are highly endemic. Updated data on prevalence and distribution have been summarized from presentations in the “96 Years of Opisthorchiasis. International Congress of Liver Flukes”. It is disturbing that despite treatment and control programs have been in place for decades, all countries of the Lower Mekong Basin are still highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high levels of CCA incidence. A common pattern that is emerging in each country is the difference in transmission of O. viverrini between lowlands which have high prevalence versus highlands which have low prevalence. This seems to be associated with wetlands, flooding patterns and human movement and settlement. A more concerted effort from all community, educational, public health and government sectors is necessary to successfully combat this fatal liver disease of the poor. PMID:21893213

Sithithaworn, Paiboon; Andrews, Ross H.; Van De, Nguyen; Wongsaroj, Thitima; Sinuon, Muth; Odermatt, Peter; Nawa, Yukifumi; Liang, Song; Brindley, Paul J.; Sripa, Banchob

2013-01-01

221

Proteomic Identification of Plasma Protein Tyrosine Phosphatase Alpha and Fibronectin Associated with Liver Fluke, Opisthorchis viverrini, Infection  

PubMed Central

Opisthorchiasis caused by Opisthorchis viverrini induces periductal fibrosis via host immune/inflammatory responses. Plasma protein alteration during host-parasite interaction-mediated inflammation may provide potential diagnostic and/or prognostic biomarkers. To search for target protein changes in O. viverrini-infected hamsters, a 1-D PAGE gel band was trypsin-digested and analyzed by a LC-MS/MS-based proteomics approach in the plasma profile of infected hamsters, and applied to humans. Sixty seven proteins were selected for further analysis based on at least two unique tryptic peptides with protein ID score >10 and increased expression at least two times across time points. These proteins have not been previously identified in O. viverrini-associated infection. Among those, proteins involved in structural (19%), immune response (13%), cell cycle (10%) and transcription (10%) were highly expressed. Western blots revealed an expression level of protein tyrosine phosphatase alpha (PTP?) which reached a peak at 1 month and subsequently tended to decrease. Fibronectin significantly increased at 1 month and tended to increase with time, supporting proteomic analysis. PTP? was expressed in the cytoplasm of inflammatory cells, while fibronectin was observed mainly in the cytoplasm of fibroblasts and the extracellular matrix at periductal fibrosis areas. In addition, these protein levels significantly increased in the plasma of O. viverrini-infected patients compared to healthy individuals, and significantly decreased at 2-months post-treatment, indicating their potential as disease markers. In conclusion, our results suggest that plasma PTP? and fibronectin may be associated with opisthorchiasis and the hamster model provides the basis for development of novel diagnostic markers in the future. PMID:23029023

Khoontawad, Jarinya; Laothong, Umawadee; Roytrakul, Sittiruk; Pinlaor, Porntip; Mulvenna, Jason; Wongkham, Chaisiri; Yongvanit, Puangrat; Pairojkul, Chawalit; Mairiang, Eimorn; Sithithaworn, Paiboon; Pinlaor, Somchai

2012-01-01

222

Carcinogenic liver fluke Opistorchis viverrini oxysterols detected by LC-MS/MS survey of soluble fraction parasite extract  

PubMed Central

Liquid chromatography in tandem mass spectrometry (LC-MS/MS) has emerged as an informative tool to investigate oxysterols (oxidized derivatives of cholesterol) in helminth parasite associated cancers. Here, we used LC-MS/MS to investigate in soluble extracts of the adult developmental stage of O. viverrini from experimentally infected hamsters. Using comparisons with known bile acids and the metabolites of estrogens, the LC-MS data indicated the existence of novel oxysterol derivatives in O. viverrini. Most of these derivatives were ramified at C-17, in similar fashion to bile acids and their conjugated salts. Several were compatible with the presence of an estrogen core, and/or hydroxylation of the steroid aromatic ring A, hydroxylation of both C-2 and C-3 of the steroid ring and further oxidation into an estradiol-2,3-quinone. PMID:23973383

Vale, Nuno; Gouveia, Maria João; Botelho, Mónica; Sripa, Banchob; Suttiprapa, Sutas; Rinaldi, Gabriel; Gomes, Paula; Brindley, Paul J.; da Costa, José Manuel Correia

2013-01-01

223

Liver Biopsy  

MedlinePLUS

A liver biopsy is a medical procedure performed in order to obtain a small sample of the liver. This is accomplished with a special needle, and ... small scar. The most common reasons for a liver biopsy include the evaluation of: ? Jaundice ? Liver inflammation ( ...

224

Systemic and local mucosal immune responses induced by orally delivered Bacillus subtilis spore expressing leucine aminopeptidase 2 of Clonorchis sinensis.  

PubMed

Human clonorchiasis caused by Clonorchis sinensis (C. sinensis) has been increasingly prevalent in recent years so that an effective measure is essential and urgent to control the infectious disease. Oral delivery of antigens from C. sinensis may be an important approach to effectively induce both systemic and local immune responses to anti-infection of the parasite. In the current study, we used Bacillus subtilis (B. subtilis) spores as a delivery vehicle to introduce leucine aminopeptidase 2 of C. sinensis (CsLAP2), an excretory/secretory antigen with high immunogenicity, expressing on their surface. SDS-PAGE, western blotting, and flow cytometry indicated that CsLAP2 was successfully expressed on the surface of B. subtilis spores (CotC-CsLAP2 spores). BALB/c mice were treated with spores intragastrically. On day 31 after the treatment, we found that mice intragastrically treated with CotC-CsLAP2 spores exhibited higher IgG, IgG1, IgG2a, and IgA level in sera as well as higher sIgA level in bile and intestinal lavage fluid compared to mice orally administrated with spores not expressing CsLAP2 (CotC spores) and naïve mice. The peak titer of IgG/IgA presented on day 31/49 after oral administration. IgG1 level was lower than IgG2a in group administrated with CotC-CsLAP2 spores. sIgA-secreting cells were obviously observed in intestinal epithelium of mice orally treated with CotC-CsLAP2 spores. After incubated with CotC-CsLAP2, the levels of IFN-?, IL-6, IL-10, IL-17A, and TNF significantly increased in the supernatant of splenocytes isolated from mice orally treated with CotC-CsLAP2 spores, while there was no statistically significant difference of IL-4 level representing Th2 response among the groups. Our study demonstrated that oral administration of CsLAP2 delivered by B. subtilis spore elicited obvious systemic and local mucosal immunity. Secretory IgA and Th1-Th17 cellular immunity might involved in mechanisms of the immune response. PMID:24906994

Qu, Hongling; Xu, Yanquan; Sun, Hengchang; Lin, Jinsi; Yu, Jinyun; Tang, Zeli; Shen, Jiqing; Liang, Chi; Li, Shan; Chen, Wenjun; Li, Xuerong; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

2014-08-01

225

Structural Basis for Inhibition of Cathepsin B Drug Target from the Human Blood Fluke, Schistosoma mansoni*  

PubMed Central

Schistosomiasis caused by a parasitic blood fluke of the genus Schistosoma afflicts over 200 million people worldwide. Schistosoma mansoni cathepsin B1 (SmCB1) is a gut-associated peptidase that digests host blood proteins as a source of nutrients. It is under investigation as a drug target. To further this goal, we report three crystal structures of SmCB1 complexed with peptidomimetic inhibitors as follows: the epoxide CA074 at 1.3 ? resolution and the vinyl sulfones K11017 and K11777 at 1.8 and 2.5 ? resolutions, respectively. Interactions of the inhibitors with the subsites of the active-site cleft were evaluated by quantum chemical calculations. These data and inhibition profiling with a panel of vinyl sulfone derivatives identify key binding interactions and provide insight into the specificity of SmCB1 inhibition. Furthermore, hydrolysis profiling of SmCB1 using synthetic peptides and the natural substrate hemoglobin revealed that carboxydipeptidase activity predominates over endopeptidolysis, thereby demonstrating the contribution of the occluding loop that restricts access to the active-site cleft. Critically, the severity of phenotypes induced in the parasite by vinyl sulfone inhibitors correlated with enzyme inhibition, providing support that SmCB1 is a valuable drug target. The present structure and inhibitor interaction data provide a footing for the rational design of anti-schistosomal inhibitors. PMID:21832058

Jílková, Adéla; ?ezá?ová, Pavlína; Lepšík, Martin; Horn, Martin; Váchová, Jana; Fanfrlík, Jind?ich; Brynda, Ji?í; McKerrow, James H.; Caffrey, Conor R.; Mareš, Michael

2011-01-01

226

Cubic crystal protein inclusions in the neodermis of the pancreatic fluke, Eurytrema pancreaticum, and Eurytrema coelomaticum.  

PubMed

Light microscopy of Eurytrema pancreaticum and Eurytrema coelomaticum collected from cattle in Japan, China, Thailand, and Brazil showed many cubic crystal inclusions in the neodermis (tegument) of all flukes. The crystal inclusions were histochemically positive for protein. Scanning electron microscopy showed many cubic protrusions containing cubic crystal protein inclusions on the surface of the neodermis. Transmission electron microscopy showed that cubic crystal protein inclusions appeared in the perikarya of subtegumental parts, passed through the cytoplasmic bridge, moved into the syncytial neodermal cytoplasm, and then protruded from, and finally separated from, the neodermal cytoplasm. Cubic crystal protein inclusions were hexahedral with each side 2-18 microm long. High-resolution microscopy of ultrathin sections of crystal inclusions showed a lattice fringe at spacings of about 0.52 nm by using a filtering processing. Diffractograms were obtained by Fourier transform of the images. The lattice structure of the crystal protein inclusions was shown by inverse Fourier transform, indicating that the cubic crystal protein inclusions were single crystals. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis estimated the molecular weight of protein in the cubic crystal inclusion as 36.6 kDa. Energy-dispersive X-ray spectroscopy proved that the cubic crystal protein inclusions were composed of protein and sulfur. PMID:17657508

Sakamoto, Tsukasa; Oikawa, Tetsuo

2007-10-01

227

Relationship between histology and aetiological factors in primary liver cancer.  

PubMed

A review of 205 primary hepatic cancers from different geographic areas reveals that HCC which forms the vast majority (86%) of these, commonly presents as the trabecular variety (76%). The compact and pseudoglandular forms are rare (18% and 6%). Relatively fewer cases of undifferentiated cancer, hepatoblastoma and cholangiocarcinoma are encountered. HCC is often associated with the presence of hepatitis B virus surface antigen (HBsAg) in the liver. This is particularly true of the trabecular variety (81%). A proportion of the compact variety as well as undifferentiated cancers do not appear to be related to HBV infection. Cholangio carcinomas are considered to be related to infection by liver flukes. Hepatoblastomas occur in infancy and childhood and show no known aetiologic association. Aflatoxin may be aetiologically related to same cases of HCC. Continued use of oral contraceptives can occasionally induce HCC. PMID:6252813

Nayak, N C

1980-04-01

228

[The reagents kit to detect Metyorchis biis, Opisthorchis viverrini and Clonorchis sinensis, Opisthorchis felineus--agents of opisthorchiasis using technique of polymerase chain reaction in real-time].  

PubMed

The helminths Opisthorchis felineus, Opisthorchis viverrini, Clonorchis sinensis, Metorchis bilis are the agents of opisthorchiasis. The actual diagnostic of parasitic diseases based on microscope analysis of samples of human feces to detect presence of ova of parasites suffers of many shortcomings, in particular low sensitivity especially at earlier stages. The purpose of this study was to compare results of detection of parasites using both classical technique and technique of specific differentiation based on extraction of nucleic acids from samples of human feces and implementation of reaction of amplification of the chosen fragment of DNA with detection of products of polymerase chain reaction in the real time. The study detected 150 out of 165 positive samples and also 6 out of 37 negative samples both validated by coproovoscopy. PMID:25552048

Seredina, T A; Petrenko, V A; Tronin, A V; Sazonov, A Iu; Sapugol'tseva, O B; Katokhin, A V; Odintsova, E S

2014-08-01

229

Liver Immunology  

PubMed Central

The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

2014-01-01

230

Liver transplant  

MedlinePLUS

... end up with fully working livers after a successful transplant. The donor liver is transported in a ... and the likelihood that a transplant will be successful. The amount of time you spend on a ...

231

Liver Transplantation  

PubMed Central

Liver transplantation has become a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure. The satisfactory outcome of liver transplantation has led to insufficient supplies of deceased donor organs, particularly in East Asia. Hence, East Asian surgeons are concentrating on developing and performing living-donor liver transplantation (LDLT). This review article describes an update on the present status of liver transplantation, mainly in adults, and highlights some recent developments on indications for transplantation, patient selection, donor and recipient operation between LDLT and deceased-donor liver transplantation (DDLT), immunosuppression, and long-term management of liver transplant recipients. Currently, the same indication criteria that exist for DDLT are applied to LDLT, with technical refinements for LDLT. In highly experienced centers, LDLT for high-scoring (>30 points) Model of End-Stage Liver Disease (MELD) patients and acute-on-chronic liver-failure patients yields comparably good outcomes to DDLT, because timely liver transplantation with good-quality grafting is possible. With increasing numbers of liver transplantations and long-term survivors, specialized attention should be paid to complications that develop in the long term, such as chronic renal failure, hypertension, diabetes mellitus, dyslipidemia, obesity, bone or neurological complications, and development of de novo tumors, which are highly related to the immunosuppressive treatment. PMID:20431740

Moon, Deok-Bog

2009-01-01

232

Liver regeneration  

Microsoft Academic Search

The liver can precisely regulate its growth and mass. Surgical resection of hepatic lobes or hepatocyte loss caused by viral or chemical injury triggers hepatocyte replication while enlarged liver mass is corrected by apoptosis. Hepatocytes have a great replicative capacity and are capable of repopulating the liver. However, “stem-like” cells proliferate when hepatocyte replication is blocked or delayed. Detailed studies

Nelson Fausto

2000-01-01

233

Mapping of the complement C9 binding domain in paramyosin of the blood fluke Schistosoma mansoni.  

PubMed

Schistosomes are believed to evade complement-mediated damage by expression of complement inhibitory proteins. Our previous results [Deng, J., Gold, D., LoVerde, P.T., Fishelson, Z., 2003. Inhibition of the complement membrane attack complex by Schistosoma mansoni paramyosin. Infect. Immun. 71, 6402-6410.] have demonstrated that paramyosin (Pmy) of the blood fluke S. mansoni binds to the human complement proteins C8 and C9, inhibits complement activation at the terminal stage and protects the parasite from complement-mediated damage. In order to locate the Pmy binding site to C8 and C9, various fragments of Pmy cDNA were PCR-cloned into a pET28a bacterial expression vector. Recombinant His-tagged Pmy fragments were expressed in BL21 Escherichia coli and purified over a nickel-nitrilotriacetic acid column. Binding assays by Western blotting with monoclonal anti-His antibody demonstrated that PmyCC (Pmy amino acids (744)Asp-(866)Met) was the only Pmy fragment that bound to human C8 and C9. Functional analyses demonstrated that PmyCC inhibited hemolysis of rabbit erythrocytes and of antibody-sensitized sheep erythrocytes by human complement. Importantly, PmyCC inhibited in vitro killing of trypsin-sensitized schistosomula of S. mansoni by human complement. In the presence of PmyCC, Zn(2+)-induced C9 polymerization was inhibited. Most of the immunodominant B-cell antigenic epitopes of Pmy are present in the PmyCC region, as antibodies collected from mice immunized with recombinant Pmy bound primarily to PmyCC. Taken together, this study has mapped the complement regulatory domain in Pmy, capable of binding to C8 and C9 and preventing polyC9 formation, to its C-terminal region. PMID:17123534

Deng, Jiusheng; Gold, Daniel; LoVerde, Philip T; Fishelson, Zvi

2007-01-01

234

Identification and characterization of microRNAs in the pancreatic fluke Eurytrema pancreaticum  

PubMed Central

Background Eurytrema pancreaticum is one of the most common flukes, which mainly infects ruminants globally and infects human beings accidentally; causing eurytremiasis that has high veterinary and economic importance. MicroRNAs (miRNAs) are small non-coding RNAs and are now considered as a key mechanism of gene regulation at the post-transcription level. Methods We investigated the global miRNA expression profile of E. pancreaticum adults using next-generation sequencing technology combined with real-time quantitative PCR. Results By using the genome of the closely-related species Schistosoma japonicum as reference, we obtained 27 miRNA candidates out of 16.45 million raw sequencing reads, with 13 of them found as known miRNAs in S. japonicum and/or S. mansoni, and the remaining 14 miRNAs were considered as novel. Five out of the 13 known miRNAs coming from one family named as sja-miR-2, including family members from miR-2a to miR-2e. Targets of 19 miRNAs were successfully predicated out of the 17401 mRNA and EST non-redundant sequences of S. japonicum. It was found that a significant high number of targets were related to “chch domain-containing protein mitochondrial precursor” (n?=?29), “small subunit ribosomal protein s30e” (n?=?21), and “insulin-induced gene 1 protein” (n?=?9). Besides, “egg protein cp3842” (n?=?2), “fumarate hydratase” (n?=?2), “ubiquitin-conjugating enzyme” (n?=?2), and “sperm-associated antigen 6” (n?=?1) were also found as targets of the miRNAs of E. pancreaticum. Conclusions The present study represents the first global characterization of E. pancreaticum miRNAs, which provides novel resources for a better understanding of the parasite, which, in turn, has implications for the effective control of the disease it causes. PMID:23351883

2013-01-01

235

Clonorchiasis control: starting from awareness  

PubMed Central

Clonorchiasis is caused by infection with food-borne liver fluke, namely Clonorchis sinensis, which is also considered to be a neglected tropical disease. It is estimated that over 10 million people are infected with C. sinensis in China and, subsequently, several thousand new cholangiocarcinoma cases occur annually. On May 18, 2014, China Central Television broadcasted an episode on the habit of raw-fish eating and its potential to cause clonorchiasis in a programme called Health on the tip of the tongue. Here, I briefly introduce the content of the episode and discuss its significance for clonorchiasis control in China. PMID:25243069

2014-01-01

236

Clonorchiasis control: starting from awareness.  

PubMed

Clonorchiasis is caused by infection with food-borne liver fluke, namely Clonorchis sinensis, which is also considered to be a neglected tropical disease. It is estimated that over 10 million people are infected with C. sinensis in China and, subsequently, several thousand new cholangiocarcinoma cases occur annually. On May 18, 2014, China Central Television broadcasted an episode on the habit of raw-fish eating and its potential to cause clonorchiasis in a programme called Health on the tip of the tongue. Here, I briefly introduce the content of the episode and discuss its significance for clonorchiasis control in China. PMID:25243069

Qian, Men-Bao

2014-01-01

237

Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors  

PubMed Central

Background Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP) constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. Methodology/Principal Findings We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs), such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9%) and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%). Cathepsin L/F (four spots, 10.5%) and transporter molecules (three spots, 7.9%) were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or intravascular trematodes. Interestingly, secretion of a 28 kDa ?-class GST (Cs28?GST3) was significantly affected by the host bile, involving reduced secretion of the 28 kDa species and augmented secretion of Cs28?GST3-related high-molecular-weight 85 kDa protein. Oxidative stressors induced upregulated secretion of 28 kDa Cs28?GST3, but not an 85 kDa species. A secretory 26 kDa ?-class GST (Cs26?GST2) was increased upon treatment with oxidative stressors and bile juice, while another 28 kDa ?-class GST (Cs28?GST1) showed negligible responses. Conclusions/Significance Our results represent the first analysis of the genuine nature of the C. sinensis ESP proteome in the presence of host bile mimicking the natural host environments. The behavioral patterns of migration and maturation of C. sinensis in the bile ducts might contribute to the secretion of copious amounts of diverse GSTs, but a smaller quantity and fewer kinds of cysteine proteases. The Cs28?GST1 and its paralog(s) detoxify endogenous oxidative molecules, while Cs28?GST3 and Cs26?GST2 conjugate xenobiotics/hydrophobic substances in the extracellular environments, which imply that diverse C. sinensis GSTs might have evolved for each of the multiple specialized functions. PMID:23696907

Bae, Young-An; Ahn, Do-Whan; Lee, Eung-Goo; Kim, Seon-Hee; Cai, Guo-Bin; Kang, Insug; Sohn, Woon-Mok; Kong, Yoon

2013-01-01

238

Liver transplantation?  

PubMed Central

Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

2007-01-01

239

Liver fibrosis  

PubMed Central

Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-?1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies. PMID:15690074

Bataller, Ramón; Brenner, David A.

2005-01-01

240

Diet and Your Liver  

MedlinePLUS

... Liver How can alcohol and medicine affect the liver? Alcohol Alcohol can damage or destroy liver cells. ... Liver Foundation www.liverfoundation.org 1-800-GO-LIVER © 2009 American Liver Foundation. All rights reserved. Increasing ...

241

21 CFR 520.45a - Albendazole suspension.  

Code of Federal Regulations, 2012 CFR

...use . For removal and control of adult liver flukes (Fasciola hepatica ); heads...use . For removal and control of adult liver flukes (Fasciola hepatica and Fascioloides...for use . For the treatment of adult liver flukes (Fasciola hepatica ) in...

2012-04-01

242

21 CFR 520.45a - Albendazole suspension.  

Code of Federal Regulations, 2013 CFR

...use . For removal and control of adult liver flukes (Fasciola hepatica ); heads...use . For removal and control of adult liver flukes (Fasciola hepatica and Fascioloides...for use . For the treatment of adult liver flukes (Fasciola hepatica ) in...

2013-04-01

243

21 CFR 520.45a - Albendazole suspension.  

Code of Federal Regulations, 2011 CFR

...use . For removal and control of adult liver flukes (Fasciola hepatica ); heads...use . For removal and control of adult liver flukes (Fasciola hepatica and Fascioloides...for use . For the treatment of adult liver flukes (Fasciola hepatica ) in...

2011-04-01

244

21 CFR 520.38a - Albendazole suspension.  

...use. For removal and control of adult liver flukes (Fasciola hepatica ); heads...use. For removal and control of adult liver flukes (Fasciola hepatica and Fascioloides...for use. For the treatment of adult liver flukes (Fasciola hepatica ) in...

2014-04-01

245

Progression of Liver Disease  

MedlinePLUS

... Handouts Education Resources Support Services Helpful Links For Liver Health Information Call 1-800-GO-LIVER (1- ... The Progression of Liver Disease The Progression of Liver Disease There are many different types of liver ...

246

Austropeplea ollula (Pulmonata: Lymnaeidae): A new molluscan intermediate host of a human intestinal fluke, Echinostoma cinetorchis (Trematoda: Echinostomatidae) in Korea  

PubMed Central

Three freshwater snail species of the family Lymnaeidae have been reported from Korea, Radix auricularia coreana, Austropeplea ollula and Fossaria truncatula. Out of 3 lymnaeid snail species, A. ollula was naturally infected with the Echinostoma cinetorchis cercariae (infection rate = 0.7%). In the experiments with the laboratory-bred snails, F. truncatula as well as A. ollula was also susceptible to the E. cinetorchis miracidia with infection rates of 25% and 40%, respectively. All of three lymnaeid snail species exposed to the E. cinetorchis cercariae were infected with the E. cinetorchis metacercariae. It is evident that A. ollula acts as the first molluscan intermediate host of E. cinetorchis in Korea, and F. truncatula may be a possible candidate for the first intermediate host of this intestinal fluke. Also, three lymnaeid snail species targeted were experimentally infected with E. cinetorchis metacercariae. PMID:11590915

Jung, Younghun; Park, Yun-Kyu; Hwang, Myung-Ki

2001-01-01

247

Defining the regulatory and inhibitory elements within the prodomain of CsCF-6, a cathepsin F cysteine protease of Clonorchis sinensis.  

PubMed

CsCF-6 is a member of the multigene family of cathepsin F cysteine proteases of Clonorchis sinensis. Similar to other papain family proteases, CsCF-6 is synthesized as a proenzyme and is converted to the mature form by autocatalytic removal of the prodomain. Here, we analyzed the regulatory and inhibitory elements within the CsCF-6 prodomain to understand the regulatory mechanism of CsCF-6 by its prodomain. The CsCF-6 prodomain played an essential role in the folding of CsCF-6. Particularly, the ERFNAQ motif within the prodomain was essential, and the minimum segment required for this event was the C-terminal part of the prodomain, including Asn(58) and downstream residues. The CsCF-6 prodomain effectively inhibited CsCF-6, in which the ERFNAQ motif played a critical role in the inhibition, but the GTFD motif was also required for complete inhibition of CsCF-6. The CsCF-6 prodomain showed broad inhibitory activity against several cysteine proteases. These results suggest that the CsCF-6 prodomain plays bi-functional roles in correct folding and inhibition of its cognate enzyme. PMID:23891948

Kang, Jung-Mi; Ju, Hye-Lim; Sohn, Woon-Mok; Na, Byoung-Kuk

2013-08-01

248

Development and evaluation of loop-mediated isothermal amplification (LAMP) for rapid detection of Clonorchis sinensis from its first intermediate hosts, freshwater snails.  

PubMed

Clonorchiasis, caused by Clonorchis sinensis, is a key foodborne zoonosis, which is mainly found in China, Korea and Vietnam. Detection of this parasite from the second intermediate host, the freshwater fish is the common method for epidemiological surveys of this parasite, but is time consuming, labour intensive and easily leads to misdiagnosis. In this study, we have developed a rapid, sensitive and reliable molecular method for the diagnosis of C. sinensis from its first intermediate hosts, freshwater snails, based on a loop-mediated isothermal amplification (LAMP) method. The specific amplified fragment from genomic DNA of C. sinensis did not cross-react with those from other relevant trematodes and a range of hosts (freshwater fish, shrimps and snails) of C. sinensis living in similar environments. The detection limit of the LAMP method was as low as 10 fg which was 1000 times more sensitive than conventional PCR, which was also demonstrated by successful application to field samples. These results show that the LAMP method is a more sensitive tool than conventional PCR for the detection of C. sinensis infection in the first intermediate hosts and, due to a simpler protocol, is an ideal molecular method for field-based epidemiological surveys of this parasite. PMID:23870065

Chen, Y; Wen, T; Lai, D-H; Wen, Y-Z; Wu, Z-D; Yang, T-B; Yu, X-B; Hide, G; Lun, Z-R

2013-09-01

249

Liver Regeneration  

PubMed Central

Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

Michalopoulos, George K.

2009-01-01

250

Successful parasitism of vector snail Biomphalaria glabrata by the human blood fluke (trematode) Schistosoma mansoni: a 2009 assessment  

PubMed Central

Schistosomiasis, caused by infections by human blood flukes (Trematoda), continues to disrupt the lives of over 200,000,000 people in over 70 countries, inflicting misery and precluding the individuals’ otherwise reasonable expectations of productive lives. Infection requires contact with freshwater in which infected snails (the intermediate hosts of schistosomes) have released cercariae larvae. Habitats suitable for the host snails continue to expand as a consequence of water resource development. No vaccine is available, and the emergence and spread of resistance to the single licensed schistosomicide drug would be devastating. Since human infections would cease if parasite infections in snails were prevented, efforts are being made to discover requirements of intra-molluscan development of these parasites. Wherever blood flukes occur, naturally resistant conspecific snails are present. To understand the mechanisms used by parasites to ensure their survival in immunocompetent hosts, one must comprehend the internal defense mechanisms that are available to the host. For one intermediate host snail (Biomphalaria glabrata) and trematodes for which it serves as vector, molecular genetic and proteomic surveys for genes and proteins influencing the outcomes on infections are yielding lists of candidates. A comparative approach drawing on data from studies in divergent species provides a robust basis for hypothesis generation to drive decisions as to which candidates merit detailed further investigation. For example, reactive oxygen and nitrogen species are known mediators or effectors in battles between infectious agents and their hosts. An approach targeting genes involved in relevant pathways has been fruitful in the Schistosoma mansoni-B. glabrata parasitism, leading to discovery of a functionally relevant gene set (encoding enzymes responsible for the leukocyte respiratory burst) that associates significantly with host resistance phenotype. This review summarizes advances in the understanding of strategies used by both this trematode parasite and its molluscan host to ensure their survival. PMID:19393158

Bayne, Christopher J.

2009-01-01

251

Characterization of SR3 reveals abundance of non-LTR retrotransposons of the RTE clade in the genome of the human blood fluke, Schistosoma mansoni  

Microsoft Academic Search

BACKGROUND: It is becoming apparent that perhaps as much as half of the genome of the human blood fluke Schistosoma mansoni is constituted of mobile genetic element-related sequences. Non-long terminal repeat (LTR) retrotransposons, related to the LINE elements of mammals, comprise much of this repetitive component of the schistosome genome. Of more than 12 recognized clades of non-LTR retrotransposons, only

Thewarach Laha; Nonglack Kewgrai; Alex Loukas; Paul J Brindley

2005-01-01

252

Blood flukes (Digenea: Aporocotylidae) of walking catfishes (Siluriformes: Clariidae): new genus and species from the Mekong River (Vietnam) with comments on related catfish aporocotylids.  

PubMed

Nomasanguinicola canthoensis gen. et sp. n. infects the branchial vessels of bighead catfish, Clarias macrocephalus Günther (Siluriformes: Clariidae), in the Mekong River near Can Tho, southern Vietnam. Nomasanguinicola differs from all other genera of fish blood flukes (Digenea: Aporocotylidae) by the combination of lacking body spines and by having an anterior sucker with two flanking columns of large denticles, an intestine comprising several short papilla-like caeca, an inverse U-shaped uterus, and an ootype located near the separate genital pores. The new species has an ootype that is posterior to the level of the female genital pore. That feature most easily differentiates it from the only other putative aporocotylid species having an anterior sucker with two flanking columns of large denticles, Plehniella dentata Paperna, 1964 and Sanguinicola clarias Imam, Marzouk, Hassan et Itman, 1984, which have an ootype that is lateral (P. dentata) or anterior (S. clarias) to the level of the female genital pore. These two species apparently lack extant type materials, infect North African catfish, Clarias gariepinus (Burchell), and herein are considered incertae sedis, but likely comprise species of Nomasanguinicola. An updated list of hosts, sites of infection and geographic localities for the six species and three genera of blood flukes that mature in catfishes is provided. The new species is the first fish blood fluke recorded from Vietnam and only the third reported from a walking catfish (Clariidae). PMID:23951931

Truong, Triet Nhat; Bullard, Stephen A

2013-07-01

253

Expression, immunolocalization, and serological reactivity of a novel sphingomyelin phosphodiesterase-like protein, an excretory/secretory antigen from Clonorchis sinensis.  

PubMed

Clonorchiasis, caused by Clonorchis sinensis infection, is a zoonotic parasitic disease of hepatobiliary system in which the proteins released by adult are major pathogenetic factors. In this study, we first characterized a putative sphingomyelin phosphodiesterase (CsSMPase) A-like secretory protein, which was highly expressed in the adult worm. The full-length gene was cloned. The putative protein is of relatively low homology comparing with SMPase from other species, and of rich T cell and B cell epitopes, suggesting that it is an antigen of strong antigenicity. The complete coding sequence of the gene was expressed in the Escherichia coli. The recombinant CsSMPase (rCsSMPase) can be recognized by C. sinensis-infected serum, and the protein immunoserum can recognize a specific band in excretory/secretory products (ESPs) of C. sinensis adult by western blotting. Immunolocalization revealed that CsSMPase was not only localized on tegument, ventral sucker of metacercaria, and the intestine of adult but also on the nearby epithelium of bile duct of the infected Sprague-Dawley rats, implying that CsSMPase was mainly secreted and excreted through adult intestine and directly interacted with bile duct epithelium. Although immunized rats evoked high level antibody response, the antigen level was low in clonorchiasis patients. And the sensitivity and specificity of rCsSMPase were 50.0 % (12/24) and 88.4 % (61/69), in sera IgG-ELISA, respectively. It is likely due to the fact that CsSMPase binding to the plasma membrane of biliary epithelium decreases the antigen immune stimulation. PMID:23568580

Huang, Yanwei; Zheng, Youwei; Li, Yuzhe; Yang, Mei; Li, Ting; Zeng, Suxiang; Yu, Xinbing; Huang, Huaiqiu; Hu, Xuchu

2013-06-01

254

Genetic variation among Clonorchis sinensis isolates from different hosts and geographical locations revealed by sequence analysis of mitochondrial and ribosomal DNA regions.  

PubMed

The present study examined genetic variability among Clonorchis sinensis isolates from four different geographical localities (Guangzhou, Nanning, Jiamusi and Daqing) and host species (cats, dogs, human and rabbits) in Mainland China by sequence analyses of two mitochondrial DNA (mtDNA) genes, namely NADH dehydrogenase subunits 2, 5 (nad2 and nad5) and ribosomal internal transcribed spacer 1 (ITS1). A portion of the ITS1, nad2 (pnad2) and nad5 (pnad5) was amplified by polymerase chain reaction separately from adult C. sinensis individuals and the amplicons were subjected to sequencing from both directions. The length of the sequences of ITS1, pnad2 and pnad5 was 643, 666 and 771 bp, respectively. The intraspecific sequence variations within C. sinensis were 0-1.7% for ITS1, 0-1.4% for pnad2 and 0-0.9% for pnad5. The interspecific sequence variations within other zoonotic trematodes, which were published previously, were 4.5-84.9% for ITS1, 21.9-43.6% for pnad2 and 19.2-48.9% for pnad5. The A+T contents of the sequences were 45.26-45.88% (ITS1), 62.91-63.51% (pnad2) and 58.24-58.63% (pnad5). Phylogenetic analyses using ribosomal and mitochondrial sequence data set, with three different computational algorithms (Bayesian inference, maximum parsimony and maximum likelihood), all revealed distinct groups with high statistical support. These findings demonstrated the existence of low-level intraspecific variations in ribosomal DNA (rDNA) and mtDNA sequences among C. sinensis isolates from four different regions and hosts in China and elucidated that mtDNA sequences and rDNA sequences provided reliable genetic markers for phylogenetic studies of zoonotic trematodes. PMID:23463938

Xiao, Jing-Ying; Gao, Jun-Feng; Cai, Lian-Shun; Dai, Yue; Yang, Chun-Jia; Luo, Lan; Agatsuma, Takeshi; Wang, Chun-Ren

2013-10-01

255

Population dynamics and host reactions in young foxes following experimental infection with the minute intestinal fluke, Haplorchis pumilio  

PubMed Central

Background Infections with fish-borne zoonotic trematodes (FZT) including the minute intestinal fluke, Haplorchis pumilio, are highly prevalent in Southeast Asia. However, little is known about the infection dynamics and clinical symptoms in the final hosts which include a range of animal species and man. We aimed to generate such information using an experimental model with H. pumilio in foxes. Method Eight commercially bred foxes were each orally infected with 2000 H. pumilio metacercariae. Another three foxes served as uninfected controls. Faecal examination for eggs was performed twice weekly. The body weight was measured, standard haematological and biochemical analysis were performed regularly. All foxes were euthanized at day 56 post infection (p.i.). Adult worms were quantified and location in the small intestine noted. Results Anorexia was observed in all infected foxes starting day 12 p.i. and lasting for approximately a week. A weight loss was noticed in the infected group in weeks 3–6 p.i. Five of eight infected foxes excreted H. pumilio eggs day 9 p.i. onwards, the remaining three started on day 13 p.i. Mean (± SD) faecal egg counts showed an initial peak at day 16–20 with a maximum of 1443?±?1176 eggs per gram of faeces (epg), where after a stable egg output around 4–500 epg was seen. Worm burdens ranged between 116–2070 adult flukes with a mean (± SD) worm recovery of 948?±?666. The majority of worms were found in the lower part of the jejunum. Total white blood cell and lymphocyte counts were significant lower in the infected group from first week p.i. onwards and throughout the study period. A significantly lower level of eosinophils was found in week 2 p.i. and transient anaemia was seen in week 2 and 4 p.i. Conclusion This study showed a short prepatency period, an initial peak in egg excretion, establishment of infection in all animals with predilection site in the lower jejunum and a marked but transient clinical effect of the infection. The findings on egg output and prepatency should be taken into consideration when control programs targeting dogs and other reservoir hosts are to be established. PMID:23289937

2013-01-01

256

Liver Hepatocellular Carcinoma  

Cancer.gov

Home Cancers Selected for Study Liver Hepatocellular Carcinoma Liver Hepatocellular Carcinoma Last Updated: May 14, 2013 What is liver cancer?Hepatocellular carcinoma is the most common form of liver cancer in the United States, making up more than

257

Liver (Hepatocellular) Cancer Screening  

MedlinePLUS

... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver. The liver is one of the largest organs ...

258

Liver transplant - series (image)  

MedlinePLUS

The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

259

Correlation of Humoral Immune Response in Southern Bluefin Tuna, T. maccoyii, with Infection Stage of the Blood Fluke, Cardicola forsteri  

PubMed Central

The blood fluke, Cardicola forsteri, is a prevalent infection in ranched southern bluefin tuna. This project aimed to define the timing and intensity of the various developmental stages of C. forsteri within southern bluefin tuna as well as to relate infection to host pathology and immune response. Archival samples from several cohorts of T. maccoyii sampled from 2008 to 2010 were used in this study. The prevalence and intensity of C. forsteri infection was described using heart flushes and histological examination. Humoral immune response, i.e. C. forsteri specific antibody, lysozyme activity, and alternative complement activity, was also described. Based on the validated and detailed C. forsteri infection timeline, relationships between infection events, physiological response, and diagnosis were proposed. Immune response developed concurrently with C. forsteri infection, with the majority of physiological response coinciding with commencing egg production. Further research is needed to confirm the origin of C. forsteri antigen which is responsible for immune response development and how T. maccoyii immune response works against infection. To aide this research, further diagnostic methods for confirmation of infection need to be developed. PMID:23029217

Kirchhoff, Nicole T.; Leef, Melanie J.; Valdenegro, Victoria; Hayward, Craig J.; Nowak, Barbara F.

2012-01-01

260

Engineering liver.  

PubMed

Interest in "engineering liver" arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nanofabrication, biomaterials, microfluidic, and other technologies potentially affords unprecedented opportunity to create microphysiological models of the human liver, but engineering design principles for how to deploy these tools effectively toward specific applications, including how to define the essential constraints of any given application (available sources of cells, acceptable cost, and user-friendliness), are still emerging. Arguably less appreciated is the parallel growth in computational systems biology approaches toward these same problems-particularly in parsing complex disease processes from clinical material, building models of response networks, and in how to interpret the growing compendium of data on drug efficacy and toxicology in patient populations. Here, we provide insight into how the complementary paths of engineering liver-experimental and computational-are beginning to interplay toward greater illumination of human disease states and technologies for drug development. PMID:24668880

Griffith, Linda G; Wells, Alan; Stolz, Donna B

2014-10-01

261

Bilirubin binding with liver cystatin induced structural and functional changes.  

PubMed

Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with bilirubin has a significant biophysical and pathophysiological significance, hence our effort to study the same. PMID:24711081

Mustafa, Mir Faisal; Bano, Bilqees

2014-05-01

262

Sequence analysis and molecular characterization of Clonorchis sinensis hexokinase, an unusual trimeric 50-kDa glucose-6-phosphate-sensitive allosteric enzyme.  

PubMed

Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

Chen, Tingjin; Ning, Dan; Sun, Hengchang; Li, Ran; Shang, Mei; Li, Xuerong; Wang, Xiaoyun; Chen, Wenjun; Liang, Chi; Li, Wenfang; Mao, Qiang; Li, Ye; Deng, Chuanhuan; Wang, Lexun; Wu, Zhongdao; Huang, Yan; Xu, Jin; Yu, Xinbing

2014-01-01

263

Sequence Analysis and Molecular Characterization of Clonorchis sinensis Hexokinase, an Unusual Trimeric 50-kDa Glucose-6-Phosphate-Sensitive Allosteric Enzyme  

PubMed Central

Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

Chen, Tingjin; Ning, Dan; Sun, Hengchang; Li, Ran; Shang, Mei; Li, Xuerong; Wang, Xiaoyun; Chen, Wenjun; Liang, Chi; Li, Wenfang; Mao, Qiang; Li, Ye; Deng, Chuanhuan; Wang, Lexun; Wu, Zhongdao; Huang, Yan; Xu, Jin; Yu, Xinbing

2014-01-01

264

Characterization of MicroRNAs from Orientobilharzia turkestanicum, a Neglected Blood Fluke of Human and Animal Health Significance  

PubMed Central

The neglected blood flukes Orientobilharzia spp. belonging to the Platyhelminthes, infect animals in a number of countries of the world, and cause cercarial dermatitis in humans, as well as significant diseases and even death in economically-important animals. MicroRNAs (miRNAs) are now considered to be a key mechanism of gene regulation. Herein, we investigated the global miRNA expression profile of adult O. turkestanicum using next-generation sequencing technology and real-time quantitative PCR, to gain further information on the role of these molecules in host invasion and the parasitic lifestyle of this species. A total of 13.48 million high quality reads were obtained out of 13.78 million raw sequencing reads, with 828 expressed miRNAs identified. Phylogenetic analysis showed that the miRNAs of O. turkestanicum were still rapidly evolving and there was a “directed mutation” pattern compared with that of other species. Target mRNAs were successfully predicted to 518 miRNAs. These targets included energy metabolism, transcription initiation factors, signal transduction, growth factor receptors. miRNAs targeting egg proteins, including major egg antigen p40, and heat shock proteins were also found. Enrichment analysis indicated enrichment for mRNAs involved in catalytic, binding, transcription regulators and translation regulators. The present study represented the first large-scale characterization of O. turkestanicum miRNAs, which provides novel resources for better understanding the complex biology of this zoonotic parasite, which, in turn, has implications for the effective control of the disease it causes. PMID:23071694

Fu, Jing-Hua; Nisbet, Alasdair J.; Chang, Qiao-Cheng; Zhou, Dong-Hui; Huang, Si-Yang; Zou, Feng-Cai; Zhu, Xing-Quan

2012-01-01

265

Living Donor Liver Transplantation  

MedlinePLUS

... around the liver after surgery. These problems include bleeding, infection, bile leaks, or damage to the bile tree (the ducts that run through the liver). Bile is a digestive juice made by the liver. Other risks can ...

266

Diet - liver disease  

MedlinePLUS

... prevent fatty buildup and damage to the liver cells. In people with badly damaged livers, proteins are not properly processed. Waste products may build up and affect the brain. Dietary changes for liver disease may ...

267

Alcoholic liver disease  

MedlinePLUS

Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Alcohol can cause inflammation in the liver . Over time, scarring ...

268

Pyogenic liver abscess  

MedlinePLUS

Liver abscess; Bacterial liver abscess ... There are many potential causes of liver abscesses, including: Abdominal infection such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

269

Amebic liver abscess  

MedlinePLUS

Hepatic amebiasis; Extraintestinal amebiasis; Abscess - amebic liver ... Amebic liver abscess is caused by Entamoeba histolytica. This is the same parasite that causes amebiasis , an intestinal infection ...

270

Laparoscopic liver resection of benign liver tumors  

Microsoft Academic Search

  Objective: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection\\u000a for benign liver tumors in a multicenter setting. Background: Despite restrictive, tailored indications for resection in benign\\u000a liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors.\\u000a Methods: A retrospective study was performed in 18

B. Descottes; D. Glineur; F. Lachachi; D. Valleix; J. Paineau; A. Hamy; M. Morino; H. Bismuth; D. Castaing; E. Savier; P. Honore; O. Detry; M. Legrand; J. S. Azagra; M. Goergen; M. Ceuterick; J. Marescaux; D. Mutter; B. Hemptinne; R. Troisi; J. Weerts; B. Dallemagne; C. Jehaes; M. Gelin; V. Donckier; R. Aerts; B. Topal; C. Bertrand; B. Mansvelt; L. Krunckelsven; D. Herman; M. Kint; E. Totte; R. Schockmel; J. F. Gigot

2003-01-01

271

Liver Disease in Pregnancy  

Microsoft Academic Search

Liver dysfunction during pregnancy can be caused by conditions that are specific to pregnancy or by liver diseases that are not related to pregnancy itself. This review attempts to summarize the epidemiology, pathophysiology, and management of the different pregnancy-related liver diseases, and to review different liver diseases not related to pregnancy and how they may affect or be effected by

Fabiana S. Benjaminov; Jenny Heathcote

2004-01-01

272

Living with Your Liver  

NSDL National Science Digital Library

Students learn the function of the liver and how biomedical engineers can use liver regeneration to help people. Students test the effects of toxic chemicals on a beef liver by adding hydrogen peroxide to various liver and salt solutions. They observe, record and graph their results.

Integrated Teaching And Learning Program

273

Liver fibrosis markers in alcoholic liver disease  

PubMed Central

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), ?-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

Chrostek, Lech; Panasiuk, Anatol

2014-01-01

274

The mitochondrial genome of Paragonimus westermani (Kerbert, 1878), the Indian isolate of the lung fluke representative of the family Paragonimidae (Trematoda)  

PubMed Central

Among helminth parasites, Paragonimus (zoonotic lung fluke) gains considerable importance from veterinary and medical points of view because of its diversified effect on its host. Nearly fifty species of Paragonimus have been described across the globe. It is estimated that more than 20 million people are infected worldwide and the best known species is Paragonimus westermani, whose type locality is probably India and which infects millions of people in Asia causing disease symptoms that mimic tuberculosis. Human infections occur through eating raw crustaceans containing metacercarie or ingestion of uncooked meat of paratenic hosts such as pigs. Though the fluke is known to parasitize a wide range of mammalian hosts representing as many as eleven families, the status of its prevalence, host range, pathogenic manifestations and its possible survivors in nature from where the human beings contract the infection is not well documented in India. We took advantage of the whole genome sequence data for P. westermani, generated by Next Generation Sequencing, and its comparison with the existing data for the P. westermani for comparative mt DNA phylogenomic analyses. Specific primers were designed for the 12 protein coding genes with the aid of existing P. westermani mtDNA as the reference. The Ion torrent next generation sequencing platform was harnessed to completely sequence the mitochondrial genome, and applied innovative approaches to bioinformatically assemble and annotate it. A strategic PCR primer design utilizing the whole genome sequence data from P. westermani enabled us to design specific primers capable of amplifying all regions of the mitochondrial genome from P. westermani. Assembly of NGS data from libraries enriched in mtDNA sequence by PCR gave rise to a total of 11 contigs spanning the entire 14.7 kb mt DNA sequence of P. westermani available at NCBI. We conducted gap-filling by traditional Sanger sequencing to fill in the gaps. Annotation of non-protein coding genes successfully identified tRNA regions for the 24 tRNAs coded in mtDNA and 12 protein coding genes. Bayesian phylogenetic analyses of the concatenated protein coding genes placed P. westermani within the family Opisthorchida. The complete mtDNA sequence of P. westermani is 15,004 base pairs long; the lung fluke is the major etiological agent of paragonimiasis and the first Indian representative for the family Paragonimidae to be fully sequenced that provides important genetic markers for ecological, population and biogeographical studies and molecular diagnostic of digeneans that cause trematodiases. PMID:25165620

Biswal, Devendra K.; Chatterjee, Anupam

2014-01-01

275

Characterization of Constituents and Anthelmintic Properties of Hagenia abyssinica  

PubMed Central

The dried female flowers of Hagenia abyssinica (Bruce) J. F. Gmel. (Rosaceae) are traditionally used as an anthelmintic remedy in Ethiopia and formerly were incorporated into the European Pharmacopoeia. One-, two- and tricyclic phloroglucinol derivatives (kosins) were suggested to be the active principles. However, polar constituents may also contribute to the activity. Therefore, we investigated for the first time the polar constituents. We isolated typical Rosaceae constituents such as quercetin 3-O-?-glucuronide, quercetin 3-O-?-glucoside and rutin. Polar kosin glycosides or derivatives could not be detected. The anthelmintic activity of fractions of different polarity were tested against the blood fluke Schistosoma mansoni, the liver flukes Clonorchis sinensis and Fasciola hepatica and the intestinal fluke Echinostoma caproni. The anthelmintic activity decreased with increasing polarity of the tested fractions. ESI-MS investigations indicated the predominant occurrence of kosins in the active fractions. Using the anthelmintic active extracts of Hagenia abyssinica we developed a simple, inexpensive bioassay against the non-parasitic nematode Caenorhabditis elegans, which can be used as an initial screening procedure for anthelmintic properties of crude extracts of plants or fungi. The anthelmintic activity of test extracts against the model organism was determined in a microtiter plate assay by enumeration of living and dead nematodes under a microscope. PMID:22896828

Thomsen, Henrieke; Reider, Katrin; Franke, Katrin; Wessjohann, Ludger A.; Keiser, Jennifer; Dagne, Ermias; Arnold, Norbert

2012-01-01

276

Food-Borne Trematodiases  

PubMed Central

Summary: An estimated 750 million people are at risk of infections with food-borne trematodes, which comprise liver flukes (Clonorchis sinensis, Fasciola gigantica, Fasciola hepatica, Opisthorchis felineus, and Opisthorchis viverrini), lung flukes (Paragonimus spp.), and intestinal flukes (e.g., Echinostoma spp., Fasciolopsis buski, and the heterophyids). Food-borne trematodiases pose a significant public health and economic problem, yet these diseases are often neglected. In this review, we summarize the taxonomy, morphology, and life cycle of food-borne trematodes. Estimates of the at-risk population and number of infections, geographic distribution, history, and ecological features of the major food-borne trematodes are reviewed. We summarize clinical manifestations, patterns of infection, and current means of diagnosis, treatment, and other control options. The changing epidemiological pattern and the rapid growth of aquaculture and food distribution networks are highlighted, as these developments might be associated with an elevated risk of transmission of food-borne trematodiases. Current research needs are emphasized. PMID:19597009

Keiser, Jennifer; Utzinger, Jürg

2009-01-01

277

Autoimmune liver disease panel  

MedlinePLUS

Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

278

What Is Liver Cancer?  

MedlinePLUS

... are known as primary liver cancers . Hepatocellular carcinoma (HCC) This is the most common form of liver ... in this document refers only to hepatocellular carcinoma (HCC). Last Medical Review: 11/19/2014 Last Revised: ...

279

Alcohol-Related Liver Disease  

MedlinePLUS

... Handouts Education Resources Support Services Helpful Links For Liver Health Information Call 1-800-GO-LIVER (1- ... Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn more about ...

280

ISOLATED POLYCYSTIC LIVER DISEASE  

PubMed Central

Isolated polycystic liver disease (PCLD) is an autosomal dominant disease with genetic and clinical heterogeneity. Apart from liver cysts, it exhibits few extra-hepatic manifestations and the majority of patients with this condition are asymptomatic or subclinical. However, a small fraction of these patients develop acute liver-cyst-related complications and/or massive cystic liver enlargement, causing morbidity and mortality. Currently, the management for symptomatic PCLD is centered on palliating symptoms and treating complications. PMID:20219621

Qian, Qi

2010-01-01

281

Cell Therapies for Liver Diseases  

PubMed Central

Cell therapies, which include bioartificial liver support and hepatocyte transplantation, have emerged as potential treatments for a variety of liver diseases. Acute liver failure (ALF), acute-on-chronic liver failure, and inherited metabolic liver diseases are examples of liver diseases that have been successfully treated with cell therapies at centers around the world. Cell therapies also have the potential for wide application in other liver diseases, including non-inherited liver diseases and liver cancer, and in improving the success of liver transplantation. Here we briefly summarize current concepts of cell therapy for liver diseases. PMID:22140063

Yu, Yue; Fisher, James E.; Lillegard, Joseph B.; Rodysill, Brian; Amiot, Bruce; Nyberg, Scott L.

2011-01-01

282

Laparoscopic Liver Resection for Malignant Liver Tumors  

PubMed Central

Objective To assess the feasibility, safety, and outcome of laparoscopic liver resection for malignant liver tumors. Summary Background Data The precise role of laparoscopy in resection of liver malignancies (hepatocellular carcinoma [HCC] and liver metastases) remains controversial despite an increasing number of publications reporting laparoscopic resection of benign liver tumors. Methods A retrospective study was performed in 11 surgical centers in Europe regarding their experience with laparoscopic resection of liver malignancies. Detailed questionnaires were sent to each surgeon focusing on patient characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. All patients had radiologic investigations at follow-up to exclude disease recurrence. Results From February 1994 to December 2000, 37 patients with malignant liver tumors were included in this study. Ten patients had HCC, including 9 with cirrhotic liver, and 27 patients had liver metastases. The mean tumor size was 3.3 cm, and 89% of the tumors were located in the left lobe or in the anterior segments of the right liver. Liver procedures included 12 wedge resections, 9 segmentectomies, 14 bisegmentectomies (including 13 left lateral segmentectomies), and 2 major hepatectomies. The transfusion rate, the use of pedicular clamping, the conversion rate (13.5% in the whole series), and the complication rate were significantly greater in patients with HCC. There were no deaths. Postoperative complications occurred in eight patients (22%). The surgical margin was less than 1 cm in 30% of the patients. During a mean follow-up of 14 months, the 2-year disease-free survival was 44% for patients with HCC and 53% for patients having hepatic metastases from colorectal cancer. No port-site metastases were observed during follow-up. Conclusions In patients with small malignant tumors, located in the left lateral segments or in the anterior segments of the right liver, laparoscopic resection is feasible and safe. The complication rate is low, except in patients with HCC on cirrhotic liver. By using laparoscopic ultrasound, a 1-cm free surgical margin should be routinely obtained. The late outcome needs to be evaluated in expert centers. PMID:12131090

Gigot, Jean-François; Glineur, David; Santiago Azagra, Juan; Goergen, Martine; Ceuterick, Marc; Morino, Mario; Etienne, José; Marescaux, Jacques; Mutter, Didier; van Krunckelsven, Ludo; Descottes, Bernard; Valleix, Dominique; Lachachi, François; Bertrand, Claude; Mansvelt, Baudouin; Hubens, Guy; Saey, Jean-Pierre; Schockmel, Romain

2002-01-01

283

Engineered Liver for Transplantation  

PubMed Central

Orthotopic liver transplantation is the only definitive treatment for end stage liver failure and the shortage of donor organs severely limits the number of patients receiving transplants. Liver tissue engineering aims to address the donor liver shortage by creating functional tissue constructs to replace a damaged or failing liver. Despite decades of work, various bottoms-up, synthetic biomaterials approaches have failed to produce a functional construct suitable for transplantation. Recently, a new strategy has emerged using whole organ scaffolds as a vehicle for tissue engineering. This technique involves preparation of these organ scaffolds via perfusion decellularization with the resulting scaffold retaining the circulatory network of the native organ. This important phenomenon allows for the construct to be repopulated with cells and to be connected to the blood torrent upon transplantation. This opinion paper presents the current advances and discusses the challenges of creating fully functional transplantable liver grafts with this whole liver engineering approach. PMID:23791465

Uygun, Basak E

2013-01-01

284

Fasciola hepatica : effects of the fasciolicide clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes  

Microsoft Academic Search

The ultrastructural changes in Fasciola hepatica induced by the fasciolicide clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepaticawere dosed orally with clorsulon at a concentration of 12.5 mg\\/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also

M. Meaney; I. Fairweather; G. P. Brennan; L. S. L. McDowell; A. B. Forbes

2003-01-01

285

Transjugular Liver Biopsy.  

PubMed

Liver biopsy is still the gold standard for evaluation of acute and chronic liver diseases, despite achievements regarding noninvasive diagnosis and staging in liver diseases. Transjugular liver biopsy (TJLB) has proved a good option when ascites and/or significant coagulopathy precludes a percutaneous approach. Because diagnostic hemodynamic procedures can be performed during the same session, it is useful in many clinical settings, regardless of the absence of percuteaneous contraindications. TJLB is a safe technique able to provide good-quality specimens with a low rate of complications. This article presents an overview of TJLB that discusses the technique, applicability, indications, contraindications, complications, and diagnostic accuracy. PMID:25438282

Ble, Michel; Procopet, Bogdan; Miquel, Rosa; Hernandez-Gea, Virginia; García-Pagán, Juan Carlos

2014-11-01

286

Liver fibrosis in overweight patients  

Microsoft Academic Search

Background & Aims: A common clinical issue is whether overweight patients with abnormal liver function test results should undergo liver biopsy. Although serious liver injury can occur, its prevalence and risk factors are not well known. Methods: Ninety-three consecutive patients with abnormal liver function tests (but without overt liver disease), body mass index (BMI) > 25 kg\\/m2, and no alcoholic,

Vlad Ratziu; Philippe Giral; Frederic Charlotte; Eric Bruckert; Vincent Thibault; Ioannis Theodorou; Lina Khalil; Gérard Turpin; Pierre Opolon; Thierry Poynard

2000-01-01

287

Hypoxia and fatty liver.  

PubMed

The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

2014-11-01

288

Hypoxia and fatty liver  

PubMed Central

The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

2014-01-01

289

What Happens After Treatment for Liver Cancer?  

MedlinePLUS

... after liver cancer What happens after treatment for liver cancer? For some people with liver cancer, treatment ... 1-800-227-2345. Follow-up after a liver transplant A liver transplant can be very effective ...

290

25 Ways to Love Your Liver  

MedlinePLUS

... run events. Please support us. Donate | Volunteer For Liver Health Information Call 1-800-GO-LIVER (1- ... Love Your Liver 25 Ways to Love Your Liver The American Liver Foundation has put together this ...

291

Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant  

ClinicalTrials.gov

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

2014-05-05

292

Emerging Therapies for Liver Fibrosis  

Microsoft Academic Search

Liver fibrosis occurs as a result of a wide range of injurious processes and in its end-stage results in cirrhosis. This gross disruption of liver architecture is associated with impaired hepatic function, portal hypertension and significant resultant morbidity and mortality. Indeed, liver fibrosis and cirrhosis represent a major worldwide healthcare burden. Recent progress in liver transplantation, the management of portal

Andrew J. Fowell; John P. Iredale

2006-01-01

293

Precision in liver surgery.  

PubMed

Continuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery. PMID:23943100

Dong, Jiahong; Yang, Shizhong; Zeng, Jianping; Cai, Shouwang; Ji, Wenbin; Duan, Weidong; Zhang, Aiqun; Ren, Weizheng; Xu, Yinzhe; Tan, Jingwang; Bu, Xiangyang; Zhang, Ning; Wang, Xuedong; Wang, Xianqiang; Meng, Xiangfei; Jiang, Kai; Gu, Wanqing; Huang, Zhiqiang

2013-08-01

294

Liver cancer - Hepatocellular carcinoma  

MedlinePLUS

... long-term (chronic) Iron overload in the body ( hemochromatosis ) Patients with hepatitis B or C are at ... amounts of alcohol. Persons with certain types of hemochromatosis may need to be screened for liver cancer. ...

295

Fusobacterium Liver Abscess  

PubMed Central

Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation. PMID:24348321

Buelow, Ben D.; Lambert, Joelle M.; Gill, Ryan M.

2013-01-01

296

Fusobacterium liver abscess.  

PubMed

Fusobacterium is well characterized as an oropharyngeal pathogen that may induce a septic thrombophlebitis by direct extension of abscess into an adjacent neck vessel (Lemierre's syndrome); its potential for visceral abscess formation, however, remains under-recognized. A 65-year-old man with a recent history of multiple rim-enhancing liver lesions presented to the emergency room with fever and abdominal pain. Based on interval increase in the size of the lesions, abscess was suspected. A liver biopsy was performed, and although no organism could be identified on routine microscopy, Warthin-Starry stain revealed Gram-negative bacilli consistent with an anaerobic Fusobacterium species as the underlying etiology of liver abscess formation. Subsequent anaerobic culture results confirmed the diagnosis. This case highlights the importance of consideration for Fusobacterium infection in the setting of liver abscess if anaerobic organisms have not yet been excluded on initial culture evaluation. PMID:24348321

Buelow, Ben D; Lambert, Joelle M; Gill, Ryan M

2013-01-01

297

Pediatric liver transplantation  

PubMed Central

In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

2009-01-01

298

Structural Basis for the Inhibition of Histone Deacetylase 8 (HDAC8), a Key Epigenetic Player in the Blood Fluke Schistosoma mansoni  

PubMed Central

The treatment of schistosomiasis, a disease caused by blood flukes parasites of the Schistosoma genus, depends on the intensive use of a single drug, praziquantel, which increases the likelihood of the development of drug-resistant parasite strains and renders the search for new drugs a strategic priority. Currently, inhibitors of human epigenetic enzymes are actively investigated as novel anti-cancer drugs and have the potential to be used as new anti-parasitic agents. Here, we report that Schistosoma mansoni histone deacetylase 8 (smHDAC8), the most expressed class I HDAC isotype in this organism, is a functional acetyl-L-lysine deacetylase that plays an important role in parasite infectivity. The crystal structure of smHDAC8 shows that this enzyme adopts a canonical ?/? HDAC fold, with specific solvent exposed loops corresponding to insertions in the schistosome HDAC8 sequence. Importantly, structures of smHDAC8 in complex with generic HDAC inhibitors revealed specific structural changes in the smHDAC8 active site that cannot be accommodated by human HDACs. Using a structure-based approach, we identified several small-molecule inhibitors that build on these specificities. These molecules exhibit an inhibitory effect on smHDAC8 but show reduced affinity for human HDACs. Crucially, we show that a newly identified smHDAC8 inhibitor has the capacity to induce apoptosis and mortality in schistosomes. Taken together, our biological and structural findings define the framework for the rational design of small-molecule inhibitors specifically interfering with schistosome epigenetic mechanisms, and further support an anti-parasitic epigenome targeting strategy to treat neglected diseases caused by eukaryotic pathogens. PMID:24086136

Marek, Martin; Kannan, Srinivasaraghavan; Hauser, Alexander-Thomas; Moraes Mourão, Marina; Caby, Stéphanie; Cura, Vincent; Stolfa, Diana A.; Schmidtkunz, Karin; Lancelot, Julien; Andrade, Luiza; Renaud, Jean-Paul; Oliveira, Guilherme; Sippl, Wolfgang; Jung, Manfred; Cavarelli, Jean; Pierce, Raymond J.; Romier, Christophe

2013-01-01

299

Granulomatous liver disease  

Microsoft Academic Search

Hepatic granulomas are often encountered on liver biopsy and may represent a primary hepatic process, a manifestation of a\\u000a systemic illness, or an innocent finding of no clinical relevance. Hepatic granulomas are a unique inflammatory response that\\u000a may be idiopathic or may be a response to a bacterial, fungal, viral, or parasitic infection; a manifestation of drug-induced\\u000a liver injury; or

Sidharth S. Bhardwaj; Romil Saxena; Paul Y. Kwo

2009-01-01

300

Fortuitously discovered liver lesions.  

PubMed

The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible. PMID:23745019

Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

2013-06-01

301

Rapid detection of Opisthorchis viverrini copro-DNA using loop-mediated isothermal amplification (LAMP)  

Microsoft Academic Search

Opisthorchis viverrini and other foodborne trematode infections are major health problem in Thailand, the Lao People's Democratic Republic, Vietnam and Cambodia. Differential diagnosis of O. viverrini based on the microscopic observation of parasite eggs is difficult in areas where Clonorchis sinensis and minute intestinal flukes coexist. We therefore established a rapid, sensitive and specific method for detecting O. viverrini infection

Yuji Arimatsu; Sasithorn Kaewkes; Thewarach Laha; Sung-Jong Hong; Banchob Sripa

302

Gut microbiota and liver diseases  

PubMed Central

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases.

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

303

Transjugular Liver Biopsy  

PubMed Central

Liver biopsy is considered the gold standard for the evaluation of acute and chronic liver disorders. Transjugular liver biopsy (TJLB) was described by Dotter in 1964 and clinically performed for the first time by Hanafee in 1967. TJLB consists of obtaining liver tissue through a rigid cannula introduced into one of the hepatic veins, typically using jugular venous access. The quality of the TJLB specimens has improved so much that the samples obtained by this method are comparable with those obtained with the percutaneous technique. TJLB is indicated for patients with coagulopathy, ascites, peliosis hepatis, morbid obesity, liver transplant, or in patients undergoing a transjugular intrahepatic portosystemic shunt procedure. The technical success rate for a TJLB procedure ranges from 87 to 97%. Sample fragmentation has been reported in 14 to 25% of the TJLB samples. The complication rates are low and range between 1.3% and 6.5%. The purpose of this article is to provide a review of the fundamental aspects of the TJLB procedure, including technique, indications, contraindications, results, and complications. PMID:23729981

Behrens, George; Ferral, Hector

2012-01-01

304

Stereoscopic liver surface reconstruction  

PubMed Central

The paper presents a practical approach to measuring liver motion, both respiratory and laparoscopic, with a tool guided in the operating room. The presented method is based on standard operating room equipment, i.e. rigid laparoscopic cameras and a single incision laparoscopic surgery trocar. The triangulation algorithm is used and stereo correspondence points are marked manually by two independent experts. To calibrate the cameras two perpendicular chessboards, a pinhole camera model and a Tsai algorithm are used. The data set consists of twelve real liver surgery video sequences: ten open surgery and two laparoscopic, gathered from different patients. The setup equipment and methodology are presented. The proposed evaluation method based on both calibration points of the chessboard reconstruction and measurements made by the Polaris Vicra tracking system are used as a reference system. In the analysis stage we focused on two specific goals, measuring respiration and laparoscopic tool guided liver motions. We have presented separate examples for left and right liver lobes. It is possible to reconstruct liver motion using the SILS trocar. Our approach was made without additional position or movement sensors. Diffusion of cameras and laser for distance measurement seems to be less practical for in vivo laparoscopic data, but we do not exclude exploring such sensors in further research. PMID:23256023

Karwan, Adam; Rudnicki, Jerzy; Wróblewski, Tadeusz

2012-01-01

305

When Your Child Needs a Liver Transplant  

MedlinePLUS

... Hereditary Hemochromatosis Blood Test: Hepatic (Liver) Function Panel Digestive System Hepatitis Your Liver Hepatitis Your Digestive System Blood Test: Liver Function Tests Hepatitis Digestive System ...

306

Alcoholic liver disease: treatment.  

PubMed

The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

2014-09-28

307

New Drug for Common Liver Disease Improves Liver Health  

MedlinePLUS

... mail For Immediate Release: Friday, November 7, 2014 New drug for common liver disease improves liver health ... are advised to avoid alcohol and unnecessary medications. New cases of NASH have grown alongside the obesity ...

308

Getting a New Liver: Facts about Liver Transplants  

MedlinePLUS

... Revised December 2006 Revised March 2012 Getting A New Liver Facts About Liver Transplants American Society of ... be able to take better care of your new transplant if you understand your illness and your ...

309

Epidemiology of liver failure.  

PubMed

The etiology of fulminant hepatitis varies in different countries and at different times. The main causes of fulminant hepatitis are viruses, paracetamol, drugs (other than paracetamol), poisons and 15-30% remained of undetermined origin. The prevalence of these etiologies varies according to the geographic region and has changed over the past 10 years. Paracetamol has now overtaken viruses (particularly hepatitis B virus) as the leading cause of fulminant hepatitis. Establishing the cause of fulminant hepatitis is an important step in the management of acute liver failure, so that specific therapy can be initiated and any contraindications to liver transplantation be eliminated. PMID:21550329

Ichai, Philippe; Samuel, Didier

2011-10-01

310

The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements  

PubMed Central

Background Of the major families of long terminal repeat (LTR) retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. Results A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs representing transcripts of Sinbad in numerous developmental stages of S. mansoni along with the identical 5'- and 3'-LTR sequences suggests that Sinbad is an active retrotransposon. Conclusion Sinbad is a Pao/BEL type retrotransposon from the genome of S. mansoni. The Pao/BEL group appears to be comprised of at least five discrete subfamilies, which tend to cluster with host species phylogeny. Pao/BEL type elements appear to have colonized only the genomes of the Animalia. The distribution of these elements in the Ecdysozoa, Deuterostomia, and Lophotrochozoa is discontinuous, suggesting horizontal transmission and/or efficient elimination of Pao-like mobile genetic elements from some genomes. PMID:15725362

Copeland, Claudia S; Mann, Victoria H; Morales, Maria E; Kalinna, Bernd H; Brindley, Paul J

2005-01-01

311

The Virtual Liver: Modeling Chemical-Induced Liver Toxicity  

EPA Science Inventory

The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

312

About the Operation: Liver Transplant  

MedlinePLUS

... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to ... The process of being admitted and preparing for transplant surgery can vary greatly. Talk to your doctor ...

313

[Drug-induced liver injury].  

PubMed

Drug-induced liver injury represents the principal cause of acute liver failure and orthotopic liver transplantation in western country. A very large number of different drugs and medicinal herbs has been associated with liver injury but just for few of them we know the process that causes liver disease. All the people which ingest a large number of drugs present a risk of developing liver injury. Diagnosis is very difficult because a specific biomarker of damage is absent and the clinical picture is common to other liver diseases. A therapeutic approach is efficacy only in few cases. When a drug-induced liver injury is suspected, cessation of the drug is the first step in their management. PMID:22430754

Abenavoli, Ludovico; Libri, Emanuela; Bosco, Domenico; Gallo, Dionisio; Luzza, Francesco

2012-02-01

314

Kava Linked to Liver Damage  

MedlinePLUS

Kava Linked to Liver Damage September 10, 2010 In March 2002, the U.S. Food and Drug Administration (FDA) issued an advisory to consumers of the potential risk of severe liver injury from the use of dietary supplements containing ...

315

Kava Linked to Liver Damage  

MedlinePLUS

... disclaimer about external links Menu Kava Linked to Liver Damage September 10, 2010 In March 2002, the ... to consumers of the potential risk of severe liver injury from the use of dietary supplements containing ...

316

Toward surface quantification of liver fibrosis progression  

E-print Network

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver ...

He, Yuting

317

Risks of Liver (Hepatocellular) Cancer Screening  

MedlinePLUS

... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver. The liver is one of the largest organs ...

318

General Information about Liver (Hepatocellular) Cancer  

MedlinePLUS

... to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver. The liver is one of the largest organs ...

319

Cholestasis Post Liver Transplantation  

Microsoft Academic Search

Cholestasis occurs frequently after liver transplantation and has a very broad differential diagnosis. Cholestasis can occur\\u000a anytime throughout the posttransplant period and may be intrahepatic or extrahepatic in origin. This chapter reviews the common\\u000a causes of cholestasis in the posttransplant setting.

Kymberly D. S. Watt; Timothy M. McCashland

320

The EPA Liver Project  

EPA Science Inventory

The v-Liver is part of a broader EPA effort on Virtual Tissues (VT) aimed at reducing the magnitude and spectrum of animal testing by integrative in silico and in vitro models, which recapitulate the properties of intact organs. The other VT projects include the Virtual Embryo (...

321

Coffee and liver health.  

PubMed

Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients. PMID:25291138

Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

2014-01-01

322

Pregnancy Complications: Liver Disorders  

MedlinePLUS

... their babies had certain inherited errors in body chemistry (fatty acid oxidation defects) (8). These disorders prevent an affected individual from properly processing certain fats. Babies with these disorders can develop life-threatening liver, heart and neuromuscular problems unless they ...

323

Liver Disease and Pulmonary Hypertension  

MedlinePLUS

www.PHAssociation.org &Liver Disease Pulmonary Hypertension PH Did you know that if you have liver disease, you are at risk for pulmonary hypertension? ... that About Pulmonary Hypertension lupus for example), chronic liver disease, congenital heart disease, or HIV infection. Finally ...

324

The liver in haemochromatosis.  

PubMed

The review deals with genetic, regulatory and clinical aspects of iron homeostasis and hereditary haemochromatosis. Haemochromatosis was first described in the second half of the 19th century as a clinical entity characterized by excessive iron overload in the liver. Later, increased absorption of iron from the diet was identified as the pathophysiological hallmark. In the 1970s genetic evidence emerged supporting the apparent inheritable feature of the disease. And finally in 1996 a new "haemochromatosis gene" called HFE was described which was mutated in about 85% of the patients. From the year 2000 onward remarkable progress was made in revealing the complex molecular regulation of iron trafficking in the human body and its disturbance in haemochromatosis. The discovery of hepcidin and ferroportin and their interaction in regulating the release of iron from enterocytes and macrophages to plasma were important milestones. The discovery of new, rare variants of non-HFE-haemochromatosis was explained by mutations in the multicomponent signal transduction pathway controlling hepcidin transcription. Inhibited transcription induced by the altered function of mutated gene products, results in low plasma levels of hepcidin which facilitate entry of iron from enterocytes into plasma. In time this leads to progressive accumulation of iron and subsequently development of disease in the liver and other parenchymatous organs. Being the major site of excess iron storage and hepcidin synthesis the liver is a cornerstone in maintaining normal systemic iron homeostasis. Its central pathophysiological role in HFE-haemochromatosis with downgraded hepcidin synthesis, was recently shown by the finding that liver transplantation normalized the hepcidin levels in plasma and there was no sign of iron accumulation in the new liver. PMID:25204225

Ulvik, Rune J

2014-08-21

325

Drug-induced Liver Injury  

PubMed Central

Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

David, Stefan; Hamilton, James P

2011-01-01

326

Liver transplantation for hepatocellular carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early, unresectable HCC particularly in the setting of chronic liver disease. Following on from disappointing initial results, the seminal study by Mazzaferro et al in 1996 established OLT as a viable treatment for HCC. In this study, the “Milan criteria” were applied achieving a 4-year survival rate similar to OLT for benign disease. Since then various groups have attempted to expand these criteria whilst maintaining long term survival rates. The technique of living donor liver transplantation has evolved over the past decade, particularly in Asia, and published outcome data is comparable to that of OLT. This article will review the evidence, indications, and the future direction of liver transplantation for liver cancer. PMID:19938188

Tanwar, Sudeep; Khan, Shahid A; Grover, Vijay Paul Bob; Gwilt, Catherine; Smith, Belinda; Brown, Ashley

2009-01-01

327

Liver transplantation and non-alcoholic fatty liver disease.  

PubMed

Non-alcoholic fatty liver disease (NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis (nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance (or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following: (1) the increasing need for liver transplantation due to NASH; (2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation; (3) the long term graft and patient outcomes after liver transplantation for NASH, and finally; and (4) the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes. PMID:25400437

Zezos, Petros; Renner, Eberhard L

2014-11-14

328

Liver transplantation and non-alcoholic fatty liver disease  

PubMed Central

Non-alcoholic fatty liver disease (NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis (nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance (or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following: (1) the increasing need for liver transplantation due to NASH; (2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation; (3) the long term graft and patient outcomes after liver transplantation for NASH, and finally; and (4) the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes. PMID:25400437

Zezos, Petros; Renner, Eberhard L

2014-01-01

329

Living donor liver transplantation: issues regarding left liver grafts  

PubMed Central

Background The necessity of widening the indications for living donor liver transplantation (LDLT) has been emphasised. Clarification of the advantages and limitations of using a left liver graft for LDLT in adults is essential for donor safety. Methods Between June 1990 and November 2002, 185 patients underwent LDLT at Shinshu University Hospital, Japan. In 97 of these, the graft comprised the left liver with or without the left portion of the caudate lobe. The peri-hepatectomy profiles of the donors, significance of left liver grafts, postoperative courses of the donors and recipients, and survival of the recipients were investigated. Results All the donors recovered well and returned to a normal lifestyle. None required banked-blood transfusion or repeat surgery, and postoperative liver function tests had satisfactory results. The cold ischaemic time for the graft was 127±54 minutes. The graft volumes (GVs) ranged from 230 to 625 ml, and GV/standard liver volume (SV) ratios varied from 22% to 65%, at the time of transplantation. Although 85% of the liver grafts had GV/SV ratios <50%, no patient developed immediate postoperative liver failure. Patient survival rates were 89%, 84% and 84% at 1, 3 and 5 years, respectively. Discussion Although LDLT using a left liver graft imposes potential postoperative complications (a small liver is more vulnerable to injury, and recipients of small grafts are at higher risk of complications during recovery), such grafts have yielded acceptable results in adult LDLT, with minimal burden to the donors. PMID:18333058

Hashikura, Y

2004-01-01

330

Fatty liver in childhood  

PubMed Central

Fatty liver is a growing health problem worldwide. It might evolve to nonalcoholic steatohepatitis, cirrhosis and cause hepatocellular carcinoma. This disease, which has increased because of eating habits, changes in food content and lifestyle, affects people from childhood. The most important risk factors are obesity and insulin resistance. Besides these factors, gender, ethnicity, genetic predisposition and some medical problems are also important. Cirrhosis in children is rare but is reported. Nonalcoholic fatty liver disease (NAFLD) has no specific symptoms or signs but should be considered in obese children. NAFLD does not have a proven treatment. Weight loss with family based treatments is the most acceptable management. Exercise and an applicable diet with low glycemic index and appropriate calorie intake are preferred. Drugs are promising but not sufficient in children for today. PMID:24653792

Ozturk, Yesim; Soylu, Ozlem Bekem

2014-01-01

331

[Antioxidants in liver protection].  

PubMed

Great importance has been attributed to antioxidants in the prevention and treatment of conditions associated with oxidative stress for many years. At the same time the antioxidants are free radicals themselves, and they can exert prooxidant activity depending on the concentration. They influence the cell redox homeostasis by their prooxidant and antioxidant activity as well. Drugs of chronic liver diseases should be considered, because free radicals are generated during the activity of the monooxygenase system, which affect the tissue oxidised status. Combined antioxidant treatment is more favourable compared with monotherapy, because antioxidants have scavenger-, compartment- and tissue-specificity and they regenerate each other directly, too. Beside their antioxidant property they may also directly regulate many important processes, e.g. cell cycle. We have some favourable results with regard combined antioxidant therapy of liver disease of different etiology. PMID:15320484

Hagymási, Krisztina; Blázovics, Anna

2004-07-01

332

Vascular liver diseases  

Microsoft Academic Search

This article reviews the primary circulatory liver diseases, which include Budd-Chiari syndrome, obstruction of the hepatic\\u000a portion of the inferior vena cava, portal vein thrombosis, sinusoidal obstruction syndrome (veno-occlusive disease), nodular\\u000a regenerative hyperplasia, and peliosis hepatis. In addition, two systemic cardiovascular diseases that impair hepatic circulation,\\u000a ischemic hepatitis and congestive hepatopathy, are briefly discussed. A characteristic of the primary circulatory

Laurie D. DeLeve

2003-01-01

333

Epigenetics in liver disease  

PubMed Central

Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable. Conclusion: The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade. (Hepatology 2014;60:1418–1425) PMID:24633972

Mann, Derek A

2014-01-01

334

Liver transplantation in Europe for patients with acute liver failure.  

PubMed

Approximately 11% of all liver transplants performed in Europe are for acute liver failure, with one-year patient survival rates ranging between 50% and 75%. This review summarizes the selection, perioperative management, and outcome of patients transplanted for acute liver failure, with particular reference to the experience at the Hôpital Paul Brousse in Paris and at King's College Hospital, London. In both centers, the decision to proceed to liver transplantation is based on criteria that predict a survival of less than 20% with medical management alone. Infectious complications and cerebral edema remain the most common causes of death, and highlight the importance of intensive monitoring and early treatment of perioperative complications. In selected patients, auxiliary partial orthotopic liver transplantation may be a therapeutic option, with the potential for native liver generation and eventual immunosuppression withdrawal in approximately two-thirds of patients. PMID:9027954

Bismuth, H; Samuel, D; Castaing, D; Williams, R; Pereira, S P

1996-11-01

335

Chronic liver disease: relaxometry in the brain after liver transplantation  

Microsoft Academic Search

Relaxometry revealed changes in the basal ganglia in T1 and T2 relaxation times due to liver disease. Manganese is probably responsible for T1 and T2 shortening (as the concentration is known to be higher in both the liver and blood due to hepatic cirrhosis). The aim of\\u000a this study was to follow possible recovery after liver transplantation by MR relaxometry.

V??t Herynek; Milan Babiš; Pavel Trune?ka; Karel Filip; Josef Vymazal; Monika Dezortová; Milan Hájek

2001-01-01

336

Role of liver progenitors in acute liver injury  

PubMed Central

Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A.; Syn, Wing-Kin

2013-01-01

337

Hot topics in liver anesthesia.  

PubMed

Anesthetic techniques for liver surgery still have many controversial issues for anesthesiologists who want to provide optimal care for their patients. There are unanswered questions: What is the best technique to prevent excessive blood loss during live donor liver dissection? What is the proper compromise of filling pressures to reduce bleeding and not compromise vital organ function? Epidural analgesia, an established method for pain relief, carries a risk of epidural hematoma formation in liver resections and especially liver transplantation because of compromised coagulation. New inhalation anesthetics would be ideal for liver surgery except for their potential for renal failure, and the IV agent propofol may have insufficient metabolism when liver function is absent. Several recent studies are reviewed to elucidate these questions. PMID:18555145

Lukanovic, N P

2008-05-01

338

Radiation-Associated Liver Injury  

SciTech Connect

The liver is a critically important organ that has numerous functions including the production of bile, metabolism of ingested nutrients, elimination of many waste products, glycogen storage, and plasma protein synthesis. The liver is often incidentally irradiated during radiation therapy (RT) for tumors in the upper- abdomen, right lower lung, distal esophagus, or during whole abdomen or whole body RT. This article describes the endpoints, time-course, and dose-volume effect of radiation on the liver.

Pan, Charlie C., E-mail: cpan@umich.ed [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Dawson, Laura A. [Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Miften, Moyed [Department of Radiation Oncology, University of Colorado, Aurora, CO (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States)

2010-03-01

339

Current advances in liver transplantation.  

PubMed

Advances in the medical and surgical management of patients undergoing liver transplantation have made transplantation the method of choice for dealing with end-stage liver disease. With the availability of anti-viral agents such as interferon and ribavirin, pre and post transplant treatment of hepatitis C, the most common indication for liver transplantation, is now possible. The use of high dose hepatitis B immune globulin (HBIG) and lamivudine has decreased the incidence and severity of recurrence of hepatitis B after liver transplantation. Multimodal therapy including chemoembolization for hepatocellular carcinoma has made liver transplantation a viable option for selected patients with primary liver cancer. The development of more potent immunosuppressive agents has dramatically decreased the incidence of acute rejection, while the search for a solution to the problem of chronic rejection continues. Alcoholic liver disease remains a challenge for transplant physicians and surgeons; however, careful patient selection results in a relatively low rate of recidivism.Surgical advances in liver transplantation have focused on eliminating associated morbidity and mortality as well as expanding the donor pool. Veno-venous bypass (VVB) and T-tube stenting, which were once considered essential techniques in liver transplantation, are now only rarely, if ever, necessary. Operative time, blood product usage, and time to extubation, as well as intensive care unit stay, have all been significantly reduced by elimination of VVB without associated morbidity. Elimination of T-tube usage has also effectively decreased morbidity. Donor expansion has become critical as the need for liver transplants exceeds donor availability. Use of marginal donors, including older donors, donors with up to 40% fat content, and donors with high pressor requirements, has proven to be a safe and effective means of increasing the donor pool. In-situ splitting of donors is the most promising technical advance in liver transplantation. This technique, along with living-related liver transplantation, is very important for providing donors to the pediatric population where donor availability is even more limited. PMID:21845116

Eason, J D; Rowell, D L

1999-01-01

340

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”  

... 2 2014-01-01 2014-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â...ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers designated as...

2014-01-01

341

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”  

Code of Federal Regulations, 2011 CFR

... 2 2011-01-01 2011-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â...ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers designated as...

2011-01-01

342

Liver Planning Software Accurately Predicts Postoperative Liver Volume and Measures Early  

E-print Network

Liver Planning Software Accurately Predicts Postoperative Liver Volume and Measures Early or remnant liver volume (RLV) after hepatic resection is a critical predictor of perioperative outcomes. This study investigates whether the accuracy of liver surgical plan- ning software for predicting

Miga, Michael I.

343

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”  

Code of Federal Regulations, 2010 CFR

... 2 2010-01-01 2010-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â...ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers designated as...

2010-01-01

344

Virtual Reality Liver Biopsy Simulator Virtual Reality, Ultrasound-guided Liver Biopsy Simulator  

E-print Network

Virtual Reality Liver Biopsy Simulator Virtual Reality, Ultrasound-guided Liver Biopsy Simulator: Development and Performance Discrimination1 Running head: Virtual Reality Liver Biopsy Simulator Word.1259/bjr/47436030 #12;Virtual Reality Liver Biopsy Simulator ABSTRACT Purpose: Identify and prospectively

Paris-Sud XI, Université de

345

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”  

Code of Federal Regulations, 2013 CFR

... 2 2013-01-01 2013-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â...ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers designated as...

2013-01-01

346

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”  

Code of Federal Regulations, 2012 CFR

... 2 2012-01-01 2012-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â...ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis; livers designated as...

2012-01-01

347

Iron homeostasis in the liver  

PubMed Central

Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

Anderson, Erik R; Shah, Yatrik M

2014-01-01

348

Acute Liver Failure  

PubMed Central

Although comprising a minority of the transplant population, acute liver failure (ALF) patients represent some of the most challenging cases in terms of the level and complexity of care required. An ALF patient requires much more than a single skilled intensivist, gastroenterologist, or surgeon. Successful care of the ALF patient begins with early diagnosis and triage to the appropriate level of care where a multitude of specialties are required to work together to maximize the chance of recovery and/or extend the window of opportunity for transplant. PMID:20827368

McDowell Torres, Dawn; Stevens, Robert D.

2010-01-01

349

Chronic liver inflammation: clinical implications beyond alcoholic liver disease.  

PubMed

Chronic alcohol exposure can lead to alcoholic liver disease, including hepatitis, cirrhosis and hepatocellular carcinoma, and chronic inflammation can simultaneously cause systemic medical illness. Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides (LPS). The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress, activation of the immune cascade, and gut-liver interactions. Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption; general anti-inflammatories such as glucocorticoid, pentoxifylline, and tumour necrosis factor-? antagonist; antioxidants such as N- acetylcysteine; gut microflora and LPS modulators such as rifaximin and/or probiotics. This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets. PMID:24605015

Park, Byoung-Jin; Lee, Yong-Jae; Lee, Hye-Ree

2014-03-01

350

Chronic liver inflammation: Clinical implications beyond alcoholic liver disease  

PubMed Central

Chronic alcohol exposure can lead to alcoholic liver disease, including hepatitis, cirrhosis and hepatocellular carcinoma, and chronic inflammation can simultaneously cause systemic medical illness. Recent evidence suggests that alcoholic liver disease is a predictor for liver-related diseases, cardiovascular disease, immunologic disease, and bone disease. Chronic inflammation in alcoholic liver disease is mediated by a direct inflammatory cascade from the alcohol detoxification process and an indirect inflammatory cascade in response to gut microflora-derived lipopolysaccharides (LPS). The pathophysiology of alcoholic liver disease and its related systemic illness is characterized by oxidative stress, activation of the immune cascade, and gut-liver interactions. Integrative therapeutic strategies for alcoholic liver disease include abstaining from alcohol consumption; general anti-inflammatories such as glucocorticoid, pentoxifylline, and tumour necrosis factor-? antagonist; antioxidants such as N- acetylcysteine; gut microflora and LPS modulators such as rifaximin and/or probiotics. This review focuses on the impact of chronic liver inflammation on systemic health problems and several potential therapeutic targets. PMID:24605015

Park, Byoung-Jin; Lee, Yong-Jae; Lee, Hye-Ree

2014-01-01

351

Liver disease in India.  

PubMed Central

One hundred and twenty-five children with chronic liver disease were seen in Pune in 13 months. Fifty-nine of them, aged 8-39 months, had Indian childhood cirrhosis histologically diagnosed. Their characteristics included an insidious onset of symptoms, a geographical clustering of cases in rural areas north-east of Pune, a high rate of parental consanguinity and affected siblings, and a very high hepatic copper concentration (790-6654 micrograms/g dry weight). Only 8 survived for 6 months, adverse prognostic features being jaundice, ascites, enlargement of the gall bladder, and severe anaemia at presentation. Clinical differentiation from other liver disorders in the same age group was clear in advanced cases but unreliable in earlier cases. Four asymptomatic siblings with hepatomegaly had a benign course. The need for non-invasive methods to diagnose early cases in the community is demonstrated. The other major diagnostic categories were: unresolved hepatitis (12); chronic active hepatitis (7); cryptogenic cirrhosis (6); neonatal hepatitis and biliary atresia (8). PMID:7181521

Bhave, S A; Pandit, A N; Pradhan, A M; Sidhaye, D G; Kantarjian, A; Williams, A; Talbot, I C; Tanner, M S

1982-01-01

352

Pediatric Liver Transplantation  

PubMed Central

The postoperative diagnostic imaging examinations of 44 children who underwent 59 orthotopic liver transplantations were reviewed. The imaging modalities used for the evaluation of suspected complications include plain roentgenography, ultrasonography (US), computed tomography (CT), nuclear scintigraphy, arteriography, percutaneous and operative cholangiography, and endoscopic retrograde cholangiopancreatography. The main postoperative complications included ischemia, thrombosis (hepatic artery and portal vein), infarction, obstruction or leakage of the biliary anastomosis, hepatic and perihepatic infection, and allograft rejection. US, the most frequently used abdominal imaging modality, was best suited for detection of biliary duct dilatation, fluid collections in or around the transplanted liver, and hepatic arterial, inferior vena caval, and portal vein thrombosis. CT was especially helpful in corroborating findings of infection and in locating abscesses. Technetium 99m sulfur colloid (early- and late-phase imaging) provided a sensitive, although nonspecific, means of assessing allograft vascularization and morphology. Angiography showed vascularity most clearly, and cholangiography was the most useful In the assessment of bile duct patency. A diagnostic imaging algorithm is proposed for evaluation of suspected complications. PMID:3901104

Dominguez, Rodrigo; Young, Lionel W.; Ledesma-Medina, Jocyline; Cienfuegos, Javier; Gartner, J. Carlton; Bron, Klaus M.; Starzl, Thomas E.

2010-01-01

353

Lipotoxicity in the liver  

PubMed Central

Obesity due to excessive food intake and the lack of physical activity is becoming one of the most serious public health problems of the 21st century. With the increasing prevalence of obesity, non-alcoholic fatty liver disease is also emerging as a pandemic. While previously this pathophysiological condition was mainly attributed to triglyceride accumulation in hepatocytes, recent data show that the development of oxidative stress, lipid peroxidation, cell death, inflammation and fibrosis are mostly due to accumulation of fatty acids, and the altered composition of membrane phospholipids. In fact, triglyceride accumulation might play a protective role, and the higher toxicity of saturated or trans fatty acids seems to be the consequence of a blockade in triglyceride synthesis. Increased membrane saturation can profoundly disturb cellular homeostasis by impairing the function of membrane receptors, channels and transporters. However, it also induces endoplasmic reticulum stress via novel sensing mechanisms of the organelle’s stress receptors. The triggered signaling pathways in turn largely contribute to the development of insulin resistance and apoptosis. These findings have substantiated the lipotoxic liver injury hypothesis for the pathomechanism of hepatosteatosis. This minireview focuses on the metabolic and redox aspects of lipotoxicity and lipoapoptosis, with special regards on the involvement of endoplasmic reticulum stress responses. PMID:24179614

Zámbó, Veronika; Simon-Szabó, Laura; Szelényi, Péter; Kereszturi, Éva; Bánhegyi, Gábor; Csala, Miklós

2013-01-01

354

Methotrexate-Induced Liver Cirrhosis  

Microsoft Academic Search

Studies on serial liver biopsies from 25 patients with methotrexate-induced liver cirrhosis, taken from 1 to 13 years after cirrhosis was established, confirm that this type is not of aggressive nature. When evaluated blind no progression was found in most of the later biopsies. Alcohol and previous use of hepatotoxic drugs such as the combination of arsenics and vitamin A

H. Zachariae; H. Søgaard

1987-01-01

355

LIVER AND THE METABOLIC SYNDROME  

EPA Science Inventory

We have developed the following specific aims: Specific Aim 1 will be to develop a model and the liver phenotype (defined as above) is maintained. In Specific Aim 2, we will demonstrate that manipulation of the host environment will induce changes in liver tissues. We will exa...

356

Toxicity of Polar Bear Liver  

Microsoft Academic Search

ACCORDING to information from the Eskimos, and records from Arctic travellers, bad effects may follow the consumption, by men and dogs, of the livers of polar bear, bearded seal, Greenland fox and Eskimo huskies, whereas livers of other Arctic mammals can usually be eaten without injury.

Kaare Rodahl

1949-01-01

357

The Liver, Regulator of Nutrition.  

ERIC Educational Resources Information Center

The purpose of this theme issue is to review the basic physiological, nutritional, and pathological facts pertaining to the liver. It is an educational tool through which university teachers and people in charge of training may enhance their teaching programs. The main liver diseases seen in young children and pregnant women in tropical regions is…

Dillon, J. C.

1995-01-01

358

Deodorization of Shark Liver Oil  

Microsoft Academic Search

SHARK liver oil, which is one of the cheapest and most plentiful sources of vitamin A in Nature, has a highly disagreeable odour which is very much more pronounced than that of cod liver oil. On account of its unpalatability it does not easily find favour with the consumers. The deodorization of the oil has to be effected in such

P. K. Mathew; P. V. Nair; T. A. Ramakrishnan; H. Sreemulanathan

1948-01-01

359

Cancer and Human Liver Catalase  

Microsoft Academic Search

SUMMARY Data presented in the present paper indicate that human liver catalase depression is related to weight loss. A statistical study was first made to determine the catalase activity in correlation of the iodotitrimetric and spectrophotometric methods for biopsy and autopsy samples from cancer and cancer-free patients. Cancer patients had a 2~ per cent lower liver catalase activity than cancer-free

EDWARD E. MASON; TING-FONG CHIN; YAO W. LI; SIDNEY E. ZIFFREN

1960-01-01

360

Overview of pediatric liver transplantation.  

PubMed

Liver transplantation is a successful and useful therapy for children with chronic or end-stage liver disease and those with a variety of extrahepatic metabolic diseases that can be corrected by liver replacement. Major developments in medical management, donor availability and procurement, operative techniques, and post-operative management all contributed to the dramatic improvement in outcome and growth of liver transplantation from its inception in 1963 [1,7,21]. The excellent long-term outcomes that have been achieved are the product of the coordinated efforts of liver transplant surgeons, specialists in pediatric hepatology and other medical areas, nurses, local practitioners, and the patients and their families. Future advances in transplant immunobiology, organ availability and infection control are likely to lead to still greater improvements in short and long-term outcome [34]. PMID:14562581

Rand, Elizabeth B; Olthoff, Kim M

2003-09-01

361

Liver transplantation in older adults.  

PubMed

Liver transplantation is the only definitive treatment therapy for end-stage liver disease. In the United States, approximately 15% of annual liver transplant recipients are 65 or older. The most common postoperative complications are infection, acute graft rejection, and acute renal failure. To prevent complications, recipients are treated with immunosuppressive medications and anti-infective agents. The long-term complications of liver transplantation are a consequence of long-term use of immunosuppressive medications and recurrence of the original disease in the liver. Nurses play a critical role in supporting and educating recipients and their primary support persons about post-transplant follow-up care, including laboratory test schedules, medication management, and infection prevention. Strict compliance with follow-up care provides the greatest possibility of avoiding complications or organ rejection. PMID:25105357

Hansen, Lissi

2014-09-01

362

Liver transplantation and transthyretin amyloidosis.  

PubMed

Liver transplantation as a specific treatment of transthyretin amyloidosis was first performed in 1990. The rationale for this treatment was that removal of the source (liver) of the amyloid precursor protein (mutated transthyretin) would stop progression of the disease. Indeed, after orthotopic liver transplantation (OLT), mutant transthyretin (TTR) is rapidly cleared from circulation. In the last 20 years, >2000 familial amyloidotic polyneuropathy (FAP) patients have received liver transplants. For these patients, prospective monitoring has shown prolongation of life compared with FAP patients who have not undergone liver transplantation. The most favorable results have been for FAP patients with the Val30Met TTR mutation. Less favorable results have been seen for patients with other TTR mutations where progression of amyloid tissue deposition has been documented as the result of amyloid fibril formation from normal (wild-type) TTR. Although it is obvious that OLT has benefited many FAP patients, there remains a need for further therapies. PMID:23169427

Benson, Merrill D

2013-02-01

363

Recurrence of nonviral liver diseases after liver transplantation.  

PubMed

Many nonviral diseases that cause liver failure may recur after liver transplantation. Although most studies have shown that a recurrent disease does not negatively affect patient and graft survival in the intermediate postoperative course, there is growing evidence that, especially in patients with primary sclerosing cholangitis and in patients with recurrent abusive alcohol drinking, disease recurrence is a significant risk factor for graft dysfunction and graft loss. Therefore, the recurrence of nonviral diseases has become a clinically important and prognostically relevant issue in the long-term management of recipients of liver transplantation. PMID:25017083

Graziadei, Ivo W

2014-08-01

364

[Focal liver lesion, incidental finding].  

PubMed

The differential diagnosis of incidentally found Focal Liver Lesions (FLL) is complex. Screening procedures so far are only defined for patients with liver cirrhosis. Characterization of a FLL begins as soon as it is detected. Taking patients history and thorough clinical examination are essential. An imaging procedure that is used to detect liver masses should also allow the examiner to determine whether the lesion is benign or malignant. Conventional B-mode US and colour Doppler imaging are effective at detecting and characterizing typical liver cysts and calcifications. Laboratory data, computed tomography, magnetic resonance imaging and imaging guided liver biopsy are complementary methods.Contrast Enhanced Ultrasound (CEUS) is a well established diagnostic imaging technique for a variety of indications and applications. One of the most important applications is in the liver where it is frequently a first-line technique for the detection and diagnosis (characterization) of focal liver lesions (FLL). In this setting the accurate differentiation of benign from malignant lesions is critical to ensure the patient undergoes the appropriate therapeutic option. This has been documented in recently published guidelines, in particular in terms of the enhancement patterns of the most common FLL hemangioma, focal nodular hyperplasia hepatocellular adenoma and their differentiation from malignant lesions. In this article the role of CEUS in the characterization of incidentally found FLL is described. PMID:23033169

Dietrich, C F; Jenssen, C

2012-10-01

365

Liver disease in cystic fibrosis  

PubMed Central

Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated “gold standard” in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

Klincewicz, Beata; Cichy, Wojciech

2014-01-01

366

[Management of pediatric liver abscess].  

PubMed

Liver abscess in the pediatric population remains uncommon in developed countries, except in cases of septicemia or in children with major debilitating diseases, granulocyte dysfunction, or immunosuppression. Although much is known about the etiopathogenesis of liver abscess, the gold standard of investigations and treatment is still debatable in developing countries. We report the case of a 6-year-old child living in Reunion Island, with no medical history, presenting with right and pyretic abdominal pain in the right upper quadrant. Ultrasound and CT scan showed a large hypodense nonenhanced area in segment IV. Final diagnosis was, by exclusion, pyogenic liver abscess based on negative serology, recent liver lesion, and normal tumor test results, even if blood culture remained negative. No percutaneous puncture was done because of positive outcome after 4 days of antibiotics. Treatment consisted in three intravenous antibiotics (ceftriaxone, aminoxide, and metronidazole) until complete biological normalization. Ultrasound remained normal 3 months later. Even if liver abscess is uncommon in developing countries, the diagnosis must be raised in cases of isolated liver tumor with fever. Management in the nonimmunosuppressed child must be discussed associating parenteral antibiotic therapy, percutaneous drainage, or surgery in very uncommon cases, according to the liver location and first day's progression. Etiological investigation such as colonoscopy in adults must be adapted to pediatric data. PMID:22463954

Fievet, L; Michel, J-L; Harper, L; Turquet, A; Moiton, M-P; Sauvat, F

2012-05-01

367

Pediatric nonalcoholic fatty liver disease.  

PubMed

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population. Increased recognition of this form of liver disease parallels the dramatic rise in childhood and adolescent obesity over the past 2 decades. Like adults, most children with NAFLD are obese, and comorbidities include insulin resistance, hypertension, and dyslipidemia. Unfortunately, pediatric NAFLD is not always a benign condition, with some children progressing to hepatic fibrosis and even cirrhosis in severe cases. The etiology of nonalcoholic steatohepatitis is not yet fully understood; however, hepatic steatosis in the context of insulin resistance and increased oxidative stress may lead to progressive disease. Although physical examination, laboratory evaluation, and radiographic findings provide clues to the potential presence of fatty liver disease, liver biopsy remains the gold standard for diagnosis. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease. Antioxidant pharmacologic therapy such as use of vitamin E has shown some benefit in patients with biopsy-proven steatohepatitis. Nutrition plays an essential role not only in the development of fatty liver disease but also potentially in the treatment and prevention of progression to more severe disease. PMID:23917437

Bozic, Molly A; Subbarao, Girish; Molleston, Jean P

2013-08-01

368

Cellular Therapy for Liver Disease  

PubMed Central

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease. PMID:24582199

Huebert, Robert C.; Rakela, Jorge

2014-01-01

369

3-Tesla MRI Response to TACE in HCC (Liver Cancer)  

ClinicalTrials.gov

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

2014-03-20

370

Interventional Radiology in Liver Transplantation  

SciTech Connect

Radiology is a key specialty within a liver transplant program. Interventional techniques not only contribute to graft and recipient survival but also allow appropriate patient selection and ensure that recipients with severe liver decompensation, hepatocellular carcinoma or portal hypertension are transplanted with the best chance of prolonged survival. Equally inappropriate selection for these techniques may adversely affect survival. Liver transplantation is a dynamic field of innovative surgical techniques with a requirement for interventional radiology to parallel these developments. This paper reviews the current practice within a major European center for adult and pediatric transplantation.

Karani, John B., E-mail: john.karani@kingsch.nhs.uk; Yu, Dominic F.Q.C.; Kane, Pauline A. [King's College Hospital (United Kingdom)

2005-04-15

371

[Liver involvement in systemic diseases].  

PubMed

Liver involvement is common in connective tissue disorders and usually asymptomatic. However, it may be symptomatic and cases of fulminant hepatitis have been reported. A diagnosis of specific hepatic involvement needs to rule out drug toxicity, viral hepatitis, or auto-immune liver disease. The large panel of auto-antibodies that is now available to the clinician is helpful to differentiate auto-immune hepatitis and specific liver involvement associated with connective tissue disease. In the latter, the outcome is generally favourable with immunosuppressive treatment. PMID:20934791

Geri, G; Saadoun, D; Cacoub, P

2011-08-01

372

Association of nonalcoholic fatty liver disease and liver cancer  

PubMed Central

AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the relationship between the presence of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis, and their risk factors, showed no significant statistical association for any of the tumors studied. CONCLUSION: NAFLD is more common in patients with liver metastases caused by colorectal cancer.

Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

2015-01-01

373

“Vanishing liver metastases”—A real challenge for liver surgeons  

PubMed Central

Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested. PMID:25392841

Zendel, Alex; Lahat, Eylon; Dreznik, Yael; Zakai, Barak Bar; Eshkenazy, Rony

2014-01-01

374

“State of the Art” in Liver Resection and Living Donor Liver Transplantation: A Worldwide Survey of 100 Liver Centers  

Microsoft Academic Search

Background  New strategies have been developed to expand indications for liver surgery. The objective was to evaluate the current practice\\u000a worldwide regarding critical liver mass and manipulation of the liver volume.\\u000a \\u000a \\u000a \\u000a Methods  A survey was sent to 133 liver centers worldwide, which focused on (a) critical liver volume, (b) preoperative manipulation\\u000a of the liver mass, and (c) use of liver biopsy and

Stefan Breitenstein; Carlos Apestegui; Henrik Petrowsky; Pierre Alain Clavien

2009-01-01

375

Role of liver biopsy in nonalcoholic fatty liver disease  

PubMed Central

Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease. PMID:25083076

Nalbantoglu, ILKe; Brunt, Elizabeth M

2014-01-01

376

Liver Transplant Program Established at OHSU  

E-print Network

Liver Transplant Program Established at OHSU The history of the liver transplant program at Oregon community. Since 1988, liver transplants in the Portland area have only been performed at the OHSU at OHSU in 1986 and during his fellowship at Harvard, established a liver transplantation program

Chapman, Michael S.

377

Liver cell dysplasia: a premalignant condition  

Microsoft Academic Search

Liver cell dysplasia is defined as cellular enlargement, nuclear pleomorphism, and multinucleation of liver cells occurring in groups or occupying whole cirrhotic nodules. The prevalence, natural history, and relationship to the Australia or hepatitis-associated antigen (HAA) have been studied in 552 Ugandan African patients with normal, cirrhotic, and cancerous livers. Liver cell dysplasia was found in only two of 200

P. P. Anthony; C. L. Vogel; L. F. Barker

1973-01-01

378

Drugs Approved for Liver Cancer  

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

379

Combination Chemotherapy for Liver Cancer  

Cancer.gov

In this clinical trial, researchers are adding a new drug called bortezomib to chemotherapy with doxorubicin to see if it can cause liver tumors to shrink or stop growing better than doxorubicin alone.

380

Liver Disease and Adult Vaccination  

MedlinePLUS

... for Adults Share Compartir Liver Disease and Adult Vaccination Vaccines are especially critical for people with health ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

381

Techniques of orthotopic liver transplantation  

PubMed Central

Background Throughout the history of liver transplantation many improvements have been made in the field of surgical technique. It is beyond the scope of this paper to review all aspects of surgical technique in liver transplantation; thus, in this review we focus on the description of our current technique in most cases, which is orthotopic liver transplantation with preservation of the inferior vena cava and temporary portocaval shunt. We advocate this technique because it has been demonstrated that it achieves better haemodynamic stability during the anhepatic phase, transfusion can be reduced and renal function is improved. The different options for vascular anastomoses are described, particularly the options for arterial anastomoses in case of finding a non-adequate recipient hepatic artery. Technical possibilities for patients with preoperative portal vein thrombosis and the procedure in case of domino or sequential liver transplantation are further explained. PMID:18333053

Lladó, L

2004-01-01

382

Cholestatic Liver Disease in Children  

PubMed Central

Inherited syndromes of intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the prime indication for liver transplantation in children. Our understanding of the pathogenesis of these diseases has increased substantially by the discovery of genetic mutations in children with intrahepatic cholestasis and the findings that inflammatory circuits are operative at the time of diagnosis of biliary atresia. Building on this solid foundation, recent studies provide new insight into genotype-phenotype relationships and how mutations produce altered bile composition and cholestasis. New evidence exists that although liver transplantation is curative for patients with end-stage liver disease owing to cholestasis, some patients may develop recurrence of cholestasis because of the emergence of autoantibodies that disrupt canalicular function in the new graft. Progress is also evident in biliary atresia, with recent studies identifying candidate modifier genes and directly implicating lymphocytes and inflammatory signals in the pathogenesis of bile duct injury and obstruction. PMID:20425482

Santos, Jorge L.; Choquette, Monique

2010-01-01

383

Enisoprost in liver transplantation.  

PubMed

Previous human studies in renal transplant recipients have shown a lower incidence of acute rejection and cyclosporine-associated acute nephrotoxicity when prostaglandins are administered in conjunction with standard immunosuppressants. This study evaluates the effects of enisoprost (EP), a synthetic PGE methyl ester analog, in a single-center, prospective, randomized, double-blind, placebo-controlled, parallel group trial in 81 consecutive adult patients undergoing orthotopic liver transplantation (OLT). The subjects received EP 100 mg p.o. t.i.d. (n = 40) or placebo (n = 41) for the first 12 weeks after OLT. Immunosuppression was based on cyclosporine, azathioprine, and corticosteroids. Effective renal plasma flow and glomerular filtration rate were determined at 4 and 12 weeks after OLT. Eighty-one patients entered the study; sixty-six patients completed the 16-week study period. There were no statistically significant differences between EP- and placebo-treated groups at 12 weeks for creatinine clearance, glomerular filtration rate, and effective renal plasma flow. At least 1 episode of cyclosporine nephrotoxicity occurred in 7/40 patients (17.5%) in the EP group compared with 9/41 patients (20.0%) in the placebo group (P = 0.781). There was no significant difference in the incidence of graft rejection episodes in the 2 groups. Enisoprost, as used in this study, does not have any beneficial effect on renal function or incidence of rejection in OLT recipients. PMID:7762065

Ismail, T; Ayres, R; Kiff, P; McMaster, P; Neuberger, J

1995-05-15

384

Model for end-stage liver disease (MELD) and allocation of donor livers  

Microsoft Academic Search

Background & Aims: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease

Russell Wiesner; Erick Edwards; Richard Freeman; Ann Harper; Ray Kim; Patrick Kamath; Walter Kremers; John Lake; Todd Howard; Robert M. Merion; Robert A. Wolfe; Ruud Krom

2003-01-01

385

Surgical anatomy of the liver.  

PubMed

Vital intrahepatic structures, especially the large veins, are of special concern to the surgeon. These intrahepatic structures are seldom taught or displayed in anatomy courses, and illustrations are often presented with the posterior surface of the liver facing the viewer, an aspect seldom seen by the surgeon. In this article, the topographical anatomy of the liver is described in a manner most useful to the practicing surgeon. For this purpose, specimens were specifically prepared to demonstrate the vascular anatomy. PMID:2928899

Ger, R

1989-04-01

386

Energy Metabolism in the Liver  

PubMed Central

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial ? oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1?, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Rui, Liangyou

2014-01-01

387

Liver involvement in cystic fibrosis  

Microsoft Academic Search

Opinion statement  The hepatobiliary manifestations of cystic fibrosis (CF) encompass a broad clinical spectrum, from mild steatosis, associated\\u000a with poor nutrition, to multilobular cirrhosis and the complications of portal hypertension. The factor(s) responsible for\\u000a the development and progression of liver disease in a subset of patients with CF are unknown. Liver disease can be silent\\u000a and progressive, manifesting only with complications

Catherine Brigman; Andrew Feranchak

2006-01-01

388

Adaptive character of liver glucokinase  

Microsoft Academic Search

Summary 1.Glucokinase is one of four glucose phos-phorylating enzymes present in rat liver. Its distinctive features are a high Km for glucose (high-Km isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-Km isozymes, exhibit low Km values for glucose and a wider substrate specificity.2.Glucokinase is present in the liver of mammals

Hermann Niemeyer; Tito Ureta; Lyllian Clark-Turri

1975-01-01

389

Liver resection for colorectal metastases.  

PubMed Central

BACKGROUND: Colorectal cancer is the second commonest malignancy in the UK. Metastases to the liver occur in greater than 50% of patients and remain the biggest determinant of outcome in these patients. Liver resection is a safe procedure that achieves good long-term survival, but surgery has traditionally been limited to select groups of patients. The improved outcome suggests that more patients could benefit from resection if more was known of what criteria are predictive of a good outcome. PATIENTS AND METHODS: A retrospective analysis was performed on all patients undergoing surgical resection of the liver for colorectal metastases between March 1989 and March 2001 in the Birmingham Liver Unit. RESULTS: During this period, 212 liver resections for colorectal cancer metastases were performed in 82 females and 130 males. The median follow-up was 16 months with an overall actuarial survival of 86% at 1 year, 54% at 3 years, and 28% at 5 years. The peri-operative mortality was 2.8%. The number and timing (metachronous or synchronous) of metastatic lesions, the gender of the patient, pathological staging of the primary lesion or surgical resection margins had no significant influence on survival. Patients with lesions less than 5 cm in size had a significantly prolonged survival compared with patients with lesions greater than 5 cm in size (P < 0.004). CONCLUSIONS: Liver resection is the only curative treatment for patients with colorectal metastases. The long-term survival reported in patients with resected colorectal metastases confined to the liver is comparable to primary surgery for solid gastrointestinal tumours. Every attempt must be made to increase the availability of liver resection to patients with hepatic metastases from colorectal cancer. PMID:14594539

Bramhall, S. R.; Gur, U.; Coldham, C.; Gunson, B. K.; Mayer, A. D.; McMaster, P.; Candinas, D.; Buckels, J. A. C.; Mirza, D. F.

2003-01-01

390

Neurologic complications after liver transplantation  

PubMed Central

Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

Živkovi?, Saša A

2013-01-01

391

Liver Transplantation for the Referring Physician.  

PubMed

Liver transplantation has become the treatment of choice for nearly all causes of end-stage liver disease, fulminant liver failure, and selected primary hepatic malignancies. The demand for liver transplantation has persistently outmatched the availability of donor organs leading to the development of novel strategies to expand the donor pool. The authors review the process of liver transplant evaluation, methods used to address the donor shortage, and disease-specific outcomes and challenges and discuss posttransplant care. PMID:25454301

Xu, Ming-Ming; Brown, Robert S

2015-02-01

392

Serum Liver Enzyme Pattern in Birth Asphyxia Associated Liver Injury  

PubMed Central

Purpose To study temporal pattern of serum liver enzymes levels in newborns with hepatic injury associated with birth asphyxia (BA). Methods Singleton term newborns with BA and ?72 hours of age admitted to neonatal intensive care unit were prospectively enrolled. Term newborns with physiological jaundice and without BA were studied as controls. Serum liver enzymes were measured at <24 hours, 24-72 hours, and at 6-12 days of age for cases and at 1-6 days of age for controls. BA was defined by 1 minute Apgar score <7 or delayed or absent cry with hypoxic ischemic encephalopathy. BA-associated liver injury was defined as serum alanine aminotransferase (ALT) elevation beyond +2 standard deviation (ALT > +2 SD) above the mean of control subjects at any of the three time points. Results Sixty controls and 62 cases were enrolled. Thirty-five cases (56%) developed BA-associated liver injury (ALT>81 IU/L). They had higher serum levels of ALT, aspartate aminotransferase, lactate dehydrogenase than the control infants, with peak at 24-72 hours. In controls, serum liver enzyme levels were significantly higher in appropriate-for-date (AFD) babies than small-for-date (SFD) babies. Serum enzyme pattern and extent of elevation were comparable between SFD and AFD babies. Degree of serum liver enzyme elevation had no relationship with severity of hypoxic encephalopathy. Conclusion Serum liver enzyme elevation is common in BA; it peaks at 24-72 hours followed by a sharp decline by 6-12 days of age. Pattern and extent of enzyme elevation are comparable between SFD and AFD babies. PMID:25349832

Chhavi, Nanda; Zutshi, Kiran; Singh, Niranjan Kumar; Awasthi, Ashish

2014-01-01

393

Toward surface quantification of liver fibrosis progression  

NASA Astrophysics Data System (ADS)

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

2010-09-01

394

Liver Autophagy in Anorexia Nervosa and Acute Liver Injury  

PubMed Central

Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13?kg/m2 or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed. PMID:25250330

Kheloufi, Marouane; Boulanger, Chantal M.; Durand, François

2014-01-01

395

Hepatic inflammation and progressive liver fibrosis in chronic liver disease  

PubMed Central

Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

Czaja, Albert J

2014-01-01

396

Targeting collagen expression in alcoholic liver disease  

PubMed Central

Alcoholic liver disease (ALD) is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. Liver fibrosis is a consequence of ALD and other chronic liver insults, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Liver fibrosis is characterized by accumulation of excess extracellular matrix components, including type?I?collagen, which disrupts liver microcirculation and leads to injury. To date, there is no therapy for the treatment of liver fibrosis; thus treatments that either prevent the accumulation of type?I?collagen or hasten its degradation are desirable. The focus of this review is to examine the regulation of type?I?collagen in fibrogenic cells of the liver and to discuss current advances in therapeutics to eliminate excessive collagen deposition. PMID:21633652

Thompson, Kyle J; McKillop, Iain H; Schrum, Laura W

2011-01-01

397

New automatic liver segmentation and extraction method  

NASA Astrophysics Data System (ADS)

Liver segmentation is critical in designing and developing computer-assisted systems that have been used for liver disease diagnosis before surgery or transplantation. The purpose of this study is to develop a computerized system for extracting liver contours and reconstructing liver volume using contrast-enhanced hepatic CT images. The automatic liver segmentation method adopted the graph optimal algorithm with ratio contour as its salient measure. This new cost function encoded the Gestalt laws and synthesized the gap length, the liver region area, the length of the closed contour and the average curvature of the closed boundary. With the extracted liver contours, a promising system to exclude tissues outside the liver was developed. It promised to save time and simplify liver volume reconstruction by minimizing intervention operations. Some 3D-rendered reconstruction results were also created to demonstrate the final results of our system.

Zhang, Pinzheng; Xu, Qinzheng; Wang, Zheng

2007-12-01

398

Liver fibrogenesis and metabolic factors.  

PubMed

Mechanisms of liver fibrosis are complex and varied. Among them, metabolic factors are particularly important in the development of fibrosis associated with nonalcoholic steatohepatitis (NASH). These factors are some of the "multiple parallel hits" responsible for liver damage during NASH. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Major profibrogenic protagonists, such as hepatic stellate cells and Kupffer cells, are activated by insulin resistance, apoptosis and local inflammation. Relations between steatosis, insulin resistance and fibrosis are complex. Initially, simple steatosis may be a way to store deleterious free fatty acid in neutral triglycerides. If the lipid storage threshold is exceeded, steatosis may become associated with lipotoxicity. Similarly, interindividual variations of adipose tissue expandability might explain various phenotypes, ranging from "metabolically obese patients with normal weight" to "metabolically normal morbidly obese patients". The metabolic abnormalities in subcutaneous and visceral adipose tissue are insulin resistance and low-grade inflammation, which are associated with increased release of free fatty acid flux and changes in adipocytokines production such as leptin, adiponectin and interleukin 6. The nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPAR?) and the endocannabinoid system might have important roles in liver fibrogenesis and are potential therapeutic targets. Finally, with the development of new molecular tools, gut microbiota has been recently identified for its pleiotropic functions, including metabolism regulation. Better knowledge of these mechanisms should lead to new strategies for the treatment of metabolic factors that play a key role in liver injuries. PMID:21742296

Anty, Rodolphe; Lemoine, Maud

2011-06-01

399

Protein metabolism and liver disease.  

PubMed

In health, the liver orchestrates the metabolism of proteins and amino acids. When the liver is diseased, the regulation of protein metabolism is frequently disturbed. The manifestations of disturbed protein metabolism in liver disease are varied and change with disease aetiology and severity. The hallmarks of protein and amino acid metabolism in liver disease are lowered concentrations of circulating branched-chain and increased concentrations of circulating aromatic amino acids with concomitantly altered amino acid kinetics. The changes in amino acid kinetics in liver disease are characterized by increased endogenous leucine flux, an indicator of protein breakdown, and leucine oxidation in the post-absorptive state (when calculated using a reciprocal-pool model and normalized for body cell mass). In addition, the increase in whole-body protein synthesis in response to an amino acid infusion may be attenuated in patients with cirrhosis. These changes are often accompanied by clinically apparent muscle wasting, manifest as protein-calorie malnutrition, and associated low levels of hepatically synthesized plasma proteins. While the pathogenesis of these changes in protein and amino acid metabolism has not been elucidated, altered levels of circulating hormones, known to affect protein metabolism, are probably important. Lowered levels of micronutrients and trace metals and elevated levels of cytokines may also play a role. PMID:9022955

Charlton, M R

1996-10-01

400

Liver transplantation: immunosuppression and oncology  

PubMed Central

Purpose of review Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed that HCC recurrence rates were halved if a minimization of CNIs was applied within the first month after liver transplant. With mammalian target of rapamycin (mTOR) inhibitors as approved immunosuppressants for liver transplant patients, pooled data from several retrospective studies have suggested their possible benefit for reducing HCC recurrence. Summary Randomized controlled trials with sufficiently long follow-up are needed to evaluate the influence of different immunosuppression protocols in preventing malignancy after LT. Currently, early minimization of CNIs with or without mTOR inhibitors or mycophenolate seems a rational strategy for patients with risk factors for de-novo malignancy or recurrence of HCC after liver transplant. A deeper understanding of the immunological pathways of rejection and cancer would allow for designing more specific and safer drugs, and thus to prevent cancer after liver transplant. PMID:24685671

Rodríguez-Perálvarez, Manuel; De la Mata, Manuel; Burroughs, Andrew K.

2014-01-01

401

Infections in liver transplant recipients  

PubMed Central

Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the “opportunistic” period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients. PMID:21603030

Romero, Fabian A; Razonable, Raymund R

2011-01-01

402

Liver transplantation and autoimmune hepatitis  

PubMed Central

Summary Liver Transplantation (LT) is an effective treatment for patients with end-stage liver disease including autoimmune hepatitis (AIH). Indication for LT for AIH does not differ basically from other liver diseases including both acute and chronic types of disease progression, although it is reported to be an infrequent indication for LT worldwide due to the therapeutic advances of immunosuppression. The outcome following LT is feasible, with current patient and graft survival exceeding 75% at 5 years. Recurrent and de-novo AIH posttranslant has also been reported; and this seems to have important clinical implications because its management differs from the standard treatment for allograft rejection. In this review, we discuss the characteristics of AIH, focusing on the indication for LT and issues raised following LT.

Tanaka, Tomohiro; Sugawara, Yasuhiko; Kokudo, Norihiro

2015-01-01

403

Treatment of alcoholic liver disease  

PubMed Central

Alcoholic liver disease (ALD) remains a major cause of liver-related mortality in the US and worldwide. The correct diagnosis of ALD can usually be made on a clinical basis in conjunction with blood tests, and a liver biopsy is not usually required. Abstinence is the hallmark of therapy for ALD, and nutritional therapy is the first line of therapeutic intervention. The role of steroids in patients with moderate to severe alcoholic hepatitis is gaining increasing acceptance, with the caveat that patients be evaluated for the effectiveness of therapy at 1 week. Pentoxifylline appears to be especially effective in ALD patients with renal dysfunction/hepatorenal syndrome. Biologics such as specific anti-TNFs have been disappointing and should probably not be used outside of the clinical trial setting. Transplantation is effective in patients with end-stage ALD who have stopped drinking (usually for ?6 months), and both long-term graft and patient survival are excellent. PMID:21317995

Frazier, Thomas H.; Stocker, Abigail M.; Kershner, Nicole A.; Marsano, Luis S.; McClain, Craig J.

2011-01-01

404

Liver transplantation for hepatocellular carcinoma  

PubMed Central

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is considered an aggressive tumor with mean survival estimated between 6 and 20 months. Hepatitis B and C are the most common etiologies. Pathological, laboratory and radiologic imaging all aid in diagnosis but much controversy exists in the utilization of any given modality. Many treatment options exist for management of HCC, each has its own limitation. Liver transplantation offers the most reasonable expectation for curative treatment while simultaneously removing the burden of the diseased liver. Still, advancements in the field have thus far not yet matched its potential, although new immunosuppressive and chemotherapy regimen may allow transplantation to push the envelope once again. PMID:24570911

Byam, Jerome; Renz, John

2013-01-01

405

Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix  

PubMed Central

Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease. PMID:20543851

Uygun, Basak E; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Izamis, Maria-Louisa; Guzzardi, Maria A; Shulman, Carley; Milwid, Jack; Kobayashi, Naoya; Tilles, Arno; Berthiaume, Francois; Hertl, Martin; Nahmias, Yaakov; Yarmush, Martin L; Uygun, Korkut

2010-01-01

406

Diagnosis of alcoholic liver disease  

PubMed Central

Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

Torruellas, Cara; French, Samuel W; Medici, Valentina

2014-01-01

407

Chronic fascioliasis in farmed and wild greater rheas ( Rhea americana)  

Microsoft Academic Search

From 50 farmed Rhea americana slaughtered for human consumption, adult forms and eggs of Fasciola hepatica were found in 4. The other three livers were free of flukes but did show lesions caused by larval fluke migration. Histological lesions were similar to those caused by flukes in cattle and sheep. The rheas were from an endemic area of ruminant fascioliasis

Mauro Pereira Soares; Sergio Silva da Silva; Leandro Quintana Nizoli; Samuel Rodrigues Felix; Ana Lucia Schild

2007-01-01

408

Hepatitis C and liver transplantation  

NASA Astrophysics Data System (ADS)

Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

Brown, Robert S.

2005-08-01

409

Liver Transplantation: Official Journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society  

NSDL National Science Digital Library

The American Association for the Study of Liver Diseases and International Liver Transplantation Society has online access to the journal Liver Transplantation and Surgery. Full-text content begins January 1998; online abstracts begin with the 1997 issues. The text is fully searchable by keyword, with hyperlinked references to Medline and other frequently cited journals. Liver Transplantation and Surgery. is made available electronically with assistance from Stanford University's HighWire Press.

410

Liver transplantation in alcoholic liver disease current status and controversies  

PubMed Central

Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

2013-01-01

411

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease  

PubMed Central

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

French, Samuel W.

2013-01-01

412

Multiscale tissue engineering for liver reconstruction.  

PubMed

The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies. PMID:24500493

Sudo, Ryo

2014-01-01

413

Regional Chemotherapy for Inoperable Liver Metastases  

Cancer.gov

In this trial, doctors are testing a method of delivering chemotherapy regionally to the liver called percutaneous isolated hepatic arterial perfusion (PHP) in patients with liver metastases from ocular (eye) or cutaneous (skin) melanoma.

414

Even Decaf Coffee May Help the Liver  

MedlinePLUS

... on this page, please enable JavaScript. Even Decaf Coffee May Help the Liver New study echoes prior ... 10, 2014 (HealthDay News) -- Another study suggests that coffee might actually be healthy for your liver, and ...

415

Multiscale tissue engineering for liver reconstruction  

PubMed Central

The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies. PMID:24500493

Sudo, Ryo

2014-01-01

416

Liver regeneration by hepatic progenitor cells   

E-print Network

The liver is the largest solid organ in the body and is frequently the site of injury. During disease, liver injury is usually compensated for by exceptionally efficient regeneration which occurs both from differentiated ...

Bird, Thomas Graham

2011-07-05

417

Humanized mice with ectopic artificial liver tissues  

E-print Network

“Humanized” mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury ...

Thomas, David K.

418

Obesity May Speed Aging of the Liver  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Obesity May Speed Aging of the Liver, Study Suggests ... MedlinePlus Pages Genes and Gene Therapy Liver Diseases Obesity MONDAY, Oct. 13, 2014 (HealthDay News) -- Extra pounds ...

419

Role of liver stem cells in hepatocarcinogenesis  

PubMed Central

Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

Xu, Lei-Bo; Liu, Chao

2014-01-01

420

Role of liver stem cells in hepatocarcinogenesis.  

PubMed

Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the "cancer stem cell hypothesis", which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

Xu, Lei-Bo; Liu, Chao

2014-11-26

421

LIVER BIOLOGY AND PATHOBIOLOGY Liver Tissue Engineering at Extrahepatic Sites in Mice  

E-print Network

LIVER BIOLOGY AND PATHOBIOLOGY BIOLOGY Liver Tissue Engineering at Extrahepatic Sites in Mice and Mark A. Kay1 Liver tissue engineering using hepatocyte transplantation has been proposed as an alterna that these engineered liver tissues also retained their native regeneration potential in vivo, we induced two different

Kay, Mark A.

422

Multiple Adaptive Mechanisms to Chronic Liver Disease Revealed at Early Stages of Liver Carcinogenesis  

E-print Network

Multiple Adaptive Mechanisms to Chronic Liver Disease Revealed at Early Stages of Liver-knockout (Mdr2-KO) mice. These mice lack the liver-specific P-glycoprotein responsible by hepatocellular carcinoma development after the age of 1 year. Liver tissue samples of Mdr2-KO mice in the early

Domany, Eytan

423

L. Slimani / Quantification of liver perfusion with PET 1 Quantification of liver perfusion with [15  

E-print Network

L. Slimani / Quantification of liver perfusion with PET 1 Quantification of liver perfusion. Running Title : Quantification of liver perfusion with PET Corresponding authors: Patricia Iozzo, MD, Ph of liver perfusion with PET 2 Abstract (204 words) Background/Aims: Hepatic perfusion plays an important

Paris-Sud XI, Université de

424

Fibrogenesis in alcoholic liver disease  

PubMed Central

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, ?brosis, cirrhosis, and hepatocellular carcinoma. Alcohol abstinence is the most effective therapy for ALD. However, targeted therapies are urgently needed for patients with severe ALD (i.e., alcoholic hepatitis) or those who do not abstain from alcohol. The lack of studies and the availability of animal models that do not reflect all the features of this disease in humans inhibit the development of new drugs for ALD. In ALD-associated fibrosis, hepatic stellate cells are the principal cell type responsible for extracellular matrix production. Although the mechanisms underlying fibrosis in ALD are largely similar to those observed in other chronic liver diseases, oxidative stress, methionine metabolism abnormalities, hepatocyte apoptosis, and endotoxin lipopolysaccharides that activate Kupffer cells may play unique roles in disease-related fibrogenesis. Lipogenesis during the early stages of ALD has recently been implicated as a risk factor for the progression of cirrhosis. Other topics include osteopontin, interleukin-1 signaling, and genetic polymorphism. In this review, we discuss the basic pathogenesis of ALD and focus on liver fibrogenesis. PMID:25009376

Fujii, Hideki; Kawada, Norifumi

2014-01-01

425

[Pulmonary hypertension in liver diseases].  

PubMed

Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ? 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH. PMID:25148949

Savale, Laurent; Sattler, Caroline; Sitbon, Olivier

2014-09-01

426

Treatment of Alcoholic Liver Disease  

Microsoft Academic Search

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60% (worse than many common cancers such as breast and prostate). The cornerstone for therapy for ALD is lifestyle modification, including drinking cessation and treatment of

Ina Bergheim; Craig J. McClain; Gavin E. Arteel

2005-01-01

427

Treating Colorectal Cancer Liver Metastases  

Cancer.gov

In this trial, colorectal cancer patients with six or fewer hepatic metastases will undergo primary surgery and/or ablation and then be treated with oxaliplatin and capecitabine. Half of the patients will receive additional chemotherapy consisting of floxuridine pumped directly into their livers through an arterial catheter and pump.

428

Predictive Models of Liver Cancer  

EPA Science Inventory

Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

429

Immune monitoring post liver transplant  

PubMed Central

Many of the causes of short and late morbidity following liver transplantation are associated with immunosuppression or immunosuppressive medications. Current care often involves close monitoring of liver biochemistry as well as therapeutic drug levels. However, the postoperative course following liver transplantation can often be associated with significant complications including infection and rejection, suggesting an inadequacy in current immune function monitoring. Many assays have been tested in the research setting to identify possible biomarkers that may be used to predict clinical events such as acute cellular rejection, and therefore allow modification of a patient’s immunosuppressive regimen prior to a clinical event. However, these generally require significant laboratory processing and have had difficulty becoming established in common clinical use outside the research setting. One assay, Cylex ImmuKnow has been food and drug administration approved but has had variable results. In this review we discuss the assays that have been used to assess monitoring of immune function after liver transplantation and consider possible future directions. PMID:24669365

Sood, Siddharth; Testro, Adam G