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Sample records for liver fluke clonorchis

  1. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

    PubMed Central

    2011-01-01

    Background Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. Results We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. Conclusions This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control. PMID:22023798

  2. Genome-wide characterization of microsatellites and marker development in the carcinogenic liver fluke Clonorchis sinensis.

    PubMed

    Nguyen, Thao T B; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J; Blair, David; Laha, Thewarach; Sripa, Banchob

    2015-06-01

    Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers that have been used for identification and genetic diversity; however, no information about microsatellites of this liver fluke is published so far. We here report microsatellite characterization and marker development for a genetic diversity study in C. sinensis, using a genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥12 base pairs) were identified from a genome database of C. sinensis, with hexanucleotide motif being the most abundant (51%) followed by pentanucleotide (18.3%) and trinucleotide (12.7%). The tetranucleotide, dinucleotide, and mononucleotide motifs accounted for 9.75, 7.63, and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72% of 547 Mb of the whole genome size, and the frequency of microsatellites was found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri-, and tetranucleotide, the repeat numbers redundant are six (28%), four (45%), and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT, and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and Opisthorchis viverrini. Seven out of 24 loci showed to be heterozygous with observed heterozygosity that ranged from 0.467 to 1. Four primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites, and the genome-wide markers developed may be a useful tool for the genetic study of C. sinensis. PMID:25782682

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

    PubMed

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

    2014-10-01

    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

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

    PubMed

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

    2014-10-01

    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.

  5. Genome-wide characterization of microsatelittes and marker development in the carcinogenic liver fluke Clonorchis sinensis

    PubMed Central

    Nguyen, Thao T.B.; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J.; Blair, David; Laha, Thewarach; Sripa, Banchob

    2015-01-01

    Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers have been used for identification and genetic diversity, however, no information about microsatellites of this liver fluke published so far. We here report microsatellite characterization and marker development for genetic diversity study in C. sinensis using genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥ 12 base pairs) were identified from genome database of C. sinensis with hexa-nucleotide motif being the most abundant (51%) followed by penta-nucleotide (18.3%) and tri-nucleotide (12.7%). The tetra-nucleotide, di-nucleotide and mononucleotide motifs accounted for 9.75 %, 7.63% and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72 % of 547 Mb of the whole genome size and the frequency of microsatellites were found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri, and tetra-nucleotide, the repeat numbers redundant are six (28%), four (45%) and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and O. viverrini. Seven out of 24 loci showed heterozygous with observed heterozygosity ranged from 0.467 to 1. Four-primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites and the genome-wide markers developed may be a useful tool for genetic study of C. sinensis. PMID:25782682

  6. Egg-specific expression of protein with DNA methyltransferase activity in the biocarcinogenic liver fluke Clonorchis sinensis.

    PubMed

    Kim, Seon-Hee; Cho, Hye-Jeong; Sohn, Woon-Mok; Ahn, Chun-Seob; Kong, Yoon; Yang, Hyun-Jong; Bae, Young-An

    2015-08-01

    Despite recent reports regarding the biology of cytosine methylation in Schistosoma mansoni, the impact of the regulatory machinery remains unclear in diverse platyhelminthes. This ambiguity is reinforced by discoveries of DNA methyltransferase 2 (DNMT2)-only organisms and the substrate specificity of DNMT2 preferential to RNA molecules. Here, we characterized a novel DNA methyltransferase, named CsDNMT2, in a liver fluke Clonorchis sinensis. The protein exhibited structural properties conserved in other members of the DNMT2 family. The native and recombinant CsDNMT2 exhibited considerable enzymatic activity on DNA. The spatiotemporal expression of CsDNMT2 mirrored that of 5-methylcytosine (5 mC), both of which were elevated in the C. sinensis eggs. However, CsDNMT2 and 5 mC were marginally detected in other histological regions of C. sinensis adults including ovaries and seminal receptacle. The methylation site seemed not related to genomic loci occupied by progenies of an active long-terminal-repeat retrotransposon. Taken together, our data strongly suggest that C. sinensis has preserved the functional DNA methylation machinery and that DNMT2 acts as a genuine alternative to DNMT1/DNMT3 to methylate DNA in the DNMT2-only organism. The epigenetic regulation would target functional genes primarily involved in the formation and/or maturation of eggs, rather than retrotransposons. PMID:26036304

  7. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.

    PubMed

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

    The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically important liver fluke species belonging to the family Opisthorchiidae and the major agent causing opisthorchiasis over a vast territory, covering Russia, Kazakhstan and several European countries. The similarity between the diseases caused by O. felineus and other liver flukes, O. viverrini and Clonorchis sinensis, in clinical manifestations and course suggests that the scenarios of their development and, possibly, complications have much in common. The International Agency for Research on Cancer classified O. viverrini and C. sinensis as group 1 agents and the major factors inducing cholangiocarcinoma in endemic regions. However, a carcinogenic potential of O. felineus is poorly studied. This review characterizes O. felineus, briefs the epidemiological situation in Western Siberia, the world's largest opisthorchiasis focus, and assesses the carcinogenic potential of this liver fluke. The review is based on a comprehensive analysis of the published medical data on opisthorchiasis and its complications in Western Siberia. Results of performed analysis reflect the actual epidemiological situation in opisthorchiasis focus and suggest an association of this disease with bile duct cancer. PMID:26740360

  8. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis

    PubMed Central

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-01-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins. PMID:26797449

  9. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis.

    PubMed

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-12-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.

  10. The tumorigenic liver fluke Opisthorchis viverrini –multiple pathways to cancer

    PubMed Central

    Sripa, Banchob; Brindley, Paul J.; Mulvenna, Jason; Laha, Thewarach; Smout, Michael J; Mairiang, Eimorn; Bethony, Jeffrey M.; Loukas, Alex

    2012-01-01

    Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and adjacent countries. In addition to infection-associated morbidity, infection with O. viverrini and the related Clonorchis sinensis are unarguable risk factors for cholangiocarcinoma, bile duct cancer. Here we review the pathogenesis of opisthorchiasis and the association of O. viverrini infection and bile duct cancer, focusing on the molecular parallels between wound healing, chronic inflammation and cancer development. We review a schema for human disease progression from fluke infection, chronic opisthorchiasis, advanced periductal fibrosis, and cholangiocarcinogenesis, and present a rationale for biomarker discovery to facilitate early intervention. We conclude by addressing post-genomic advances with a view to developing new control strategies to combat this infectious cancer. PMID:22947297

  11. Chinese liver flukes in latrine sediments from Wong Nim's property, San Bernardino, California: archaeoparasitology of the Caltrans District Headquarters.

    PubMed

    Reinhard, Karl J; Araújo, Adauto; Sianto, Luciana; Costello, Julia G; Swope, Karen

    2008-02-01

    Parasitological analysis of 5 sediment samples from San Bernardino, California latrine deposits spanning the time period from about 1880 to the 1930s are presented. Two sediment samples are from a latrine used by European-Americans. Three sediment samples are from latrines used by Chinese-Americans on the property of Wong Nim, an important member of the Chinese community. Two of the Chinese latrines were positive for human parasites. The human parasites encountered include the human whipworm (Trichuris trichiura), the giant intestinal roundworm (Ascaris lubricoides, c.f.), and the Chinese liver fluke (Clonorchis sinensis). Evidence of the liver fluke is especially important. This parasite cannot complete its life cycle outside of its endemic range in Asia because suitable intermediate hosts are not present in the American continents. Its presence signals that at least some of the Chinese-Americans who used the latrines were immigrants who were infected in Asia and then sustained infections while in the Americas.

  12. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

    PubMed

    Pakharukova, Mariya Y; Vavilin, Valentin A; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J; Mordvinov, Viatcheslav A

    2015-12-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

  13. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus

    PubMed Central

    Pakharukova, Mariya Y.; Vavilin, Valentin A.; Sripa, Banchob; Laha, Thewarach; Brindley, Paul J.; Mordvinov, Viatcheslav A.

    2015-01-01

    The basic metabolic cytochrome P450 (CYP) system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium) are considered by the International Agency for Research on Cancer (IARC) as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i) to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii) to assess CYP ability to metabolize xenobiotics, and (iii) to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR) in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target. PMID:26625139

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

    PubMed Central

    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

    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

  15. Progress in development of liver fluke vaccines.

    PubMed

    Spithill, T W; Dalton, J P

    1998-12-01

    Infection of ruminants by Fasciola spp continues to cause large economic losses worldwide. Recent results from several laboratories have demonstrated that animals can be significantly protected against infection by vaccination with defined Fasciola antigens. Apart from reducing fluke burdens, some vaccines can elicit a concurrent reduction in parasite egg production. The expectation of a commercially feasible vaccine that might also reduce parasite transmission in the field is now realistic, although major hurdles still exist. Here, Terry Spithill and John Dalton review the results of several recent vaccine trials and discuss the future prospects for vaccine development.

  16. Apoptosis of cholangiocytes modulated by thioredoxin of carcinogenic liver fluke.

    PubMed

    Matchimakul, Pitchaya; Rinaldi, Gabriel; Suttiprapa, Sutas; Mann, Victoria H; Popratiloff, Anastas; Laha, Thewarach; Pimenta, Rafael N; Cochran, Christina J; Kaewkes, Sasithorn; Sripa, Banchob; Brindley, Paul J

    2015-08-01

    Chronic infection with the food-borne liver fluke, Opisthorchis viverrini, frequently induces cancer of the bile ducts, cholangiocarcinoma. Opisthorchiasis is endemic in Thailand, Lao PDR, Cambodia and Vietnam, where eating undercooked freshwater fish carrying the juvenile stage of this pathogen leads to human infection. Because inhibition of apoptosis facilitates carcinogenesis, this study investigated modulation by thioredoxin from O. viverrini of apoptosis of bile duct epithelial cells, cholangiocytes. Cells of a cholangiocyte line were incubated with the parasite enzyme after which they were exposed hydrogen peroxide. Oxidative stress-induced apoptosis was monitored using flow cytometry, growth in real time and imaging of living cells using laser confocal microscopy. Immunolocalization revealed liver fluke thioredoxin within cholangiocytes. Cells exposed to thioredoxin downregulated apoptotic genes in the mitogen activated protein kinases pathway and upregulated anti-apoptosis-related genes including apoptosis signaling kinase 1, caspase 9, caspase 8, caspase 3, survivin and others. Western blots of immunoprecipitates of cell lysates revealed binding of thioredoxin to apoptosis signaling kinase 1. Together the findings indicated that thioredoxin from O. viverrini inhibited oxidative stress-induced apoptosis of bile duct epithelial cells, which supports a role for this liver fluke oxidoreductase in opisthorchiasis-induced cholangiocarcinogenesis. PMID:26007234

  17. Molecular Changes in Opisthorchis viverrini (Southeast Asian Liver Fluke) during the Transition from the Juvenile to the Adult Stage

    PubMed Central

    Sripa, Jittiyawadee; Hall, Ross S.; Scheerlinck, Jean-Pierre; Laha, Thewarach; Sripa, Banchob; Gasser, Robin B.

    2012-01-01

    Background The Southeast Asian liver fluke (Opisthorchis viverrini) chronically infects and affects tens of millions of people in regions of Asia, leading to chronic illness and, importantly, inducing malignant cancer ( = cholangiocarcinoma). In spite of this, little is known, at the molecular level, about the parasite itself, its interplay with its hosts or the mechanisms of disease and/or carcinogenesis. Methodology/Principal Findings Here, we generated extensive RNA-Seq data (Illumina) representing adult and juvenile stages of O. viverrini, and combined these sequences with previously published transcriptomic data (454 technology) for this species, yielding a combined assembly of significantly increased quality and allowing quantitative assessment of transcription in the juvenile and adult stage. Conclusions This enhanced assembly reveals that, despite the substantial biological similarities between the human liver flukes, O. viverinni and Clonorchis sinensis, there are previously unrecognized differences in major aspects of their molecular biology. Most notable are differences among the C13 and cathepsin L-like cysteine peptidases, which play key roles in tissue migration, immune evasion and feeding, and, thus, represent potential drug and/or vaccine targets. Furthermore, these data indicate that major lineages of cysteine peptidases of socioeconomically important trematodes have evolved through a process of gene loss rather than independent radiation, contrasting previous proposals. PMID:23209858

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

    PubMed Central

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

    2014-01-01

    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 3,330 bp in length, encoded 1,101 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 five femtograms 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

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

    PubMed

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

    2014-01-01

    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

  20. [Secretome of the adult liver fluke Opisthorchis felineus].

    PubMed

    L'vova, M N; Duzhak, T G; Tsentalovich, Iu P; Katokhin, A V; Mordvinov, V A

    2014-01-01

    The opisthorchiasis caused by Opisthorchis felineus, the Siberian liver fluke remains a serious public health problem in Russia and Eastern Europe. Proteomic identification of the proteins in the excretory-secretory products (ESPs) released by O. felineus is an important key for the investigation of host-parasite interactions and understanding the mechanisms involved in parasite survival within the host. In the ESP of O. felineus we have identified 37 proteins using high-resolution proteomics approach (LTQ-FT-ICR mass spectrometer). The O. felineus secretes either excretes a complex mixture of proteins including: glycolytic enzymes (enolase, aldolase, fructose-1 ,6-bisphosphatase and other); detoxification proteins (4 isoform of glutathione S-transferases, Cu/Zn superoxide dismutase, thioredoxin peroxidase, thioredoxin); cytoskeletal proteins (beta tubulin and paramyosin); a number of proteases (cathepsin F, B1, leucin aminopeptidase 2); protease inhibitors (putative cys1 protein, leukocyte elastase inhibitor), binding proteins (ferritin, myoglobin, FABP) and other. In the O. felineus ESP we also identified Of-HDM protein belonging to a novel family "helminth defence molecules" (HDMs). The O. felineus proteins identified in this study provide necessary information for the further investigation of molecular mechanisms of opisthorchiasis pathogenesis and some of them would be of interest as potential antigens for vaccine and immunodiagnostics development and as potential new anthelmintic drug targets. PMID:25693323

  1. Citrate synthase from the liver fluke Fasciola hepatica.

    PubMed

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

    2013-06-01

    Citrate synthase catalyses the first step of the Krebs' tricarboxylic acid cycle. A sequence encoding citrate synthase from the common liver fluke, Fasciola hepatica, has been cloned. The encoded protein sequence is predicted to fold into a largely α-helical protein with high structural similarity to mammalian citrate synthases. Although a hexahistidine-tagged version of the protein could be expressed in Escherichia coli, it was not possible to purify it by nickel-affinity chromatography. Similar results were obtained with a version of the protein which lacks the putative mitochondrial targeting sequence (residues 1 to 29). However, extracts from bacterial cells expressing this version had additional citrate synthase activity after correcting for the endogenous, bacterial activity. The apparent K m for oxaloacetate was found to be 0.22 mM, which is higher than that observed in mammalian citrate synthases. Overall, the sequence and structure of F. hepatica citrate synthase are similar to ones from other eukaryotes, but there are enzymological differences which merit further investigation.

  2. Zoonotic potential of infection with Fasciola spp. by consumption of freshly prepared raw liver containing immature flukes.

    PubMed

    Taira, N; Yoshifuji, H; Boray, J C

    1997-07-01

    Mice were successfully infected with metacercariae of the Japanese Fasciola sp., resulting in the recovery of a mean number of 110 live immature flukes per mouse 4-5 days after inoculation. Twenty-four mice were then inoculated orally, each with a mean number of 68 freshly recovered immature flukes. The livers of 7 of the 24 recipient mice showed migratory lesions of capsular and subcapsular granulomatous infiltration and 2 of those mice also had haemorrhagic lesions. The lesions were typical of those caused by active migration of early immature flukes. However, no flukes were found in the livers of the recipient mice at necropsy when the flukes were aged 14 weeks. In another experiment, 10 piglets were given fresh livers of mice harbouring approximately 2000 live immature flukes aged 3-7 days. Two additional piglets were inoculated with 2000 metacercariae of Fasciola. All pigs were killed when the flukes were 14 days old. Granulomatous lesions were present in all pigs, except in those that were given livers containing flukes aged 7 days. The lesions were localized, forming well-defined foci, different from the typical migratory lesions normally observed in mouse or sheep liver at the early stage of fluke migration. From the 10 pigs given livers, 65 live flukes were recovered at necropsy, 0.29% of the estimated number of immature flukes given. From the 2 pigs which received 2000 metacercariae each, a total of 198 flukes were recovered (5%). The results of the experiments suggest that humans consuming raw liver dishes prepared from fresh livers infected with immature Fasciola spp. could become infected with liver fluke. PMID:9279579

  3. Knowledge, attitude and practice related to liver fluke infection in northeast Thailand

    PubMed Central

    Kaewpitoon, Natthawut; Kaewpitoon, Soraya J; Pengsaa, Prasit; Pilasri, Chutigan

    2007-01-01

    AIM: To investigate the knowledge, attitude and practice (KAP) in prevention and control of liver fluke infection in northeast Thailand. METHODS: A descriptive KAP survey pertaining to liver fluke infection was carried out in June 2005 to October 2006 using structured questionnaires. Data were collected by questionnaires consisting of general parameters, knowledge, attitude, practice, and a history of participation in the prevention and control of liver fluke infection. RESULTS: A total of 1077 persons who were inter-viewed and completed the questionnaires were enrolled in the study. The majority were females (69.5%) and many of them were 15-20 years of age (37.26%). The questionnaires revealed that information resources on liver fluke infection included local public health volunteers (31.37%), public health officers (18.72%), televisions (14.38%), local heads of sub-districts (12.31%), doctors and nurses (9.18%), newspaper (5.72), internets (5.37%), and others (12.95%). Fifty-five point eleven percent of the population had a good level of liver fluke knowledge concerning the mode of disease transmission and 79.72% of the population had a good level of prevention and control knowledge with regards to defecation and consumption. The attitude and practice in liver fluke prevention and control were also at a good level with a positive awareness, participation, and satisfaction of 72.1% and 60.83% of the persons studied. However, good health behavior was found in 39.26% and 41.42% of the persons studied who had unhygienic defecation and ate raw cyprinoid’s fish. The result also showed that 41.25% of the persons studied previously joined prevention and control campaigns. CONCLUSION: The persons studied have a high level of liver fluke knowledge and positive attitude. However, improvement is required regarding personal hygiene specifically with hygienic defecation and consumption of undercooked fish. PMID:17465477

  4. Simulating the Risk of Liver Fluke Infection using a Mechanistic Hydro-epidemiological Model

    NASA Astrophysics Data System (ADS)

    Beltrame, Ludovica; Dunne, Toby; Rose, Hannah; Walker, Josephine; Morgan, Eric; Vickerman, Peter; Wagener, Thorsten

    2016-04-01

    Liver Fluke (Fasciola hepatica) is a common parasite found in livestock and responsible for considerable economic losses throughout the world. Risk of infection is strongly influenced by climatic and hydrological conditions, which characterise the host environment for parasite development and transmission. Despite on-going control efforts, increases in fluke outbreaks have been reported in recent years in the UK, and have been often attributed to climate change. Currently used fluke risk models are based on empirical relationships derived between historical climate and incidence data. However, hydro-climate conditions are becoming increasingly non-stationary due to climate change and direct anthropogenic impacts such as land use change, making empirical models unsuitable for simulating future risk. In this study we introduce a mechanistic hydro-epidemiological model for Liver Fluke, which explicitly simulates habitat suitability for disease development in space and time, representing the parasite life cycle in connection with key environmental conditions. The model is used to assess patterns of Liver Fluke risk for two catchments in the UK under current and potential future climate conditions. Comparisons are made with a widely used empirical model employing different datasets, including data from regional veterinary laboratories. Results suggest that mechanistic models can achieve adequate predictive ability and support adaptive fluke control strategies under climate change scenarios.

  5. Multiple liver abscesses in a dog secondary to the liver fluke Metorchis conjunctus treated by percutaneous transhepatic drainage and alcoholization.

    PubMed

    Lemetayer, Julie D; Snead, Elizabeth C; Starrak, Greg S; Wagner, Brent A

    2016-06-01

    A 1-year-old German shepherd × husky cross dog was diagnosed with multiple liver abscesses and severe cholangitis secondary to the liver fluke Metorchis conjunctus. The dog was successfully treated with 2 percutaneous transhepatic drainage and alcoholization procedures, and a prolonged course of antibiotics and praziquantel.

  6. Behavioral Modification Regarding Liver Fluke and Cholangiocarcinoma with a Health Belief Model Using Integrated Learning.

    PubMed

    Phatisena, Panida; Eaksanti, Tawatchai; Wichantuk, Pitsanee; Tritipsombut, Jaruwan; Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkhuwattapong, Parichart; Tongtawee, Taweesak; Matrakool, Likit; Panpimanmas, Sukij; Norkaew, Jun; Kujapun, Jirawoot; Chavengkun, Wasugree; Kompor, Porntip; Pothipim, Mali; Ponphimai, Sukanya; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    This study aimed to modify behavior regarding liver fluke and cholangiocarcinoma prevention in Chumphuang district, Nakhon Ratchasima province, Thailand through integrated learning. A total of 180 participants were included through purposive selection of high-risk scores on verbal screening. Participants attended the health education program which applied the health belief model included family based, knowledge station based, academic merit based and community based learning. Data were collected using a questionnaire composed of 4 parts: 1) personal information, 2) knowledge, 3) perceived susceptibility, severity, benefits, and barriers, 4) practice regarding liver fluke and cholangiocarcinoma prevention. The result revealed that the majority were female (79.9%), age ≥60 years old (33.2%), primary school educational level (76.1%), and agricultural occupation (70.1%). The mean scores of knowledge, perception, and practice to liver fluke and cholangiocarcinoma prevention, before participated the integrative learning were low, moderate, and low, respectively. Meanwhile, the mean score of knowledge, perceived susceptibility, severity, benefits, and barriers, and practice regarding liver fluke and cholangiocarcinoma prevention, were higher with statistical significance after participation in the integrated learning. This finding indicates that health education programs may successfully modify health behavior in the rural communities. Therefore they may useful for further work behavior modification in other epidemic areas. PMID:27356708

  7. Association between Liver Fluke Infection and Hepatobiliary Pathological Changes: A Systematic Review and Meta-Analysis

    PubMed Central

    Xia, Jing; Jiang, Shi-chen; Peng, Hong-Juan

    2015-01-01

    Objective To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes. Methods Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0. Result A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical

  8. Health Behavior Regarding Liver Flukes among Rural People in Nakhon Ratchasima, Thailand.

    PubMed

    Painsing, Sirinapa; Sripong, Anan; Vensontia, Orramon; Pengsaa, Prasit; Kompor, Pontip; Kootanavanichapong, Nusorn; Kaewpitoon, Soraya J; Kaewpitoon, Natthawut

    2016-01-01

    Opisthorchiasis is a health problem in Thailand particularly in northeast and north regions where have been reported the highest of cholangiocarcinoma. Active surveillance is required, therefore a cross-sectional surveyed was conducted in Nong Bunnak sub-district of Nakhon Ratchasima province, Thailand. A total of 367 participants were selected by multistage sampling from 5 villages located near natural water resources. Participants completed a predesigned questionnaire containing behavior questions regarding liver fluke disease, covering reliability and validity knowledge (Kuder-Richardon-20) = 0.80, attitude and practice (Cronbach's alpha coefficient) = 0.82 and 0.79, respectively. Descriptive statistics included frequencies, percentages, means, and standard deviations. The majority of the participants were female (58.3%), age group between 21-30 years old (42.5%), with primary school education (59.9%), occupation in agriculture (38.1%), and married (80.9%). They had past histories of raw fish consumption (88.3%), stool examination (1.4%), anti-parasite medication used (4.6%). Heads of villages, village health volunteers, television, and village newstations were the main sources for disease information. Participants had a moderate level of behavior regarding liver fluke disease. The mean scored of knowledge regarding liver fluke life cycle, transmission, severities, treatment, prevention and control was 10.9 (SD=0.5), most of them had a moderate level, 95.1%. The mean score for attitude regarding liver fluke prevention and control was 45.7 (SD=9.7), and for practice was 30.6 (SD=10.5). Participants had a moderate level of attitude and practice, 94.5% and 47.7, respectively. This study indicates that health education is required in this community including stool examination for liver fluke as further active surveillance screening. PMID:27221904

  9. Ostertagia spp., rumen fluke and liver fluke single- and poly-infections in cattle: An abattoir study of prevalence and production impacts in England and Wales.

    PubMed

    Bellet, C; Green, M J; Vickers, M; Forbes, A; Berry, E; Kaler, J

    2016-09-15

    This study aims at investigating the occurrence, risk factors and production impacts on beef carcass parameters of three of the most important cattle helminth infections in England and Wales. Abomasa, reticulorumens and livers from healthy cattle were collected and examined post-mortem quarterly over a one year period in an abattoir in South-West England. Specific viscera from 974 cattle were collected, examined and scored for Ostertagia spp., adult rumen fluke and liver fluke lesions/presence. A total of 89%, 25% and 29% of the carcasses had lesions/presence of Ostertagia spp., rumen fluke and liver fluke, respectively, and 39% had presence of helminth co-infection. Animal demographic and carcass parameters associated with helminth infections were investigated using multilevel multinomial and multilevel linear mixed models respectively. After adjusting for other factors, significant differences in the distribution of helminth infections were observed among cattle by type of breed, animal category (cow, heifer, steer and young bull), age, season and concurrent helminth infections. Compared to carcasses free of helminths, carcasses presenting solely Ostertagia Spp. lesions or adult rumen fluke had significantly lower cold carcass weight (coef.: -30.58 [-50.92;-10.24] and -50.34 [-88.50;-12.18]) and fat coverage (coef.: -3.28 [-5.56;-1.00] and -5.49 [-10.28;-0.69]) and carcasses presenting solely liver fluke lesions had significantly lower conformation grade (coef.: -3.65 [-6.98;-0.32]). Presence of helminth poly-infections was negatively associated with cold carcass weight. PMID:27664452

  10. Development of the large American liver fluke, Fascioloides magna, in white-tailed deer, cattle, and sheep.

    PubMed

    Foreyt, W J; Todd, A C

    1976-02-01

    The comparative development of Fascioloides magna in white-tailed deer, cattle and sheep has been studied. Flukes were recovered from 72% of 32 deer administered 40 to 500 metacercariae, from 82% of 11 cattle administered 10 to 500 metacercariae, and from 53% of 15 sheep administered 8 to 200 metacercariae. The percentage recovery of the flukes administered as metacercariae was 4.1% of 6,130 in deer, 5.7% of 2,510 in cattle, and 4.7% of 1,213 in sheep. Flukes were recovered only from livers of infected deer, while in cattle, 1 fluke was also found in the lungs of each of 2 animals. In sheep, all but 10 flukes were recovered from the livers; 6 were found in the lungs and 4 in the abdominal cavities. The black iron porphyrin pigment associated with F. magna infection was found to be most widespread in cattle and sheep, but was also a pathognomonic feature in deer. Growth of the fluke was similar in all 3 host species tested, but eggs were passed only from deer, the normal definitive host. In cattle, the eggs were retained in the liver, and F. magna was lethal to sheep before its own maturity was attained. In cattle and deer, flukes matured approximately 7 months after exposure, but immature migrating flukes were found 12 months after infection and apparently can remain in this retarded state for an undetermined period of time.

  11. A model to assess the efficacy of vaccines for control of liver fluke infection

    PubMed Central

    Turner, Joanne; Howell, Alison; McCann, Cathy; Caminade, Cyril; Bowers, Roger G.; Williams, Diana; Baylis, Matthew

    2016-01-01

    Fasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance. PMID:27009747

  12. A model to assess the efficacy of vaccines for control of liver fluke infection.

    PubMed

    Turner, Joanne; Howell, Alison; McCann, Cathy; Caminade, Cyril; Bowers, Roger G; Williams, Diana; Baylis, Matthew

    2016-01-01

    Fasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3 billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance. PMID:27009747

  13. Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.

    PubMed

    Capobianco, I; Frank, M; Königsrainer, A; Sipos, B; Menzel, M; Sturm, E; Nadalin, S

    2015-12-01

    Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.

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

    PubMed Central

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

    1977-01-01

    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

  15. Untangling the Complexity of Liver Fluke Infection and Cholangiocarcinoma in NE Thailand Through Transdisciplinary Learning.

    PubMed

    Ziegler, A D; Echaubard, P; Lee, Y T; Chuah, C J; Wilcox, B A; Grundy-Warr, C; Sithithaworn, P; Petney, T N; Laithevewat, L; Ong, X; Andrews, R H; Ismail, T; Sripa, B; Khuntikeo, N; Poonpon, K; Tungtang, P; Tuamsuk, K

    2016-06-01

    This study demonstrates how a transdisciplinary learning approach provided new insights for explaining persistent Opisthorchis viverrini infection in northern Thailand, as well as elucidating problems of focusing solely on the parasite as a means of addressing high prevalence of cholangiocarcinoma. Researchers from diverse backgrounds collaborated to design an investigative homestay program for 72 Singaporean and Thai university students in five northeast Thai villages. The students explored how liver fluke infection and potential cholangiocarcinoma development are influenced by local landscape dynamics, aquatic ecology, livelihoods, food culture and health education. Qualitative fieldwork was guided daily by the researchers in a collaborative, co-learning process that led to viewing this health issue as a complex system, influenced by interlinked multidimensional factors. Our transdisciplinary experience has led us to believe that an incomplete understanding of these linkages may reduce the efficacy of interventions. Further, viewing liver fluke infection and cholangiocarcinoma as the same issue is inadvisable. Although O. viverrini infection is an established risk factor for the development of cholangiocarcinoma, multiple factors are known to influence the likelihood of acquiring either. Understanding the importance of the current livelihood transition, landscape modification and the resulting mismatch between local cultures and new socio-ecological settings on cholangiocarcinoma initiation and liver fluke transmission is of critical importance as it may help readjust our view of the respective role of O. viverrini and other socioeconomic risk factors in cholangiocarcinoma etiology and refine intervention strategies. As demonstrated in this study, transdisciplinary approaches have the potential to yield more nuanced perspectives to complex diseases than research that focuses on specific aspects of their epidemiology. They may therefore be valuable when designing

  16. Nutritional Status among Rural Community Elderly in the Risk Area of Liver Fluke, Surin Province, Thailand.

    PubMed

    Kaewpitoon, Soraya J; Namwichaisirikul, Niwatchai; Loyd, Ryan A; Churproong, Seekaow; Ueng-Arporn, Naporn; Matrakool, Likit; Tongtawee, Taweesak; Rujirakul, Ratana; Nimkhuntod, Porntip; Wakhuwathapong, Parichart; Kaewpitoon, Natthawut

    2015-01-01

    Thailand is becoming an aging society, this presenting as a serious problem situation especially regarding health. Chronic diseases found frequently in the elderly may be related to dietary intake and life style. Surin province has been reported as a risk area for liver fluke with a high incidence of cholangiocarcinma especially in the elderly. Therefore, this study aimed to determine the nutritional status and associated factors among elderly in Surin province, northeast of Thailand. A community-based cross-sectional study was conducted among 405 people aged 60 years and above, between September 2012 and July 2014. The participants were selected through a randomized systematic sampling method and completed a pre-designed questionnaire with general information, food recorded, weight, height, waist circumference, and behavior regarding to food consume related to liver fluke infection. The data were analyzed using descriptive statistics and Spearman's rank correlation coefficients. The majority of participants was female (63.5%), age between 60-70 years old (75.6%), with elementary school education (96.6%), living with their (78.9%), and having underlying diseases (38.3%). Carbohydrate (95.3%) was need to improve the consumption. The participants demonstrated under-nutrition (24.4%), over-nutrition (16.4%), and obesity (15.4%). Elderly had a waist circumference as the higher than normal level (34.0%). Gender, female, age 71-80 years old, elementary school and underlying diseases were significantly associated with poor nutritional status. The majority of them had a high knowledge (43.0%), moderate attitude (44.4%), and moderate practice (46.2%) regarding food consumption related to liver fluke infection. In conclusion, these findings data indicated that elderly age group often have an under- or over-nutritional status. Carbohydrate consumption needs to be improved. Some elderly show behavior regarding food consumption that is related to liver fluke infection hat needs

  17. Modifying Health Behavior for Liver Fluke and Cholangiocarcinoma Prevention with the Health Belief Model and Social Support Theory.

    PubMed

    Padchasuwan, Natnapa; Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkuwattapong, Parichart; Norkaew, Jun; Kujapun, Jirawoot; Ponphimai, Sukanya; Chavenkun, Wasugree; Kompor, Pontip; Kaewpitoon, Natthawut

    2016-01-01

    The liver fluke Opisthorchis viverrini is a serious health problem in Thailand. Infection is associated with cholangiocarcinoma (CCA), endemic among human populations in northeast and north Thailand where raw fish containing fluke metacercariae are frequently consumed. Recently, Thailand public health authorities have been organized to reduce morbidity and mortality particularly in the northeast through O. viverrini and CCA screening projects. Health modfication is one of activities included in this campaign, but systemic guidelines of modifying and developing health behavior for liver flukes and CCA prevention in communities towards health belief and social support theory are still various and unclear. Here we review the guidelines for modifying and developing health behavior among populations in rural communities to strengthen understanding regarding perceived susceptibility, severity, benefits, and barriers to liver fluke and CCA prevention. This model may be useful for public health of cancers and related organizations to further health behavior change in endemic areas. PMID:27644606

  18. Proteomic profile of Bithynia siamensis goniomphalos snails upon infection with the carcinogenic liver fluke Opisthorchis viverrini

    PubMed Central

    Prasopdee, Sattrachai; Tesana, Smarn; Cantacessi, Cinzia; Laha, Thewarach; Mulvenna, Jason; Grams, Rudi; Loukas, Alex; Sotillo, Javier

    2014-01-01

    The snail Bithynia siamensis goniomphalos acts as the first intermediate host for the human liver fluke Opisthorchis viverrini, the major cause of cholangiocarcinoma (CCA) in Northeast Thailand. The undisputed link between CCA and O. viverrini infection has precipitated efforts to understand the molecular basis of host-parasite interactions with a view to ultimately developing new control strategies to combat this carcinogenic infection. To date most effort has focused on the interactions between the parasite and its human host, and little is known about the molecular relationships between the liver fluke and its snail intermediate host. In the present study we analyse the protein expression changes in different tissues of B. siamensis goniomphalos induced by infection with larval O. viverrini using iTRAQ labelling technology. We show that O. viverrini infection downregulates the expression of oxidoreductases and catalytic enzymes, while stress-related and motor proteins are upregulated. The present work could serve as a basis for future studies on the proteins implicated in the susceptibility/resistance of B. siamensis goniomphalos to O. viverrini, as well as studies on other pulmonate snail intermediate hosts of various parasitic flukes that infect humans. PMID:25284051

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

    PubMed Central

    2014-01-01

    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

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

    PubMed Central

    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

    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 σ-class glutathione transferase (FheσGST). 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; FheσGST 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

  1. Opisthorchis viverrini (liver fluke) as the lot of baleful parasite of tropical region-A replete synopsis

    PubMed Central

    Gundamaraju, Rohit; Vemuri, Ravi Chandra

    2014-01-01

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts which is highly prominent in the tropical regions. Infection occurs through ingestion of fluke-infested fresh-water raw fish. Opisthorchis viverrini is the biggest causative organism for this disease. Adult flukes get into the body of humans and settle in the small intrahepatic bile ducts, and then they live there for few decades. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts, and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. Major complications of the disease also include pancreatitis, bile duct obstruction etc. The majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the appulse of this food-borne malady on accessible bloom and the astringent accessible analytic consequences, alarmist accident infection should not be abandoned or neglected. This review acts as a complete picture in elucidating the information regarding the parasite and disease condition thereby supporting the researchers worldwide.

  2. GIS-based spatial statistical analysis of risk areas for liver flukes in Surin Province of Thailand.

    PubMed

    Rujirakul, Ratana; Ueng-arporn, Naporn; Kaewpitoon, Soraya; Loyd, Ryan J; Kaewthani, Sarochinee; Kaewpitoon, Natthawut

    2015-01-01

    It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini, for proper allocation of prevention and control measures. This study aimed to investigate the human behavior, and environmental factors influencing the distribution in Surin Province of Thailand, and to build a model using stepwise multiple regression analysis with a geographic information system (GIS) on environment and climate data. The relationship between the human behavior, attitudes (<50%; X111), environmental factors like population density (148-169 pop/km2; X73), and land use as wetland (X64), were correlated with the liver fluke disease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equations OV=-0.599+0.005(population density (148-169 pop/km2); X73)+0.040 (human attitude (<50%); X111)+0.022 (land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver fluke infection, R Square=0.878, and, Adjust R Square=0.849. By GIS analysis, we found Si Narong, Sangkha, Phanom Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highest distributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulate the spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning of prevention and control measures. PMID:25824758

  3. GIS-based spatial statistical analysis of risk areas for liver flukes in Surin Province of Thailand.

    PubMed

    Rujirakul, Ratana; Ueng-arporn, Naporn; Kaewpitoon, Soraya; Loyd, Ryan J; Kaewthani, Sarochinee; Kaewpitoon, Natthawut

    2015-01-01

    It is urgently necessary to be aware of the distribution and risk areas of liver fluke, Opisthorchis viverrini, for proper allocation of prevention and control measures. This study aimed to investigate the human behavior, and environmental factors influencing the distribution in Surin Province of Thailand, and to build a model using stepwise multiple regression analysis with a geographic information system (GIS) on environment and climate data. The relationship between the human behavior, attitudes (<50%; X111), environmental factors like population density (148-169 pop/km2; X73), and land use as wetland (X64), were correlated with the liver fluke disease distribution at 0.000, 0.034, and 0.006 levels, respectively. Multiple regression analysis, by equations OV=-0.599+0.005(population density (148-169 pop/km2); X73)+0.040 (human attitude (<50%); X111)+0.022 (land used (wetland; X64), was used to predict the distribution of liver fluke. OV is the patients of liver fluke infection, R Square=0.878, and, Adjust R Square=0.849. By GIS analysis, we found Si Narong, Sangkha, Phanom Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri, and Rattanaburi to have the highest distributions in Surin province. In conclusion, the combination of GIS and statistical analysis can help simulate the spatial distribution and risk areas of liver fluke, and thus may be an important tool for future planning of prevention and control measures.

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

    PubMed

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

    2013-08-01

    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

  5. [Studies on the molluscicidal and cercariacidal effects of various pesticides in liver fluke

    PubMed

    Kim, Jung Man

    1965-12-01

    Clonorchiasis for which no specific therapy is available has been recognized as one of the serious public health problems in terms of waste of human productivity in Korea today and an urgent consideration must be given to its prevention and control. For past several years, the author has been finding that the infection rate of liver fluke in fish from the Kum-Ho river which has long been recognized as the world's notorious prevalent area of the disease, has been decreasing gradually. Here the author formulated the hypothesis that the decreasing of infection rate might be influenced by the common use of pesticide in plants along the river. Basing this hypothesis, the effective use of pesticide may contribute to the control of the disease by cutting the life cycle of liver fluke. To test above hypothesis, molluscicidal effect on Parafossarulus manchouricus and cercariacidal effect of various pesticides in liver fluke have been determined and the following results were obtained. 1. In molluscicidal effect, the most potent agent in low concentration was Bayer 73 which is 3 to 70 times stronger than other pesticides. When compared with NaPCP which has been widely used for the eradication of Onchomelania, Bayer 73 shows 5 to 10 times stronger effect. The order of pesticide in molluscicidal effect was: Bayer 73, Nicotin, NaPCP, Sevin, Parathion, Copper sulfate and Lindane. 2. In cercariacidal effect, the most potent agent was Parathion which had 2 to 5 times stronger effect than Bayer 73 or NaPCP. The order of pesticide in the cercariacidal effect was: Parathion, Bayer73, NaPCP, Lindane, Nicotin,Sevin, and Copper sulfate. 3. By applying the common used concentration of pesticides considering the toxicity to plants, Bayer 73 is most potent in molluscicidal effect and then Nicotin, NaPCP, Copper sulfate, Sevin, Parathion and Lindane in order. In cercariacidal effect, Parathion is the most potent and NaPCP, Bayer 73, Lindane, and Copper sulfate are followed. 4. Considering

  6. Liver fluke disease (fascioliasis): epidemiology, economic impact and public health significance.

    PubMed

    Saleha, A A

    1991-12-01

    Liver fluke disease (fascioliasis) is an important parasitic disease found worldwide affecting sheep, goats, cattle and buffalo, as well as other domestic ruminants. The common causative agents are Fasciola hepatica and F. gigantica which require various species of Lymnaea, fresh water snails, as their intermediate hosts. The epidemiology of the disease and its prevalence in Malaysia is mentioned briefly. The disease causes considerable impact on the economy of the livestock industry. The economic losses consist of costs of anthelmintics, drenches, labor, liver condemnation at meat inspection; and losses in production due to mortality, reduction in meat, milk and wool production; and reduction in growth rate, fertility and draught power. The disease also has public health significance, causing human fascioliasis and "halzoun".

  7. Clonorchis sinensis and Opisthorchis spp. in Vietnam: current status and prospects.

    PubMed

    Doanh, Pham N; Nawa, Yukifumi

    2016-01-01

    Clonorchis sinensis and Opisthorchis viverrini are clinically important small liver flukes because of their known association with development of cholangiocarcinoma. In Vietnam, high prevalence of C. sinensis infection in humans was previously reported in northern provinces, and O. viverrini infection has been detected in several central provinces. However, diagnosis of C. sinensis and O. viverrini infections in the past was merely based on faecal egg examination. This method alone can lead to misidentification at the species level because of morphological similarity between the eggs of these liver flukes and minute intestinal trematodes of the family Heterophyidae. In fact, recent surveys in Vietnam revealed that infection with several minute intestinal flukes, such as Haplorchis pumilio and H. taichui, are much more common than infection with C. sinensis or O. viverrini, and they often co-infect humans. Thus, previously reported prevalence of small liver fluke infection in Vietnam was likely over-estimated due to mis identification of parasites in copro-parasitological examinations. In addition, there is some confusion about identification of cercariae, metacercariae and also adults of C. sinensis and O. viverrini in intermediate and definitive hosts. The aim of this review is, therefore, to draw realistic pictures of the past and present scientific reports on the epidemiology and biology of C. sinensis and Opisthorchis spp. infection in Vietnam.

  8. Current status of Clonorchis sinensis and clonorchiasis in China.

    PubMed

    Lai, De-Hua; Hong, Xiao-Kun; Su, Bi-Xiu; Liang, Chi; Hide, Geoff; Zhang, Xiaoli; Yu, Xinbing; Lun, Zhao-Rong

    2016-01-01

    The oriental liver fluke, Clonorchis sinensis, a pathogen causing clonorchiasis, is of major socio-economic importance in East Asia, including China, Korea and Vietnam. This parasite is now recognized as a biocarcinogen strongly linked to cholangiocarcinoma in humans. Here, we describe the status of clonorchiasis in China, where it has been estimated that more than 15 million patients are affected. This paper also summarizes the major advances in the field of clonorchiasis research during last decade, including diagnosis techniques, pathogenesis and genome/transcriptome/proteome studies in the last years. We strongly hope that our work can stimulate the governments of the countries or regions where clonorchiasis is endemic to pay more attention to this disease and establish related guidelines to prevent and control it. PMID:26740359

  9. Current status of Clonorchis sinensis and clonorchiasis in China.

    PubMed

    Lai, De-Hua; Hong, Xiao-Kun; Su, Bi-Xiu; Liang, Chi; Hide, Geoff; Zhang, Xiaoli; Yu, Xinbing; Lun, Zhao-Rong

    2016-01-01

    The oriental liver fluke, Clonorchis sinensis, a pathogen causing clonorchiasis, is of major socio-economic importance in East Asia, including China, Korea and Vietnam. This parasite is now recognized as a biocarcinogen strongly linked to cholangiocarcinoma in humans. Here, we describe the status of clonorchiasis in China, where it has been estimated that more than 15 million patients are affected. This paper also summarizes the major advances in the field of clonorchiasis research during last decade, including diagnosis techniques, pathogenesis and genome/transcriptome/proteome studies in the last years. We strongly hope that our work can stimulate the governments of the countries or regions where clonorchiasis is endemic to pay more attention to this disease and establish related guidelines to prevent and control it.

  10. In vitro screening of Cymbopogon jwarancusa and Conyza canadensis against liver flukes.

    PubMed

    Shafiq, Andeela; Kanwal, Rabia; Ullah Qureshi, Rahamat; Riaz Chaudhry, Farhana

    2015-09-01

    Aim of present study was to screen medicinal plants for flukicidal activity in vitro to develop alternative sources of treatment for trematodes infection. For this purpose, crude methanolic extracts (CME) of Cymbopogn jwarancusa and Conyza canadensis were prepared and live adult flukes viz; Fasciola gigantica, and Paramphistomum cervi isolated from liver and bile ducts of slaughtered buffalo were subjected to different drug concentrations as well as positive and negative control. Motility inhibition and paralysis leading to the death of parasites was considered as flukicidal activity of plants extracts. The results revealed that CME of C. jwarancusa and C. canadensis showed significant (P<0.05) flukicidal activity compared to positive control. Also there was a significant effect of different concentrations (P<0.05) and exposure of time on the flukes (P<0.05). Furthermore, ED50 for C. jwarancusa and C. canadensis against F. gigantica were 13.1 and 41.4 mg/ml, respectively. In the case of P. cervi, it was 10.8 and 29.0 mg/ml. It can be concluded that both tested plants showed greater flukicidal activity as compared to positive control with Albendazole till the 8(th) hr. These potent plants needs further studies invivo to elucidate their mode of action. PMID:26695200

  11. Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype

    PubMed Central

    Chaiyadet, Sujittra; Sotillo, Javier; Smout, Michael; Cantacessi, Cinzia; Jones, Malcolm K.; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Potriquet, Jeremy; Laohaviroj, Marut; Mulvenna, Jason; Brindley, Paul J.; Bethony, Jeffrey M.; Laha, Thewarach; Sripa, Banchob; Loukas, Alex

    2015-01-01

    Background. Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization. Results. EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. Conclusions. This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer. PMID:25985904

  12. In vitro screening of Cymbopogon jwarancusa and Conyza canadensis against liver flukes.

    PubMed

    Shafiq, Andeela; Kanwal, Rabia; Ullah Qureshi, Rahamat; Riaz Chaudhry, Farhana

    2015-09-01

    Aim of present study was to screen medicinal plants for flukicidal activity in vitro to develop alternative sources of treatment for trematodes infection. For this purpose, crude methanolic extracts (CME) of Cymbopogn jwarancusa and Conyza canadensis were prepared and live adult flukes viz; Fasciola gigantica, and Paramphistomum cervi isolated from liver and bile ducts of slaughtered buffalo were subjected to different drug concentrations as well as positive and negative control. Motility inhibition and paralysis leading to the death of parasites was considered as flukicidal activity of plants extracts. The results revealed that CME of C. jwarancusa and C. canadensis showed significant (P<0.05) flukicidal activity compared to positive control. Also there was a significant effect of different concentrations (P<0.05) and exposure of time on the flukes (P<0.05). Furthermore, ED50 for C. jwarancusa and C. canadensis against F. gigantica were 13.1 and 41.4 mg/ml, respectively. In the case of P. cervi, it was 10.8 and 29.0 mg/ml. It can be concluded that both tested plants showed greater flukicidal activity as compared to positive control with Albendazole till the 8(th) hr. These potent plants needs further studies invivo to elucidate their mode of action.

  13. The Carcinogenic Liver Fluke Opisthorchis viverrini is a Reservoir for Species of Helicobacter

    PubMed Central

    Deenonpoe, Raksawan; Chomvarin, Chariya; Pairojkul, Chawalit; Chamgramol, Yaowalux; Loukas, Alex; Brindley, Paul J; Sripa, Banchob

    2016-01-01

    There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters (p≤0.001). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverrini-infected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively (p≤0.001). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and

  14. The carcinogenic liver fluke Opisthorchis viverrini is a reservoir for species of Helicobacter.

    PubMed

    Deenonpoe, Raksawan; Chomvarin, Chariya; Pairojkul, Chawalit; Chamgramol, Yaowalux; Loukas, Alex; Brindley, Paul J; Sripa, Banchob

    2015-01-01

    There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters (p≤0.001). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverrini- infected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively (p≤0.001). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori

  15. An expanding population of the giant liver fluke (Fascioloides magna) in elk (Cervus canadensis) and other ungulates in Canada.

    PubMed

    Pybus, Margo J; Butterworth, Eric W; Woods, John G

    2015-04-01

    Giant liver fluke (Fascioloides magna) populations readily expand under suitable conditions. Although extirpated from the eastern slopes of the Canadian Rocky Mountains in the early 1960s, the fluke reappeared following natural spread through mountain passes from British Columbia. Herein, we assessed epizootiology of the fluke population two decades later. Between 1984 and 1991, 534 ungulates, including 381 elk (Cervus canadensis), 68 mule deer (Odocoileus hemionus hemionus), 54 white-tailed deer (Odocoileus virginianus), and 31 moose (Alces alces) from adjacent areas of Alberta (AB) and British Columbia (BC), Canada, were examined for giant liver flukes. Prevalence in elk increased from 53% to 79% (1984-91) in Banff National Park (BNP) in AB and 77% to 100% (1985-89) in Kootenay National Park (KNP) in BC. Super-infections (>100 flukes) were more common in later years. Generally, prevalence increased over time and with increasing age of elk. Intensity was lowest in young-of-year (BNP 8±5, KNP 3), but similar in yearlings (BNP 36±11, KNP 23±8) and adults (BNP 33±5, KNP 32±6). Prevalence was similar in male and female elk. Intensity was higher in males (BNP 47±7, KNP 46±12) than in females (BNP 28±6, KNP 22±4), although the maximum number of flukes (545) occurred in a female elk. Prevalence and intensity differed among other species of ungulates but patterns were similar in each park. Prevalence was lower in mule deer (BNP 6%, KNP 4%) than in white-tailed deer (BNP 44%, KNP 28%) and moose (BNP 52%, KNP 63%). Intensity differed among these species but never exceeded 30 flukes. Gravid flukes occurred only in elk and white-tailed deer. Transmission occurred primarily in late summer-fall and in wet habitats. At least seven elk died as a direct result of fluke infection. In this region, elk and white-tailed deer maintain the F. magna population with spillover into moose and, rarely, mule deer. PMID:25647594

  16. An expanding population of the giant liver fluke (Fascioloides magna) in elk (Cervus canadensis) and other ungulates in Canada.

    PubMed

    Pybus, Margo J; Butterworth, Eric W; Woods, John G

    2015-04-01

    Giant liver fluke (Fascioloides magna) populations readily expand under suitable conditions. Although extirpated from the eastern slopes of the Canadian Rocky Mountains in the early 1960s, the fluke reappeared following natural spread through mountain passes from British Columbia. Herein, we assessed epizootiology of the fluke population two decades later. Between 1984 and 1991, 534 ungulates, including 381 elk (Cervus canadensis), 68 mule deer (Odocoileus hemionus hemionus), 54 white-tailed deer (Odocoileus virginianus), and 31 moose (Alces alces) from adjacent areas of Alberta (AB) and British Columbia (BC), Canada, were examined for giant liver flukes. Prevalence in elk increased from 53% to 79% (1984-91) in Banff National Park (BNP) in AB and 77% to 100% (1985-89) in Kootenay National Park (KNP) in BC. Super-infections (>100 flukes) were more common in later years. Generally, prevalence increased over time and with increasing age of elk. Intensity was lowest in young-of-year (BNP 8±5, KNP 3), but similar in yearlings (BNP 36±11, KNP 23±8) and adults (BNP 33±5, KNP 32±6). Prevalence was similar in male and female elk. Intensity was higher in males (BNP 47±7, KNP 46±12) than in females (BNP 28±6, KNP 22±4), although the maximum number of flukes (545) occurred in a female elk. Prevalence and intensity differed among other species of ungulates but patterns were similar in each park. Prevalence was lower in mule deer (BNP 6%, KNP 4%) than in white-tailed deer (BNP 44%, KNP 28%) and moose (BNP 52%, KNP 63%). Intensity differed among these species but never exceeded 30 flukes. Gravid flukes occurred only in elk and white-tailed deer. Transmission occurred primarily in late summer-fall and in wet habitats. At least seven elk died as a direct result of fluke infection. In this region, elk and white-tailed deer maintain the F. magna population with spillover into moose and, rarely, mule deer.

  17. A retrospective survey of liver flukes in livestock based on abattoir data in Kermanshah, west of Iran.

    PubMed

    Shahbazi, Yasser; Hashemnia, Mohammad; Safavi, Ehsan Allah Afshari

    2016-09-01

    A retrospective study was carried from 2008 to 2013 to estimate the prevalence of liver flukes in ruminants slaughtered at the abattoir of Kermanshah province, west of Iran. A total of 663,633 animals slaughtered in the 5-year period and totally 1.95 % of livers were condemned due to liver flukes. Fasciolosis were responsible for 0.8, 0.7 and 1.5 % of liver condemnations, whereas 1, 0.8 and 1 % of liver were condemned because of Dicrocoelium dendriticum infection in the sheep, goats and cattle, respectively. A significant difference in the prevalence of liver flukes were observed among studied animals (p < 0.001) and the highest and lowest prevalence were detected in cattle and goats, respectively. Data showed significant seasonal pattern for distomatosis in sheep and goat (p < 0.001). Liver condemnations due to fasciolosis were prevalent in sheep and goats and cattle slaughtered during winter, summer and autumn, respectively, whereas dicrocoeliosis were common in autumn season for sheep and cattle and in winter for goats. This survey provides baseline data for the future monitoring of these potentially important parasitic infections in the region. PMID:27605816

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

    PubMed Central

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

    2008-01-01

    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

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

    PubMed

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

    2012-03-01

    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

  20. Raw Fish Consuming Behavior Related to Liver Fluke Infection among Populations at Risk of Cholangiocarcinoma in Nakhon Ratchasima Province, Thailand.

    PubMed

    Chavengkun, Wasugree; Kompor, Pontip; Norkaew, Jun; Kujapun, Jirawoot; Pothipim, Mali; Ponphimai, Sukanya; Kaewpitoon, Soraya J; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    Opisthorchiasis is a health problem in rural communities of Thailand, particularly in the northeast and north regions. Therefore, this study aimed to investigate raw fish consuming behavior related to liver fluke infection among the population at risk for opisthorchiasis and cholangiocarcinoma (CCA). A cross-sectional descriptive study was conducted in Meuang Yang district, Nakhon Ratchasima province, northeast Thailand, between June and October 2015. Participants were screened for CCA, and samples who had a high score of CCA risk were purposively selected. A predesigned questionnaire was utilized to collect the data from all participants. X2-test was used for analysis of associations between demographic data and raw fish consumption. The results revealed that participants had past histories of stool examination (33.0%), liver fluke infection (21.0%), praziquantel use (24.0%), raw fish consumption (78.0%), relatives family consuming raw fish (73.0%), and relatives family with CCA (3.0%). Participants consumed several dished related to liver fluke infection, mainly raw fermented fish (13.0%), under smoked catfish (5.00%), raw pickled fish (4.00%), and raw spicy minced fish salad (3.00%). The most common types of cyprinoid fish were Barbodes gonionotus (39%), Hampala dispar (38%), Puntius brevis (37%), Cyclocheilichthys armatus (33%), Puntioplites proctozysron (32%), and Luciosoma bleekeri (30%), respectively. Participants had a low level of knowledge (mean=3.79, SD=0.74), moderate attitude (mean=7.31, SD=7.31) and practice (mean=38.64, SD=6.95) regarding liver fluke prevention and control. Demographic variables like age (>36 years old; X2-test=17.794, p-value=0.001), education (primary school; X2-test=18.952, p-value=0.001), marital status (married; X2-test=12.399, p-value=0.002), and income (<5,000 baht; X2-test=27.757, p-value=0.015) were significantly associated with raw fish consumption. This result indicates that the population had risk consumption for liver

  1. Molecular evidence shows that the liver fluke Fasciola gigantica is the predominant Fasciola species in ruminants from Pakistan.

    PubMed

    Chaudhry, U; van Paridon, B; Shabbir, M Z; Shafee, M; Ashraf, K; Yaqub, T; Gilleard, J

    2016-03-01

    Fascioliasis is an important disease affecting livestock, with great costs to producers worldwide. It has also become a serious issue for human populations in some endemic areas as an emerging zoonotic infection. There are two Fasciola species of liver fluke responsible for this disease, which occur worldwide, Fasciola hepatica and Fasciola gigantica. Identifying these two species on the basis of adult or egg morphology requires specialist knowledge due to the similarity of characters, and may misidentify putative intermediate or hybrid forms. In this study we sequenced the internal transcribed spacer 2 (ITS-2) rDNA of liver flukes collected from multiple species of hosts from seven localities in the Punjab and Baluchistan provinces of Pakistan, to determine the distribution of these two species. All 46 flukes processed in this study, collected from seven sites, showed the rDNA ITS-2 genotype corresponding to F. gigantica, contradicting previous reports, based on adult and egg morphology, that both species are present in Pakistan, with F. hepatica being the more common.

  2. Cloning and characterization of a female genital complex cDNA from the liver fluke Fasciola hepatica.

    PubMed Central

    Zurita, M; Bieber, D; Ringold, G; Mansour, T E

    1987-01-01

    A cDNA clone whose RNA is abundant in the female genital complex of the liver fluke Fasciola hepatica has been isolated from a cDNA library in lambda gt10 by differential screening. The pattern of expression in different fluke tissues and at different stages of miracidium formation suggests that this gene is expressed in the F. hepatica vitelleria. The nucleotide sequence of the cloned cDNA was determined and the primary structure of the putative protein was deduced. The proposed protein is rich in glycine, lysine, and tyrosine and its overall amino acid composition agrees with that reported for the F. hepatica egg shell. The clone has homology with DNA from other trematodes; this homology is higher in organisms in which egg development is similar to that of F. hepatica and suggests that the protein is conserved in organisms in which miracidium formation occurs in fresh water. Images PMID:3470798

  3. Fasciola hepatica: Histological changes in the somatic and reproductive tissues of liver fluke following closantel treatment of experimentally-infected sheep.

    PubMed

    Scarcella, S; Hanna, R E B; Brennan, G P; Solana, H; Fairweather, I

    2016-01-15

    Lambs infected with the Cullompton isolate of Fasciola hepatica were treated orally or subcutaneously with 10mg/kg of closantel at 16 weeks post-infection. Adult flukes were recovered from the liver of individual animals at 12h, 24h, or 36h post-treatment. The flukes were processed for histological analysis. In general, degenerative changes in the reproductive and somatic tissues were progressive, and were most marked in flukes exposed to closantel in vivo for 36h. However, flukes from a 12h subcutaneously-treated lamb showed marked deterioration of the testis, possibly because a portion of the dose has been delivered intravenously. Fewer intact eggs were seen in the uterus of flukes exposed to closantel for longer times (whether administered subcutaneously or orally to the host). The most conspicuous closantel-induced effect in flukes from treated hosts was progressive damage to the tegumental syncytium. While the flukes from 24h-treated hosts showed relatively minor damage to limited areas of the syncytium, towards the posterior end, the flukes from 36h-treated hosts (and flukes from the lamb that putatively received intravenous dosage) had lost large areas of the surface syncytium from the posterior end and dorsal surface, although the syncytium over the anterior end and the anterior ventral surface was largely spared. In areas where the syncytium had sloughed, the underlying structures such as the vitelline follicles, gut profiles and testis profiles, showed marked degeneration and breakdown. Other changes included cell depletion and early stage apoptosis in the testis, ovary and vitelline follicles. This study establishes a model for histological changes in closantel-sensitive F. hepatica exposed to closantel in vivo. Histopathological studies could be complementary to the efficacy controlled test for for closantel resistance in fluke populations. PMID:26790736

  4. Fasciola hepatica: Histological changes in the somatic and reproductive tissues of liver fluke following closantel treatment of experimentally-infected sheep.

    PubMed

    Scarcella, S; Hanna, R E B; Brennan, G P; Solana, H; Fairweather, I

    2016-01-15

    Lambs infected with the Cullompton isolate of Fasciola hepatica were treated orally or subcutaneously with 10mg/kg of closantel at 16 weeks post-infection. Adult flukes were recovered from the liver of individual animals at 12h, 24h, or 36h post-treatment. The flukes were processed for histological analysis. In general, degenerative changes in the reproductive and somatic tissues were progressive, and were most marked in flukes exposed to closantel in vivo for 36h. However, flukes from a 12h subcutaneously-treated lamb showed marked deterioration of the testis, possibly because a portion of the dose has been delivered intravenously. Fewer intact eggs were seen in the uterus of flukes exposed to closantel for longer times (whether administered subcutaneously or orally to the host). The most conspicuous closantel-induced effect in flukes from treated hosts was progressive damage to the tegumental syncytium. While the flukes from 24h-treated hosts showed relatively minor damage to limited areas of the syncytium, towards the posterior end, the flukes from 36h-treated hosts (and flukes from the lamb that putatively received intravenous dosage) had lost large areas of the surface syncytium from the posterior end and dorsal surface, although the syncytium over the anterior end and the anterior ventral surface was largely spared. In areas where the syncytium had sloughed, the underlying structures such as the vitelline follicles, gut profiles and testis profiles, showed marked degeneration and breakdown. Other changes included cell depletion and early stage apoptosis in the testis, ovary and vitelline follicles. This study establishes a model for histological changes in closantel-sensitive F. hepatica exposed to closantel in vivo. Histopathological studies could be complementary to the efficacy controlled test for for closantel resistance in fluke populations.

  5. Development of Mitochondrial Loop-Mediated Isothermal Amplification for Detection of the Small Liver Fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes)

    PubMed Central

    Nguyen, Nga Thi Bich; Truong, Nam Hai; De, Nguyen Van

    2012-01-01

    Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10−4 ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis. PMID:22322346

  6. Development of mitochondrial loop-mediated isothermal amplification for detection of the small liver fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes).

    PubMed

    Le, Thanh Hoa; Nguyen, Nga Thi Bich; Truong, Nam Hai; De, Nguyen Van

    2012-04-01

    Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10(-4) ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis. PMID:22322346

  7. Development of mitochondrial loop-mediated isothermal amplification for detection of the small liver fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes).

    PubMed

    Le, Thanh Hoa; Nguyen, Nga Thi Bich; Truong, Nam Hai; De, Nguyen Van

    2012-04-01

    Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10(-4) ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis.

  8. Fine-scale mapping of vector habitats using very high resolution satellite imagery: a liver fluke case-study.

    PubMed

    De Roeck, Els; Van Coillie, Frieke; De Wulf, Robert; Soenen, Karen; Charlier, Johannes; Vercruysse, Jozef; Hantson, Wouter; Ducheyne, Els; Hendrickx, Guy

    2014-01-01

    The visualization of vector occurrence in space and time is an important aspect of studying vector-borne diseases. Detailed maps of possible vector habitats provide valuable information for the prediction of infection risk zones but are currently lacking for most parts of the world. Nonetheless, monitoring vector habitats from the finest scales up to farm level is of key importance to refine currently existing broad-scale infection risk models. Using Fasciola hepatica, a parasite liver fluke, as a case in point, this study illustrates the potential of very high resolution (VHR) optical satellite imagery to efficiently and semi-automatically detect detailed vector habitats. A WorldView2 satellite image capable of <5m resolution was acquired in the spring of 2013 for the area around Bruges, Belgium, a region where dairy farms suffer from liver fluke infections transmitted by freshwater snails. The vector thrives in small water bodies (SWBs), such as ponds, ditches and other humid areas consisting of open water, aquatic vegetation and/or inundated grass. These water bodies can be as small as a few m2 and are most often not present on existing land cover maps because of their small size. We present a classification procedure based on object-based image analysis (OBIA) that proved valuable to detect SWBs at a fine scale in an operational and semi-automated way. The classification results were compared to field and other reference data such as existing broad-scale maps and expert knowledge. Overall, the SWB detection accuracy reached up to 87%. The resulting fine-scale SWB map can be used as input for spatial distribution modelling of the liver fluke snail vector to enable development of improved infection risk mapping and management advice adapted to specific, local farm situations.

  9. The effect of lysergic acid diethylamide, 5-hydroxytryptamine, and related compounds on the liver fluke, Fasciola hepatica.

    PubMed

    MANSOUR, T E

    1957-12-01

    The rhythmical activity of the liver fluke, Fasciola hepatica, was stimulated by 5-hydroxytryptamine and by lysergic acid diethylamide at very low concentrations. The effect was peripheral and was not mediated through the central ganglion. Other amines also stimulated rhythmical activity, the most potent being the indolamines.Bromolysergic acid diethylamide, and other analogues such as yohimbine, harmine, and dopamine depressed rhythmical movement and antagonized the stimulant action of 5-hydroxytryptamine and lysergic acid diethylamide. Evidence which suggests the presence of tryptamine receptors in the trematode is discussed.

  10. A Case of Probable Mixed-Infection with Clonorchis sinensis and Fasciola sp.: CT and Parasitological Findings

    PubMed Central

    Kim, Tae Yun; Lee, Yun-Sik; Yun, Ji Hye; Kim, Jeong Ju; Choi, Won Hyung; Oh, In Hwan; Song, Hyun Ouk

    2010-01-01

    We report here a human case probably mixed-infected with Clonorchis sinensis and Fasciola sp. who was diagnosed by computed tomography (CT) scan, serological findings, and/or fecal examination. The patient was a 43-year-old Korean female and was admitted to Kyung Hee University Hospital with the complaints of fever and abdominal pain. On admission, marked eosinophilia was noted in her peripheral blood. CT scan showed specific lesions for clonorchiasis and fascioliasis in the liver, along with lesions suggestive of amebic abscess. Micro-ELISA revealed positive results for the 2 helminthic infections. Eggs of C. sinensis and trophozoites of Entamoeba histolytica were observed in the stool. Treatment with praziquantel followed by metronidazole and tinidazole reduced abnormalities in the liver and eosinophilia. This is the first case report of a possible co-infection with 2 kinds of liver flukes in the Republic of Korea. PMID:20585533

  11. Mitochondrial DNA haplotype analysis of liver fluke in bison from Bialowieza Primaeval Forest indicates domestic cattle as the likely source of infection.

    PubMed

    Walker, Stephen M; Demiaszkiewicz, Aleksander W; Kozak, Monika; Wedrychowicz, Halina; Teofanova, Denitsa; Prodohl, Paulo; Brennan, Gerry; Fairweather, Ian; Hoey, Elizabeth M; Trudgett, Alan

    2013-01-16

    We have determined the mitochondrial genotype of liver fluke present in Bison (Bison bonasus) from the herd maintained in the Bialowieza National Park in order to determine the origin of the infection. Our results demonstrated that the infrapopulations present in the bison were genetically diverse and were likely to have been derived from the population present in local cattle. From a consideration of the genetic structure of the liver fluke infrapopulations we conclude that the provision of hay at feeding stations may be implicated in the transmission of this parasite to the bison. This information may be of relevance to the successful management of the herd.

  12. The first comprehensive study of praziquantel effects in vivo and in vitro on European liver fluke Opisthorchis felineus (Trematoda).

    PubMed

    Pakharukova, Mariya Y; Shilov, Alexander G; Pirozhkova, Darya S; Katokhin, Alexey V; Mordvinov, Viatcheslav A

    2015-07-01

    The European liver fluke Opisthorchis felineus (Rivolta, 1884) is an epidemiologically important parasite infecting mammals, including humans. Opisthorchis felineus is widespread in Russia, Kazakhstan and Eastern European countries. Praziquantel (PZQ) is the drug of choice for the treatment of opisthorchiasis, but the effects of this drug on O. felineus are poorly studied. The aims of this work were (i) to perform a study of PZQ effects in vitro, (ii) to identify morphological markers of PZQ action on O. felineus, (iii) to analyse damage to the worm surface and (iv) to assess the efficacy of PZQ in vivo in a hamster model. Light microscopy, optical sectioning and fluorescence microscopy were used to study morphological changes. In vivo, PZQ at a dose of 400mg/kg reduced the rate of infection in experimental acute and chronic opisthorchiasis in hamsters by 70% and 79%, respectively. In vitro, the drug caused destruction and vacuolisation of the tegument of O. felineus, contractions of the worm musculature, paralysis, and irreversible changes in morphology (IC50=0.14μg/mL). Differences in susceptibility to the drug between adult and newly excysted metacercariae were also observed. Qualitative effects of PZQ in vivo and in vitro were similar to the drug's effects on other trematodes, including epidemiologically important liver flukes. Nevertheless, high heterogeneity of O. felineus specimens in terms of susceptibility to the drug was observed. In addition, we describe for the first time the high rate of recovery of O. felineus following the destructive action of PZQ. PMID:25862308

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  15. Liver fluke (Fasciola hepatica) naturally infecting introduced European brown hare (Lepus europaeus) in northern Patagonia: phenotype, prevalence and potential risk.

    PubMed

    Cuervo, Pablo F; Cataldo, Sophia Di; Fantozzi, M Cecilia; Deis, Erika; Isenrath, Gabriela Diaz; Viberti, Gabriela; Artigas, Patricio; Peixoto, Raquel; Valero, M Adela; Sierra, Roberto Mera Y; Mas-Coma, Santiago

    2015-09-01

    Fascioliasis has recently been included in the WHO list of Neglected Zoonotic Diseases. Besides being a major veterinary health problem, fascioliasis has large underdeveloping effects on the human communities affected. Though scarcely considered in fascioliasis epidemiology, it is well recognized that both native and introduced wildlife species may play a significant role as reservoirs of the disease. The objectives are to study the morphological characteristics of Fasciola hepatica adults and eggs in a population of Lepus europaeus, to assess liver fluke prevalence, and to analyze the potential reservoir role of the European brown hare in northern Patagonia, Argentina, where fascioliasis is endemic. Measures of F. hepatica found in L. europaeus from northern Patagonia demonstrate that the liver fluke is able to fully develop in wild hares and to shed normal eggs through their faeces. Egg shedding to the environment is close to the lower limit obtained for pigs, a domestic animal whose epidemiological importance in endemic areas has already been highlighted. The former, combined with the high prevalence found (14.28%), suggest an even more important role in the transmission cycle than previously considered. The results obtained do not only remark the extraordinary plasticity and adaptability of this trematode species to different host species, but also highlight the role of the European brown hare, and other NIS, as reservoirs capable for parasite spillback to domestic and native cycle, representing a potentially important, but hitherto neglected, cause of disease emergence.

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

    PubMed

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

    2015-01-30

    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

  17. Development of a Health Education Modification Program Regarding Liver Flukes and Cholangiocarcinoma in High Risk Areas of Nakhon Ratchasima Province Using Self-Efficacy and Motivation Theory.

    PubMed

    Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkuwattapong, Parichart; Benjaoran, Fuangfa; Norkaew, Jun; Kujapun, Jirawoot; Ponphimai, Sukanya; Chavenkun, Wasugree; Kompor, Porntip; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    A quasi-experimental study was conducted to develop a health education modification program based on self-efficacy and motivation regarding liver flukes and cholangiocarcinoma development in Keang Sanam Nang district, Nakhon Ratchasima province, Thailand. A total of 36 individuals were invited to participate in the program and were screened for population at risk of liver fluke infection and cholangiocarcinoma using SUT-OV-001 and SUT-CCA-001. Development of health education modification program regarding liver fluke and cholangiocarcinoma prevention included 3 steps: (1) preparation, (2) health education program, and (3) follow-up and evaluation. The study was implemented for 10 weeks. Pre-and-post-test knowledge was measured with questionnaires, Kuder-Richardson-20: KR-20 = 0.718,and Cronbach's Alpha Coefficient = 0.724 and 0.716 for perception and outcome expectation questionnaires. Paired and independent t-tests were applied for data analysis. The majority of the participants were female (55.6%), aged between ≤50 and 60 years old (36.1%), married (86.1%), education level of primary school (63.9%), agricultural occupation (80.6%), and income <4,000 Baht (44.4%). The results revealed that after the health education program, the experimental group had a mean score of knowledge, perception, and outcome expectation regarding liver fluke and cholangiocarcinoma prevention significantly higher than before participation and in the control group. In conclusion, this successful health education modification program for liver fluke and cholangiocarcinoma, therefore may useful for further work behavior modification in other epidemic areas. PMID:27356716

  18. Development of a Health Education Modification Program Regarding Liver Flukes and Cholangiocarcinoma in High Risk Areas of Nakhon Ratchasima Province Using Self-Efficacy and Motivation Theory.

    PubMed

    Kaewpitoon, Soraya J; Rujirakul, Ratana; Wakkuwattapong, Parichart; Benjaoran, Fuangfa; Norkaew, Jun; Kujapun, Jirawoot; Ponphimai, Sukanya; Chavenkun, Wasugree; Kompor, Porntip; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    A quasi-experimental study was conducted to develop a health education modification program based on self-efficacy and motivation regarding liver flukes and cholangiocarcinoma development in Keang Sanam Nang district, Nakhon Ratchasima province, Thailand. A total of 36 individuals were invited to participate in the program and were screened for population at risk of liver fluke infection and cholangiocarcinoma using SUT-OV-001 and SUT-CCA-001. Development of health education modification program regarding liver fluke and cholangiocarcinoma prevention included 3 steps: (1) preparation, (2) health education program, and (3) follow-up and evaluation. The study was implemented for 10 weeks. Pre-and-post-test knowledge was measured with questionnaires, Kuder-Richardson-20: KR-20 = 0.718,and Cronbach's Alpha Coefficient = 0.724 and 0.716 for perception and outcome expectation questionnaires. Paired and independent t-tests were applied for data analysis. The majority of the participants were female (55.6%), aged between ≤50 and 60 years old (36.1%), married (86.1%), education level of primary school (63.9%), agricultural occupation (80.6%), and income <4,000 Baht (44.4%). The results revealed that after the health education program, the experimental group had a mean score of knowledge, perception, and outcome expectation regarding liver fluke and cholangiocarcinoma prevention significantly higher than before participation and in the control group. In conclusion, this successful health education modification program for liver fluke and cholangiocarcinoma, therefore may useful for further work behavior modification in other epidemic areas.

  19. Fasciola hepatica cathepsin L-like proteases: biology, function, and potential in the development of first generation liver fluke vaccines.

    PubMed

    Dalton, John P; Neill, Sandra O; Stack, Colin; Collins, Peter; Walshe, Alan; Sekiya, Mary; Doyle, Sean; Mulcahy, Grace; Hoyle, Deborah; Khaznadji, Eric; Moiré, Nathalie; Brennan, Gerard; Mousley, Angela; Kreshchenko, Natalia; Maule, Aaron G; Donnelly, Sheila M

    2003-09-30

    Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit similarities in their substrate specificities to these enzymes they differ in having a wider pH range for activity and an enhanced stability at neutral pH. There are presently 13 Fasciola cathepsin L cDNAs deposited in the public databases representing a gene family of at least seven distinct members, although the temporal and spatial expression of each of these members in the developmental stage of F. hepatica remains unclear. Immunolocalisation and in situ hybridisation studies, using antibody and DNA probes, respectively, show that the vast majority of cathepsin L gene expression is carried out in the epithelial cells lining the parasite gut. Within these cells the enzyme is packaged into secretory vesicles that release their contents into the gut lumen for the purpose of degrading ingested host tissue and blood. Liver flukes also express a novel multi-domain cystatin that may be involved in the regulation of cathepsin L activity. Vaccine trials in both sheep and cattle with purified native FheCL1 and FheCL2 have shown that these enzymes can induce protection, ranging from 33 to 79%, to experimental challenge with metacercariae of F. hepatica, and very potent anti-embryonation/hatch rate effects that would block parasite transmission. In this article we review the vaccine trials carried out over the past 8 years, the role of antibody and T cell responses in mediating protection and discuss the prospects of the cathepsin Ls in the development of first generation recombinant liver fluke vaccines.

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

    PubMed Central

    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

    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

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

    PubMed

    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

    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

  2. Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach☆

    PubMed Central

    Cwiklinski, Krystyna; Allen, Katherine; LaCourse, James; Williams, Diana J.; Paterson, Steve; Hodgkinson, Jane E.

    2015-01-01

    The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host–parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n = 10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages. PMID:25796359

  3. Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach.

    PubMed

    Cwiklinski, Krystyna; Allen, Katherine; LaCourse, James; Williams, Diana J; Paterson, Steve; Hodgkinson, Jane E

    2015-06-01

    The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host-parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83 Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n=10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages.

  4. Landscape influence on spatial patterns of meningeal worm and liver fluke infection in white-tailed deer.

    PubMed

    Vanderwaal, Kimberly L; Windels, Steve K; Olson, Bryce T; Vannatta, J Trevor; Moen, Ron

    2015-04-01

    Parasites that primarily infect white-tailed deer (Odocoileus virginianus), such as liver flukes (Fascioloides magna) and meningeal worm (Parelaphostrongylus tenuis), can cause morbidity and mortality when incidentally infecting moose (Alces alces). Ecological factors are expected to influence spatial variation in infection risk by affecting the survival of free-living life stages outside the host and the abundance of intermediate gastropod hosts. Here, we investigate how ecology influenced the fine-scale distribution of these parasites in deer in Voyageurs National Park, Minnesota. Deer pellet groups (N = 295) were sampled for the presence of P. tenuis larvae and F. magna eggs. We found that deer were significantly more likely to be infected with P. tenuis in habitats with less upland deciduous forest and more upland mixed conifer forest and shrub, a pattern that mirrored microhabitat differences in gastropod abundances. Deer were also more likely to be infected with F. magna in areas with more marshland, specifically rooted-floating aquatic marshes (RFAMs). The environment played a larger role than deer density in determining spatial patterns of infection for both parasites, highlighting the importance of considering ecological factors on all stages of a parasite's life cycle in order to understand its occurrence within the definitive host.

  5. Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo.

    PubMed

    Keiser, J; Adelfio, R; Vargas, M; Odermatt, P; Tesana, S

    2013-06-01

    Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16 μg/ml and 0.05 μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini. PMID:22892101

  6. Light and electron microscopy observations of embryogenesis and egg development in the human liver fluke, Opisthorchis viverrini (Platyhelminthes, Digenea).

    PubMed

    Khampoosa, Panita; Jones, Malcolm K; Lovas, Erica M; Srisawangwong, Tuanchai; Laha, Thewarach; Piratae, Supawadee; Thammasiri, Chalida; Suwannatrai, Apiporn; Sripanidkulchai, Bungorn; Eursitthichai, Veerachai; Tesana, Smarn

    2012-02-01

    Eggs of most species digenean flukes hatch in the external environment to liberate larvae that seek and penetrate a snail intermediate host. Those of the human liver flukes, Opisthorchis viverrini, hatch within the gastrointestinal canal of their snail hosts. While adult parasites are primarily responsible for the pathology in cases of human opisthorchiasis, their eggs also contribute by inducing granulomata and in serving as nidi for gallstone formation. In view of the peculiar biology of O. viverrini eggs and their contribution to pathology, we investigated embryogenesis in this species by light and transmission electron microscopy. Egg development was traced from earliest stages of coalescence in the ootype until full embryonation in the distal region of the uterus. Fully mature eggs were generally impermeable to resin and could not be examined by conventional electron microscopy methods. However, the use of high-pressure freezing and freeze-substitution fixation of previously fixed eggs enabled the internal structure of mature eggs, particularly the subshell envelopes, to be elucidated. Fertilization occurs in the ootype, and the large zygote is seen therein with a single spermatozoon wrapped around its plasma membrane. As the zygote begins to divide, the spent vitellocytes are pushed to the periphery of the eggs, where they progressively degrade. The early eggshell is formed in the ootype by coalescing eggshell precursor material released by approximately six vitelline cells. The early eggs have a thinner eggshell and are larger than, but lack the characteristic shape of, mature eggs. Characteristic shell ornamentation, the "muskmelon" appearance of eggs, appears after eggshell polymerization in the ootype. Pores are not present in the shell of O. viverrini eggs. The inner and outer envelopes are poorly formed in this species, with the outer envelope evident beneath the eggshell at the opercular pole of the mature egg. The miracidium has a conical anterior end

  7. Pharmacological and morphological characteristics of the muscular system of the giant liver fluke (Fascioloides magna - Bassi 1875).

    PubMed

    Trailović, Saša M; Marinković, Darko; Trailović, Jelena Nedeljković; Milovanović, Mirjana; Marjanović, Djordje S; Aničić, Milan R

    2015-12-01

    Motility is required for feeding, reproduction and maintenance of the fluke in the host's liver. According to that, the neuromuscular system can be an attractive drugable target for chemotherapy. Musculature of the Fascioloides magna is organized into three layers, an outer circular layer, beneath this layer the longitudinal layer, and third, the oblique, or diagonal layer underlies the longitudinal layer. In our study, the administration of atropine or caffeine did not cause classic muscle contractions of F. magna muscle strips. However, the Electrical Field Stimulation (EFS) induced stable and repeatable contractions, which enabled us to examine their sensitivity to the various substances. Acetylcholine (ACh) (300 μM and 1 mM), caused only a slight relaxation, without affecting the amplitude of spontaneous contractions or the amplitude of contractions induced by EFS. Contrary to that, atropine (100 μM) caused a significant increase in the basal tone and an increase of EFS-induced contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes, the described effects of atropine are achieved by the blockade of inhibitory neurotransmission. On the other hand, with respect to the process of excitation-contraction coupling, the plant alkaloid ryanodine (30 μM) significantly reduced the basal tone, as well as EFS-induced contractions of F. magna muscle strips. Ryanodine inhibited the potentiating effect of atropine on the basal tone and contractions caused by EFS, which indicates that the contractile effect of atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500 μM) caused relaxation of fluke muscle strips and at the same time significantly enhanced the EFS-induced contractions. Both effects of caffeine can be explained by entry of extracellular Ca(++) into muscle cells. The muscle contractility of F. magna depends both on the entry of extracellular calcium, and calcium release from intracellular stores, which are

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

    PubMed

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

    2015-03-01

    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 μM) 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.

  9. 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

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

    2014-02-24

    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.

  10. Efficacy of treatment of cattle for liver fluke at housing: influence of differences in flukicidal activity against juvenile Fasciola hepatica.

    PubMed

    Forbes, A B; Reddick, D; Stear, M J

    2015-03-28

    Flukicides are commonly administered at housing to cattle that have grazed fluke-infected pastures or that have been purchased from endemic areas. The choice of product is determined by numerous factors, one of which is the stages of Fasciola hepatica that are killed. Flukicides can be categorised into three main groups: (A) those that kill all juvenile stages and adults; (B) those that kill juveniles from six to eight weeks of age and adults and (C) those that kill adults only. This study was conducted on a commercial beef farm in Scotland and was designed to compare the efficacy of flukicides from each of these three classes in terms of their effects on faecal egg output, coproantigen and liveweight gain. The majority of animals in the untreated control group were positive for coproantigen, fluke eggs or both throughout the study duration of 16 weeks. Egg reappearance interval following housing treatment was eight weeks for clorsulon and 13 weeks for nitroxynil, though patent infections in both groups developed in only a small minority of animals; no fluke eggs were recovered from cattle treated with triclabendazole. Coproantigen was detected four weeks before the reappearance of fluke eggs in the dung. Animals treated with flukicides had significantly fewer faecal samples positive for eggs (P<0.006) and coproantigen (P<0.05) following treatment compared with the controls. Despite differences in the efficacy profiles among the flukicide-treated groups, there were no significant differences (P>0.05) in growth rates among any of the four treatment groups. There was, however, a significant negative association (P<0.001) between fluke positivity at housing and subsequent growth performance, irrespective of treatment group.

  11. 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)

    Samiphak, Sara

    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.

  12. Accuracy of the Kato-Katz method and formalin-ether concentration technique for the diagnosis of Clonorchis sinensis, and implication for assessing drug efficacy

    PubMed Central

    2013-01-01

    Background Clonorchiasis is a chronic neglected disease caused by a liver fluke, Clonorchis sinensis. Chemotherapy is the mainstay of control and treatment efficacy is usually determined by microscopic examination of fecal samples. We assessed the diagnostic accuracy of the Kato-Katz method and the formalin-ether concentration technique (FECT) for C. sinensis diagnosis, and studied the effect of diagnostic approach on drug efficacy evaluation. Methods Overall, 74 individuals aged ≥18 years with a parasitological confirmed C. sinensis infection at baseline were re-examined 3 weeks after treatment. Before and after treatment, two stool samples were obtained from each participant and each sample was subjected to triplicate Kato-Katz thick smears and a single FECT examination. Results Thirty-eight individuals were still positive for C. sinensis according to our diagnostic ‘gold’ standard (six Kato-Katz thick smears plus two FECT). Two FECT had a significantly lower sensitivity than six Kato-Katz thick smears (44.7% versus 92.1%; p <0.001). Examination of single Kato-Katz and single FECT considerably overestimated cure rates. Conclusions In settings where molecular diagnostic assays are absent, multiple Kato-Katz thick smears should be examined for an accurate diagnosis of C. sinensis infection and for assessing drug efficacy against this liver fluke infection. PMID:24499644

  13. ClonorESTdb: a comprehensive database for Clonorchis sinensis EST sequences

    PubMed Central

    2014-01-01

    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

  14. The ultrastructural characterization of the tegument of Clonorchis sinensis (Cobbold, 1875) cercaria.

    PubMed

    Fujino, T; Ishii, Y; Choi, D W

    1979-11-01

    The tegumental ultrastructure of the cercaria of the liver fluke, Clonorchis sinensis (Cobbold, 1875), was studied by scanning and transmission electron microscopy. The body surface is almost encircled by many rows of regularly arranged spines. The tegumental syncytium of the body contains many rod-shaped dense granules and central electron-lucent bodies, neither of which are present in the tail tegument. There are four rows of hooked teeth and modified spines on the oral cone. These teeth are differentiated morphologically and probably functionally from the other body spines. Disc-shaped papillae with long or short cilia are distributed on the body in a bilaterally symmetrical pattern dorsally and ventrally. There are 30 to 37 papillae with much longer cilia laterally. Four pairs of papillae were found on the tail. From their structure and location these papillae appear to have a mainly tango- or rheoreceptive function. Another type of sheathed papillae is situated around the oral sucker. The cuticular tegument is expanded laterally at the base of the tail, forming a characteristic sac-like structure. PMID:394497

  15. Unlocking the Transcriptomes of Two Carcinogenic Parasites, Clonorchis sinensis and Opisthorchis viverrini

    PubMed Central

    Young, Neil D.; Campbell, Bronwyn E.; Hall, Ross S.; Jex, Aaron R.; Cantacessi, Cinzia; Laha, Thewarach; Sohn, Woon-Mok; Sripa, Banchob; Loukas, Alex; Brindley, Paul J.; Gasser, Robin B.

    2010-01-01

    The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma) that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO) as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput) sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies. PMID:20582164

  16. Cloning and Expression of the Major Secreted Cathepsin B-Like Protein from Juvenile Fasciola hepatica and Analysis of Immunogenicity following Liver Fluke Infection

    PubMed Central

    Law, Ruby H. P.; Smooker, Peter M.; Irving, James A.; Piedrafita, David; Ponting, Rebecca; Kennedy, Nicholas J.; Whisstock, James C.; Pike, Robert N.; Spithill, Terry W.

    2003-01-01

    The functions of the cathepsin B-like proteases in liver flukes are unknown and analysis has been hindered by a lack of protein for study, since the protein is produced in small amounts by juvenile flukes. To circumvent this, we isolated and characterized a cDNA encoding the major secreted cathepsin B from Fasciola hepatica. The predicted preproprotein is 339 amino acids in length, with the mature protease predicted to be 254 amino acids long, and shows significant similarity to parasite and mammalian cathepsin B. Only one of the two conserved histidine residues required for cathepsin B exopeptidase activity is predicted to be present. Recombinant preproprotein was produced in yeast, and it was shown that the recombinant proprotein can undergo a degree of self-processing in vitro to the mature form, which is active against gelatin and synthetic peptide substrates. The recombinant protein is antigenic in vaccinated rats, and antibodies to the protein are detected early after infection of rats and sheep with F. hepatica. The kinetics of the response to cathepsin B and cathepsin L after infection of sheep and rats confirm the temporal expression of these proteins during the life cycle of the parasite. PMID:14638781

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

    PubMed Central

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

    2014-01-01

    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 1β 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

  18. A cross-sectional study on the potential transmission of the carcinogenic liver fluke Opisthorchis viverrini and other fishborne zoonotic trematodes by aquaculture fish.

    PubMed

    Pitaksakulrat, Opal; Sithithaworn, Paiboon; Laoprom, Nonglak; Laha, Thewarach; Petney, Trevor N; Andrews, Ross H

    2013-01-01

    Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases.

  19. Gene expression profile of Clonorchis sinensis metacercariae.

    PubMed

    Cho, Pyo Yun; Kim, Tae Im; Whang, Seong Man; Hong, Sung-Jong

    2008-01-01

    Clonorchis sinensis develop through miracidium, sporocyst, redia, cercaria, and metacercaria stages before becoming egg-laying adult flukes. The authors undertook this analysis of gene expression profiles during developmental stages to increase our understanding of the biology of C. sinensis and of host-parasite relationships. From a C. sinensis metacercariae complementary deoxyribonucleic acid library, 419 expressed sequence tags (ESTs) of average length of 668 bp were collected and assembled into 322 genes containing 70 clusters and 252 singletons. The genes were annotated using BLAST searches and categorized into ten major functional categories. Genes expressed abundantly were those of proteases and metabolic, transcription, and translation housekeeping proteins. Genes expressed higher in C. sinensis metacercariae than in adults coded structural and cytoskeletal proteins, transcription and translation machinery proteins, and energy metabolism-related proteins. This EST information supports the notion that C. sinensis metacercariae in fish hosts have a physiology and metabolism that is quite different from that of its adult form in mammals. PMID:17924144

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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)-β 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-β 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-β. 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-β through activation of extracellular signal-regulated kinase 1/2. PMID:24480801

  2. Intestinal and liver flukes of birds of prey (Accipitriformes, Falconiformes, Strigiformes) from Slovakia: uniform or diverse compound?

    PubMed

    Komorová, Petronela; Sitko, Jiljí; Špakulová, Marta; Hurníková, Zuzana

    2016-07-01

    During 2012-2014 up to 286 birds of the orders Falconiformes (5 species), Accipitriformes (11 species), and Strigiformes (7 species) were examined for trematodes and this represents the first detailed study in Slovakia. A total of 12 trematode species belonging to the families Diplostomidae, Cyathocotylidae, Strigeidae, and Opisthorchiidae were identified. Rare infections were found in falcons where only two species (40 %) and three of 85 examined birds (3.5 %) were infected with a low range of two to four worms of generalists Strigea falconis or Plagiorchis elegans. Contrary to that, ten accipitriformes species (90.9 %) and 63 of 156 bird individuals (40.4 %) were infected with nine flukes: Conodiplostomum perlatum, Conodiplostomum spathula, Neodiplostomum attenuatum, Neodiplostomum spathoides, Parastrigea flexilis, Strigea falconis, Strigea vandenbrokae, Paracoenogonimus ovatus, and Metorchis bilis. S. falconis and N. attenuatum were the most frequent, occurring in parallel in eight and four bird species, in numbers up to 575 and 224. The intensity of infection with other fluke species was low ranging from one to 13 worms. Three owl (Strigiformes) representatives (42.9 %) were exclusive hosts for Neodiplostomum canaliculatum and Strigea strigis, and the proportion of positive and dissected individual birds was 10:45 (22.2 %). Both trematodes occurred in two or three owl species. In conclusion, apparent dissimilarity of trematode load of three unrelated lines of falcons, eagles, and owls was revealed. The present study extends our knowledge on the composition of the trematode fauna in Slovakia as all species except S. falconis and P. elegans that represent new host and species records in Slovakia. PMID:27055533

  3. Intestinal and liver flukes of birds of prey (Accipitriformes, Falconiformes, Strigiformes) from Slovakia: uniform or diverse compound?

    PubMed

    Komorová, Petronela; Sitko, Jiljí; Špakulová, Marta; Hurníková, Zuzana

    2016-07-01

    During 2012-2014 up to 286 birds of the orders Falconiformes (5 species), Accipitriformes (11 species), and Strigiformes (7 species) were examined for trematodes and this represents the first detailed study in Slovakia. A total of 12 trematode species belonging to the families Diplostomidae, Cyathocotylidae, Strigeidae, and Opisthorchiidae were identified. Rare infections were found in falcons where only two species (40 %) and three of 85 examined birds (3.5 %) were infected with a low range of two to four worms of generalists Strigea falconis or Plagiorchis elegans. Contrary to that, ten accipitriformes species (90.9 %) and 63 of 156 bird individuals (40.4 %) were infected with nine flukes: Conodiplostomum perlatum, Conodiplostomum spathula, Neodiplostomum attenuatum, Neodiplostomum spathoides, Parastrigea flexilis, Strigea falconis, Strigea vandenbrokae, Paracoenogonimus ovatus, and Metorchis bilis. S. falconis and N. attenuatum were the most frequent, occurring in parallel in eight and four bird species, in numbers up to 575 and 224. The intensity of infection with other fluke species was low ranging from one to 13 worms. Three owl (Strigiformes) representatives (42.9 %) were exclusive hosts for Neodiplostomum canaliculatum and Strigea strigis, and the proportion of positive and dissected individual birds was 10:45 (22.2 %). Both trematodes occurred in two or three owl species. In conclusion, apparent dissimilarity of trematode load of three unrelated lines of falcons, eagles, and owls was revealed. The present study extends our knowledge on the composition of the trematode fauna in Slovakia as all species except S. falconis and P. elegans that represent new host and species records in Slovakia.

  4. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    PubMed

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection. PMID:26391171

  5. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    PubMed

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

  6. Prevalence of Liver Fluke (Fasciola hepatica) in Wild Red Deer (Cervus elaphus): Coproantigen ELISA Is a Practicable Alternative to Faecal Egg Counting for Surveillance in Remote Populations.

    PubMed

    French, Andrew S; Zadoks, Ruth N; Skuce, Philip J; Mitchell, Gillian; Gordon-Gibbs, Danielle K; Craine, Alexandra; Shaw, David; Gibb, Stuart W; Taggart, Mark A

    2016-01-01

    Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson's R = 0.89, p < 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable

  7. Prevalence of Liver Fluke (Fasciola hepatica) in Wild Red Deer (Cervus elaphus): Coproantigen ELISA Is a Practicable Alternative to Faecal Egg Counting for Surveillance in Remote Populations

    PubMed Central

    French, Andrew S.; Zadoks, Ruth N.; Skuce, Philip J.; Mitchell, Gillian; Gordon-Gibbs, Danielle K.; Craine, Alexandra; Shaw, David; Gibb, Stuart W.; Taggart, Mark A.

    2016-01-01

    Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p < 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable

  8. Molecular Differentiation of Opisthorchis viverrini and Clonorchis sinensis Eggs by Multiplex Real-Time PCR with High Resolution Melting Analysis

    PubMed Central

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

    2013-01-01

    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

  9. Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.

    PubMed

    Chaiyadet, Sujittra; Smout, Michael; Johnson, Michael; Whitchurch, Cynthia; Turnbull, Lynne; Kaewkes, Sasithorn; Sotillo, Javier; Loukas, Alex; Sripa, Banchob

    2015-10-01

    Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south

  10. Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.

    PubMed

    Chaiyadet, Sujittra; Smout, Michael; Johnson, Michael; Whitchurch, Cynthia; Turnbull, Lynne; Kaewkes, Sasithorn; Sotillo, Javier; Loukas, Alex; Sripa, Banchob

    2015-10-01

    Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south

  11. Identity of rumen fluke in deer.

    PubMed

    O'Toole, Ailis; Browne, John A; Hogan, Sean; Bassière, Thomas; DeWaal, Theo; Mulcahy, Grace; Zintl, Annetta

    2014-11-01

    As evidence is growing that in many temperate areas paramphistome infections are becoming more common and widespread, this study was undertaken to determine the role of deer as reservoirs for rumen fluke infections in livestock. A total of 144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples from sika, sika/red deer hybrids) were screened for the presence of fluke eggs. Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+), fluke eggs were identified to species level. Our results indicate that, of the 3 deer species, fallow deer had the highest fluke infection rates. Two rumen fluke species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically distinct eggs, were identified. Concurrent infections of the two paramphistome species and liver fluke, Fasciola hepatica, were common. Considering the comparatively low egg burdens observed in this study, it is unlikely that deer represent a significant source of infection for Irish livestock.

  12. Identity of rumen fluke in deer.

    PubMed

    O'Toole, Ailis; Browne, John A; Hogan, Sean; Bassière, Thomas; DeWaal, Theo; Mulcahy, Grace; Zintl, Annetta

    2014-11-01

    As evidence is growing that in many temperate areas paramphistome infections are becoming more common and widespread, this study was undertaken to determine the role of deer as reservoirs for rumen fluke infections in livestock. A total of 144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples from sika, sika/red deer hybrids) were screened for the presence of fluke eggs. Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+), fluke eggs were identified to species level. Our results indicate that, of the 3 deer species, fallow deer had the highest fluke infection rates. Two rumen fluke species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically distinct eggs, were identified. Concurrent infections of the two paramphistome species and liver fluke, Fasciola hepatica, were common. Considering the comparatively low egg burdens observed in this study, it is unlikely that deer represent a significant source of infection for Irish livestock. PMID:25127736

  13. Characterization of nine microsatellite loci for Dicrocoelium dendriticum, an emerging liver fluke of ungulates in North America, and their use to detect clonemates and random mating.

    PubMed

    van Paridon, Bradley J; Goater, Cameron P; Gilleard, John S; Criscione, Charles D

    2016-05-01

    This study characterizes polymorphic microsatellite loci from adults of the liver fluke Dicrocoelium dendriticum sampled from a population of sympatric beef cattle and wapiti in a region of emergence in southern Alberta, Canada. We also scrutinized the markers to validate their use in studying the population genetics of this complex life cycle parasite. Among the nine loci described, four deviated significantly from Hardy Weinberg Equilibrium (HWE) due to technical artefacts. The remaining five loci were in HWE. These five provided sufficient resolution to identify clonemates produced from the obligate asexual reproduction phase of the life cycle in snails and to assess the impact of non-random transmission of clonemates on measures of FIS, FST and genotypic disequilibrium. Excluding clonemates, we show that the sub-population of worms was in HWE, that average FIS within hosts was 0.003 (p=0.4922) and that there was no population genetic structure among hosts FST=0.001 (p=0.3243). These markers will be useful for studies of Dicrocoelium dendriticum ecology, transmission, and evolution. PMID:27188658

  14. 2D-PAGE analysis of the soluble proteins of the tropical liver fluke, Fasciola gigantica and biliary amphistome, Gigantocotyle explanatum, concurrently infecting Bubalus bubalis.

    PubMed

    Khan, Yasir A; Khan, Mohd Abdul Hannan; Abidi, S M A

    2016-09-01

    The digenetic trematodes, Fasciola gigantica and Gigantocotyle explanatum, belonging to the family Fasciolidae and Paramphistomidae respectively, have been often found to concurrently infect the liver of Indian water buffalo Bubalus bubalis, causing serious pathological damage to the vital organ, incurring huge economic losses. In the present study the soluble gene products of both F. gigantica and G. explanatum were analyzed by 2 dimensional polyacrylamide gel electrophoresis. The soluble proteomic profile revealed considerable similarity as well as differences in the size, distribution pattern, total number, the isoelectric point (pI) and molecular weight (Mr) of the resolved polypeptide spots. The maximum number of polypeptide spots with a molecular weight range of >10 to 160 kDa were recorded with a pI range of 7-9 followed by pI range of 5-7, 9-10 and 3-5 in both the parasites. However, considerable variation was recorded in the Mr of the polypeptides belonging to each pI range. The genetic heterogeneity could be an obvious contributing factor for such differences but some polypeptides appeared to be conserved in the two species. The molecular similarities and the habitat preference by these worms may be a consequence of microenvironmental cues that guide these flukes to reach their habitat through different routes and establish a successful host-parasite relationship.

  15. 2D-PAGE analysis of the soluble proteins of the tropical liver fluke, Fasciola gigantica and biliary amphistome, Gigantocotyle explanatum, concurrently infecting Bubalus bubalis.

    PubMed

    Khan, Yasir A; Khan, Mohd Abdul Hannan; Abidi, S M A

    2016-09-01

    The digenetic trematodes, Fasciola gigantica and Gigantocotyle explanatum, belonging to the family Fasciolidae and Paramphistomidae respectively, have been often found to concurrently infect the liver of Indian water buffalo Bubalus bubalis, causing serious pathological damage to the vital organ, incurring huge economic losses. In the present study the soluble gene products of both F. gigantica and G. explanatum were analyzed by 2 dimensional polyacrylamide gel electrophoresis. The soluble proteomic profile revealed considerable similarity as well as differences in the size, distribution pattern, total number, the isoelectric point (pI) and molecular weight (Mr) of the resolved polypeptide spots. The maximum number of polypeptide spots with a molecular weight range of >10 to 160 kDa were recorded with a pI range of 7-9 followed by pI range of 5-7, 9-10 and 3-5 in both the parasites. However, considerable variation was recorded in the Mr of the polypeptides belonging to each pI range. The genetic heterogeneity could be an obvious contributing factor for such differences but some polypeptides appeared to be conserved in the two species. The molecular similarities and the habitat preference by these worms may be a consequence of microenvironmental cues that guide these flukes to reach their habitat through different routes and establish a successful host-parasite relationship. PMID:27605808

  16. Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

    PubMed

    Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

    2015-07-01

    Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis. PMID:25877387

  17. Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

    PubMed

    Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

    2015-07-01

    Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis.

  18. RNA-Seq Reveals Infection-Induced Gene Expression Changes in the Snail Intermediate Host of the Carcinogenic Liver Fluke, Opisthorchis viverrini

    PubMed Central

    Prasopdee, Sattrachai; Sotillo, Javier; Tesana, Smarn; Laha, Thewarach; Kulsantiwong, Jutharat; Nolan, Matthew J.

    2014-01-01

    Background Bithynia siamensis goniomphalos is the snail intermediate host of the liver fluke, Opisthorchis viverrini, the leading cause of cholangiocarcinoma (CCA) in the Greater Mekong sub-region of Thailand. Despite the severe public health impact of Opisthorchis-induced CCA, knowledge of the molecular interactions occurring between the parasite and its snail intermediate host is scant. The examination of differences in gene expression profiling between uninfected and O. viverrini-infected B. siamensis goniomphalos could provide clues on fundamental pathways involved in the regulation of snail-parasite interplay. Methodology/Principal Findings Using high-throughput (Illumina) sequencing and extensive bioinformatic analyses, we characterized the transcriptomes of uninfected and O. viverrini-infected B. siamensis goniomphalos. Comparative analyses of gene expression profiling allowed the identification of 7,655 differentially expressed genes (DEGs), associated to 43 distinct biological pathways, including pathways associated with immune defense mechanisms against parasites. Amongst the DEGs with immune functions, transcripts encoding distinct proteases displayed the highest down-regulation in Bithynia specimens infected by O. viverrini; conversely, transcription of genes encoding heat-shock proteins and actins was significantly up-regulated in parasite-infected snails when compared to the uninfected counterparts. Conclusions/Significance The present study lays the foundation for functional studies of genes and gene products potentially involved in immune-molecular mechanisms implicated in the ability of the parasite to successfully colonize its snail intermediate host. The annotated dataset provided herein represents a ready-to-use molecular resource for the discovery of molecular pathways underlying susceptibility and resistance mechanisms of B. siamensis goniomphalos to O. viverrini and for comparative analyses with pulmonate snail intermediate hosts of other

  19. Fasciola hepatica phenotypic characterization in Andean human endemic areas: valley versus altiplanic patterns analysed in liver flukes from sheep from Cajamarca and Mantaro, Peru.

    PubMed

    Valero, M Adela; Perez-Crespo, Ignácio; Khoubbane, Messaoud; Artigas, Patricio; Panova, Miroslava; Ortiz, Pedro; Maco, Vicente; Espinoza, José R; Mas-Coma, Santiago

    2012-03-01

    Fascioliasis is a zoonotic parasitic disease caused by Fasciola hepatica and Fasciola gigantica. Of both species, F. hepatica is the only one described in the Americas, mainly transmitted by lymnaeid snail vectors of the Galba/Fossaria group. Human fascioliasis endemic areas are mainly located in high altitude areas of Andean countries. Given the necessity to characterize F. hepatica populations involved, the phenotypic features of fasciolid adults infecting sheep present in human fascioliasis endemic areas were analysed in the Cajamarca Valley and Mantaro Valley (valley transmission patterns) and the northern Bolivian Altiplano (altiplanic transmission pattern). A computer image analysis system (CIAS) was applied on the basis of standardized measurements. The aforementioned highland populations were compared to standard lowland natural and experimental populations of European origin. Liver fluke size was studied by multivariate analyses. Two phenotypic patterns could be distinguished in F. hepatica adult size: the valley pattern (Cajamarca and Mantaro, Peru) and the altiplanic pattern (northern Altiplano, Bolivia). Results showed that the Andean valley population and European standard populations presented a phenotypic homogeneity. The Altiplano population showed a large size range with a pronouncedly lower minimum size indicating that uterus gravidity is reached at a smaller size than in valley populations. The results of this study demonstrate that there is no apparent relationship between the shape of fasciolid adults with regard to altitudinal difference or geographical origin and that allometry-free shape appears as a more stable trait than size in fasciolid species. Results are analysed in terms of intensity/crowding effect aspects and permanent/seasonal transmission characteristics.

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

    PubMed

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

    2011-06-10

    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.

  1. Immunosuppressive prednisolone enhances early cholangiocarcinoma in Syrian hamsters with liver fluke infection and administration of N-nitrosodimethylamine.

    PubMed

    Juasook, Amornrat; Boonmars, Thidarut; Wu, Zhiliang; Loilome, Watcharin; Veteewuthacharn, Kulathida; Namwat, Nissana; Sudsarn, Pakkayanee; Wonkchalee, Orasa; Sriraj, Pranee; Aukkanimart, Ratchadawan

    2013-01-01

    Chronic infection with Opisthorchis viverrini for many years has been associated with the development of hepatobiliary diseases including cholangiocarcinoma. It is well known that inflammation is a key component of the tumor microenvironment, and that chronic inflammation plays an important role in tumorigenesis. Therefore, in this study cholangiocarcinogenesis was induced in Syrian hamsters in order to observe the cancer-related inflammation. The Syrian hamsters were divided into 5 groups: uninfected controls; normal Syrian hamsters infected with O. viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were later observed for gross pathology and histopathological changes; COX2 was analyzed by immunohistochemical staining. We found a decreased number of inflammatory cells surrounding the hepatic bile duct in the OVis group, but not in the OV and CCAis groups. However, in the CCAis group (with suppressed immunity) early appearance and greater severity of cholangiocarcinoma were observed; gross pathological examination revealed many cancer nodularities on the liver surface, and histopathological studies showed the presence of cancer cells, findings which correlated with the predominant expression of COX2. The present study suggests that host immune responses are intended to ameliorate pathology, and they are also crucially associated with pathogenesis in O. viverrini infection; the unbalancing of host immunity may enhance cancer-related inflammation.

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

    PubMed

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

    2014-08-01

    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 < 0.05). Specifically, 50 μg/ml of CsESPs showed the strongest effect on cell proliferation in methyl thiazolyl tetrazolium (MTT) assay which could also be demonstrated by flow cytometry analysis (p < 0.01). Furthermore, expression level of human type III collagen in LX-2 cells treated with CsESPs was significantly higher than that in control cells measured by molecular beacon and semiquantitative reverse transcription (RT)-PCR approaches (p < 0.01). Finally, CsESPs before and after incubation with LX-2 cells were subjected to two-dimensional gel electrophoresis (2-DE) analysis and matrix associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. Nine proteins with abundance change above threefold were Rho GTPase-activating protein, mitochondrial cytochrome c oxidase subunit Va, α-enolase, phospholipase C, interleukin-15, insect-derived growth factor, cytochrome c oxidase subunit VI, DNAH1 protein, and kinesin light chain. Taken together, we identified potential CsESP candidates capable of binding and activating human hepatic stellate cells, providing more direct evidences that are previously unknown to accelerate strategies

  3. Biochemical Characterization and Differential Expression of a 16.5-Kilodalton Tegument-Associated Antigen from the Liver Fluke Fasciola hepatica

    PubMed Central

    Gaudier, José F.; Cabán-Hernández, Kimberly; Osuna, Antonio

    2012-01-01

    A cDNA encoding a 16.5-kDa protein termed FhTP16.5 was identified by immunoscreening of a cDNA library from Fasciola hepatica adult flukes using pooled sera from rabbits infected with F. hepatica for 4 weeks. Quantitative reverse transcriptase PCR (qPCR) analysis revealed that FhTP16.5 is not expressed in unembryonated eggs. It is poorly expressed in miracidia and highly expressed at the juvenile and adult stages; however, significant differences were found between the expression levels of FhTP16.5 in juveniles versus adult flukes. Recombinant FhTP16.5 was expressed at high levels in Escherichia coli, purified by affinity chromatography, and used to raise anti-FhTP16.5 polyclonal antibodies in rabbits. Immunoblot analysis using the anti-FhTP16.5 IgG antibody identified FhTP16.5 in crude and tegumental extracts and in excretory-secretory products of F. hepatica. The protein was not detected in crude extracts of Schistosoma mansoni or Schistosoma japonicum. Antibodies to FhTP16.5 were detected in the sera of rabbits at 3 to 12 weeks of F. hepatica infection as well as in the sera of humans with chronic fascioliasis; these findings suggest that FhTP16.5 could be a good antigen for serodiagnosis of fascioliasis. Immunohistochemistry demonstrated that FhTP16.5 localizes to the surface of the tegument of various developmental stages and in parenchymal tissues of the adult fluke. Such specific localization makes FhTP16.5 an attractive target for immunoprophylaxis or chemotherapy. PMID:22278327

  4. Production and deformation of Clonorchis sinensis eggs during in vitro maintenance.

    PubMed

    Uddin, Md Hafiz; Bae, Young Mee; Choi, Min-Ho; Hong, Sung-Tae

    2012-01-01

    Clonorchis sinensis is a carcinogenic human liver fluke. The present study monitored eggs produced by long-term maintained adult worms of C. sinensis to confirm their egg productivity in vitro. The worms from infected rabbits were incubated in vitro in 1× Locke's solution and broth media (RPMI-1640, DMEM and IMDM). Numbers of expelled eggs were counted sequentially and their morphological changes were monitored by microscopy after 1, 30, 60, and 90 days of cultivation. On the 1-3 days of cultivation, the eggs counted maximum 4,756±202 eggs/worm/day in IMDM medium. The number of eggs gradually decreased less than 1,000 at 7-14 days and below 100 at 21days but continued to pass eggs after 56 days in all media. Length of the eggs were reduced about 1 µm at 30 days, and the length/width ratio was maintained around 1.8 at 30 days but decreased to 1.7 at 60 days and 1.5 at 90 days. Faust-Meleney index (FMI) decreased as the cultivation duration increased and lowest FMI (5662.9±974.7) observed in IMDM media at day 90 (P = 0.001). Microscopic findings of the eggs recognized the miracidium in most of eggs at 60 days but not in those at 90 days. Instead, the eggs contained dark granules or vacuoles in the deformed shell at 90 days. Scanning electron microscopy revealed partial loss of wrinkles on the deformed egg surface and prominent abopercular knob. Eggs viability decreased as the cultivation progressed and showed significant positive correlation with FMI and length/width ratio. In conclusion, the cultivated worms pass only the eggs which are preformed in their uterus before cultivation. One gravid C. sinensis contains about 37,000 eggs in its uterus and produces about 4,000 eggs every day. The deformed eggs with FMI less than 7,000 and length/width ratio lower than 1.7 are non-viable. PMID:23285144

  5. Microscopic identification of possible Clonorchis/Opisthorchis infection in two Ghanaian women with undiagnosed abdominal discomfort: two case reports

    PubMed Central

    2014-01-01

    Introduction The impact of foodborne trematode infections is gaining recognition worldwide. Clonorchiasis and opisthorchiasis are some of the most neglected tropical foodborne diseases that pose a significant threat to human health. Persistent or chronic infection of Clonorchis/Opisthorchis often leads to hepatobiliary diseases including cholangitis, cholelithiasis, cholecystitis, pancreatitis, hepatic fibrosis, cholangiocarcinoma and liver cancer. Two cases of Clonorchis/Opisthorchis infection in humans in the Central Region of Ghana are reported. Case presentation Eggs suspected to be from Clonorchis sinensis or Opisthorchis species were detected in the stools of a 29-year-old Ghanaian woman and an 18-year-old Ghanaian woman in two clinics in the Central Region of Ghana. The diagnosis was based on clinical symptoms as well as detection of the eggs of the trematode in the faeces of the patients using light microscopy after staining with Giemsa or Ziehl–Neelsen stains. Conclusions To the best of our knowledge these are the first documented cases of Clonorchis sinensis or Opisthorchis species infection in Ghana. The detection of this infection in these patients in Ghana should be of concern to clinicians because the infection can be easily misdiagnosed since the accompanying clinical symptoms are malaria-like. Consideration should therefore be given to Clonorchis sinensis and Opisthorchis species when diagnosing patients presenting with malaria-like symptoms. PMID:25399721

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

    PubMed

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

    2016-01-01

    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

  7. Antigenic profile and localization of Clonorchis sinensis proteins in the course of infection

    PubMed Central

    Kim, Tae Yun; Song, Kye-Yong; Sohn, Woon-Mok; Kang, Shin-Yong

    2001-01-01

    In the course of Clonorchis sinensis infection, antigens presented to the hosts may be in a close relation to growth of the fluke. The antigenic proteins stimulating IgG antibody production were chronologically identified by immunoblot and localized by immunohistochemical staining. In the early stage of infection until 12 weeks post-infection (PI), antigens were proteins with molecular mass larger than 34 kDa which were derived from the tegument, testes and intrauterine eggs. After 20 weeks PI, antigens recognized were 29, 27 and 26 kDa proteins from the intestine, excretory bladder and reproductive organs. It is suggested that the tegumental proteins are the most potent antigens and the excretory-secretory proteins with middle molecular mass of 26-45 kDa contribute to the high level production of antibodies after 20 weeks of the C. sinensis infection. PMID:11775331

  8. Liver fluke control on sheep farms in Northern Ireland: A survey of changing management practices in relation to disease prevalence and perceived triclabendazole resistance.

    PubMed

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

    2016-01-30

    Reports of resistance to triclabendazole (TCBZ) among fluke populations have increased in recent years. Allied to this, there has been a rise in the prevalence of the disease, which has been linked to climate change. Results from questionnaire surveys conducted in Northern Ireland (NI) in 2005 (covering the years 1999-2004) and 2011 (covering the years 2008-2011) have provided an opportunity to examine the extent to which fluke control practices have changed over a prolonged time-frame, in light of these changes. A number of differences were highlighted. There was a significant shift away from the use of TCBZ over time, with it being replaced largely by closantel. The timing of treatments had moved earlier in the year, perhaps in response to climate change (and an altered pattern of disease). In relation to the frequency of drug treatments, there were no major changes in the overall pattern of drug treatments between the two survey points, although on both occasions approximately one-third of flock owners gave more than 3 treatments per year to ewes. In lowland areas in 2011, flock owners were rotating drug classes more often (each year and at each treatment) than in 2005, whereas in upland areas, flock owners were rotating less often and more were not rotating at all. Between 2005 and 2011, the percentage of flock owners giving quarantine treatments to bought-in stock had halved, to a very low level (approximately 10%). Using data from a complementary TCBZ resistance survey (Hanna et al., 2015), it has been shown that the way in which data are selected and which efficacy formula is applied can influence the calculation of drug efficiency and impact on diagnosis of resistance.

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

    SciTech Connect

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-04-22

    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

  10. Effect of artemether, artesunate, OZ78, praziquantel, and tribendimidine alone or in combination chemotherapy on the tegument of Clonorchis sinensis.

    PubMed

    Keiser, Jennifer; Vargas, Mireille

    2010-09-01

    We investigated the morphological effects of half-strength treatments with praziquantel, artemether, artesunate, OZ78 and tribendimidine as well as combinations of praziquantel with artemether, artesunate, OZ78 and tribendimidine and an artesunate-tribendimidine combination in rats harboring adult Clonorchis sinensis. Rats were infected with C. sinensis, dosed orally with single agents or combination treatments and flukes recovered at 3 or 5 days post-treatment. The number of flukes was counted, the viability recorded and surface changes monitored by scanning electron microscopy. Drug effects induced by the individual drugs at sub-curative doses 3 days post-treatment were minor with the exception of flukes recovered from rats treated with artemether and tribendimidine. Treatment with the praziquantel combinations of artesunate, OZ78 and tribendimidine did not produce a greater disruption of the tegument than the individual drugs 3 days post-treatment. On the other hand, at this time point many worms treated with artemether-praziquantel had died and eruptions, roughening or blebbing were observed on all worms examined. Five days post-treatment flukes exposed to any of the praziquantel combinations in rats had died. Rats treated with an artesunate-tribendimidine combination resulted in a rapid death of flukes, 3 days post-treatment all worms had been expelled. In conclusion, we have confirmed the promising clonorchicidal properties of different drug combinations in rats. Differences in the extent and time-scale of tegumental disruption have been observed. The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model. PMID:20416396

  11. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice

    PubMed Central

    Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

  12. The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice.

    PubMed

    Yan, Chao; Zhang, Bei-Bei; Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-01-01

    Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

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

    PubMed Central

    2010-01-01

    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 μg.h/ml) was similar to that obtained after TCBZ co-administered with IVM and MTZ (650.7 ± 122.8 μg.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

  14. PRKAR1A overexpression is associated with increased ECPKA autoantibody in liver fluke-associated cholangiocarcinoma: application for assessment of the risk group.

    PubMed

    Loilome, Watcharin; Yooyuen, Sasithorn; Namwat, Nisana; Sithithaworn, Paiboon; Puapairoj, Anucha; Kano, Junko; Noguchi, Masayuki; Miwa, Masanao; Yongvanit, Puangrat

    2012-12-01

    Cholangiocarcinoma (CCA) associated with Opisthorchis viverrini (Ov) chronic infection is the most frequent primary liver cancer in Thailand, and current approaches to early diagnosis and curative treatments are largely disappointing. We hypothesize a role for protein kinase A (PKA) in Ov-induced CCA. First, we studied the PKA isozyme switching in the liver from the hamster CCA model using quantitative (q) PCR, in situ hybridization, and immunohistochemical and western blot analysis. Second, the presence of extracellular PKA (ECPKA) in CCA cell lines and their conditioned media was demonstrated by western blot and PKA activity assay. Third, we determined the association between PRKAR1A expression and serum ECPKA autoantibody in patients with CCA by ELISA. We demonstrated that an increased PRKAR1A expression is restricted to the biliary cells starting from week 1, with remarkable up-regulation when CCA has completely developed by week 24. The switching of the PKA regulatory subunit isoforms from PRKAR2B/PKAII to PRKAR1A/PKAI is significantly associated with cholangiocyte proliferation. Further, we observed that human CCA cell lines express PRKAR1A but not PRKAR2B and excrete ECPKA. Finally, ECPKA autoantibodies are detected in serum of patients with CCA, adenocarcinoma, and Ov infection with periductal fibrosis, but not from Ov-infected subjects without periductal fibrosis lesion and healthy controls. We conclude that PKA isozyme switching and the PRKAR1A/PKAI pathway might contribute to the induction of cholangiocyte transformation and proliferation in Ov-induced CCA. Overexpression of PRKAR1A leads to secretion of ECPKA which is associated with serum autoantibody that may constitute a biomarker for human CCA genesis. PMID:22922884

  15. [The development of Clonorchis sinensis in mice].

    PubMed

    Liu, Ji-xin; Sun, Yan-hong; Guo, Jia; Yao, Shu-juan; Sun, Yan; Zhang, Hao; Zhang, Chun-jing

    2014-10-01

    Freshwater fish were caught from Nenjiang River in Qiqihaer City, and examined for metacercariae of Clonorchis sinensis by the artificial digestion (pepsin-HCl) method. The metacercariae (35-40) were given orally into stomach to each Kunming mouse of infection group (50 mice). The mice in control group were given the same amount of normal saline. The mice were sacrificed on the 5th, 10th, 15th, 20th, 25th, and 30th day after infection. Worms were collected, fixed and stained with carmine acetate, and observed under microscope. The egg-laying capacity of C. sinensis was observed in mice. 96%(48/50) mice were infected with metacercariae of C. sinensis. The recovery rate of adult worms on the 5th, 10th, 15th, 20th, 25th, and 30th day post-infection was 42.1%, 52.6%, 63.2%, 62.2%, 63.3%, and 63.2%, respectively. The first appearance of eggs in utero and feces was on the 15th and 20th day after infection, respectively. The branch of testis in worms was observed after 20 days of infection. PMID:25726612

  16. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients

    PubMed Central

    Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-01-01

    Background Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Principal Findings Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Conclusions/Significance Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine. PMID:27348302

  17. Foodborne Intestinal Flukes in Southeast Asia

    PubMed Central

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

    2009-01-01

    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

  18. Microscopic Examination of Gallbladder Stones Improves Rate of Detection of Clonorchis sinensis Infection

    PubMed Central

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

    2013-01-01

    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

  19. [Dolphin's flukes: A mathematical model of rigid wing].

    PubMed

    Romanenko, E V; Pushkov, S G; Lopatin, V N

    2015-01-01

    New analytical method is used to estimate hydrodynamic forces produced by dolphin's flukes. A mathematical model is proposed that describes dolphin's flukes as a flat rigid rectangular wing whose pitch axis location varies, heaving and pitching amplitudes are sufficiently large, and the phase angle shift for the combined oscillations can change arbitrarily. The dolphin's flukes kinematic parameters are obtained and used to estimate hydrodynamic forces.

  20. [Dolphin's flukes: A mathematical model of rigid wing].

    PubMed

    Romanenko, E V; Pushkov, S G; Lopatin, V N

    2015-01-01

    New analytical method is used to estimate hydrodynamic forces produced by dolphin's flukes. A mathematical model is proposed that describes dolphin's flukes as a flat rigid rectangular wing whose pitch axis location varies, heaving and pitching amplitudes are sufficiently large, and the phase angle shift for the combined oscillations can change arbitrarily. The dolphin's flukes kinematic parameters are obtained and used to estimate hydrodynamic forces. PMID:26852573

  1. [Progress on the Relationship between Clonorchis sinensis Infection and Cholangiocarcinoma].

    PubMed

    2015-04-01

    Currently, 12.49 million people are infected with Clonorchis sinensis in China. The incidence of bile duct carcinoma increased for recent years. More than a century ago, some scholars have put forward the idea about the relations between C. sinensis infection and cholangiocarcinoma, and committed to research the mechanism. However, the intrinsic mechanisms involved in these processes remain obscure. It is therefore important to pay more attention to the further investigation of the relevance between C. sinensis infection and bile duct carcinoma. This review summarizes the possible mechanism of cholangiocarcinoma caused by C. sinensis, which is displayed on mechanical damage, stimulation of the worms and their excretory-secretory products (ESP), abnormity of immunoreaction and molecular genetic lesions. PMID:26245128

  2. Identification and Molecular Characterization of Parkin in Clonorchis sinensis

    PubMed Central

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

    2015-01-01

    Clonorchis sinensis habitating in the bile duct of mammals causes clonorchiasis endemic in East Asian countries. Parkin is a RING-between-RING protein and has E3-ubiquitin ligase activity catalyzing ubiquitination and degradation of substrate proteins. A cDNA clone of C. sinensis was predicted to encode a polypeptide homologous to parkin (CsParkin) including 5 domains (Ubl, RING0, RING1, IBR, and RING2). The cysteine and histidine residues binding to Zn2+ were all conserved and participated in formation of tertiary structural RINGs. Conserved residues were also an E2-binding site in RING1 domain and a catalytic cysteine residue in the RING2 domain. Native CsParkin was determined to have an estimated molecular weight of 45.7 kDa from C. sinensis adults by immunoblotting. CsParkin revealed E3-ubiquitin ligase activity and higher expression in metacercariae than in adults. CsParkin was localized in the locomotive and male reproductive organs of C. sinensis adults, and extensively in metacercariae. Parkin has been found to participate in regulating mitochondrial function and energy metabolism in mammalian cells. From these results, it is suggested that CsParkin play roles in energy metabolism of the locomotive organs, and possibly in protein metabolism of the reproductive organs of C. sinensis. PMID:25748711

  3. Identification and molecular characterization of Parkin in Clonorchis sinensis.

    PubMed

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

    2015-02-01

    Clonorchis sinensis habitating in the bile duct of mammals causes clonorchiasis endemic in East Asian countries. Parkin is a RING-between-RING protein and has E3-ubiquitin ligase activity catalyzing ubiquitination and degradation of substrate proteins. A cDNA clone of C. sinensis was predicted to encode a polypeptide homologous to parkin (CsParkin) including 5 domains (Ubl, RING0, RING1, IBR, and RING2). The cysteine and histidine residues binding to Zn(2+) were all conserved and participated in formation of tertiary structural RINGs. Conserved residues were also an E2-binding site in RING1 domain and a catalytic cysteine residue in the RING2 domain. Native CsParkin was determined to have an estimated molecular weight of 45.7 kDa from C. sinensis adults by immunoblotting. CsParkin revealed E3-ubiquitin ligase activity and higher expression in metacercariae than in adults. CsParkin was localized in the locomotive and male reproductive organs of C. sinensis adults, and extensively in metacercariae. Parkin has been found to participate in regulating mitochondrial function and energy metabolism in mammalian cells. From these results, it is suggested that CsParkin play roles in energy metabolism of the locomotive organs, and possibly in protein metabolism of the reproductive organs of C. sinensis. PMID:25748711

  4. Molecular Cloning and Characterization of a Paramyosin from Clonorchis sinensis

    PubMed Central

    Park, Tae-Joon; Kang, Jung-Mi; Na, Byoung-Kuk

    2009-01-01

    Paramyosin is a myofibrillar protein present in helminth parasites and plays multifunctional roles in host-parasite interactions. In this study, we identified the gene encoding paramyosin of Clonorchis sinensis (CsPmy) and characterized biochemical and immunological properties of its recombinant protein. CsPmy showed a high level of sequence identity with paramyosin from other helminth parasites. Recombinant CsPmy (rCsPmy) expressed in bacteria had an approximate molecular weight of 100 kDa and bound both human collagen and complement 9. The protein was constitutively expressed in various developmental stages of the parasite. Imunofluorescence analysis revealed that CsPmy was mainly localized in the tegument, subtegumental muscles, and the muscle layer surrounding the intestine of the parasite. The rCsPmy showed high levels of positive reactions (74.6%, 56/75) against sera from patients with clonorchiasis. Immunization of experimental rats with rCsPmy evoked high levels of IgG production. These results collectively suggest that CsPmy is a multifunctional protein that not only contributes to the muscle layer structure but also to non-muscular functions in host-parasite interactions. Successful induction of host IgG production also suggests that CsPmy can be applied as a diagnostic antigen and/or vaccine candidate for clonorchiasis. PMID:19967083

  5. Painless Jaundice Caused by Clonorchis sinensis Infection: A Case Report

    PubMed Central

    Hao, Yuhua; Bao, Wanguo; Jin, Meishan; Li, Yuxiang; Wang, Feng

    2016-01-01

    A man with only yellowing of the skin and eye sclera was diagnosed with clonorchiasis, which rarely manifested jaundice as the initial symptom. However, because of a lack of evidence for a diagnostic gold standard, the time until definitive diagnosis was more than a week. The diagnostic process relied on inquiring about the patient’s history, including the place of residence, dietary habits, and symptoms, as well as on serological findings, an imaging examination, and pathological findings. MRCP and CT results showed mild dilatation of intrahepatic ducts and increased periductal echogenicity. The eggs were ultimately found in stool by water sedimentation method after the negative report through direct smear. DNA sequencing of PCR production of the eggs demonstrated 98-100% homology with ITS2 of Clonorchis sinensis. After anti-parasite medical treatment, the patient’s symptoms were gradually relieved. Throughout the diagnostic procedure, besides routine examinations, the sedimentation method or concentration method could be used as a sensitive way for both light and heavy C. sinensis infection in the definite diagnosis. PMID:27417088

  6. Improving animal and human health through understanding liver fluke immunology.

    PubMed

    Piedrafita, D; Spithill, T W; Smith, R E; Raadsma, H W

    2010-08-01

    Sheep, goats and cattle represent the most numerous and economically important agricultural species worldwide used as sources for milk, fibre and red meat. In addition, in the developing world, these species often represent the sole asset base for small-holder livestock farmers and cattle/buffaloes often provide the majority of draught power for crop production. Production losses caused by helminth diseases of these animals are a major factor in extending the cycle of poverty in developing countries and a major food security issue for developed economies. Fasciola spp. are one of the most important zoonotic diseases with a global economic impact in livestock production systems and a poorly defined but direct effect on human health. Improvements in human and animal health will require a concerted research effort into the development of new accurate and simple diagnostic tests and increased vaccine and drug development against Fasciola infections. Here, the use of definitive natural host breeds with contrasting resistance to Fasciola infections is discussed as a resource to contrast parasite-host interactions and identify parasite immune evasion strategies. Such studies are likely to boost the discovery of new vaccine, drug and diagnostic candidates and provide the foundation for future genetic selection of resistant animals. PMID:20626812

  7. Exome sequencing of liver fluke-associated cholangiocarcinoma.

    PubMed

    Ong, Choon Kiat; Subimerb, Chutima; Pairojkul, Chawalit; Wongkham, Sopit; Cutcutache, Ioana; Yu, Willie; McPherson, John R; Allen, George E; Ng, Cedric Chuan Young; Wong, Bernice Huimin; Myint, Swe Swe; Rajasegaran, Vikneswari; Heng, Hong Lee; Gan, Anna; Zang, Zhi Jiang; Wu, Yingting; Wu, Jeanie; Lee, Ming Hui; Huang, DaChuan; Ong, Pauline; Chan-on, Waraporn; Cao, Yun; Qian, Chao-Nan; Lim, Kiat Hon; Ooi, Aikseng; Dykema, Karl; Furge, Kyle; Kukongviriyapan, Veerapol; Sripa, Banchob; Wongkham, Chaisiri; Yongvanit, Puangrat; Futreal, P Andrew; Bhudhisawasdi, Vajarabhongsa; Rozen, Steve; Tan, Patrick; Teh, Bin Tean

    2012-06-01

    Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.

  8. Molecular identification, immunolocalization, and characterization of Clonorchis sinensis triosephosphate isomerase.

    PubMed

    Zhou, Juanjuan; Liao, Hua; Li, Shan; Zhou, Chenhui; Huang, Yan; Li, Xuerong; Liang, Chi; Yu, Xinbing

    2015-08-01

    Clonorchis sinensis triosephosphate isomerase (CsTIM) is a key regulatory enzyme of glycolysis and gluconeogenesis, which catalyzes the interconversion of glyceraldehyde 3-phosphate to dihydroxyacetone phosphate. In this study, the biochemical characterizations of CsTIM have been examined. A full-length complementary DNA (cDNA; Cs105350) sequence encoding CsTIM was obtained from our C. sinensis cDNA library. The open reading frame of CsTIM contains 759 bp which encodes 252 amino acids. The amino acid sequence of CsTIM shares 60-65% identity with other species. Western blot analysis displayed that recombinant CsTIM (rCsTIM) can be probed by anti-rCsTIM rat serum and anti-C. sinensis excretory/secretory products (anti-CsESPs) rat serum. Quantitative reverse transcription (RT)-PCR and western blotting analysis revealed that CsTIM messenger RNA (mRNA) and protein were differentially expressed in development cycle stages of the parasite, including adult worm, metacercaria, excysted metacercaria, and egg. In addition, immunolocalization assay showed that CsTIM was located in the seminal vesicle, eggs, and testicle. Moreover, rCsTIM exhibited active enzyme activity in catalytic reactions. The Michaelis constant (K m) of rCsTIM was 0.33 mM, when using glyceraldehyde 3-phosphate as the substrate. The optimal temperature and pH of CsTIM were 37 °C and 7.5-9.5, respectively. Collectively, these results suggest that CsTIM is an important protein involved in glycometabolism, and CsTIM possibly take part in many biological functions in the growth and development of C. sinensis. PMID:25990061

  9. Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

    PubMed Central

    Qian, Men-Bao; Yap, Peiling; Yang, Yi-Chao; Liang, Hai; Jiang, Zhi-Hua; Li, Wei; Tan, Yu-Guang; Zhou, Hui; Utzinger, Jürg; Zhou, Xiao-Nong; Keiser, Jennifer

    2013-01-01

    Background. Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative. Methods. We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose. Results. A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%–98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05). Conclusions. Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis–infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration. Controlled-Trials.com, ISRCTN80829842. PMID:23223597

  10. Molecular phylogenetic analysis of Fasciola flukes from eastern India.

    PubMed

    Hayashi, Kei; Ichikawa-Seki, Madoka; Mohanta, Uday Kumar; Singh, T Shantikumar; Shoriki, Takuya; Sugiyama, Hiromu; Itagaki, Tadashi

    2015-10-01

    Fasciola flukes from eastern India were characterized on the basis of spermatogenesis status and nuclear ITS1. Both Fasciola gigantica and aspermic Fasciola flukes were detected in Imphal, Kohima, and Gantoku districts. The sequences of mitochondrial nad1 were analyzed to infer their phylogenetical relationship with neighboring countries. The haplotypes of aspermic Fasciola flukes were identical or showed a single nucleotide substitution compared to those from populations in the neighboring countries, corroborating the previous reports that categorized them in the same lineage. However, the prevalence of aspermic Fasciola flukes in eastern India was lower than those in the neighboring countries, suggesting that they have not dispersed throughout eastern India. In contrast, F. gigantica was predominant and well diversified, and the species was thought to be distributed in the area for a longer time than the aspermic Fasciola flukes. Fasciola gigantica populations from eastern India were categorized into two distinct haplogroups A and B. The level of their genetic diversity suggests that populations belonging to haplogroup A have dispersed from the west side of the Indian subcontinent to eastern India with the artificial movement of domestic cattle, Bos indicus, whereas populations belonging to haplogroup B might have spread from Myanmar to eastern India with domestic buffaloes, Bubalus bubalis.

  11. [Epidemiological Studies On Clonorchis Sinensis Infection Along The Nam-River In Gyeongnam Province, Korea

    PubMed

    Bae, Kyoung Hoon; Ahn, Yung Kyum; Soh, Chin Thack; Tsutsumi, Hiroshi

    1983-12-01

    An epidemiological study on Clonorchis sinensis infection along the Nam-river (total length; 186km) flowing in Gyeongsang-nam-do, southern part of Korea, was carried out. Formalin-ether concentration technique and Stoll's egg counting method were employed to figure out the prevalence of C. sinensis infection. For the detection of cercariae from Parafossarulus sp., the snail host of C. sinensis, each snail was placed in aerated tap water, and examined for expelled cercariae. For observing the metacercariae the fresh water fish favorably eaten in raw conditions were prepared by means of pressing the muscles between tow slide glasses and/or by digesting them with artificial gastric juice. The fresh water fish were fed to the rabbits to get the worms and to identify the morphology of adult C. sinensis. The results are summarized as follows: 1. Overall prevalence of C. sinensis infection was 38.7% form 5,291 examinees; 44.1% (1,408 out of 3,196) in male and 30.4% (637 out of 2,095) in female. 2. The prevalence rates were 42.0% at the upper stream, 41.2% around the vicinity of Jinyang-lake, 34.2% at Jinju city, 34.2% at middle stream and 40.3% at down stream regions, respectively. 3. By age, the highest positive rate (53.4~54.3%) was observed in 30 to 59 years of age. In this age group, the rate in males was 59.7~62.2%, and in females 42.2~44.4%. In the age group of less than 19years it was 7.5~20.9%. 4. By social strata, the positive rate was 16.5% in the primary school children, 22.6% in school students, 46.2% in teachers and local officers and 49.6% in the general inhabitants. 5. The quantitative examinations with the stool collected from clonorchiasis cases revealed that the light infection (less than 4,000/EPG) was 53.6%, moderate infection (4,001~10,000/EPG) 30.3% and heavy infection (more than 10,001/EPG) 16.1, respectively. More than half of total cases examined were light infection, and 73.2% of female examinees were lightly infected with this fluke. 6. The

  12. Prevalence of Opisthorchis viverrini-Like Fluke Infection in Ducks in Binh Dinh Province, Central Vietnam.

    PubMed

    Dao, Thanh Thi Ha; Abatih, Emmanuel Nji; Nguyen, Thanh Thi Giang; Tran, Ha Thi Lam; Gabriël, Sarah; Smit, Suzanne; Le, Phap Ngoc; Dorny, Pierre

    2016-06-01

    Following the first report of Opisthorchis viverrini infection in a domestic duck in Phu My District of Binh Dinh Province, Central Vietnam, many other cases were observed in the province. We determined the infection rate and intensity of O. viverrini infection in ducks in 4 districts of the province. A total of 178 ducks were randomly selected from 34 farms for examination of flukes in the liver and gall bladder. An infection rate of 34.3% (range 20.7-40.4% among districts) was found; the intensity of infection was 13.8 worms per infected duck (range 1-100). These findings show the role of ducks as a host for O. viverrini, duck genotype, which is sympatric with the human O. viverrini genotype in this province. It also stresses the need for investigations on the zoonotic potential and the life cycle of this parasite. PMID:27417094

  13. Identification of thyroid hormone receptor homologs in the fluke Opisthorchis felineus (Platyhelminthes).

    PubMed

    Pakharukova, Maria Y; Ershov, Nikita I; Vorontsova, Elena V; Shilov, Alexander G; Merkulova, Tatyana I; Mordvinov, Viatcheslav A

    2014-01-01

    The liver fluke, Opisthorchis felineus of the Opisthorchiidae family, is a well-known causative agent of opisthorchiasis in Russia and Europe. The aim of this work was to identify genes encoding thyroid hormone receptors in O. felineus, and to analyze the expression of possible target genes in response to treatment with exogenous thyroid hormones. We identified two genes encoding thyroid hormone receptors in the O. felineus genome, THRA and THRB. The genes were differentially expressed through the life cycle. The maximal level of mRNA expression of THRA1 and THRB was observed in adult worms. Treatment of the worms with triiodothyronine and thyroxine resulted in an increase in glucose 6-phosphatase mRNA expression and a decrease in malate dehydrogenase mRNA expression, potential gene targets of thyroid hormones. These data indicate that thyroid hormone receptors may perform essential roles in physiological processes in adult O. felineus.

  14. Prevalence of Opisthorchis viverrini-Like Fluke Infection in Ducks in Binh Dinh Province, Central Vietnam

    PubMed Central

    Dao, Thanh Thi Ha; Abatih, Emmanuel Nji; Nguyen, Thanh Thi Giang; Tran, Ha Thi Lam; Gabriël, Sarah; Smit, Suzanne; Le, Phap Ngoc; Dorny, Pierre

    2016-01-01

    Following the first report of Opisthorchis viverrini infection in a domestic duck in Phu My District of Binh Dinh Province, Central Vietnam, many other cases were observed in the province. We determined the infection rate and intensity of O. viverrini infection in ducks in 4 districts of the province. A total of 178 ducks were randomly selected from 34 farms for examination of flukes in the liver and gall bladder. An infection rate of 34.3% (range 20.7-40.4% among districts) was found; the intensity of infection was 13.8 worms per infected duck (range 1-100). These findings show the role of ducks as a host for O. viverrini, duck genotype, which is sympatric with the human O. viverrini genotype in this province. It also stresses the need for investigations on the zoonotic potential and the life cycle of this parasite. PMID:27417094

  15. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

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

    PubMed

    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

    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 IκBα and nuclear translocation of NF-κB subunits (p65 and p50). CsFHC-induced NF-κB 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-1β and IL-6, in NF-κB-dependent manner. Our results indicate that CsFHC-triggered free radical-mediated NF-κB signaling is an important factor in the chronic inflammation caused by C. sinensis infection.

  17. C3H/He Mice as an Incompatible Cholangiocarcinoma Model by Clonorchis sinensis, Dicyclanil and N-Nitrosodimethylamine

    PubMed Central

    Uddin, Md. Hafiz; Li, Shunyu; Jin, Yan; Choi, Min-Ho; Jang, Ja June; Hong, Sung-Tae

    2016-01-01

    Clonorchis sinensis is a Group-I bio-carcinogen, associated with cholangiocarcinoma (CCA). The hamster is the only experimental model of C. sinensis-mediated CCA, but we oblige another animal model. The present study intended to develop a C. sinensis (Cs) mediated CCA model using C3H/He mice, co-stimulated with N-nitrosodimethyl-amine (NDMA) and dicyclanil (DC). The mice were divided into 8 groups with different combinations of Cs, NDMA, and DC. Six months later the mice were sacrificed and subjected to gross and histopathological examination. The body weights were significantly reduced among the groups treated with 2 or more agents (eg. Cs+NDMA, Cs+DC, NDMA+DC, and Cs+NDMA+DC). In contrast, liver weight percentages to body weight were increased in above groups by 4.1% to 4.7%. A Change of the spleen weight was observed only in Cs+NDMA group. Though C. sinensis infection is evident from hyperplastic changes, only 1 worm was recovered. T wo mice, 1 from Cs and the other from Cs+DC group, showed mass forming lesions; 1 (281.2 mm3) from the Cs group was a hepatocellular adenoma and the other (280.6 mm3) from the Cs+DC group was a cystic mass (peliosis). Higher prevalence of gray-white nodules was observed in Cs group (42.9%) followed by Cs+NDMA+DC group (21.4%). The mice of the Cs+NDMA+DC group showed hyper-proliferation of the bile duct with fibrotic changes. No characteristic change for CCA was recognized in any of the groups. In conclusion, C3H/He mice produce no CCA but extensive fibrosis when they are challenged by Cs, NDMA, and DC together. PMID:27417082

  18. [Excystation Time and Location of Metacercariae of Clonorchis sinensis in Mice].

    PubMed

    Sun, Yan-hong; Liu, Ji-xin

    2015-06-01

    Metacercariae of Clonorchis sinensis (20 per mouse) were given orally to Kunming mice. The mice were sacrificed at 0.5, 1, 2, 4, 8, 16, 32, and 64 h after infection. The results showed that the excystation of the metacercariae occurred in the stomach and small intestine, mainly in the duodenum. Excystation occurred mainly at 2, 4, 8, and 16 h post-infection. Juveniles were found in hepatic duct on 0.5 h post-infection. The number of juveniles increased with the extension of infection time, which kept unchanged in hepatic duct from 32 h after infection. PMID:26541046

  19. [Epidemiological studies of Clonorchis sinensis prevailed in the peoples of Kyungpook Province

    PubMed

    Shin, Dae Shik

    1964-06-01

    The author studied the infection rates of Clonorchiis sinensis in the inhabitants of Kyungpook Province, and surveyed infestation rates of Clonorchis metacercarias in the twelve kinds of fresh water fishes for the purpose of the eradication. plan of clonorchiasis of Kyungpook Province. The examination was continued from April 1960 to October 1962 with 24,252 inhabitants ranging from four months to over sixty aged. All the family were tested intradermally with Clonorchis antigen and then confirmed the eggs by M.G.L. technique. The results of the examination were summarized as follows. I. The infection rate of the inhabitants; 1) In the people tested, 27.7 per cent was infected with Clonorchis sinensis. 2) There were no remarkable differences in the infection rates among each Districts; River side inhabitants(Yungchun-Gun 23.6 percent, Andong-Gun 27.4 %), paddy field inhabitants(Yungchun-Gun 23.6 %, Sangchu-Gun 29.1 %) and mountain side inhabitants (Chungsong-Gun 23.8 %, Yungyang-Gun 27.7%). However, the infection rates of the river side peoples were slightly higher than that of the districts far from the river. 3) The infection rate of the male was 34.98 percent (4,628 out of 12,230), while the female was 18.96 per cent (2,090 out of 11,022). 4) The maximum infection rate of the male group was observed in the 35-39 age group (73.8 %) and in female, 55-59 age group (34.l percent) respectively, however it was gradually decreased in the senile group. II. The infection rates of the family group; 1) Those infected in both husband and wife were 28 percent(357 out of 1,289), husband only was 52 percent (672 out of 1,289) and wife only was 4 percent (50 out of 1,289). 2) The children of the infected parents revealed higher morbidity than that of the non-infected parents. 3) The children of the infected father revealed much morbidity than that of the mother's side. On the contrary, children's morbidity rate of the infected widow was higher than that of the widower. III. The

  20. [Epidemiological studies of Clonorchis sinensis prevailed in the peoples of Kyungpook Province

    PubMed

    Shin, Dae Shik

    1964-06-01

    The author studied the infection rates of Clonorchiis sinensis in the inhabitants of Kyungpook Province, and surveyed infestation rates of Clonorchis metacercarias in the twelve kinds of fresh water fishes for the purpose of the eradication. plan of clonorchiasis of Kyungpook Province. The examination was continued from April 1960 to October 1962 with 24,252 inhabitants ranging from four months to over sixty aged. All the family were tested intradermally with Clonorchis antigen and then confirmed the eggs by M.G.L. technique. The results of the examination were summarized as follows. I. The infection rate of the inhabitants; 1) In the people tested, 27.7 per cent was infected with Clonorchis sinensis. 2) There were no remarkable differences in the infection rates among each Districts; River side inhabitants(Yungchun-Gun 23.6 percent, Andong-Gun 27.4 %), paddy field inhabitants(Yungchun-Gun 23.6 %, Sangchu-Gun 29.1 %) and mountain side inhabitants (Chungsong-Gun 23.8 %, Yungyang-Gun 27.7%). However, the infection rates of the river side peoples were slightly higher than that of the districts far from the river. 3) The infection rate of the male was 34.98 percent (4,628 out of 12,230), while the female was 18.96 per cent (2,090 out of 11,022). 4) The maximum infection rate of the male group was observed in the 35-39 age group (73.8 %) and in female, 55-59 age group (34.l percent) respectively, however it was gradually decreased in the senile group. II. The infection rates of the family group; 1) Those infected in both husband and wife were 28 percent(357 out of 1,289), husband only was 52 percent (672 out of 1,289) and wife only was 4 percent (50 out of 1,289). 2) The children of the infected parents revealed higher morbidity than that of the non-infected parents. 3) The children of the infected father revealed much morbidity than that of the mother's side. On the contrary, children's morbidity rate of the infected widow was higher than that of the widower. III. The

  1. An integrated pipeline for next generation sequencing and annotation of the complete mitochondrial genome of the giant intestinal fluke, Fasciolopsis buski (Lankester, 1857) Looss, 1899.

    PubMed

    Biswal, Devendra Kumar; Ghatani, Sudeep; Shylla, Jollin A; Sahu, Ranjana; Mullapudi, Nandita; Bhattacharya, Alok; Tandon, Veena

    2013-01-01

    Helminths include both parasitic nematodes (roundworms) and platyhelminths (trematode and cestode flatworms) that are abundant, and are of clinical importance. The genetic characterization of parasitic flatworms using advanced molecular tools is central to the diagnosis and control of infections. Although the nuclear genome houses suitable genetic markers (e.g., in ribosomal (r) DNA) for species identification and molecular characterization, the mitochondrial (mt) genome consistently provides a rich source of novel markers for informative systematics and epidemiological studies. In the last decade, there have been some important advances in mtDNA genomics of helminths, especially lung flukes, liver flukes and intestinal flukes. Fasciolopsis buski, often called the giant intestinal fluke, is one of the largest digenean trematodes infecting humans and found primarily in Asia, in particular the Indian subcontinent. Next-generation sequencing (NGS) technologies now provide opportunities for high throughput sequencing, assembly and annotation within a short span of time. Herein, we describe a high-throughput sequencing and bioinformatics pipeline for mt genomics for F. buski that emphasizes the utility of short read NGS platforms such as Ion Torrent and Illumina in successfully sequencing and assembling the mt genome using innovative approaches for PCR primer design as well as assembly. We took advantage of our NGS whole genome sequence data (unpublished so far) for F. buski and its comparison with available data for the Fasciola hepatica mtDNA as the reference genome for design of precise and specific primers for amplification of mt genome sequences from F. buski. A long-range PCR was carried out to create an NGS library enriched in mt DNA sequences. Two different NGS platforms were employed for complete sequencing, assembly and annotation of the F. buski mt genome. The complete mt genome sequences of the intestinal fluke comprise 14,118 bp and is thus the shortest

  2. Worm recovery and precipitin antibody response in guinea pigs and rats infected with Clonorchis sinensis.

    PubMed

    Su, K E; Wang, F Y; Chi, P Y

    1998-12-01

    Guinea pigs (Hartley strain) and rats (Wistar strain) were each fed 200 and 100 Clonorchis sinensis metacercariae, respectively. Five animals from each species were sacrificed weekly between 1-8 weeks postinfection (WPI) and then at 12, 16, 20 and 30 WPI for collection of worms, bile and sera. The overall worm recovery rates for guinea pigs and rats were 18.7% and 12.4%, respectively. Only one of the five rats examined at 20 WPI still harbored one worm, while all were worm-free at 30 WPI. By a double diffusion test, no antibodies were detected against C. sinensis adult antigens in the bile juice. Serum antibodies were detected in at least 95% of the infected guinea pigs between 4-30 WPI and rats between 3-16 WPI. Precipitin antibodies seemed to be correlated with the presence of live worms in rats that had been infected for more than 12 weeks.

  3. Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control.

    PubMed

    Tang, Ze-Li; Huang, Yan; Yu, Xin-Bing

    2016-01-01

    Clonorchiasis, caused by Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease and one of the most common zoonoses. Currently, it is estimated that more than 200 million people are at risk of C. sinensis infection, and over 15 million are infected worldwide. C. sinensis infection is closely related to cholangiocarcinoma (CCA), fibrosis and other human hepatobiliary diseases; thus, clonorchiasis is a serious public health problem in endemic areas. This article reviews the current knowledge regarding the epidemiology, disease burden and treatment of clonorchiasis as well as summarizes the techniques for detecting C. sinensis infection in humans and intermediate hosts and vaccine development against clonorchiasis. Newer data regarding the pathogenesis of clonorchiasis and the genome, transcriptome and secretome of C. sinensis are collected, thus providing perspectives for future studies. These advances in research will aid the development of innovative strategies for the prevention and control of clonorchiasis. PMID:27384714

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

    PubMed Central

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

    2014-01-01

    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

  5. Immunogenicity of recombinant Bacillus subtilis spores expressing Clonorchis sinensis tegumental protein.

    PubMed

    Zhou, Zhenwen; Xia, Huimin; Hu, Xuchu; Huang, Yan; Ma, Changling; Chen, Xiaoxiang; Hu, Fengyu; Xu, Jin; Lu, Fangli; Wu, Zhongdao; Yu, Xinbing

    2008-01-01

    Clonorchis sinensis, which causes clonorchiasis, is of major socioeconomic importance in China. In this study, we report the use of CotC, a major component of the Bacillus subtilis spore coat, as a fusion partner for the expression of C. sinensis TP20.8 (Tegumental Protein 20.8 kDa) on the spore coat. Western blotting was used to identify TP20.8 surface expression on spores. Recombinant spores displaying the TP20.8 antigen were used for oral immunization and were shown to generate mucosal response in rats. TP20.8-specific secretory IgA in feces reached significant levels 2 weeks after oral dosing. This report shows that surface display of recombinant C. sinensis TP20.8 on B. subtilis spores was immunogenic and B. subtilis spores can be used as a mucosal immunization vehicle for parasite prevention and control.

  6. [Epidemiological Studies Of Clonorchis Sinensis In Mangyeong Riverside Areas In Korea

    PubMed

    Rhee, Jae Ku; Baek, Byeong Kirl; Lee, Sang Bork; Koh, Hong Bum

    1983-12-01

    In an attempt to clarify the epidemiological feature of C. sinensis in Mangyeong riverside area, the prevalence of clonorchiasis, infestation rate of the cercariae in Parafossarulus manchouricus, and detection rate of the metacercariae in fresh-water fishes were investigated from March 1 to September 30, 1983 at the upper, middle and lower reaches of the river. The results obtained were summarized as follows:Detection rate of C. sinensis egg among inhabitants was 8.2 % out of a total of 1,266 persons. but the differences in detection rates were not statistically signifcant among upper, middle and 1ower reaches. According to sex, the detection rates were 10.3 % in male and 6.1 % in female (p<0.05), but by age groups, increases of the rates were observed as increase in age (p<0.05). Out of a total of 380 fresh-water fishes of 32 different species, 93 fishes (25 %) of 12 species were found positive with Clonorchis metacercariae, and there were differences in infection rates of the metacercariae among the fishes in 3 parts of the river; 11 % in upper, 35 % in middle, and 34 % in lower reaches respectively. The metacercarial detection rates from various fishes were 97 % in Pseudorasbora parva, Cultriculus eigenmanni (85 %), Gnathopogon strigatus (67 %), Microphysogobio yaluensis (50 %), Gnathopogon coreanus (47 %), Pungtungia herzi(44 %), Abbottina rivularis (40 %), Moroco oxycephalus (33 %), Coreoleuciscus splendidus (32 %), Gnathopogon majimae (26 %), Rhodeus ocellatus (7 %), and Aphyocypris chinensis (3 %) respectively. Although very few P. manchouricus were collected at upper reach, 12 snails (0.7 %) among a total of 1,713 were found infected with Clonorchis cercariae. Also the cercariae of Echinochasmus japonicus (7.99 %), Lexogenes liberum (0.99 %), Cyathocotyle orientalis (0.75 %), Exorchis oviformis (0.23 %) and Asymphylodora japonica (0.05 %) were detected from the snails.

  7. Intestinal fluke infection as a result of eating sushi.

    PubMed

    Adams, K O; Jungkind, D L; Bergquist, E J; Wirts, C W

    1986-11-01

    Severe diarrhea in a female outpatient was caused by an intestinal fluke, identified as Heterophyes heterophyes, a natural parasite of humans and domesticated and wild fish-eating mammals. This parasite is endemic in the Orient and the Middle East. A detailed case history revealed that the woman had never traveled outside the continental United States but became infected while eating raw fresh-water fish (sushi) that had been served at a local Japanese restaurant. The restaurant specialized in serving a great variety of fresh-water and salt-water fish that were flown in from the Orient and other parts of the world. The authors' findings indicate that a person does not have to travel to an endemic area to become infected with this organism.

  8. [Intestinal parasite and Clonorchis sinensis infection among the inhabitants in the upper stream of Taechong Dam, Kumgang (River)].

    PubMed

    Kim, C H; Na, Y E; Kim, N M; Shin, D W; Chang, D Y

    1994-12-01

    The prevalence of intestinal parasites and Clonorchis sinensis infection was observed among inhabitants in the upper stream of Kumgang (River) from January to October 1991. A total of 743 fecal specimens was examined by cellophane thick smear and formalin-ether concentration technique. The parasite positive rate including helminth eggs and protozoan cysts was 40.8%, the positive rates for every species were: Clonorchis sinensis 30.8%, Metagonimus spp. 14.5%, Fasciola spp. 0.7%, Taenia spp. 1.5%, Ascaris lumbricoides 0.4%, Enterobius vermicularis 0.1%, Hookworm 0.1%, Trichuris trichiura 1.6%, Entamoeba coli 0.7%, E. histolytica 0.3%, Endolimax nana 0.3%, Giardia lamblia 0.3% and Iodamoeba buetschlii 0.1%, respectively. The cumulative positive rate in Okchon-gun showed 51.1%, in the Kumsan-gun 50.8% and in the Muju-gun 28.6%. Through this survey, it was concluded that the soil transmitted intestinal parasites including helminthseggs and protozoan cysts have been decreased remarkably among the inhabitants along the upper stream of Taechong Dam, Kum-gang (River), on the other side, Clonorchis sinensis, Metagonimus spp. and Taenia spp. are still morderate prevalent.

  9. Invasion of Flukes of the Echinostomatidae Family in Racing Pigeon ( Columba livia var. domestica) Lofts.

    PubMed

    Ledwoń, Aleksandra; Dolka, Beata; Piasecki, Tomasz; Dolka, Izabella; Szeleszczuk, Piotr

    2016-06-01

    Over 4 years, only two known cases of fluke invasions were diagnosed in racing pigeons ( Columba livia ) originating from different regions of Poland. In both cases, the invasion was characterized by a very high mortality (approximately 70%), and the source of the infestation was snails of the Lymnaeidae family eaten by pigeons. Fluke invasions in pigeons are extremely rare and to date have not been described in Poland. Therefore, the occurrence of the symptoms of hemorrhagic diarrhea and sudden deaths of either adult pigeons or nestlings were suspected to be associated with poisoning. Autopsy revealed an invasion of flukes causing hemorrhagic enteritis. Renal failure and spleen atrophy were also found in the birds. Using molecular biology techniques, infestation with the fluke Echinostoma revolutum was determined in the second case. PMID:27309299

  10. Invasion of Flukes of the Echinostomatidae Family in Racing Pigeon ( Columba livia var. domestica) Lofts.

    PubMed

    Ledwoń, Aleksandra; Dolka, Beata; Piasecki, Tomasz; Dolka, Izabella; Szeleszczuk, Piotr

    2016-06-01

    Over 4 years, only two known cases of fluke invasions were diagnosed in racing pigeons ( Columba livia ) originating from different regions of Poland. In both cases, the invasion was characterized by a very high mortality (approximately 70%), and the source of the infestation was snails of the Lymnaeidae family eaten by pigeons. Fluke invasions in pigeons are extremely rare and to date have not been described in Poland. Therefore, the occurrence of the symptoms of hemorrhagic diarrhea and sudden deaths of either adult pigeons or nestlings were suspected to be associated with poisoning. Autopsy revealed an invasion of flukes causing hemorrhagic enteritis. Renal failure and spleen atrophy were also found in the birds. Using molecular biology techniques, infestation with the fluke Echinostoma revolutum was determined in the second case.

  11. Advanced Enzymology, Expression Profile and Immune Response of Clonorchis sinensis Hexokinase Show Its Application Potential for Prevention and Control of Clonorchiasis

    PubMed Central

    Tang, Zeli; Xie, Zhizhi; Lin, Zhipeng; Sun, Hengchang; Wan, Shuo; Li, Xuerong; Huang, Yan; Yu, Xinbing; Xu, Jin

    2015-01-01

    Background Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. Principal Findings There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Conclusions/Significance Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis. PMID:25799453

  12. Observations on the biology, epidemiology and economic relevance of rumen flukes (Paramphistomidae) in cattle kept in a temperate environment.

    PubMed

    Sargison, Neil; Francis, Emily; Davison, Chloe; Bronsvoort, Barend M deC; Handel, Ian; Mazeri, Stella

    2016-03-30

    There is concern about the probable recent introduction, increased prevalence and potential economic impact of rumen fluke infection of United Kingdom cattle. A study of 339 cattle slaughtered in a Scottish red meat abattoir was undertaken with the aims of describing the prevalence and geographical distribution of rumen fluke infection, estimating its effect on production, and evaluating faecal egg counts (FECs) as a tool to diagnose infection in live animals and study the epidemiology of the disease. The overall proportion of cattle consigned to the abattoir from northern United Kingdom with rumen fluke infection in the forestomachs was 0.29. Rumen flukes were distributed predominantly in the cranial sac of the rumen and adjacent to the reticular groove. Overall, a mean of 213 and median of 44 rumen flukes was identified in the forestomachs of rumen fluke-positive cattle. The mean and median FECs of animals were 26.01 and 5.20 eggs per gram (epg), respectively. There was a significant difference between the mean FECs per rumen fluke of 0.08 and 0.13 epg during summer/autumn and winter sampling periods, respectively. The overall correlation between rumen fluke FECs and the number of flukes in the forestomach was high, albeit lower in the summer/autumn than in the winter period. The sensitivities of rumen fluke FECs for the identification of flukes in the forestomach during the summer/autumn and winter sampling periods were 0.65 and 0.85, respectively. These results will aid in the interpretation of rumen fluke FECs when monitoring cattle health and production and studying the parasite's epidemiology in a temperate environment, thereby informing rational, precise and sustainable disease control.

  13. Prevalence of Clonorchis sinensis Infection among Residents along 5 Major Rivers in the Republic of Korea.

    PubMed

    Jeong, Young-Il; Shin, Hee-Eun; Lee, Sang-Eun; Cheun, Hyeng-Il; Ju, Jung-Won; Kim, Jung-Yeon; Park, Mi Yeoun; Cho, Shin-Hyeong

    2016-04-01

    Clonorchis sinensis is currently the most important parasite affecting public health problems in the Republic of Korea. We investigated the prevalence of C. sinensis infection among residents living along 5 major rivers in Korea. A total of 42,562 individual stool samples were collected from 37 localities and examined using the formalin-ether sedimentation technique. Helminth eggs were detected in 4,052 (9.5%) residents and 3,586 (8.4%) were infected with C. sinensis. The egg positive rate of C. sinensis in Nakdong, Seomjin, Geum, Yeongsan, and Han River was 11.7%, 9.9%, 6.5%, 3.1%, and 1.0%, respectively. The overall prevalence of clonorchiasis by sex was 11.2% in males and 6.2% in females. The age-prevalence was the highest in the 50-59 years band. It has been reconfirmed that the endemicity of clonorchiasis is higher in southern areas of Korea, especially along Nakdong and Seomjin Rivers. A combination of continuous control programs with health education initiatives is urgently required in these highly endemic areas of clonorchiasis in Korea.

  14. Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment

    PubMed Central

    Shen, Chenghua; Kim, Jae-hwan; Lee, Jeong-Keun; Bae, Young Mee; Oh, Jin-Kyoung; Lim, Min Kyung; Shin, Hai-Rim; Hong, Sung-Tae

    2007-01-01

    A cohort was established for evaluation of cancer risk factors in Sancheong-gun, Gyeongsangnam-do, Korea. As one of the cohort studies, stools of 947 residents (403 males and 544 females, age range: 29-86 years) were screened for Clonorchis sinensis eggs using both Kato-Katz method and formalin-ether sedimentation technique. The overall egg positive rate of C. sinensis was 37.7% and individual EPG (eggs per gram of feces) counts ranged from 24 to 28,800. Eight egg positive residents voluntarily joined a process of collection of the passed worms after praziquantel treatment. A total of 158 worms were recovered from 5 of the 8 treated persons, ranged from 3 to 108 in each individual. The worms were 15-20 mm × 2-3 mm in size, and showed brown-pigmented, red, or white body colors. This is the first collection record of C. sinensis adult worms from humans through anthelmintic treatment and purgation. The adult worms of C. sinensis may be paralyzed by praziquantel and then discharged passively through bile flow in the bile duct and by peristaltic movement of the bowel. PMID:17570980

  15. Prevalence of Clonorchis sinensis Infection among Residents along 5 Major Rivers in the Republic of Korea

    PubMed Central

    Jeong, Young-Il; Shin, Hee-Eun; Lee, Sang-Eun; Cheun, Hyeng-Il; Ju, Jung-Won; Kim, Jung-Yeon; Park, Mi Yeoun; Cho, Shin-Hyeong

    2016-01-01

    Clonorchis sinensis is currently the most important parasite affecting public health problems in the Republic of Korea. We investigated the prevalence of C. sinensis infection among residents living along 5 major rivers in Korea. A total of 42,562 individual stool samples were collected from 37 localities and examined using the formalin-ether sedimentation technique. Helminth eggs were detected in 4,052 (9.5%) residents and 3,586 (8.4%) were infected with C. sinensis. The egg positive rate of C. sinensis in Nakdong, Seomjin, Geum, Yeongsan, and Han River was 11.7%, 9.9%, 6.5%, 3.1%, and 1.0%, respectively. The overall prevalence of clonorchiasis by sex was 11.2% in males and 6.2% in females. The age-prevalence was the highest in the 50-59 years band. It has been reconfirmed that the endemicity of clonorchiasis is higher in southern areas of Korea, especially along Nakdong and Seomjin Rivers. A combination of continuous control programs with health education initiatives is urgently required in these highly endemic areas of clonorchiasis in Korea. PMID:27180582

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

    PubMed

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

    2004-05-01

    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 DTT, but was inhibited dose-dependently by a cysteine protease inhibitor, iodoacetic acid. Two active protease bands of 28 and 40 kDa were identified in the ESP of metacercariae by gelatin substrate SDS-PAGE. Scanning electron microscopy demonstrated that the larvae in solutions of DTT and ESP migrated through a small hole on the metacercarial wall, whereas larvae were liberated by entire wall disruption in trypsin solution. These results suggest that trypsin is a major extrinsic factor of the rapid excystment of C. sinensis metacercariae, and that endogenous cysteine proteases are also involved in metacercarial excystment.

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

    PubMed

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

    2014-03-10

    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.

  18. The genome of the blood fluke Schistosoma mansoni

    PubMed Central

    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

    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

  19. 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

    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

    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

  20. 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

    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

    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

  1. A case of a facultative life-cycle diversification in the fluke Pleurogenoides sp. (Lecithodendriidae, Plagiorchiida).

    PubMed

    Hassl, Andreas R

    2010-10-01

    Numerous specimens of the native, intestinal digenean fluke Pleurogenoides sp. (Lecithodendriidae, Plagiorchiida), a genus known for the simultaneous co-existence of genuine adults and progenetic, adult-like metacercaria, were found by chance parasitizing in the oesophagus of a recently imported, tropical Bristly Bush Viper (Atheris hispida). The snake had before been force-fed with native water frogs, the assumed definitive host of these flukes. Hence water frogs act as the second intermediate host or as a paratenic host for Pleurogenoides flukes, as they must house progenetic fluke larvae, which develop to genuine adults when transmitted to an appropriate consecutive host, the ancestral definitive host, a reptile. The European Pleurogenoides fluke species seem to display a facultative life-cycle diversification, they can adjust their life-history strategy according to their immediate transmission opportunities. This phenotypic plasticity allows the parasite to respond quickly to any changes in the abundance of a host; usually this biological oddity results in a life-cycle truncation by the elimination of the definitive host.

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

    PubMed Central

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

    2014-01-01

    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

  3. Characterization of a gut-associated asparaginyl endopeptidase of Clonorchis sinensis.

    PubMed

    Kang, Jung-Mi; Lee, Jinyoung; Ju, Hye-Lim; Ju, Jung Won; Kim, Jong-Hyun; Pak, Jhang Ho; Kim, Tong-Soo; Hong, Yeonchul; Sohn, Woon-Mok; Na, Byoung-Kuk

    2015-06-01

    Asparaginyl endopeptidases (AEP: EC 3.4.22.34) are a family of cysteine proteases classified into the MEROPS clan CD, family C13. In this study, we characterized the biochemical and antigenic properties of an AEP of Clonorchis sinensis (CsAEP). The recombinant CsAEP showed hydrolytic activity at pH values ranging from acidic to neutral with optimum activity at pH 6.0. While the recombinant CsAEP was stable at neutral pHs, it was unstable at acidic pHs and resulted in loss of enzymatic activity. The recombinant enzyme was effectively inhibited by iodoacetic acid and N-ethylmaleimide, but not by E-64. The partially purified native CsAEP showed biochemical properties similar to the recombinant enzyme. Native CsAEP is likely to be cleaved into an N-terminal mature enzyme and a C-terminal fragment via autocatalytic activation at acidic pHs. Polyclonal antibody raised against the recombinant CsAEP recognized three forms of CsAEP, proenzyme, the N-terminal mature enzyme and the C-terminal fragment, in the worm extract (WE) of C. sinensis. However, only the C-terminal fragment was mainly found in the excretory and secretory (ES) products of the parasite. Strong CsAEP activity was found in the WE, but only a trace level of CsAEP activity was detected in the ES products of the parasite. CsAEP was expressed in various developmental stages of C. sinensis, from metacercariae to adults, and was found to be localized in the intestine of the parasite as well as in intestinal contents. Sera from rats experimentally infected with C. sinensis reacted with CsAEP beginning 4 weeks after infection. These results suggest that CsAEP is a gut-associated enzyme synthesized in the intestine of C. sinensis and subsequently secreted into the intestinal lumen of the parasite. PMID:25819296

  4. Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2

    PubMed Central

    2013-01-01

    Background Clonorchis sinensis (C. sinensis, Cs) is a trematode parasite that often causes chronic cumulative infections in the hepatobiliary ducts of the host and can lead to pathological changes by continuously released excretory/secretory proteins (ESPs). A T2 ribonuclease in trematode ESPs, has been identified as a potent regulator of dendritic cell (DCs) modulation. We wondered whether there was a counterpart present in CsESPs with similar activity. To gain a better understanding of CsESPs associated immune responses, we identified and characterized RNASET2 of C. sinensis (CsRNASET2) in this paper. Methods We expressed CsRNASET2 in Pichia pastoris and identified its molecular characteristics using bioinformatic analysis and experimental approaches. The immune modulation activities of CsRNASET2 were confirmed by evaluating cytokine production and surface markers of recombinant CsRNASET2 (rCsRNASET2) co-cultured DCs, and monitoring levels of IgG isotypes from rCsRNASET2 administered BALB/c mice. Results CsRNASET2 appeared to be a glycoprotein of T2 ribonuclease family harboring conserved CAS motifs and rich in B-cell epitopes. Furthermore, CsRNASET2 was present in CsESPs and was able to modulate cytokine production of DCs. In addition, rCsRNASET2 could significantly suppress the expression of lipopolysaccharide-induced DCs maturation markers. In addition, when subcutaneously administered with rCsRNASET2 there was a marked effect on IgG isotypes in mouse sera. Conclusion Collectively, we revealed that CsRNASET2, a T2 ribonuclease present in CsESPs, could modulate DCs maturation and might play an important role in C. sinensis associated immune regulation in the host. PMID:24365605

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

    PubMed Central

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

    2014-01-01

    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

  6. Molecular cloning and functional characterization of a glucose transporter (CsGLUT) in Clonorchis sinensis.

    PubMed

    Ahn, Seong Kyu; Cho, Pyo Yun; Na, Byoung-Kuk; Hong, Sung-Jong; Nam, Ho-Woo; Sohn, Woon-Mok; Ardelli, Bernadette F; Park, Yun-Kyu; Kim, Tong-Soo; Cha, Seok Ho

    2016-01-01

    A complementary DNA (cDNA) encoding a glucose transporter of Clonorchis sinensis (CsGLUT) was isolated from the adult C. sinensis cDNA library. The open reading frame of CsGLUT cDNA consists of 1653 base pairs that encode a 550-amino acid residue protein. Hydropathy analysis suggested that CsGLUT possess 12 putative membrane-spanning domains. The Northern blot analysis result using poly(A)(+)RNA showed a strong band at ~2.1 kb for CsGLUT. When expressed in Xenopus oocytes, CsGLUT mediated the transport of radiolabeled deoxy-D-glucose in a time-dependent but sodium-independent manner. Concentration-dependency results showed saturable kinetics and followed the Michaelis-Menten equation. Nonlinear regression analyses yielded a Km value of 588.5 ± 53.0 μM and a Vmax value of 1500.0 ± 67.5 pmol/oocyte/30 min for [1,2-(3)H]2-deoxy-D-glucose. No trans-uptakes of bile acid (taurocholic acid), amino acids (tryptophan and arginine), or p-aminohippuric acid were observed. CsGLUT-mediated transport of deoxyglucose was significantly and concentration-dependently inhibited by radio-unlabeled deoxyglucose and D-glucose. 3-O-Methylglucose at 10 and 100 μM inhibited deoxyglucose uptake by ~50 % without concentration dependence. No inhibitory effects by galactose, mannose, and fructose were observed. This work may contribute to the molecular biological study of carbohydrate metabolism and new drug development of C. sinensis. PMID:26450594

  7. Molecular Cloning and Characterization of Taurocyamine Kinase from Clonorchis sinensis: A Candidate Chemotherapeutic Target

    PubMed Central

    Tokuhiro, Shinji; Nagataki, Mitsuru; Jarilla, Blanca R.; Nomura, Haruka; Kim, Tae Im; Hong, Sung-Jong; Agatsuma, Takeshi

    2013-01-01

    Background Adult Clonorchis sinensis lives in the bile duct and causes endemic clonorchiasis in East Asian countries. Phosphagen kinases (PK) constitute a highly conserved family of enzymes, which play a role in ATP buffering in cells, and are potential targets for chemotherapeutic agents, since variants of PK are found only in invertebrate animals, including helminthic parasites. This work is conducted to characterize a PK from C. sinensis and to address further investigation for future drug development. Methology/Principal findings A cDNA clone encoding a putative polypeptide of 717 amino acids was retrieved from a C. sinensis transcriptome. This polypeptide was homologous to taurocyamine kinase (TK) of the invertebrate animals and consisted of two contiguous domains. C. sinensis TK (CsTK) gene was reported and found consist of 13 exons intercalated with 12 introns. This suggested an evolutionary pathway originating from an arginine kinase gene group, and distinguished annelid TK from the general CK phylogenetic group. CsTK was found not to have a homologous counterpart in sequences analysis of its mammalian hosts from public databases. Individual domains of CsTK, as well as the whole two-domain enzyme, showed enzymatic activity and specificity toward taurocyamine substrate. Of the CsTK residues, R58, I60 and Y84 of domain 1, and H60, I63 and Y87 of domain 2 were found to participate in binding taurocyamine. CsTK expression was distributed in locomotive and reproductive organs of adult C. sinensis. Developmentally, CsTK was stably expressed in both the adult and metacercariae stages. Recombinant CsTK protein was found to have low sensitivity and specificity toward C. sinensis and platyhelminth-infected human sera on ELISA. Conclusion CsTK is a promising anti-C. sinensis drug target since the enzyme is found only in the C. sinensis and has a substrate specificity for taurocyamine, which is different from its mammalian counterpart, creatine. PMID:24278491

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

    PubMed

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

    2010-09-01

    Pearl River Delta region is a high clonorchiasis-endemic area in China. However, no complete epidemiological data exist regarding 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 encysted metacercariae of C. sinensis were detected by digesting these specimens with artificial gastric juice. The mean infection rate of freshwater fishes was 37.09% (2,160/5,824) with a mean number of 14.269 encysted metacercariae in every infected fish and 0.460 encysted metacercariae in every gram of fish meat. Of these freshwater fishes, 5,219 were domesticated, and the infection rate was 36.69% with a mean number of 10.743 encysted metacercariae in every infected fish and 0.312 encysted metacercariae in every gram of fish meat; the other 605 were wild, and the infection rate was 40.50% with a mean number of 41.829 encysted metacercariae in every infected fish and 8.812 encysted metacercariae in every gram of fish meat. A total of 228 shrimps were examined, and 3.07% of them were infected with a mean number of 1.00 encysted metacercariae in every infected shrimp. Pseudorasbora parva and Ctenopharyngodon idellus had the highest infection rate and degree of infection in the fishes studied. The results demonstrated a high incidence of C. sinensis infection in freshwater fishes and shrimps within Pearl River Delta region and a great difference in the infection rate among different collection sites and different fish species.

  9. The importance of wild fish in the epidemiology of Clonorchis sinensis in Vietnam.

    PubMed

    Bui, Thanh Ngoc; Pham, Thanh Thi; Nguyen, Nguyen Thi; Nguyen, Ha Van; Murrell, Darwin; Phan, Van Thi

    2016-09-01

    Preliminary findings of a high prevalence of Clonorchis sinensis in wild-caught fish in a North Vietnam reservoir (Thac Ba reservoir, Yen Bai Province) prompted a longitudinal epidemiological study of fish infections. Monthly collections of fish from September 2014 to August 2015 were processed for recovery of metacercariae; 1219 fish, representing 22 species, were examined. Seven species were infected with C. sinensis metacercariae. Four species, Toxabramis houdemeri, Hemiculter leucisculus, Cultrichthys erythropterus, and Culter recurvirostris, had high prevalence (31.1 to 76.7 %); metacercarial intensities ranged from 3.9 to 65.7 metacercariae/fish. A seasonal variation of C. sinensis prevalence was observed in T. houdemeri. Variation in intensity of infection occurred in C. erythropterus and H. leucisculus. Intensity and prevalence of C. sinensis in the most highly infected species, T. houdemeri, varied by fish size; prevalence was higher in fish weighing more than 3 g, and intensity was higher in fish weighing more than 5 g. The distribution of metacercariae in the body region of T. houdemeri was significantly higher in the caudal fin (14.7 metacercariae/g), compared to the body and head regions (0.7 and 1.4 metacercariae/g, respectively). Further epidemiological investigations on C. sinensis in this reservoir region should include assessing the relative risk of the different fish species for humans based on the latter's food preferences, and the prevalence of C. sinensis in the community. The snail intermediate host(s) in the reservoir should also be identified along with the ecological factors influencing its exposure to C. sinensis eggs and its subsequent transmission of cercariae to fish. Also needed are investigations on the relative importance of wild and domestic reservoir hosts as sources of egg contamination of the reservoir.

  10. Identification and immunological characterization of thioredoxin transmembrane-related protein from Clonorchis sinensis.

    PubMed

    Zhou, Chenhui; Bian, Meng; Liao, Hua; Mao, Qiong; Li, Ran; Zhou, Juanjuan; Wang, Xiaoyun; Li, Shan; Liang, Chi; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2013-04-01

    Thioredoxin transmembrane related protein (TMX), a member of thioredoxin superfamily, is localized to the endoplasmic reticulum and possesses a thioredoxin-like domain that plays an important role as an oxidoreductase. The functions of TMX in Clonorchis sinensis remain to be elucidated. In this study, we cloned and characterized a novel TMX of C. sinensis (CsTMX). The CsTMX cDNA sequence contained a 414-nucleotide open-reading frame encoding a protein of 137 amino acids. A thioredoxin domain was found in the position of aa21-117 and contained the putative active-site motif Cys-Pro-Ala-Cys. BLASTx analysis showed that CsTMX shared 39-57% amino acid identities with TMX of other organisms. Quantitative RT-PCR analysis demonstrated that CsTMX was differentially transcribed, with the highest level of expression in the adult worm stage and the lowest expression in egg stage. In addition, immunofluorescence assay showed CsTMX was localized in the tegument, vitelline gland, intestine, and intrauterine eggs of adult worm. Besides, immunoblot assay revealed that the recombinant CsTMX (rCsTMX) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by excretory-secretory products. Furthermore, analysis of the antibody isotype profile revealed that rats subcutaneously immunized with rCsTMX developed rCsTMX-specific antibody, which is dominance of IgG2a in sera. Meanwhile, production of IFN-γ was elevated strongly in the supernatants of spleen cell. The results collectively indicated that CsTMX might play an important role in the host-parasite interaction, as well as CsTMX probably involved in immunoregulation of host by inducing Th1-type dominated immune response in rats. PMID:23403994

  11. Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New Caledonia.

    PubMed

    Cauquil, Laura; Hüe, Thomas; Hurlin, Jean-Claude; Mitchell, Gillian; Searle, Kate; Skuce, Philip; Zadoks, Ruth

    2016-01-01

    An abattoir survey was performed in the French Melanesian archipelago of New Caledonia to determine the prevalence of paramphistomes in cattle and deer and to generate material for molecular typing at species and subspecies level. Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and batch level (81%). Prevalence was lower in calves at both levels (33% of 484 calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70), respectively. Using ITS-2 sequencing, 3 species of paramphistomes were identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and Orthocoelium streptocoelium. All three species were detected in cattle as well as deer, suggesting the possibility of rumen fluke transmission between the two host species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum population comprises two clades, both of which occur in cattle as well as deer. The results suggest two distinct routes of rumen fluke introduction into this area. This approach has wider applicability for investigations of the origin of rumen fluke infections and for the possibility of parasite transmission at the livestock-wildlife interface. PMID:27043709

  12. Two New Genera of Fish Blood Flukes (Digenea: Aporocotylidae) from Catfishes in the Peruvian Amazon.

    PubMed

    Orélis-Ribeiro, Raphael; Bullard, Stephen A

    2016-06-01

    Cladocaecum tomasscholzi n. gen., n. sp. infects the heart (lumen of ventricle) of driftwood catfish, Ageneiosus inermis Linnaeus, 1766 (Siluriformes: Auchenipteridae) from the Nanay River (Amazon River Basin, near Iquitos, Peru). It differs from all other aporocotylid genera by having a highly branched intestine comprising a central cecum that terminates immediately anterior to the ovary and that has numerous laterally directed diverticula. Kritsky platyrhynchi ( Guidelli, Isaac, and Pavanelli, 2002 ) n. gen., n. comb. (= Plehniella p.) is redescribed based on paratypes plus new specimens collected from the body cavity of the type host (porthole shovelnose catfish, Hemisorubim platyrhynchos Valenciennes, 1840) (Pimelodidae) from the nearby Itaya River. Kritsky differs from Sanguinicola Plehn, 1905 , Plehniella Szidat, 1951 , Nomasanguinicola Truong and Bullard, 2013 , and Cladocaecum by the combination of having a spinous anterior sucker, an intestine comprising 6 asymmetrical ceca, a lanceolate body, a straight vas deferens, an ovary with finger-like lateral projections, a small and spheroid oötype, numerous, minute, spheroid uterine eggs, and separate genital pores. An updated list of hosts, tissues infected, and geographic localities for the catfish blood flukes (9 spp.; 5 genera) is provided. This is the first report of a fish blood fluke infecting a member of Auchenipteridae and first proposal of a new genus of blood fluke (Schistosomatoidea) from South America in 64 yr. It brings the total number of Amazonian fish blood flukes to a mere 4 species.

  13. Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New Caledonia.

    PubMed

    Cauquil, Laura; Hüe, Thomas; Hurlin, Jean-Claude; Mitchell, Gillian; Searle, Kate; Skuce, Philip; Zadoks, Ruth

    2016-01-01

    An abattoir survey was performed in the French Melanesian archipelago of New Caledonia to determine the prevalence of paramphistomes in cattle and deer and to generate material for molecular typing at species and subspecies level. Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and batch level (81%). Prevalence was lower in calves at both levels (33% of 484 calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70), respectively. Using ITS-2 sequencing, 3 species of paramphistomes were identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and Orthocoelium streptocoelium. All three species were detected in cattle as well as deer, suggesting the possibility of rumen fluke transmission between the two host species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum population comprises two clades, both of which occur in cattle as well as deer. The results suggest two distinct routes of rumen fluke introduction into this area. This approach has wider applicability for investigations of the origin of rumen fluke infections and for the possibility of parasite transmission at the livestock-wildlife interface.

  14. Two New Genera of Fish Blood Flukes (Digenea: Aporocotylidae) from Catfishes in the Peruvian Amazon.

    PubMed

    Orélis-Ribeiro, Raphael; Bullard, Stephen A

    2016-06-01

    Cladocaecum tomasscholzi n. gen., n. sp. infects the heart (lumen of ventricle) of driftwood catfish, Ageneiosus inermis Linnaeus, 1766 (Siluriformes: Auchenipteridae) from the Nanay River (Amazon River Basin, near Iquitos, Peru). It differs from all other aporocotylid genera by having a highly branched intestine comprising a central cecum that terminates immediately anterior to the ovary and that has numerous laterally directed diverticula. Kritsky platyrhynchi ( Guidelli, Isaac, and Pavanelli, 2002 ) n. gen., n. comb. (= Plehniella p.) is redescribed based on paratypes plus new specimens collected from the body cavity of the type host (porthole shovelnose catfish, Hemisorubim platyrhynchos Valenciennes, 1840) (Pimelodidae) from the nearby Itaya River. Kritsky differs from Sanguinicola Plehn, 1905 , Plehniella Szidat, 1951 , Nomasanguinicola Truong and Bullard, 2013 , and Cladocaecum by the combination of having a spinous anterior sucker, an intestine comprising 6 asymmetrical ceca, a lanceolate body, a straight vas deferens, an ovary with finger-like lateral projections, a small and spheroid oötype, numerous, minute, spheroid uterine eggs, and separate genital pores. An updated list of hosts, tissues infected, and geographic localities for the catfish blood flukes (9 spp.; 5 genera) is provided. This is the first report of a fish blood fluke infecting a member of Auchenipteridae and first proposal of a new genus of blood fluke (Schistosomatoidea) from South America in 64 yr. It brings the total number of Amazonian fish blood flukes to a mere 4 species. PMID:26859799

  15. Prevalence and Sequence-Based Identity of Rumen Fluke in Cattle and Deer in New Caledonia

    PubMed Central

    Cauquil, Laura; Hüe, Thomas; Hurlin, Jean-Claude; Mitchell, Gillian; Searle, Kate; Skuce, Philip; Zadoks, Ruth

    2016-01-01

    An abattoir survey was performed in the French Melanesian archipelago of New Caledonia to determine the prevalence of paramphistomes in cattle and deer and to generate material for molecular typing at species and subspecies level. Prevalence in adult cattle was high at animal level (70% of 387 adult cattle) and batch level (81%). Prevalence was lower in calves at both levels (33% of 484 calves, 51% at batch level). Animals from 2 of 7 deer farms were positive for rumen fluke, with animal-level prevalence of 41.4% (29/70) and 47.1% (33/70), respectively. Using ITS-2 sequencing, 3 species of paramphistomes were identified, i.e. Calicophoron calicophorum, Fischoederius elongatus and Orthocoelium streptocoelium. All three species were detected in cattle as well as deer, suggesting the possibility of rumen fluke transmission between the two host species. Based on heterogeneity in ITS-2 sequences, the C. calicophorum population comprises two clades, both of which occur in cattle as well as deer. The results suggest two distinct routes of rumen fluke introduction into this area. This approach has wider applicability for investigations of the origin of rumen fluke infections and for the possibility of parasite transmission at the livestock-wildlife interface. PMID:27043709

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

    PubMed Central

    2014-01-01

    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

  17. Identification and characterization of a member of Rab subfamily, Rab8, from Clonorchis sinensis.

    PubMed

    Liang, Pei; He, Lei; Yu, Jinyun; Xie, Zhizhi; Chen, Xueqing; Mao, Qiang; Liang, Chi; Huang, Yan; Lu, Gang; Yu, Xinbing

    2015-05-01

    The Rabs act as a binary molecular switch that utilizes the conformational changes associated with the GTP/GDP cycle to elicit responses from target proteins. It regulates a broad spectrum of cellular processes including cell proliferation, cytoskeletal assembly, and intracellular membrane trafficking in eukaryotes. The Rab8 from Clonorchis sinensis (CsRab8) was composed of 199 amino acids. The deduced amino acid sequence shared above 50% identities with other species from trematode, tapeworm, mammal, insecta, nematode, and reptile, respectively. The homologous analysis of sequences showed the conservative domains: G1 box (GDSGVGKS), G2 box (T), G3 box (DTAG), G4 box (GNKCDL), and G5 box. In addition, the structure modeling had also shown other functional domains: GTP/Mg(2+) binding sites, switch I region, and switch II region. A phylogenic tree analysis indicated that the CsRab8 was clustered with the Rab from Schistosoma japonicum, and trematode and tapeworm came from the same branch, which was different from an evolutional branch built by other species, such as mammal animal, insecta, nematode, and reptile. The recombinant CsRab8 protein was expressed in Escherichia coli and the purified protein was a soluble molecule by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. CsRab8 was identified as a component of excretory/secretory products of C. sinensis by western blot analysis. The transcriptional level of CsRab8 at metacercaria stage was the highest at the four stages and higher by 56.49-folds than that at adult worm, 1.23-folds than that at excysted metacercaria, and 2.69-folds than that at egg stage. Immunohistochemical localization analysis showed that CsRab8 was specifically distributed in the tegument, vitellarium, eggs, and testicle of adult worms, and detected on the vitellarium and tegument of metacercaria. Combined with the results, CsRab8 is indispensable for survival and development of parasites, especially for regulating

  18. Molecular identification and characterization of leucine aminopeptidase 2, an excretory-secretory product of Clonorchis sinensis.

    PubMed

    Deng, Chuanhuan; Sun, Jiufeng; Li, Xuerong; Wang, Lexun; Hu, Xuchu; Wang, Xiaoyun; Chen, Wenjun; Lv, Xiaoli; Liang, Chi; Li, Wenfang; Huang, Yan; Li, Ran; Wu, Zhongdao; Yu, Xinbing; Xu, Jin

    2012-10-01

    Aminopeptidases serve vital roles in metabolism of hormones, neurotransmission, turnover of proteins and immunological regulations. Leucine aminopeptidases catalyze the hydrolysis of amino-acid residues from the N-terminus of proteins and peptides. In the present study, leucine aminopeptidase 2 (LAP2) gene of Clonorchis sinensis (C. sinensis) was isolated and identified from an adult cDNA library of C. sinensis. Recombinant CsLAP2 was expressed and purified in Escherichia coli BL21. The open reading frame of LAP2 contains 1,560 bp equivalent to 519 amino acids, a similarity analysis showed a relatively low homology with Homo sapiens (19.0 %), Trypanosoma cruzi (18.0 %), Mus musculus (19.3 %), and relatively high homology with Schistosoma mansoni (65.6 %). The optimum condition of rCsLAP2 enzyme activity was investigated using a fluorescent substrate of Leu-MCA at 37 °C and pH 7.5. The K (m) and V (max) values of rCsLAP2 were 18.2 μM and 10.7 μM/min, respectively. CsLAP2 gene expression can be detected at the stages of the adult worm, metacercaria, excysted metacercaria and egg of C. sinensis using real-time PCR, no difference was observed at the stages of the adult worm, metacercaria and egg. However, CsLAP2 showed a higher expression level at the stage of excysted metacercaria than the adult worm (3.90-fold), metacercaria (4.60-fold) and egg (4.59-fold). Histochemistry analysis showed that CsLAP2 was located at the tegument and excretory vesicle of metacercaria, and the tegument and intestine of adult worm. The immune response specific to rCsLAP2 was characterized by a mixed response patterns of Th1 and Th2, indicating a compounded humoral and cellular immune response. The combined results from the present study indicate that CsLAP2 was an important antigen exposed to host immune system, and probably implicated as potential role in interaction with host cells in clonorchiasis.

  19. Identification, immunolocalization, and immunological characterization of nitric oxide synthase-interacting protein from Clonorchis sinensis.

    PubMed

    Bian, Meng; Li, Shan; Wang, Xiaoyun; Xu, Yanquan; Chen, Wenjun; Zhou, Chenhui; Chen, Xueqing; He, Lei; Xu, Jin; Liang, Chi; Wu, Zhongdao; Huang, Yan; Li, Xuerong; Yu, Xinbing

    2014-05-01

    Recently, accumulating evidences indicate that nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions, signaling pathways, and variety of pathological processes. In the present study, using data from the published genomic for Clonorchis sinensis (C. sinensis), we investigated a gene encoding nitric oxide synthase-interacting protein (NOSIP) of C. sinensis. Recombinant CsNOSIP (rCsNOSIP) was expressed and purified from Escherichia coli BL21. The open reading frame of CsNOSIP comprises 867 bp which encodes 289 amino acids and shares 72.9, 45.2, 47, 46.4, and 45.8% identity with NOSIP from Schistosoma mansoni, Xenopus laevis, Rattus norvegicus, Mus musculus, and Homo sapiens, respectively. Bioinformatics analysis suggested that the full-length sequence contains an eNOS-interacting domain and numerous B-cell epitopes. Quantitative RT-PCR indicated that CsNOSIP differentially transcribed throughout the adult worms, metacercariae, and egg stages of C. sinensis, and were highly expressed in the adult worms. Moreover, western blot analysis showed that the rCsNOSIP could be detected by the serum from BALB/c mice infected with C. sinensis and the serum from BALB/c mice immunized with excretory/secretory products (ESPs). Furthermore, immunolocalization assay showed that CsNOSIP was specifically localized in the intestine, vitellarium, and eggs of adult worm. Both immunoblot and immunolocalization results demonstrated that CsNOSIP was one component of ESPs of C. sinensis, which could be supported by SignalP analysis. Moreover, analysis of the antibody subclass and cytokine profile demonstrated that subcutaneously immunized BALB/c mice with rCsNOSIP could significantly enhance serum IgG1 level and up-regulate expression of IL-4 and IL-6 in the splenocytes. Our results suggested that CsNOSIP was an important antigen exposed to host immune system and probably involved in immune regulation of host by inducing Th2-polarized immune response. PMID

  20. Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

    PubMed Central

    Uddin, Md. Hafiz; Choi, Min-Ho; Kim, Woo Ho; Jang, Ja-June; Hong, Sung-Tae

    2015-01-01

    Background Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model. Methods Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting. Principal Findings CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model. Conclusions/Significance The present findings suggest that oncogenes, PSMD10 and CDK4

  1. Biliary parasitic diseases including clonorchiasis, opisthorchiasis and fascioliasis.

    PubMed

    Lim, Jae Hoon; Mairiang, Eimorn; Ahn, Geung Hwan

    2008-01-01

    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 duct dilatation, mechanical obstruction, and bile duct wall thickening. On imaging, peripheral small intrahepatic bile ducts are dilated, but the large bile ducts and extrahepatic bile ducts are not dilated or slightly dilated. There is no visible caused of obstruction. Sometimes, in heavy infection, adult flukes are demonstrated on sonography, CT or MR cholangiography as small intraluminal lesions. The flukes in the gallbladder may appear as floating, small objects on sonography. Chronic infection may result in cholangiocarcinoma of the liver parenchyma or along the bile ducts. Human infection of Fasciola hepatica, a cattle flukes, may occur inadvertently, and the flukes migrate in the liver (hepatic phase) and reside the bile ducts (biliary phase). Image findings in the hepatic phase present with multiple, small, clustered, necrotic cavities or abscesses in the peripheral parts of the liver, showing "tunnels and caves" sign, reflecting parasite migration in the liver parenchyma. In the biliary phase, the flukes are demonstrated in the intra- and extrahepatic bile ducts and the gallbladder as small intraluminal flat objects, sometimes moving spontaneously. Bile ducts are dilated.

  2. Aberrant Expression of NF-κB in Liver Fluke Associated Cholangiocarcinoma: Implications for Targeted Therapy

    PubMed Central

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

    2014-01-01

    Background Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Methodology Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB 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-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n  =  48) over-expressed all NF-κB subunits. Inhibiting NF-κB 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-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy. PMID:25170898

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

    PubMed

    Kassai, T; Takáts, C; Fok, E; Redl, P

    1988-01-01

    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.

  4. Combined effects of social stress and liver fluke infection in a mouse model.

    PubMed

    Avgustinovich, Damira F; Marenina, Mariya K; Zhanaeva, Svetlana Ya; Tenditnik, Mikhail V; Katokhin, Alexey V; Pavlov, Konstantin S; Sivkov, Anton Yu; Vishnivetskaya, Galina B; Lvova, Maria N; Tolstikova, Tatiana G; Mordvinov, Viatcheslav A

    2016-03-01

    The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20 days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced. Simultaneous action of both factors caused the hypertrophy of adrenal glands, as well as elevated the activity of cathepsins B and L in the spleen. This effect on the activity of the cysteine proteases in the hippocampus and hypothalamus following O. felineus invasion was the predominant result of simultaneous action with social stress. Acute opisthorchiasis, social stress, and their combination caused an increase in the level of blood IL-6 in approximately 30% of the animals. Social stress induced a more pronounced effect on mouse plus-maze behavior than O. felineus invasion. Our results suggest a more severe negative effect of the simultaneous influence of both factors on most of the parameters that were investigated. PMID:26778779

  5. Combined effects of social stress and liver fluke infection in a mouse model.

    PubMed

    Avgustinovich, Damira F; Marenina, Mariya K; Zhanaeva, Svetlana Ya; Tenditnik, Mikhail V; Katokhin, Alexey V; Pavlov, Konstantin S; Sivkov, Anton Yu; Vishnivetskaya, Galina B; Lvova, Maria N; Tolstikova, Tatiana G; Mordvinov, Viatcheslav A

    2016-03-01

    The effects of two influences, social stress and acute opisthorchiasis, were investigated in inbred C57BL/6J male mice. In the model of social stress, mice were repeatedly attacked and defeated by aggressive outbred ICR male mice and were in continuous sensory contact with an aggressive conspecific mouse in their home cage for 20 days. Acute opisthorchiasis was provoked by invasion of Opisthorchis felineus (50 larvae per animal) on the fourth day after the social stress was induced. Simultaneous action of both factors caused the hypertrophy of adrenal glands, as well as elevated the activity of cathepsins B and L in the spleen. This effect on the activity of the cysteine proteases in the hippocampus and hypothalamus following O. felineus invasion was the predominant result of simultaneous action with social stress. Acute opisthorchiasis, social stress, and their combination caused an increase in the level of blood IL-6 in approximately 30% of the animals. Social stress induced a more pronounced effect on mouse plus-maze behavior than O. felineus invasion. Our results suggest a more severe negative effect of the simultaneous influence of both factors on most of the parameters that were investigated.

  6. Detection of the Carcinogenic Liver Fluke Opisthorchis viverrini Using a Mini Parasep SF Faecal Parasite Concentrator.

    PubMed

    Kaewpitoon, Soraya J; Rujirakul, Ratana; Tongtawee, Taweesak; Matrakul, Likit; Panpimanmas, Sukij; Wakkuwattapong, Parichart; Loyd, Ryan A; Kaewpitoon, Natthawut

    2016-01-01

    The Mini Parasep SF fecal parasite concentrator (MPSFC) is a new modification of the closed concentration system, which can easily be adopted in any routine clinical pathology laboratory. Here we describe our experience with the system in diagnosing Opisthorchis viverrini. A total of 199 fecal samples was submitted for routine examination in the clinical pathology laboratory of Suranaree University of Technology hospital, Nakhon Ratchasima province, Thailand, during August to October 2015. Out of all samples examined, 10 (5.03%) were positive with intestinal parasites including O. viverrini (2.01%), followed by Strongyloided stercoralis (1.51%), Hookworm (0.5%), Taenia spp. (0.5%), and Entamoeba coli (0.5%). Regarding the distribution of intestinal parasites in relation to the methods used, and found that 4 samples (2.01%) were positive using the direct wet smear method while 10 (5.03%) were positive with the Mini Parasep SF method; the difference was statistically significant (X2-test = 116.506, p-value =0.001). Mean time for processing using the Parasep system was 6.03 min/ sample, the conventional direct wet smear method at 0.3 min/sample. Cost per test, conventional direct wet smear method costing less than the Parasep method at USD 0.74/sample versus USD 1.47/sample. This first report of O. viverrini detection using MPSFC indicates that Parasep concentration test is useful in the routine laboratory, increasing the yield of parasites as compared to direct microscopy, but with greater processing time and cost. Further comparisons between the Parasep concentration test and common methods for O. viverrini detection are required, particularly concerning use in epidemiological surveys. PMID:26838241

  7. Comparative characterization of microRNAs from the liver flukes Fasciola gigantica and F. hepatica.

    PubMed

    Xu, Min-Jun; Ai, Lin; Fu, Jing-Hua; Nisbet, Alasdair J; Liu, Qing-You; Chen, Mu-Xin; Zhou, Dong-Hui; Zhu, Xing-Quan

    2012-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcription level. The present study specifically explored and compared the miRNA expression profiles of F. gigantica and F. hepatica using an integrated sequencing and bioinformatics platform and quantitative real-time PCR. Nineteen and 16 miRNA candidates were identified from F. gigantica and F. hepatica, respectively. The two parasites shared 11 miRNAs, with 8 also showing similarity to miRNAs of Schistosoma japonicum. Another 8 miRNAs were identified as F. gigantica-specific and 5 as F. hepatica-specific, most of which were novel. Predicted target analysis with 11465 mRNA and EST sequences of F. hepatica and F. gigantica revealed that all of the miRNAs had more than one target, ranging from 2 to 398 with an average of 51 targets. Some functions of the predicted targets were only found in F. gigantica, such as "transcription regulator", while some others were only found in F. hepatica, such as "reproduction" and "response to stimulus", indicating the different metabolism and gene regulation patterns of the two parasites. The present study represents the first global comparative characterization of miRNA expression profiles of F. gigantica and F. hepatica, which has provided novel valuable resources for a better understanding of the two zoonotic trematodes.

  8. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  9. New Genus of Blood Fluke (Digenea: Schistosomatoidea) from Malaysian Freshwater Turtles (Geoemydidae) and its Phylogenetic Position Within Schistosomatoidea.

    PubMed

    Roberts, Jackson R; Platt, Thomas R; Orélis-Ribeiro, Raphael; Bullard, Stephen A

    2016-08-01

    :  Baracktrema obamai n. gen., n. sp. infects the lung of geoemydid turtles (black marsh turtle, Siebenrockiella crassicollis [type host] and southeast Asian box turtle, Cuora amboinensis ) in the Malaysian states of Perak, Perlis, and Selangor. Baracktrema and Unicaecum Stunkard, 1925 are the only accepted turtle blood fluke genera having the combination of a single cecum, single testis, oviducal seminal receptacle, and uterine pouch. Baracktrema differs from Unicaecum by having a thread-like body approximately 30-50× longer than wide and post-cecal terminal genitalia. Unicaecum has a body approximately 8-12× longer than wide and terminal genitalia that are anterior to the distal end of the cecum. The new genus further differs from all other accepted turtle blood fluke genera by having a cecum that is highly convoluted for its entire length, a spindle-shaped ovary between the cirrus sac and testis, a uterine pouch that loops around the primary vitelline collecting duct, a Laurer's canal, and a dorsal common genital pore. Phylogenetic analysis of the D1-D3 domains of the nuclear large subunit ribosomal DNA (28S) revealed, with high nodal support and as predicted by morphology, that Baracktrema and Unicaecum share a recent common ancestor and form a clade sister to the freshwater turtle blood flukes of Spirorchis, paraphyletic Spirhapalum, and Vasotrema and that, collectively, these flukes were sister to all other tetrapod blood flukes (Hapalorhynchus + Griphobilharzia plus the marine turtle blood flukes and schistosomes). Pending a forthcoming emended morphological diagnosis of the family, the clade including Spirorchis spp., paraphyletic Spirhapalum, Vasotrema, Baracktrema, and Unicaecum is a likely placeholder for "Spirorchiidae Stunkard, 1921 " (type genus Spirorchis MacCallum, 1918 ; type species Spirorchis innominatus Ward, 1921 ). The present study comprises the 17th blood fluke known to infect geoemydid turtles and the first proposal of a new genus of

  10. Phyllodistomum kanae sp. nov. (Trematoda: Gorgoderidae), a bladder fluke from the Ezo salamander Hynobius retardatus.

    PubMed

    Nakao, Minoru

    2015-10-01

    The Ezo salamander, Hynobius retardatus, is endemic only to Hokkaido, the northernmost island of Japan. Gravid flukes of the family Gorgoderidae were discovered from the urinary bladder of H. retardatus. The parasites were identified as a new species named Phyllodistomum kanae sp. nov. In the neighboring Honshu island another bladder fluke, Phyllodistomum patellare, has already been found from the Japanese newt. The new species clearly differs from P. patellare in having a spherical ovary and very weakly lobed testes. The discovery of species of Phyllodistomum from urodelan amphibians is very uncommon in Eurasia. A molecular phylogeny based on 28S ribosomal DNA suggests that sphaeriid bivalves may serve as the first intermediate host for the new species.

  11. Phyllodistomum kanae sp. nov. (Trematoda: Gorgoderidae), a bladder fluke from the Ezo salamander Hynobius retardatus.

    PubMed

    Nakao, Minoru

    2015-10-01

    The Ezo salamander, Hynobius retardatus, is endemic only to Hokkaido, the northernmost island of Japan. Gravid flukes of the family Gorgoderidae were discovered from the urinary bladder of H. retardatus. The parasites were identified as a new species named Phyllodistomum kanae sp. nov. In the neighboring Honshu island another bladder fluke, Phyllodistomum patellare, has already been found from the Japanese newt. The new species clearly differs from P. patellare in having a spherical ovary and very weakly lobed testes. The discovery of species of Phyllodistomum from urodelan amphibians is very uncommon in Eurasia. A molecular phylogeny based on 28S ribosomal DNA suggests that sphaeriid bivalves may serve as the first intermediate host for the new species. PMID:25892565

  12. Bile components and amino acids affect survival of the newly excysted juvenile Clonorchis sinensis in maintaining media.

    PubMed

    Li, Shunyu; Kim, Tae Im; Yoo, Won Gi; Cho, Pyo Yun; Kim, Tong-Soo; Hong, Sung-Jong

    2008-10-01

    Clonorchis sinensis thrives on bile juice. The effects of bile and bile acids on newly excysted juvenile C. sinensis (CsNEJ) were studied in terms of survival. Survival of CsNEJs maintained in 1x Locke's solution, Dulbecco's modified Eagle's medium, NCTC 109, Eagle's, RPMI 1640, and 0.1% glucose was high, but dropped rapidly in 2x Locke's, 0.85% NaCl, and phosphate-buffered saline. Most amino acids in the media favored CsNEJ survival; however, aspartic and glutamic acids and adenine reduced survival. Survival was also significantly lower in media containing more than 0.1% bile. CsNEJs preconditioned in low bile media survived longer in higher bile media. All bile acids and conjugated bile salts were found to favor CsNEJ survival, except for lithocholic acid (LCA) which was toxic. NCTC 109 medium was found to be optimal for the in vitro maintenance of CsNEJs and 1x Locke's solution to be suitable for analyzing the biological effects of bioactive compounds and molecules. Based on these results, we propose that bile acids enhance activity of CsNEJs, but LCA deteriorate CsNEJs.

  13. Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases.

    PubMed

    Hanna, Robert

    2015-01-01

    This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis' gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24-96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products

  14. Fasciola hepatica: Histology of the Reproductive Organs and Differential Effects of Triclabendazole on Drug-Sensitive and Drug-Resistant Fluke Isolates and on Flukes from Selected Field Cases

    PubMed Central

    Hanna, Robert

    2015-01-01

    This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis’ gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24–96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products

  15. CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response.

    PubMed

    Xu, Yanquan; Lin, Jinsi; Bian, Meng; Chen, Wenjun; Liang, Pei; Wang, Xiaoyun; Shang, Mei; Qu, Hongling; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2015-06-01

    Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). However, it is unclear whether CsRNASET2 can induce adaptive immune response. In this study, we carried out further investigations on biochemical features of CsRNASET2. Besides, we immunized Balb/c mice with CsRNASET2 and orally infected Balb/c mice with C. sinensis, respectively. Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. Splenocytes of experimental mice were isolated and stimulated in vitro. The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. Taken together, these data suggested that CsRNASET2 was important for C. sinensis to trigger Th2 immune response. PMID:25828812

  16. Inducible nitric oxide synthase response and associated cytokine gene expression in the spleen of mice infected with Clonorchis sinensis.

    PubMed

    Shen, Ji-Qing; Yang, Qing-Li; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-05-01

    Clonorchis sinensis is a food-borne parasite that induces a permanent increase of nitrosation in the body upon infection. The spleen is an important secondary lymphoid organ for the regulation of immune responses locally and in the whole body. However, the functions and mechanisms of the spleen in nitric oxide (NO) responses after C. sinensis infection remain unknown. In this study, BALB/c mice were infected with 20, 40, and 80 C. sinensis metacercariae to simulate mild, moderate, and severe infections, respectively. We examined the expression of inducible nitric oxide synthase (iNOS) in the spleen and the relevant cytokine transcription in splenocytes from the mice infected with different amounts of metacercariae. The iNOS of the mice infected with 80 metacercariae was expressed in the spleen as early as 10 days post-infection (dpi) and gradually increased until 90 dpi. The iNOS expression in the mice infected with 40 metacercariae was detected only at 45 and 90 dpi, but not in the mice infected with 20 metacercariae. The level of interferon (IFN)-γ messenger RNA (mRNA) transcription in splenocytes significantly increased at 10 and 20 dpi (P < 0.05) in response to mild/moderate infection but gradually decreased to normal levels after 45 dpi. The level of IL-12p35 mRNA transcription did not change at 10 and 20 dpi but significantly decreased after 45 dpi under moderate/severe infection (P < 0.05/0.01/0.001). The level of IL-18 mRNA transcription significantly increased at 10 dpi (P < 0.05/0.01) but significantly decreased after 20 dpi (P < 0.05/0.01/0.001). These results suggest that spleen is an important organ for iNOS/NO responses, which correspond to the severity of C. sinensis infection, but cannot be attributed to the expression of the Th1 cytokines.

  17. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms. 311.25 Section 311.25 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

  18. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms. 311.25 Section 311.25 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

  19. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder-worms. 311.25 Section 311.25 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY...

  20. Fasciola hepatica: tegumental alterations in adult flukes following in vitro and in vivo administration of artesunate and artemether.

    PubMed

    Keiser, Jennifer; Morson, Gianni

    2008-02-01

    The tegumental changes in adult Fasciola hepatica induced by artemether and artesunate were assessed utilizing scanning electron microscopy (SEM). F. hepatica were incubated with artemether and artesunate for 48h at a concentration of 10microg/ml in the absence or presence of haemin. For the latter experiment both, a triclabendazole-resistant and sensitive F. hepatica isolate were used. For the in vivo studies rats were treated with single 200mg/kg oral doses of artemether and artesunate and flukes recovered from the bile ducts after 24-96h. SEM analysis of the flukes incubated in the presence of the drugs without haemin showed only minor and localized damage of the tegument. In the presence of haemin extensive tegumental damage, including sloughing, blebbing and eruptions, particularly in the ventral and dorsal mid-body and tail region, was evident. No difference in the extent of damage could be observed between artemether and artesunate and between the triclabendazole-resistant and non-resistant flukes. After 24h in vivo disruption of the tegument was evident in the artemether-treated flukes, and the damage increased in severity 48-72h post-treatment. Sloughing, swelling and extensive furrowing of the tegument was observed in several flukes, in particular in the tail region and the ventral apical cone region. In the artesunate treatment, tegumental damage was evident after 72h, but seemed slightly less pronounced when compared to the artemether-treated specimens examined at the same time point. Concluding our experiments confirm that artemether and artesunate are potent fasciocidal drugs and the tegument of adult F. hepatica appears to be a target for the action of these drugs.

  1. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  2. Risk Factors for Opisthorchis viverrini and Minute Intestinal Fluke Infections in Lao PDR, 2009–2011

    PubMed Central

    Yoon, Hee Jung; Ki, Moran; Eom, Keeseon; Yong, Tai-Soon; Chai, Jong-Yil; Min, Duk-Young; Rim, Han-Jong; Sohn, Woon-Mok; Insisiengmay, Bounnaloth; Phommasack, Bounlay

    2014-01-01

    The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato–Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9–133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered. PMID:24980495

  3. Helminths and helminthoses in Central Europe: general overview and diseases caused by trematodes (flukes).

    PubMed

    Auer, Herbert; Aspöck, Horst

    2014-10-01

    Parasitic helminths and helminthoses do not only occur in the tropics and subtropics but are also prevalent in Austria and other Central European countries. Their prevalence is, however, more or less rather low. In total, we know more than 20 helminth species, which are diagnosed regularly in Austria; some of them occur in Austria autochthonously, some others are acquired abroad and are transferred as souvenirs to Central Europe. The spectrum of helminths described in this overview comprises species of the trematodes (flukes), cestodes (tapeworms), and nematodes (roundworms).The topic "Helminths and helminthoses in Central Europe" is divided into three parts: The first part comprises a short introduction into the field of medical helminthology and is primarily dedicated to the description of trematodes and trematode-caused diseases.

  4. Risk factors for Opisthorchis viverrini and minute intestinal fluke infections in Lao PDR, 2009-2011.

    PubMed

    Yoon, Hee Jung; Ki, Moran; Eom, Keeseon; Yong, Tai-Soon; Chai, Jong-Yil; Min, Duk-Young; Rim, Han-Jong; Sohn, Woon-Mok; Insisiengmay, Bounnaloth; Phommasack, Bounlay

    2014-08-01

    The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato-Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9-133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered.

  5. Pathological changes in cattle naturally infected by Calicophoron daubneyi adult flukes.

    PubMed

    Fuertes, Miguel; Pérez, Valentín; Benavides, Julio; González-Lanza, M Camino; Mezo, Mercedes; González-Warleta, Marta; Giráldez, Francisco Javier; Fernández, Miguel; Manga-González, M Yolanda; Ferreras, M Carmen

    2015-04-30

    Local host response and parasite distribution were studied in the forestomachs, abomasum, duodenum and regional lymph nodes of cattle suffering from bovine paramphistomosis. The parasites were found attached, by its ventral sucker, to small conical papillae of the rumen and reticulum. Affected papillae, showed morphological changes denoted by very narrow stalks and expanded heads. Histologically, these changes were characterized by epithelial acanthosis-hyperkeratosis of the epithelium. Infiltration of inflammatory cells was often related with the epithelial changes, although it was also found in the duodenal mucosa and submucosa. These cells were arranged as aggregates or follicles but sparse infiltration of eosinophils, globule leukocytes, mast cells or macrophages was also observed in the lamina propria. Tissue damage and inflammatory reaction were more severe in the ruminal atrium, where the largest number of flukes and affected papillae were observed. In contrast, lesions in the ruminal dorsal sac were absent or mild. Statistical correlation between lesion severity and parasite burden was confirmed. PMID:25801360

  6. Risk factors for Opisthorchis viverrini and minute intestinal fluke infections in Lao PDR, 2009-2011.

    PubMed

    Yoon, Hee Jung; Ki, Moran; Eom, Keeseon; Yong, Tai-Soon; Chai, Jong-Yil; Min, Duk-Young; Rim, Han-Jong; Sohn, Woon-Mok; Insisiengmay, Bounnaloth; Phommasack, Bounlay

    2014-08-01

    The purpose of this report is to compare the prevalence of Opisthorchis viverrini/minute intestinal fluke (Ov/MIF) in Lao People's Democratic Republic according to different regions and evaluate the effect of ingestion of raw freshwater fish on the infection. Demographic data, behavioral data, and symptoms were obtained, and the Kato-Katz method was used for the diagnosis of Ov/MIF. In total, 3,046 individuals were enrolled. The risk factors associated with acquisition of Ov/MIF were raw fish consumption and province. Khong Island showed the highest prevalence (odds ratio = 80.1, 95% confidence interval = 47.9-133.9, P < 0.001) compared with other districts, and raw fish consumption was related to Ov/MIF infection. Administration of praziquantel to entire populations, education (avoiding consumption of raw food dishes and improved hygiene), and access to clean water and sanitation should be considered. PMID:24980495

  7. Inducible nitric oxide synthase response and associated cytokine gene expression in the spleen of mice infected with Clonorchis sinensis.

    PubMed

    Shen, Ji-Qing; Yang, Qing-Li; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-05-01

    Clonorchis sinensis is a food-borne parasite that induces a permanent increase of nitrosation in the body upon infection. The spleen is an important secondary lymphoid organ for the regulation of immune responses locally and in the whole body. However, the functions and mechanisms of the spleen in nitric oxide (NO) responses after C. sinensis infection remain unknown. In this study, BALB/c mice were infected with 20, 40, and 80 C. sinensis metacercariae to simulate mild, moderate, and severe infections, respectively. We examined the expression of inducible nitric oxide synthase (iNOS) in the spleen and the relevant cytokine transcription in splenocytes from the mice infected with different amounts of metacercariae. The iNOS of the mice infected with 80 metacercariae was expressed in the spleen as early as 10 days post-infection (dpi) and gradually increased until 90 dpi. The iNOS expression in the mice infected with 40 metacercariae was detected only at 45 and 90 dpi, but not in the mice infected with 20 metacercariae. The level of interferon (IFN)-γ messenger RNA (mRNA) transcription in splenocytes significantly increased at 10 and 20 dpi (P < 0.05) in response to mild/moderate infection but gradually decreased to normal levels after 45 dpi. The level of IL-12p35 mRNA transcription did not change at 10 and 20 dpi but significantly decreased after 45 dpi under moderate/severe infection (P < 0.05/0.01/0.001). The level of IL-18 mRNA transcription significantly increased at 10 dpi (P < 0.05/0.01) but significantly decreased after 20 dpi (P < 0.05/0.01/0.001). These results suggest that spleen is an important organ for iNOS/NO responses, which correspond to the severity of C. sinensis infection, but cannot be attributed to the expression of the Th1 cytokines. PMID:25687522

  8. Detection of Clonorchis sinensis Circulating Antigen in Sera from Chinese Patients by Immunomagnetic Bead ELISA Based on IgY

    PubMed Central

    Nie, Ge; Wang, Ting; Lu, Shengjun; Liu, Wenqi; Li, Yonglong; Lei, Jiahui

    2014-01-01

    Background Clonorchiasis, caused by Clonorchis sinensis, is widely distributed in Southeast Asia including China. Clonorchiasis is included in control programs of neglected tropical diseases by World Health Organization (WHO) because it is one of the major health problems in most endemic areas. Diagnosis of clonorchiasis plays a key role in the control programs. However, so far, there is no satisfactory method for clonorchiasis because of low sensitivity, poor practicality and high false positivity of available diagnostic tools. Methodology/Principal Findings We developed an immunomagnetic bead enzyme-linked immunosorbent assay (ELISA) based on IgY (egg yolk immunoglobulin) against cysteine proteinase of C. sinensis for detection of circulating antigen in serum samples of patients infected with C. sinensis. The polyclonal IgY, coated with magnetic beads, was used as a capture antibody and a monoclonal IgG labeled with horseradish peroxidase as a detection antibody in the IgY-based immunomagnetic bead ELISA system (IgY-IMB-ELISA). The results showed that the sensitivity of IgY-IMB-ELISA was 93.3% (14 of 15) in cases of heavy infection (5000 to 9999 eggs per gram feces, i.e, EPG 5000–9999), 86.7% (13 of 15) in cases of moderate infection (EPG 1000–4999) and 75.0% (9 of 12) in cases of light infection (EPG <1000) of clonorchiasis. Together 36 of total 42 (85.7%) serum samples of human clonorchiasis gave a positive reaction. There was a significant correlation between ELISA optical density and egg counts (EPG) with a correlation coefficient of 0.83 in total 42 patients. There were no positive results in patients with trichinosis (n = 10) or cysticercosis (n = 10). Cross-reactivity was 6.7% (2 of 30) with schistosomiasis japonica and 10.0% (3 of 30) with paragonimiasis, respectively. No positive reaction was found in 20 healthy persons. Conclusions Our findings suggest that IgY-IMB-ELISA appears to be a sensitive and specific assay for detection of

  9. Factors affecting abundance and prevalence of blood fluke, Cardicola forsteri, infection in commercially ranched southern bluefin tuna, Thunnus maccoyii, in Australia.

    PubMed

    Aiken, Hamish M; Hayward, Craig J; Nowak, Barbara F

    2015-05-30

    A survey of blood fluke, Cardicola forsteri, infection in ranched southern bluefin tuna, Thunnus maccoyii, was undertaken over three farming seasons, from March 2004 to September 2006. Analyses of covariance and logistic regression were used to explore the effects of company, year, season, time in culture, and condition index on intensity, abundance and prevalence of blood fluke infection. Average prevalence of blood fluke infection was 62.64% over the period of the survey. Average intensity was 6.20 (± 0.57) fluke per infected host and the average abundance was 3.70 (± 0.57) fluke per host. Year did not influence mean intensity or abundance although a significant decrease in prevalence in 2005 was evident. Tuna harvested in winter had a significantly greater abundance and prevalence of blood fluke than the tuna harvested in autumn. No effect of intensity or abundance of infection was observed on the condition of the infected tuna. A universal factor in explaining variation in C. forsteri intensity, abundance and prevalence was company. Differences in infection levels between tuna from different companies may be related to differences in husbandry measures employed on each farm, or due to different average sizes of tuna farmed by each of the companies, or due to the location of the operations.

  10. Liver Facts

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Liver Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ...

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

    PubMed Central

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

    2013-01-01

    [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

  12. Guillain-Barré Syndrome in a Boy With Lung Fluke Infection: Case Report and Literature Review.

    PubMed

    Yang, Cui-Wei; Gao, Feng; Xia, Zhe-Zhi

    2015-08-01

    Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.

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

    PubMed Central

    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

    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

  14. Plasma IgG autoantibody against actin-related protein 3 in liver fluke Opisthorchis viverrini infection.

    PubMed

    Rucksaken, R; Haonon, O; Pinlaor, P; Pairojkul, C; Roytrakul, S; Yongvanit, P; Selmi, C; Pinlaor, S

    2015-07-01

    Opisthorchiasis secondary to Opisthorchis viverrini infection leads to cholangiocellular carcinoma through chronic inflammation of the bile ducts and possibly inducing autoimmunity. It was hypothesized that plasma autoantibodies directed against self-proteins are biomarkers for opisthorchiasis. Plasma from patients with opisthorchiasis was tested using proteins derived from immortalized cholangiocyte cell lines, and spots reacting with plasma were excised and subjected to LC-MS/MS. Seven protein spots were recognized by IgG autoantibodies, and the highest matching scored protein was actin-related protein 3 (ARP3). The antibody against ARP3 was tested in plasma from 55 O. viverrini-infected patients, 24 patients with others endemic parasitic infections and 17 healthy controls using Western blot and ELISA. Immunoreactivity against recombinant ARP3 was significantly more prevalent in opisthorchiasis compared to healthy controls at Western blotting and ELISA (P < 0.05). Plasma ARP3 autoantibody titres were also higher in opisthorchiasis compared to healthy individuals (P < 0.01) and other parasitic infections including Strongyloides stercoralis (P < 0.001), echinostome (P < 0.05), hookworms (P < 0.001) and Taenia spp. (P < 0.05). It was further characterized in that the ARP3 autoantibody titre had a sensitivity of 78.18% and specificity of 100% for opisthorchiasis. In conclusion, it may be suggested that plasma anti-ARP3 might represent a new diagnostic antibody for opisthorchiasis. PMID:25809205

  15. Role of the lymnaeid snail Pseudosuccinea columella in the transmission of the liver fluke Fasciola hepatica in Egypt.

    PubMed

    Dar, Y; Vignoles, P; Rondelaud, D; Dreyfuss, G

    2015-11-01

    Experimental infections of three Egyptian Pseudosuccinea columella populations with sympatric miracidia of Fasciola sp., coming from cattle- or sheep-collected eggs, were carried out to determine the capacity of this lymnaeid to support larval development of the parasite. Using microsatellite markers, the isolates of Egyptian miracidia were identified as Fasciola hepatica. Apart from being independent of snail origin, prevalences ranging from 60.4 to 75.5% in snails infected with five miracidia of F. hepatica were significantly higher than values of 30.4 to 42.2% in snails with bi-miracidial infections. The number of metacercariae ranged from 243 to 472 per cercarial-shedding snail and was independent of snail origin, parasite origin and miracidial dose used for infection. If P. columella was subjected to two successive bi-miracidial infections with F. hepatica, prevalence of infection was 63.3%, with a mean of 311 metacercariae per snail. These values were clearly greater than those already reported for Radix natalensis infected with the same parasite and the same protocol. Successful experimental infection of P. columella with F. hepatica suggests that this lymnaeid snail is an important intermediate host for the transmission of fascioliasis in Egypt.

  16. Proteomic identification of plasma protein tyrosine phosphatase alpha and fibronectin associated with liver fluke, Opisthorchis viverrini, infection.

    PubMed

    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

    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 (PTPα) 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. PTPα 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 PTPα and fibronectin may be associated with opisthorchiasis and the hamster model provides the basis for development of novel diagnostic markers in the future.

  17. The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.

    PubMed

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

    2012-03-01

    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.

  18. Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease

    PubMed Central

    Friant, Sagan; Brown, Kelsey; Saari, Mason T.; Segel, Nicholas H.; Slezak, Julia; Goldberg, Tony L.

    2015-01-01

    Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs. PMID:26543803

  19. Heterophysiasis, an intestinal fluke infection of man and vertebrates transmitted by euryhaline gastropods and fish

    NASA Astrophysics Data System (ADS)

    Taraschewski, H.

    1984-03-01

    Heterophyes heterophyes, agent of human heterophyiasis in the Near East, is transmitted in marine lagoons and saline inland waters, where the euryhaline intermediate hosts are abundant. In Egypt, mullets, the predominant second intermediate hosts, are customarily consumed raw; thus man becomes infected easily. Symptoms of human infections are usually considered mild. Mullets do not seem to be affected by the metacercariae encysted in the muscles, whereas the growth of the snail host Pirenella conica was found to be enhanced due to the infestation by the trematodes. In laboratory experiments, the flukes were found to be well developed in dogs, foxes and cats, but failed to reach sexual maturity in several other potentially piscivorous mammals and birds. In nature, dogs probably serve as the major reservoir hosts. Heterophyiasis is most prevalent in the Nile Delta, a huge brackish water area which is densely populated by humans and, consequently, also by dogs and cats. In the Far East, besides Heterophyes nocens, several other heterophysids with marine or fresh-water life-cycles are known to infect humans.

  20. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age

    PubMed Central

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P.; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People’s Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  1. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age.

    PubMed

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People's Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  2. Liver Wellness

    MedlinePlus

    ... to liver wellness. • There are more than 100 liver diseases. • Liver disease is one of the top 10 causes of ... out of every 10 Americans is affected by liver disease. • Some liver diseases such as hepatitis A, hepatitis ...

  3. 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 ...

  4. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  5. Liver Transplant

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  6. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  7. HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni

    PubMed Central

    Mann, Victoria H.; Dubrovsky, Larisa; Yan, Hong-bin; Huckvale, Thomas; Protasio, Anna V.; Pushkarsky, Tatiana; Iordanskiy, Sergey; Bukrinsky, Michael I.

    2016-01-01

    Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the RNA genome reverse transcribed. Anchored PCR analysis, sequencing HIV-1-specific anchored Illumina libraries and Whole Genome Sequencing (WGS) of schistosomes confirmed chromosomal integration; >8,000 integrations were mapped, distributed throughout the eight pairs of chromosomes including the sex chromosomes. The rate of integrations in the genome exceeded five per 1,000 kb and HIV-1 integrated into protein-encoding loci and elsewhere with integration bias dissimilar to that of human T cells. We estimated ~ 2,100 integrations per schistosomulum based on WGS, i.e. about two or three events per cell, comparable to integration rates in human cells. Accomplishment in schistosomes of post-entry processes essential for HIV-1replication, including integrase-catalyzed integration, was remarkable given the phylogenetic distance between schistosomes and primates, the natural hosts of the genus Lentivirus. These enigmatic findings revealed that HIV-1 was active within cells of S. mansoni, and provided the first demonstration that HIV-1 can integrate into the genome of an invertebrate. PMID:27764257

  8. Three new species of blood flukes (Digenea: Aporocotylidae) infecting pufferfishes (Teleostei: Tetraodontidae) from off Bali, Indonesia.

    PubMed

    Yong, R Q-Y; Cutmore, S C; Bray, R A; Miller, T L; Semarariana, I W Y; Palm, H W; Cribb, T H

    2016-10-01

    We describe three new species of blood flukes (Aporocotylidae) and propose their classification within the genus Psettarium Goto & Ozaki, 1929. All three species were collected from the circulatory systems of pufferfishes caught off Bali, central Indonesia. Psettarium pulchellum n. sp. was found in the gills of both the narrow-lined puffer (Arothron manilensis de Procé) and the spiny blaasop (Tylerius spinosissimus Regan), while P. ogawai n. sp. and P. jimbaranense n. sp. were found in the gills of the reticulated puffer (Arothron reticularis Bloch & Schneider). The morphological characteristics of these taxa necessitated emendation of the diagnosis for the genus Psettarium, to accommodate the presence of an oral sucker, multiple or entirely post-caecal testes and a degenerate posterior testis. Features such as proportion of body length occupied by the oesophagus, and posterior caeca being ≥7× the length of anterior caeca, are no longer regarded as useful genus-level characters. Additionally, Sasala nolani is reassigned to this genus as Psettarium nolani n. comb. In phylogenetic analyses of the 28S and ITS2 rDNA regions, all three new taxa form a well-supported clade, together with Psettarium sinense and Psettarium nolani n. comb., the two other species of tetraodontid-infecting aporocotylids for which comparative rDNA data were available. The short branch lengths within this clade, despite dramatic morphological differences between the five species, suggest that rapid morphological diversification has occurred among the tetraodontid-infecting aporocotylids. The genus Psettarium has long been considered problematic. Further commentary is given on the history of this genus and how the issues presented might be resolved.

  9. Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

    PubMed Central

    Fajtová, Pavla; Štefanić, Saša; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, James H.; Caffrey, Conor R.; Mareš, Michael; Horn, Martin

    2015-01-01

    Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. Methodology/Principal Findings We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. Conclusions/Significance We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs. PMID:26039195

  10. Helminths in human carcinogenesis.

    PubMed

    Fried, Bernard; Reddy, Aditya; Mayer, David

    2011-06-28

    This review examines the salient literature on selected helminths involved in carcinogenicity in humans and updates information in an earlier review on cancer and helminths by Mayer and Fried (2007, Advances in Parasitology 65, 239-296). The earlier review was concerned with various helminths, i.e., trematodes, cestodes, and nematodes, that are definitely implicated as being carcinogenic. This review examines only those helminths, all of which turn out to be trematodes, that are definitely implicated as being carcinogenic. These trematodes are the blood flukes Schistosoma haematobium, associated with inducing human carcinoma of the urinary bladder and the liver flukes Opisthorchis viverrini and Clonorchis sinensis, associated with inducing cancer of the bile duct (cholangiocarcinoma) and cancer of the liver (hepatocarcinoma) in humans. The review examines mainly the epidemiology and pathology of these helminthic infections in humans and considers what we know about the mechanisms associated with the carcinogenicity of these three trematodes in humans.

  11. Liver regeneration.

    PubMed

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  12. Liver Regeneration

    PubMed Central

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-01-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review will provide an overview of the models of study currently utilized in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus will be placed on clinical applications of current knowledge in liver regeneration including small for size liver transplant. Furthermore, cutting edge topics in liver regeneration including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a three dimensional scaffold for liver repopulation will be proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration. PMID:24495569

  13. MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum

    PubMed Central

    Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E.; Cheng, Guofeng

    2016-01-01

    Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production. PMID:26871705

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

    PubMed Central

    Dvořák, Jan; Mashiyama, Susan T.; Sajid, Mohammed; Braschi, Simon; Delcroix, Melaine; Schneider, Eric L.; McKerrow, Wilson H.; Bahgat, Mahmoud; Hansell, Elizabeth; Babbitt, Patricia C.; Craik, Charles S.; McKerrow, James H.; Caffrey, Conor R.

    2009-01-01

    Background Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins. Methodology/Principal Findings We identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence data. An ortholog is present in Schistosoma japonicum. SmCL3 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH activity range against peptidyl substrates and is inhibited by Clan CA protease inhibitors. Consistent with a function in degrading host proteins, SmCL3 hydrolyzes serum albumin and hemoglobin, is localized to the adult gastrodermis, and is expressed mainly in those life stages infecting the mammalian host. The predominant form of SmCL3 in the parasite exists as a zymogen, which is unusual for proteases. This zymogen includes an unusually long prodomain with alpha helical secondary structure motifs. The striking specificity of SmCL3 for amino acids with large aromatic side chains (Trp and Tyr) at the P2 substrate position, as determined with positional scanning-synthetic combinatorial library, is consistent with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN) view clusters SmCL3 and other cathepsins L in accordance with previous large-scale phylogenetic analyses that identify six super kingdoms. Conclusions/Significance SmCL3 is a gut-associated cathepsin L that may contribute to the network of proteases involved in degrading host blood proteins as nutrients. Furthermore, this enzyme exhibits some unusual sequence and biophysical features that may result in additional functions. The visualization of network inter-relationships among cathepsins L suggests that these enzymes are suitable

  15. American Liver Foundation

    MedlinePlus

    ... LALD) Intrahepatic Cholestasis of Pregnancy (ICP) Liver Biopsy Liver Cancer Liver Cysts Liver Function Tests Liver Transplant Newborn ... community. It's Liver Awareness Month- and it's also Liver Cancer Awareness Month, so we've teamed with Bayer ...

  16. The effectiveness of repeated tank treatments of copper sulfate and formalin on gill flukes and Ich in naturally infested white bass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ectoparasites infesting the gills of juvenile fish reared in tanks can cause serious fish losses. Multiple treatments of formalin and copper sulfate (CuSO4) were evaluated for effectiveness against a natural infestation of gill flukes Onchocleidus mimus (Monogenoidea: Ancyrocephalidae) and Ichthyop...

  17. Liver Biopsy

    MedlinePlus

    ... PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is a ... to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that involves ...

  18. Liver transplantation☆

    PubMed Central

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

    2007-01-01

    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

  19. Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

    PubMed Central

    He, Lei; Wang, Xiaoyun; Liang, Pei; Chen, Wenjun; Bian, Meng; Ren, Mengyu; Lin, Jinsi; Liang, Chi; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2013-01-01

    Background Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. Methodology/Principal Findings There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. Conclusions/Significance Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC

  20. Mapping of the putative epitope domain of Clonorchis sinensis paramyosin (CsPmy) recognized by CsPmy-specific immunoglobulin G in sera of human clonorchiasis.

    PubMed

    Kang, Jung-Mi; Ju, Hye-Lim; Lee, Jinyoung; Kim, Tae Im; Cho, Shin-Hyeong; Kim, Tong-Soo; Sohn, Woon-Mok; Na, Byoung-Kuk

    2015-05-01

    Paramyosin of Clonorchis sinensis (CsPmy) is a myofibrillar protein localized in subtegumental muscle, tegument, and the muscle layer surrounding the intestine of the parasite. Previously, we have identified that CsPmy reacted with sera of human clonorchiasis and this protein had a potential as a candidate antigen for serodiagnosis of clonorchiasis. However, we also found that CsPmy is able to bind to human immunoglobulin G (IgG) in non-specific manners, which can affect the diagnostic value of the protein. Here, we mapped CsPmy-specific IgG binding site on CsPmy to analyze the putative epitopes recognized by CsPmy-specific IgG in sera of human clonorchiasis. The fragmental expression of CsPmy followed by immunoblot analyses with sera from patients with clonorchiasis and non-specific human IgG revealed that the middle portion of CsPmy (CsPmyC: 301-600 amino acid residues) had epitopes responsible for CsPmy-specific IgG recognition. The precise CsPmy-specific IgG binding site was further narrowed down to a fragment (CsPmyC-2), which harbors 151 amino acid residues (375-525) of CsPmy. Specific antibodies for CsPmyC-2 were produced in rats after two-weeks of post-experimental infection. The CsPmyC-2 showed low levels of cross reactivity against the sera from patients with other helminth parasites. Our results suggested that CsPmyC-2 has real epitopes recognized by CsPmy-specific IgG in sera of human clonorchiasis and the fragment can be useful as a reliable serodiagnostic antigen to develop a serodiagnostic method for clonorchiasis. PMID:26099940

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

    PubMed

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

    2013-06-01

    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.

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

    PubMed

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

    2010-03-01

    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 of the genes suggested they belonged to the cathepsin F-like enzyme family and further clustered into three different subfamilies. Enzymatic and proteomic analysis of C. sinensis excretory and secretory products (ESP) revealed that multiple isoforms of CsCF were the major proteins present in the ESP and the proteolytic activity of the ESP is mainly attributable to the enzymes. Comparative analysis of representative enzymes for each subfamily, CsCF-4, CsCF-6, and CsCF-11, showed that they share similar biochemical properties typical for cathepsin F-like enzymes, but significant differences were also identified. The enzymes were expressed throughout various developmental stages of the parasite and the transcripts increased gradually in accordance with the maturation of the parasite. Immunolocalization analysis of CsCFs showed that they were mainly localized in the intestine and intestinal contents of the parasite. These results collectively suggested that CsCFs, which are apparently synthesized in the epithelial cells lining the parasite intestine and secreted into the intestinal lumen of the parasite, might have a cooperative role for nutrient uptake in the parasite. Furthermore, they were eventually secreted into outside of the parasite and may perform additional functions for host-parasite interactions.

  3. Larval stages of the bluefin tuna blood fluke Cardicola opisthorchis (Trematoda: Aporocotylidae) found from Terebella sp. (Polychaeta: Terebellidae).

    PubMed

    Sugihara, Yukitaka; Yamada, Toshiyuki; Tamaki, Akio; Yamanishi, Ryohei; Kanai, Kinya

    2014-04-01

    We found aporocotylid larval stages (sporocysts and cercariae) from five individuals of terebellid polychaete Terebella sp., which were collected from seabed substrate and ropes and floats attached to tuna cages in a tuna farm on the coast of Tsushima Island, Nagasaki, Japan. Nucleotide sequences of the regions of internal transcribed spacer 2 ribosomal DNA and 28S ribosomal DNA from these larval stages were 100% identical to those of Cardicola opisthorchis registered in GenBank. C. opisthorchis is a pathogen causing blood fluke infection of Pacific bluefin tuna Thunnus orientalis, which is considered to have a significant impact on the Japanese Pacific bluefin tuna aquaculture industry. This is the first description of the intermediate host of C. opisthorchis. This indicates that the life cycle of C. opisthorchis is completed within tuna farms in this area.

  4. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    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

  5. Stellantchasmus falcatus (Digenea: Heterophyidae) in Cambodia: Discovery of Metacercariae in Mullets and Recovery of Adult Flukes in an Experimental Hamster

    PubMed Central

    Chai, Jong-Yil; Sohn, Woon-Mok; Na, Byoung-Kuk; Jeoung, Hoo-Gn; Sinuon, Muth; Socheat, Duong

    2016-01-01

    Stellantchasmus falcatus (Digenea: Heterophyidae) is first reported from Cambodia through recovery of the metacercariae from mullet fish and adult flukes from an experimentally infected hamster. We purchased 7 mullets, Chelon macrolepis, in a local market of Phnom Penh, Cambodia, and each of them was examined by the artificial digestion method on May 2010. The metacercariae of S. falcatus were detected in all mullets (100%) examined, and their average density was 177 per fish. They were elliptical, 220×168 μm in average size. They were orally infected to an hamster to obtain adult flukes. Adults recovered at day 10 post infection were observed with a light microscope and a scanning electron microscope (SEM). They were small, 450×237 μm in average size, had a small oral sucker (41×50 μm), subglobular pharynx (29×21 μm), slender esophagus (57 μm), long and thick-walled expulsor (119×32 μm), spherical ovary (58×69 μm), and 2 ovoid testes (right: 117×74 μm; left: 114×63 μm). Eggs were small, yellow, and 23×12 μm in average size. In SEM observations, tegumental spines were densely distributed on the whole tegument, and single small type I sensory papillae were distributed around the lip of oral sucker. The small ventral sucker was dextrally located and had 8 type I sensory papillae on the left margin. It has been first confirmed in the present study that the mullet, C. macrolepis, is playing the role of a second intermediate host of S. falcatus in Cambodia. PMID:27658608

  6. Stellantchasmus falcatus (Digenea: Heterophyidae) in Cambodia: Discovery of Metacercariae in Mullets and Recovery of Adult Flukes in an Experimental Hamster.

    PubMed

    Chai, Jong-Yil; Sohn, Woon-Mok; Na, Byoung-Kuk; Jeoung, Hoo-Gn; Sinuon, Muth; Socheat, Duong

    2016-08-01

    Stellantchasmus falcatus (Digenea: Heterophyidae) is first reported from Cambodia through recovery of the metacercariae from mullet fish and adult flukes from an experimentally infected hamster. We purchased 7 mullets, Chelon macrolepis, in a local market of Phnom Penh, Cambodia, and each of them was examined by the artificial digestion method on May 2010. The metacercariae of S. falcatus were detected in all mullets (100%) examined, and their average density was 177 per fish. They were elliptical, 220×168 μm in average size. They were orally infected to an hamster to obtain adult flukes. Adults recovered at day 10 post infection were observed with a light microscope and a scanning electron microscope (SEM). They were small, 450×237 μm in average size, had a small oral sucker (41×50 μm), subglobular pharynx (29×21 μm), slender esophagus (57 μm), long and thick-walled expulsor (119×32 μm), spherical ovary (58×69 μm), and 2 ovoid testes (right: 117×74 μm; left: 114×63 μm). Eggs were small, yellow, and 23×12 μm in average size. In SEM observations, tegumental spines were densely distributed on the whole tegument, and single small type I sensory papillae were distributed around the lip of oral sucker. The small ventral sucker was dextrally located and had 8 type I sensory papillae on the left margin. It has been first confirmed in the present study that the mullet, C. macrolepis, is playing the role of a second intermediate host of S. falcatus in Cambodia. PMID:27658608

  7. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

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

    PubMed Central

    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

    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

  9. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    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

  10. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  11. Benign Liver Tumors

    MedlinePlus

    ... Search: Your Liver Liver Health and Wellness Recipes Liver Disease Information Patients & Families Caregiver's FAQ Become an Organ ... 2013 Liver Awareness Month Personal Story - David Roncori Liver Disease - The Big Picture 13 Ways to a Healthy ...

  12. Liver Panel

    MedlinePlus

    ... liver; the best test for detecting hepatitis Alkaline phosphatase (ALP) – an enzyme related to the bile ducts ... only moderately elevated or close to normal. Alkaline phosphatase (ALP) ALP may be significantly increased with obstructed ...

  13. Liver transplant

    MedlinePlus

    ... toxins in the blood Storing sugars, fats, iron, copper, and vitamins The most common reason for a ... cirrhosis or primary sclerosing cholangitis Metabolic disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant ...

  14. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  15. Description of a new lung fluke species, Paragonimus vietnamensis sp. nov. (Trematoda, Paragonimidae), found in northern Vietnam.

    PubMed

    Doanh, Pham Ngoc; Shinohara, Akio; Horii, Yoichiro; Habe, Shigehisa; Nawa, Yukifumi; Le, Nguyen Thi

    2007-11-01

    Based on morphology of metacercariae and adult worms together with molecular data from our previous study, we describe herein a new lung fluke species named Paragonimus vietnamensis sp. nov. Metacercariae of this new species is round and extremely large in size (nearly 800 mum in diameter) having a fragile outer cyst of variable thickness and a thin fragile inner cyst. There are little or no space between metacercaria and the inner cyst wall. These and other morphological features of metacercariae of P. vietnamensis sp. nov. are not completely identical with but have some similarities with those of P. microrchis, P. proliferus, or P. menglaensis. On the other hand, adult worms obtained by experimental infection of these large metacercariae are oval in shape, having a ventral sucker slightly larger than the oral one, and having singly arranged relatively short cuticular spines. These morphological features of adult worms are partly similar to but not identical with those of P. microrchis, P. skrjabini, P. yunnanenis, P. xiangshanensis, or P. harinasutai. Taken these morphological data and our previous molecular phylogenetic analyses of ITS2 and CO1 sequences of metacercariae and adult worms together, P. vietnamensis sp. nov. is different from any other known Paragonimus spp.

  16. Detection by ELISA of circulating anti-blood fluke (Carettacola, Hapalotrema, and Learedius) immunoglobulins in Hawaiian green turtles (Chelonia mydas).

    PubMed

    Graczyk, T K; Aguirre, A A; Balazs, G H

    1995-06-01

    An enzyme-linked immunosorbent assay (ELISA) is described utilizing the surface glycocalyx crude antigen of adult blood trematodes Learedius learedi, Hapalotrema dorsopora, and Carettacola hawaiiensis, for the detection of circulating antibodies (Ab) in Hawaiian green turtles (Chelonia mydas) naturally infected with the parasites and with or without green turtle fibropapillomatosis (GTFP). A concentration of 10.0 micrograms/ml of antigen was optimal in terms of test specificity and sensitivity. A direct ELISA with anti-reptilian/amphibian phosphatase-labeled IgG identified C. mydas Ab at a dilution of 1/12,800. Utilizing indirect ELISA, it was possible to detect Ab to blood flukes at a dilution of 1/3,200. The gross lesions and histopathology were typical for cardiovascular spirorchidiasis in C. mydas. No significant relationship was found between the size of turtles and the degree of GTFP severity. Forty-seven of 59 (80%) samples, from 5 sites, gave a positive ELISA reaction; 6 of the 47 (13%) specimens gave significantly (P < 0.001) higher absorbance values, with 5 from the same location. All 12 (20%) ELISA-negative turtles originated from 1 site, and the absorbance values of the 41 animals from this location were significantly lower (P < 0.015) when compared with the other 4 sites. The proposed assay is fast, has the feature of visual scoring, and can be used for determination of exposure of C. mydas to the spirorchid trematodes.

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

    PubMed Central

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

    2012-01-01

    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

  18. Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus.

    PubMed

    Pomaznoy, Mikhail Yu; Logacheva, Maria D; Young, Neil D; Penin, Aleksey A; Ershov, Nikita I; Katokhin, Alexey V; Mordvinov, Viatcheslav A

    2016-02-01

    Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a causative agent of the infection called opisthorchiasis or liver fluke infection. Being a close relative of Opisthorchis viverrini and Clonorchis sinensis (oriental liver flukes) it is encountered in northern Eurasia, especially in Russia, Kazakhstan, Belarus, Ukraine, and Baltic countries. Whole genome data for oriental liver flukes revealed their adaptations for life in the bile duct but our knowledge of O. felineus is scarce. To address this knowledge gap and uncover evolutionary aspect of the adaptations on the transcriptomic level, we used RNA-sequencing approach to investigate two stages of the parasite residing in different hosts. Bioinformatic analysis revealed specific features affecting various biochemical pathways and gene networks. Namely, we observed the loss of genes involved in polyamine synthesis, methionine salvage and peroxisome biogenesis. Some of the gene families, like MD-2 lipid binding proteins, calmodulins and cathepsins on the contrary have expanded compared to free living eukaryotes. We identified significant differences between the stages in homeodomain-containing genes, G-protein coupled receptors, and neuroactive signaling systems. Granulin-like growth factors specific for O. felineus were also identified. In this work, we provide the first whole transcriptome investigation of this parasite. We also hope that these results will create a background for further molecular research of helminth infections and opisthorchiasis in particular. PMID:26363139

  19. Characterization of microRNAs from Orientobilharzia turkestanicum, a neglected blood fluke of human and animal health significance.

    PubMed

    Wang, Chun-Ren; Xu, Min-Jun; Fu, Jing-Hua; Nisbet, Alasdair J; Chang, Qiao-Cheng; Zhou, Dong-Hui; Huang, Si-Yang; Zou, Feng-Cai; Zhu, Xing-Quan

    2012-01-01

    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.

  20. Corset liver

    SciTech Connect

    Philips, D.M.; LaBrecque, D.R.; Shirazi, S.S.

    1985-08-01

    The authors describe four patients with a benign hepatic malformation most consistent with the rarely described anomaly known as corset liver. Three of these patients were extensively evaluated to rule out a malignancy because of an abdominal mass. These patients illustrate several features which may help in making the diagnosis and avoiding unnecessary surgery.

  1. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  2. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  3. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  4. [New occurrences of metacercariae of Austrodiplostomum compactum (Lutz, 1928) (Platyhelminthes: Digenea) eye flukes of fish from the Paraná Basin].

    PubMed

    Yamada, Fábio Hideki; Moreira, Luis Henrique De A; Ceschini, Tiago L; Takemoto, Ricardo Massato; Pavanelli, Gilberto Cezar

    2008-01-01

    Austrodiplostomum compactum (Platyhelminthes, Digenea) eye flukes of several species of fishes. The presence of this parasite, in extreme cases, can cause swelling of the eyelids, displacement of the retina, opacity of the crystalline lens and blindness or even death. The present study it registers new occurrences of this metacercariae infecting the eyes of four new hosts of fish, Serrasalmus maculatus collected in the Rosana reservoir in the Paranapanema river and Hypostomus regani, Schizodon borellii and Auchenipterus osteomystax collected in the the Upper Paraná River floodplain.

  5. Similarity of a 16.5kDa tegumental protein of the human liver fluke Opisthorchis viverrini to nematode cytoplasmic motility protein.

    PubMed

    Labbunruang, Nipawan; Phadungsil, Wansika; Tesana, Smarn; Smooker, Peter M; Grams, Rudi

    2016-05-01

    Opisthorchis viverrini is the causative agent of human opisthorchiasis in Thailand and long lasting infection with the parasite has been correlated with the development of cholangiocarcinoma. In this work we have molecularly characterized the first member of a protein family carrying two DM9 repeats in this parasite (OvDM9-1). InterPro and other protein family databases describe the DM9 repeat as a protein domain of unknown function that has been first noted in Drosophila melanogaster. Two paralogous proteins have been partially characterized in the genus Fasciola, Fasciola hepatica TP16.5, a novel tegumental antigen in human fascioliasis and, recently F. gigantica DM9-1, a parenchymal protein with structural similarity to nematode cytoplasmic motility protein (MFP2). In this study, we show further evidence that this family of trematode proteins is related to MFP2 in sequence and structure. Soluble recombinant OvDM9-1 was used for structural analyses and for production of specific antisera. The native protein was detected in soluble and insoluble crude worm extracts and in seemingly various oligomeric forms in the latter. The potential for oligomerization was supported by cross-linking experiments of recombinant OvDM9-1. Structure prediction suggested a β-rich secondary structure of the protein and this was supported by a circular dichroism analysis. Molecular modeling in Phyre2 identified both MFP2 domains as distant homologs of OvDM9-1. The protein was located in tegumental type tissue and the cecal epithelium in the mature parasite. Recombinant OvDM9-1 was used as target in indirect ELISA but sera from infected hamsters showed only marginal reactivity towards it. It is proposed that OvDM9-1 and other members of this protein family have a role in cellular transport through functions on the cytoskeleton. PMID:27140280

  6. Natural prevalence in Cuban populations of the lymnaeid snail Galba cubensis infected with the liver fluke Fasciola hepatica: small values do matter.

    PubMed

    Vázquez, Antonio A; Sánchez, Jorge; Alba, Annia; Pointier, Jean-Pierre; Hurtrez-Boussès, Sylvie

    2015-11-01

    Natural infections of lymnaeid snails by Fasciola hepatica are of primary importance to study transmission. Also, infected snails in the field can be used to explore the existing compatibility in host-parasite interactions. This paper aimed to describe the infection rate of Galba cubensis populations in fasciolosis transmission areas. Eight sites were sampled in western Cuba and 24 infected snails at six sites were found. The mean prevalence was 2.94% and the maximum value was 11.4%. The intensity of parasite infection was assessed as the number of rediae inside a single snail. High variation within the sites examined was observed, but a maximum of 76 rediae was recovered from one individual. Although the presence of two other trematode families (Schistosomatidae and Paramphistomatidae) was discovered in dissected individuals, no co-infection with F. hepatica was observed. This is the first time a study of natural prevalence of F. hepatica infection is carried out in Cuba, considered a hyper endemic country for bovine fasciolosis. Our results suggest that fasciolosis transmission may occur even when the number of infected snails remains relatively low.

  7. Insights into the biological features of the antigenic determinants recognized by four monoclonal antibodies in redia and adult stages of the liver fluke Fasciola hepatica.

    PubMed

    Alba, Annia; Sánchez, Jorge; Hernández, Hilda; Mosqueda, Maryani; Rodríguez, Suanel Y; Capó, Virginia; Otero, Oscar; Alfonso, Carlos; Marcet, Ricardo; Sarracent, Jorge

    2016-09-01

    Fasciola hepatica is a digenean trematode which infects a wide variety of domestic animals and also humans. Previous studies have demonstrated that four monoclonal antibodies (Mabs) against the total extract of F. hepatica redia (named as 1E4, 6G11, 4E5 and 4G11) also recognized the excretion - secretion antigens (ES Ag) of adult parasites, which is a biologically-relevant mixture of molecules with functional roles during infection and immune evasion on definitive hosts. In the present report we describe the partial characterization of the epitopes recognized by these Mabs by heat treatment, mercaptoethanol reduction, pronase proteolysis and sodium peryodate oxidation, which suggested their predominant protein and conformational nature. Also, a comparative study using immunodetection assays on crude extracts and on histological sections of both rediae and adults of F. hepatica were performed to explore the expression pattern of the antigenic determinants in these developmental stages. From these experiments it was found that the Mabs reacted most likely with the same proteins of approximately 64 and 105 kDa present on both rediae and adult's extracts. However, the 1E4, 6G11 and 4E5 Mabs also recognized other molecules of the total extract of F. hepatica adults, a fact that constitutes an evidence of the antigenic variation between both stages and points at a certain biological relevance of the recognized antigenic determinants. Immunolocalization studies on histological sections revealed that all Mabs reacted with the tegument of F. hepatica in both rediae and adults stages, while the epitopes recognized by 1E4, 6G11 and 4E5 antibodies were also preferentially localized in the intestinal caeca and in different organs of the reproductive system of adult specimens. The immunogenicity of these antigenic determinants, their conserved status among different stages of the life cycle of F. hepatica and their presence in both tegument and ES Ag of adult parasites, are suitable features that suggest their potential use for developing an epitope-based vaccine for fasciolosis control.

  8. Differences in the compatibility of infection between the liver flukes Fascioloides magna and Fasciola hepatica in a Colombian population of the snail Galba sp.

    PubMed

    Dreyfuss, G; Correa, A C; Djuikwo-Teukeng, F F; Novobilský, A; Höglund, J; Pankrác, J; Kašný, M; Vignoles, P; Hurtrez-Boussès, S; Pointier, J P; Rondelaud, D

    2015-11-01

    Experimental infections of Galba sp. (origin, Colombia) with allopatric isolates of Fasciola hepatica from France or Fascioloides magna from the Czech Republic were carried out during five successive snail generations to determine if this lymnaeid might sustain complete larval development of either parasite. In snails exposed to F. hepatica, 7 of 400 snails harboured several rediae and only two snails contained a small number of free cercariae on day 50 post-exposure. In contrast, the intensity of F. magna infection in Galba sp. progressively increased from the F1 to F5 generations. Spontaneous cercarial shedding of F. magna occurred in 7 of 100 Galba sp. belonging to the F5 generation and the number of shed cercariae did not differ significantly from that noted in control Galba truncatula of French origin. Galba sp. from Colombia can be added to the list of potential intermediate hosts for F. magna.

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

    PubMed Central

    Biswal, Devendra K.; Chatterjee, Anupam

    2014-01-01

    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

  10. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  11. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  12. Progression of Liver Disease

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  13. 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 ...

  14. Diet and Your Liver

    MedlinePlus

    ... scarring of your liver (cirrhosis). For people with liver disease, even a small amount of alcohol can make ... time. Eating an unhealthy diet can lead to liver disease. For example, a person who eats a lot ...

  15. LIVER MICROSOMES

    PubMed Central

    Palade, G. E.; Siekevitz, P.

    1956-01-01

    Rat liver, liver homogenates, and microsome fractions separated therefrom were examined systematically in the electron microscope in sections of OsO4-fixed, methacrylate-embedded tissue and pellets. It was found that most microsomes are morphologically identical with the rough surfaced elements of the endoplasmic reticula of hepatic cells. They appear as isolated, membrane-bound vesicles, tubules, and cisternae which contain an apparently homogeneous material of noticeable density, and bear small, dense particles (100 to 150 A) attached to their outer aspect. In solutions of various osmolar concentrations they behave like osmometers. The findings suggest that they derive from the endoplasmic reticulum by a generalized pinching-off process rather than by mechanical fragmentation. The microsome fractions contain in addition relatively few vesicles free of attached particles, probably derived from the smooth surfaced parts of the endoplasmic reticula. Dense, peribiliary bodies represent a minor component of the same fractions. The microsomes derived from 1 gm. wet weight liver pulp contained (averages of 10 experiments) 3.09 mg. protein N, 3.46 mg. RNA (RNA/protein N = 1.12), and 487 µg. phospholipide P. They displayed DPNH-cytochrome c reductase activity and contained an alcohol-soluble hemochromogen. The microsome preparations proved resistant to washing and "aging." Treatment with versene and incubation with ribonuclease (30 minutes at 37°C.) resulted in appreciable losses of RNA and in partial or total disappearance of attached particles. Treatment with deoxycholate (0.3 to 0.5 per cent, pH = 7.5) induced a partial clarification of the microsome suspensions which, upon centrifugation, yielded a small pellet of conglomerated small, dense particles (100 to 150 A) with only occasionally interspersed vesicles. The pellet contained ∼80 to 90 per cent of the RNA and ∼20 per cent of the protein N of the original microsomes. The supernatant accounted satisfactorily

  16. Amebic liver abscess

    MedlinePlus

    ... liver in response to an intestinal parasite called Entamoeba histolytica . ... Amebic liver abscess is caused by Entamoeba histolytica. This ... dysentery. After an infection has occurred, the parasite may ...

  17. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  18. Food-Borne Trematodiases

    PubMed Central

    Keiser, Jennifer; Utzinger, Jürg

    2009-01-01

    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

  19. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

  20. Engineering Liver

    PubMed Central

    Griffith, Linda G.; Wells, Alan; Stolz, Donna Beer

    2014-01-01

    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 nano-fabrication, biomaterials, microfluidic, and other technologies potentially afford unprecedented opportunity to create microphysiological models of human liver, but engineering design principles for how to deploy these tools effectively towards specific applications, including how to define the essential constraints of any given application (including available sources of cells, acceptable cost, and user-friendliness) are still emerging. Arguably less appreciated is the parallel growth in computational systems biology approaches towards 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 towards greater illumination of human disease states and technologies for drug development. PMID:24668880

  1. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure. PMID:25951555

  2. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    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), α-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

  3. Fasciola hepatica: Specificity of a coproantigen ELISA test for diagnosis of fasciolosis in faecal samples from cattle and sheep concurrently infected with gastrointestinal nematodes, coccidians and/or rumen flukes (paramphistomes), under field conditions.

    PubMed

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

    2015-09-15

    Chronic fasciolosis is often diagnosed by faecal egg counting (FEC), following concentration of the eggs in the sample by a zinc sulphate floatation method. However, concentration by a sedimentation technique gives improved sensitivity. Interpretation of FEC results for fasciolosis is complicated by factors such as the long pre-patent period and irregular egg shedding. Thus, FEC reduction tests (FECRT), when used alone, are not completely reliable for diagnosis of anthelmintic susceptibility or resistance in local fluke populations, especially when parasite burdens are small. A Fasciola hepatica coproantigen ELISA test has been introduced which more accurately reflects the presence of flukes in the host bile ducts in late pre-patent infections, and absence of flukes following successful chemotherapeutic intervention. The aim of the present study was to elucidate the specificity of the F. hepatica coproantigen ELISA technique, particularly regarding potential cross-reactivity with rumen fluke (paramphistome), gastrointestinal nematode and coccidian infections. The method involved parallel testing of a large battery of faecal samples from field-infected cattle and sheep using floatation and sedimentation FECs and coproantigen analysis. No evidence was found for significant false positivity in the F. hepatica coproantigen ELISA due to paramphistome, coccidian and/or gastrointestinal nematode co-infections. With sedimentation FECs less than 10 F. hepatica eggs per gram (epg), the likelihood of a positive coproantigen result for the sample progressively decreased. Diagnosis of fasciolosis should be based on consideration of both FEC and coproantigen ELISA findings, to ensure optimum sensitivity for pre-patent and low-level infections.

  4. Biomarkers for liver fibrosis

    SciTech Connect

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  5. Bioartificial liver: current status.

    PubMed

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  6. Antioxidants in liver health

    PubMed Central

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  7. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  8. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Liver cancer is not common in the United States. Liver cancer is the fourth most common cancer and the third leading cause of cancer death in the world. In the United States, men, especially Chinese American men, have an increased ...

  9. 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 ...

  10. Acute nontraumatic liver lesions.

    PubMed

    Caremani, Marcello; Tacconi, Danilo; Lapini, Laura

    2013-11-26

    The principal conditions requiring emergency/urgent intervention in patients with nontraumatic liver lesions are hemorrhage (with or without tumor rupture), rupture of hydatid cysts (with or without infection), complications arising from liver abscesses or congenital liver cysts, rupture related to peliosis hepatis, and in rare cases spontaneous hemorrhage. This article examines each of these conditions, its appearance on ultrasound (the first-line imaging method of choice for assessing any urgent nontraumatic liver lesion) and indications for additional imaging studies.

  11. Percutaneous liver biopsy.

    PubMed

    Rustagi, Tarun; Newton, Eric; Kar, Premashish

    2010-01-01

    Percutaneous liver biopsy has been performed for more than 120 years, and remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis and management of liver diseases but have not made liver biopsy obsolete. This comprehensive review article will discuss the history of development of percutaneous liver biopsy, its indications, contraindications, complications and the various aspects of the biopsy procedure in detail.

  12. Imaging in liver transplantation

    PubMed Central

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2009-01-01

    The aim of this study was to illustrate the role of non-invasive imaging tools such as ultrasonography, multi-detector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation. PMID:19222090

  13. Immune mediated liver failure

    PubMed Central

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of “immune coagulation”, which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure. PMID:26417328

  14. Where are the South American freshwater turtle blood flukes (Trematoda: Spirorchiidae)? The first morphological and molecular analysis of spirorchiid cercariae from freshwater snails in Brazil.

    PubMed

    Pinto, Hudson Alves; de Melo, Alan Lane; Brant, Sara Vanessa

    2015-12-01

    Trematodes belonging to the family Spirorchiidae are blood parasites mainly of turtles with a worldwide distribution. These flukes were recently reported in some marine turtles from South America, where the occurrence of spirorchiids in freshwater definitive and intermediate hosts is so far unknown. In the present study, three morphotypes of brevifurcate apharyngeate distome cercariae found in freshwater molluscs from an urban reservoir in Brazil were used for morphological and molecular (nuclear 28S rDNA) evaluation. Two morphotypes of cercariae, probably congeneric species, were found in 12/17,465 specimens of Biomphalaria spp. and differ from each other by body size and sequences (0.1%). They present morphology similar to North American freshwater spirorchiids (Spirorchis spp.), however surprisingly molecular data reveals that these lineages are more closely related to marine spirorchiids. A third species found in 2/777 Pomacea sp. differs morphologically from all previously described spirorchiid cercariae and genetically from spirorchiids with available sequences (16-19%), grouping in the phylogenetic tree with freshwater North American species. This is the first report of freshwater spirorchiids in South America and the first molecular confirmation of the involvement of a caenogastropod in the life cycle of spirorchiids.

  15. Discovery of intermediate hosts for two species of blood flukes Cardicola orientalis and Cardicola forsteri (Trematoda: Aporocotylidae) infecting Pacific bluefin tuna in Japan.

    PubMed

    Shirakashi, Sho; Tani, Kazuki; Ishimaru, Katsuya; Shin, Sang Phil; Honryo, Tomoki; Uchida, Hiro'omi; Ogawa, Kazuo

    2016-04-01

    Fish blood flukes (Aporocotylidae) are important pathogens of farmed finfish around the world. Among them, Cardicola spp. infecting farmed tuna are considered to be serious threats to tuna farming and have received tremendous attention. We conducted periodical samplings at a tuna farming site in Japan between January and May, 2015 to determine the life cycle of Cardicola spp. We collected over 4700 terebellid polychaetes from ropes, floats and frames of tuna culture cages and found nearly 400 infected worms. Sporocysts and cercariae found in Nicolea gracilibranchis were genetically identified as Cardicola orientalis by 28S and ITS2 ribosomal DNA sequences. This was the first discovery of the intermediate host for this parasite species. Infection prevalence and the abundance of N. gracilibranchis significantly varied between sampling points and the highest number of infected terebellids were collected from ropes. We also demonstrated morphologically and molecularly that asexual stages found in a single Amphitrite sp. (Terebellidae) and adult worms isolated from farmed juvenile tuna were Cardicola forsteri. This is the first report of C. forsteri in Pacific bluefin tuna (PBT) Thunnus orientalis in Japan. Our results demonstrated that all three species of Cardicola orientalis, C. forsteri and Cardicola opisthorchis exist in Japanese farmed PBTs and that they all use terebellid polychaetes as the intermediate hosts.

  16. Where are the South American freshwater turtle blood flukes (Trematoda: Spirorchiidae)? The first morphological and molecular analysis of spirorchiid cercariae from freshwater snails in Brazil.

    PubMed

    Pinto, Hudson Alves; de Melo, Alan Lane; Brant, Sara Vanessa

    2015-12-01

    Trematodes belonging to the family Spirorchiidae are blood parasites mainly of turtles with a worldwide distribution. These flukes were recently reported in some marine turtles from South America, where the occurrence of spirorchiids in freshwater definitive and intermediate hosts is so far unknown. In the present study, three morphotypes of brevifurcate apharyngeate distome cercariae found in freshwater molluscs from an urban reservoir in Brazil were used for morphological and molecular (nuclear 28S rDNA) evaluation. Two morphotypes of cercariae, probably congeneric species, were found in 12/17,465 specimens of Biomphalaria spp. and differ from each other by body size and sequences (0.1%). They present morphology similar to North American freshwater spirorchiids (Spirorchis spp.), however surprisingly molecular data reveals that these lineages are more closely related to marine spirorchiids. A third species found in 2/777 Pomacea sp. differs morphologically from all previously described spirorchiid cercariae and genetically from spirorchiids with available sequences (16-19%), grouping in the phylogenetic tree with freshwater North American species. This is the first report of freshwater spirorchiids in South America and the first molecular confirmation of the involvement of a caenogastropod in the life cycle of spirorchiids. PMID:26253761

  17. Acute liver failure and liver transplantation.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  18. Coffee and Liver Disease.

    PubMed

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895

  19. FXR and liver carcinogenesis

    PubMed Central

    Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

    2015-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

  20. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  1. Liver transplantatation- an overview.

    PubMed

    Rai, Rakesh

    2013-06-01

    Liver transplantation is a therapeutic option of choice for acute and chronic end-stage liver disease. Indications, contraindications, and surgical procedures for the liver transplantation have become well established. In most part of the world, the main source of liver for transplantation remains the donation after brain death (DBD), but in view of increasing death on the waiting list due to shortage of brain dead organs other options such as split liver transplantation, living donor liver transplantation (LDLT), and donation after cardiac death (DCD) have been used. In the pretransplantation era, liver failure was nearly universally fatal, with mortality from fulminant hepatic failure of 80-90 %, and 1-year mortality in decompensated cirrhosis of more than 50 %. In contrast, liver transplantation patient survival is presently more than 85 % at 1 year and more than 70 % at 5 years, emphasizing the clinical benefit of liver transplantation for either acute or chronic liver failure. PMID:24426424

  2. Clonorchicidal properties of the synthetic trioxolane OZ78.

    PubMed

    Keiser, Jennifer; Xiao, Shu-Hua; Dong, Yuxiang; Utzinger, Jürg; Vennerstrom, Jonathan L

    2007-10-01

    Because the synthetic trioxolane OZ78 is active against the liver fluke Fasciola hepatica, we were motivated to investigate the in vivo and in vitro activity against another liver fluke, namely Clonorchis sinensis. Rats infected with C. sinensis for 2 and 5 wk were treated orally with single doses of OZ78 (75, 150, or 300 mg/kg). Worm burden reductions were assessed against untreated control rats. Scanning electron microscopy (SEM) was used to observe adult C. sinensis after recovery from rats 1-3 days posttreatment with a single 300 mg/kg oral dose of OZ78 and after in vitro exposure to concentrations of 1, 10, and 100 microg/ml of OZ78. A single 300 mg/kg oral dose of OZ78 resulted in worm burden reductions of 78.5% and 98.5% against juvenile and adult C. sinensis, respectively. SEM observations revealed tegumental surface alterations, including blebbing and sloughing. OZ78 emerges as a new compound with a broad spectrum of activity against major foodborne trematode infections.

  3. [Liver and sport].

    PubMed

    Watelet, J

    2008-11-01

    The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

  4. Tolerance Induction in Liver.

    PubMed

    Karimi, M H; Geramizadeh, B; Malek-Hosseini, S A

    2015-01-01

    Liver is an exclusive anatomical and immunological organ that displays a considerable tolerance effect. Liver allograft acceptance is shown to occur spontaneously within different species. Although in human transplant patients tolerance is rarely seen, the severity level and cellular mechanisms of transplant rejection vary. Non-paranchymal liver cells, including Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells, and resident dendritic cells may participate in liver tolerogenicity. The mentioned cells secret anti-inflammatory cytokines such as TGF-β and IL-10 and express negative co-stimulatory molecules like PD-L1 to mediate immunosuppression. Other mechanisms such as microchimerism, soluble major histocompatibility complex and regulatory T cells may take part in tolerance induction. Understanding the mechanisms involved in liver transplant rejection/tolerance helps us to improve therapeutic options to induce hepatic tolerance. PMID:26082828

  5. Acute liver failure.

    PubMed

    Slack, Andy; Wendon, Julia

    2011-06-01

    ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation. PMID:21902079

  6. Robotic liver surgery

    PubMed Central

    Leung, Universe

    2014-01-01

    Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

  7. Robotic liver surgery.

    PubMed

    Leung, Universe; Fong, Yuman

    2014-10-01

    Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

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

    PubMed Central

    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

    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 α/β 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

  9. Volatile nitrosamines and tobacco-specific nitrosamines in the smoke of Thai cigarettes: a risk factor for lung cancer and a suspected risk factor for liver cancer in Thailand.

    PubMed

    Mitacek, E J; Brunnemann, K D; Hoffmann, D; Limsila, T; Suttajit, M; Martin, N; Caplan, L S

    1999-01-01

    In Thailand, smoking of commercial cigarettes and of handmade cigarettes has drastically increased in recent decades. Cancer of the lung and of the upper aero-digestive tract have also increased in Thailand as they have in many other countries. It is our working hypothesis that the increase of primary cancer of the liver, especially of cholangiocarcinoma in the north-eastern provinces of Thailand is associated with the use of tobacco in men infested with the liver fluke Opisthorchis viverrini (OV). Bioassays have shown that volatile nitrosamines and tobacco-specific nitrosamines induce cholangiocarcinoma in laboratory animals and that the hepatocarcinogenic action of nitrosodimethylamine in hamsters is significantly increased by infestation with the liver fluke OV. The endogenous formation of nitrosamines is significantly increased by OV infestation. This report presents analytical data on the concentration of volatile nitrosamines and tobacco-specific nitrosamines in mainstream smoke of nine leading brands of commercially produced Thai cigarettes which represent approximately 85% of the market share in Thailand. Observed ranges (ng/cigarette) were 8.5-31.9 for nitrosodimethylamine, 8.8-49.6 for nitrosopyrrolidine and 4.2-18.9 for nitrosodi-n-butylamine. These values are exceptionally high compared with the smoke of light and blended cigarettes from North America and Western Europe. Among the tobacco-specific nitrosamines, the range was 28-730 for nitrosonornicotine and 16-370 for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. There was a correlation between volatile and tobacco-specific nitrosamines, and tar and nicotine deliveries in the mainstream smoke. The analytical data are in line with the rate for lung cancer and support our working hypothesis that nitrosamines, and especially the tobacco-specific nitrosamines, are associated with the increased risk for primary liver cancer among those Thai people who smoke cigarettes and also carry OV infestation.

  10. About the Operation: Liver Transplant

    MedlinePlus

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both ...

  11. Nutrition and liver diseases.

    PubMed

    Teran, J C

    1999-08-01

    Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended. PMID:10980970

  12. Hepatitis C: liver transplantation.

    PubMed

    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma account for approximately 40% of the 6,000 adult liver transplantations performed each year in the United States. Survival rates are 76% to 83% at 2 years and 69% to 72% at 5 years. If eligible for surgery and in the absence of contraindications, any patient with HCV infection who develops decompensated liver disease or hepatocellular carcinoma is a candidate for liver transplantation. Most transplantation programs require that a patient with a history of alcohol or drug abuse be abstinent for at least 6 months and active in a substance abuse rehabilitation program. Prioritization for transplantation is based primarily on a patient's model for end-stage liver disease score, though other factors are considered. Complications after liver transplantation include recurrence of HCV infection, rejection of the transplanted liver, and an increased rate of infection because of immunosuppression. Various drugs are used to prevent infection and organ rejection. Liver transplant recipients also develop diabetes, hypertension, hyperlipidemia, renal dysfunction, osteopenia, and cancers at high rates, likely because of the effects of immunosuppressive drugs, particularly steroids and calcineurin inhibitors. The family physician's role in caring for liver transplant recipients often involves detection and management of these conditions. PMID:25478647

  13. Hypoxia and fatty liver.

    PubMed

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

    2014-11-01

    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

  14. [Treatment of liver fibrosis].

    PubMed

    Domínguez, Marlene; Colmenero, Jordi; Bataller, Ramón

    2009-11-01

    Liver fibrosis is the progressive deposition of extracellular matrix in the liver parenchyma that precedes the development of cirrhosis. In the last few years, knowledge of the cellular and molecular bases of liver fibrosis has increased considerably. Environmental and genetic factors have been described that influence the progression of liver fibrosis, while non-invasive methods have been developed that allow the grade of fibrosis to be estimated without the need for liver biopsy. Currently, the only clearly effective treatment to attenuate or reverse liver fibrosis is elimination of the causative agent. When this is not feasible, fibrogenic factors (such as insulin resistance, obesity, alcohol intake, cannabis consumption, etc.) should be identified and treated. However, several agents are able to reduce liver fibrosis in experimental models of chronic liver damage. Few controlled clinical trials have been performed that evaluate the efficacy and safety of these agents and consequently the level of evidence supporting their use as anti-fibrogenic therapy is still low. The efficacy of the anti- fibrogenic drugs, renin-angiotensin system inhibitors, is currently being evaluated.

  15. Liver Cell Culture Devices

    PubMed Central

    Andria, B.; Bracco, A.; Cirino, G.; Chamuleau, R. A. F. M.

    2010-01-01

    In the last 15 years many different liver cell culture devices, consisting of functional liver cells and artificial materials, have been developed. They have been devised for numerous different applications, such as temporary organ replacement (a bridge to liver transplantation or native liver regeneration) and as in vitro screening systems in the early stages of the drug development process, like assessing hepatotoxicity, hepatic drug metabolism, and induction/inhibition studies. Relevant literature is summarized about artificial human liver cell culture systems by scrutinizing PubMed from 2003 to 2009. Existing devices are divided in 2D configurations (e.g., static monolayer, sandwich, perfused cells, and flat plate) and 3D configurations (e.g., liver slices, spheroids, and different types of bioreactors). The essential features of an ideal liver cell culture system are discussed: different types of scaffolds, oxygenation systems, extracellular matrixes (natural and artificial), cocultures with nonparenchymal cells, and the role of shear stress problems. Finally, miniaturization and high-throughput systems are discussed. All these factors contribute in their own way to the viability and functionality of liver cells in culture. Depending on the aim for which they are designed, several good systems are available for predicting hepatotoxicity and hepatic metabolism within the general population. To predict hepatotoxicity in individual cases genomic analysis might be essential as well. PMID:26998397

  16. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. PMID:24951302

  17. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice.

  18. Pathogenesis of liver cirrhosis

    PubMed Central

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-01-01

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

  19. Pathogenesis of liver cirrhosis.

    PubMed

    Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

    2014-06-21

    Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

  20. Proteoglycans in liver cancer

    PubMed Central

    Baghy, Kornélia; Tátrai, Péter; Regős, Eszter; Kovalszky, Ilona

    2016-01-01

    Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects. PMID:26755884

  1. Arsenic and liver disease.

    PubMed

    Guha Mazumder, D N

    2001-06-01

    The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

  2. Liver support systems.

    PubMed

    Santoro, Antonio; Mancini, Elena; Ferramosca, Emiliana; Faenza, Stefano

    2007-01-01

    Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity of toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile acids or mercaptans) are released into the systemic circulation, thus altering many enzymatic cellular processes. Patients frequently die while on the transplantation waiting list because of organ scarcity. Systems supporting liver function may be useful to avoid further complications due to the typical toxic state, 'bridging' the patients to the transplantation, or, in the event of an acute decompensation of a chronic liver disease, sustain liver function long enough to permit the organ's regeneration and functional recovery. An ideal liver support system should substitute the main functions of the liver (detoxification, synthesis and regulation). Extracorporeal systems now available may be totally artificial or bioartificial. While the first are only able to perform detoxification, the second may add the functions of synthesis (plasma proteins, coagulation factors) and regulation (neurotransmitters). Bioartificial liver working with isolated hepatocytes and a synthetic membrane in an extracorporeal system are however still far from being ready for clinical use. At present, liver insufficiency may be treated with an extracorporeal support technology aimed either at detoxification alone or at a real purification. Charcoal hemoperfusion or exchange/absorption resins may be used for blood detoxification. Blood or plasma exchange, from a theoretical point of view, could be suitable for a polyvalent intoxication, such as liver failure; however, the multicompartmental distribution of some solutes largely endangers the efficacy of these procedures. Selective plasmapheresis techniques are now available for some solutes (e.g. styrene for bilirubin) and may progressively reduce the plasma levels and presumably the deposits of the solute. Novel treatments introduced to improve detoxification, mainly of

  3. Robotic liver resection technique.

    PubMed

    Hart, Marquis E; Precht, Andrew

    2013-01-01

    The robotic approach to hepatic resection has evolved because of advances in laparoscopy and digital technology and based on the modern understanding of hepatic anatomy. Robotic technology has allowed for the development of a minimally invasive approach, which is conceptually similar to the open approach. The major differences are improved visualization and smaller incisions without a haptic interface. As a result, the operative strategy is reliant on visual cues and knowledge of hepatic surgical anatomy. Development of a robotic liver resection program ideally occurs in the setting of a comprehensive liver program with significant experience in all aspects of surgical liver care.

  4. Pasteurella multocida liver abscess.

    PubMed

    Cortez, J C; Shapiro, M; Awe, R J

    1986-08-01

    A previously healthy 61-year-old woman was seen with an abnormal chest roentgenogram and a 3-week history of fever, chills, malaise, and right upper quadrant pain. Blood cultures revealed Pasteurella multocida sensitive to penicillin. Liver spleen radioisotope scan and CT scan revealed space occupying lesions in the right lobe of the liver. The patient was a gardener with no pets or animal exposure. This case illustrates P. multocida septicemia and a liver abscess in a patient without animal exposure. In addition, the possibility of soil as another reservoir of infection is raised. PMID:3487981

  5. Elucidating the transcriptome of Fasciola hepatica - a key to fundamental and biotechnological discoveries for a neglected parasite.

    PubMed

    Young, Neil D; Hall, Ross S; Jex, Aaron R; Cantacessi, Cinzia; Gasser, Robin B

    2010-01-01

    Liver flukes of animals are parasitic flatworms (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Fasciola hepatica and F. gigantica, cause "liver fluke disease" (= fascioliasis), which is of major animal health significance worldwide. In particular, F. hepatica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. This parasite is also a major food-borne pathogen of humans throughout parts of the Middle East, Asia and South America. Currently, there is a significant focus on the development of new approaches for the prevention and control of fascioliasis in livestock. Recent technological advances in genomics and bioinformatics provide unique opportunities for the identification and prevalidation of drug targets and vaccines through a better understanding of the biology of F. hepatica and related species as well as their relationship with their hosts at the molecular level. Surprisingly, despite the widespread socioeconomic impact of fascioliasis, genomic datasets for F. hepatica are scant, limiting the molecular biological research of this parasite. The present article explores specifically the transcriptome of the adult stage of F. hepatica using an integrated genomic-bioinformatic platform. The analysis of the current data reveals numerous molecules of biological relevance, some of which are inferred to be involved in key biological processes or pathways that could serve as targets for new trematocidal drugs or vaccines. Improved insights into the transcriptome of F. hepatica should pave the way for future, comparative analysis of the transcriptomes of other developmental stages of this and related parasites, such as F. gigantica, cancer-causing flatworms (Clonorchis sinensis and Opisthorchis viverrini) and blood flukes (Schistosoma mansoni and S. japonicum). Prediction of the

  6. Research Areas: Liver Disease

    MedlinePlus

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: New medication shows promise against liver fibrosis ... linked to biliary atresia in newborn animals Support Research NIDDK invests in basic, clinical and translational research ...

  7. Fatty liver - nonalcoholic

    MedlinePlus

    ... may have the following tests to measure liver function: Complete blood count Prothrombin time Blood albumin level Your health care provider may ask for certain imaging tests, including: Ultrasound is often ...

  8. Liver function tests

    MedlinePlus

    ... laboratory results. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ... liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ...

  9. Liver (Hepatocellular) Cancer Screening

    MedlinePlus

    ... United States than in other parts of the world. Liver cancer is uncommon in the United States, ... is the fourth most common cancer in the world. In the United States, men, especially Chinese American ...

  10. Liver Transplant: Nutrition

    MedlinePlus

    ... VHA Forms & Publications Quality & Safety Quality of Care Ethics VA/DOD Clinical Practice Guidelines Hospital Quality Data ... decreases the strain on your liver and other organs, and will make your recovery from surgery easier. ...

  11. Hepatic (Liver) Function Panel

    MedlinePlus

    ... AST). This enzyme, which plays a role in processing proteins, is found in the liver, heart, muscles, ... doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, ...

  12. Alcoholic liver disease

    MedlinePlus

    ... weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver ... result of too much fluid Reddened palms Red spider-like blood vessels on the skin Small testicles ...

  13. Liver transplantation: current concepts.

    PubMed Central

    Wall, W J

    1988-01-01

    In this decade liver transplantation has been established as the preferred treatment for children and adults with irreversible end-stage liver disease. Biliary atresia in children and nonalcoholic cirrhosis in adults are the most common indications for the procedure. Transplantation currently plays only a minor role in the treatment of hepatic malignant disease. Blood group compatibility between donor and recipient is preferred, but histocompatibility matching (tissue typing) currently has no significant role in the selection of recipients. Approximately 70% of recipients survive for 1 year, and these patients have an excellent prospect of long-term survival. The emerging evidence indicates that the quality of life and rehabilitation of most liver recipients are good. The current success of liver transplantation can be attributed to critical selection of recipients, modern anesthetic and surgical techniques, improved perioperative care, accurate diagnosis of rejection and superior immunosuppression with cyclosporine. PMID:3289710

  14. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease. PMID:23628170

  15. [Diabetes in liver cirrhosis].

    PubMed

    García-Compeán, Diego; Jáquez-Quintana, Joel O; González-González, José A; Lavalle-González, Fernando J; Villarreal-Pérez, Jesús Z; Maldonado-Garza, Hector J

    2013-01-01

    The prevalence of overt diabetes mellitus (DM) in liver cirrhosis is about 30%. However, DM or impaired glucose tolerance can be observed in 90% after an oral glucose tolerance test in patients with normal fasting plasma glucose. Type 2 DM may produce cirrhosis, whereas DM may be a complication of cirrhosis. The latter is known as «hepatogenous diabetes». Overt and subclinical DM is associated with liver complications and death in cirrhotic patients. Treating diabetes is difficult in cirrhotic patients because of the metabolic impairments due to liver disease and because the most appropriate pharmacologic treatment has not been defined. It is also unknown if glycemic control with hypoglycemic agents has any impact on the course of the liver disease.

  16. Pediatric liver transplantation

    PubMed Central

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

    2009-01-01

    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

  17. Liver Sinusoidal Endothelial Cells.

    PubMed

    Sørensen, Karen Kristine; Simon-Santamaria, Jaione; McCuskey, Robert S; Smedsrød, Bård

    2015-10-01

    The liver sinusoidal endothelial cell (LSEC) forms the fenestrated wall of the hepatic sinusoid and functions as a control post regulating and surveying the trafficking of molecules and cells between the liver parenchyma and the blood. The cell acts as a scavenger cell responsible for removal of potential dangerous macromolecules from blood, and is increasingly acknowledged as an important player in liver immunity. This review provides an update of the major functions of the LSEC, including its role in plasma ultrafiltration and regulation of the hepatic microcirculation, scavenger functions, immune functions, and role in liver aging, as well as issues that are either undercommunicated or confusingly dealt with in the literature. These include metabolic functions, including energy metabolic interplay between the LSEC and the hepatocyte, and adequate ways of identifying and distinguishing the cells.

  18. Cod Liver Oil

    MedlinePlus

    ... cod liver oil on their skin to speed wound healing. When taken in appropriate doses by mouth, cod ... young children. Heart disease. Systemic lupus erythematosus (SLE). Wound healing. Glaucoma. Other conditions. More evidence is needed to ...

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

    ClinicalTrials.gov

    2015-03-25

    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

  20. Analgesia after liver transplantation

    PubMed Central

    Milan, Zoka

    2015-01-01

    This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222

  1. Acute liver failure in children.

    PubMed

    Devictor, Denis; Tissieres, Pierre; Afanetti, Mickael; Debray, Dominique

    2011-06-01

    The management of children with acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but clinical studies have mainly concerned adult patients. There are no specific medical therapies, except for a few metabolic diseases presenting with acute liver failure. Liver transplantation still remains the only definitive therapy in most instances. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to liver transplantation, for providing metabolic support during liver failure and for replacing liver transplantation in certain metabolic liver diseases.

  2. Liver disease and malnutrition.

    PubMed

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  3. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  4. The Liver in Critical Illness.

    PubMed

    Damm, Tessa W; Kramer, David J

    2016-07-01

    Caring for critically ill patients with acute and/or chronic liver dysfunction poses a unique challenge. Proper resuscitation and early consideration for transfer to liver transplant centers have resulted in improved outcomes. Liver support devices and cellular models have not yet shown mortality benefit, but they hold promise in the critical care of patients with liver disease. This article reviews pertinent anatomic and physiologic considerations of the liver in critical illness, followed by a selective review of associated organ dysfunction. PMID:27339681

  5. THEMES OF LIVER TRANSPLANTATION

    PubMed Central

    Starzl, Thomas E.; Fung, John J.

    2010-01-01

    Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as

  6. Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting.

    PubMed

    Reddy, Mettu Srinivas; Rajalingam, Rajesh; Rela, Mohamed

    2015-10-01

    Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure. PMID:25788191

  7. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    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. PMID:25684933

  8. Imaging in pediatric liver transplantation.

    PubMed

    Monti, L; Soglia, G; Tomà, P

    2016-05-01

    Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors. PMID:26909515

  9. Stereoscopic liver surface reconstruction

    PubMed Central

    Karwan, Adam; Rudnicki, Jerzy; Wróblewski, Tadeusz

    2012-01-01

    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

  10. Liver dysfunction in haemophilia.

    PubMed

    Steven, M M; Small, M; Pettigrew, A; Lowe, G D; Sturrock, R D; Follett, E A; Forbes, C D

    1986-04-01

    Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.

  11. Natural trematode infection in liver of water buffalo (Bubalus bubalis): histopathological investigation.

    PubMed

    Haque, Masoodul; Mohan, Chandra; Ahmad, Imtiaz

    2011-06-01

    This study reports the infection of liver and bile ducts, carried out from November 2008 to April 2010, on 730 randomly selected water buffaloes-Bubalusbubalis, infected with the amphistome trematode parasite Explanatum explanatum (Creplin, 1847) Fukui, 1929. Macroscopic examination revealed massive infection of adult fluke in bile ducts and intrahepatic ductules in 131 (18%) cases. The predominant features were multifocal granulomatous nodules throughout the luminal surface of the bile ducts. Histopathological study of 4 μm thick tissue sections cut adjacent to and through the site of attachment of individual worm and stained with hematoxylin and eosin revealed intense infiltration of inflammatory cells such as lymphocytes, macrophages, plasma cells, eosinophils as well as fibrocytes. This was associated with fibrosis and thickening of the bile ducts. Due to high level of prevalence and intensity of natural infection, amphistomiasis appears to be endemic in this geographical region and probably represent one of the most important animal health problems. It is hoped that the study may draw attention to the need for educating farmers, regarding the economic importance of infection of these amphistome parasites and also for the development of control strategies to prevent the spread of infection to ruminants.

  12. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  13. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections.

  14. Immunobiology of liver xenotransplantation

    PubMed Central

    Ekser, Burcin; Burlak, Christopher; Waldman, Joshua P; Lutz, Andrew J; Paris, Leela L; Veroux, Massimiliano; Robson, Simon C; Rees, Michael A; Ayares, David; Gridelli, Bruno; Tector, A Joseph; Cooper, David KC

    2013-01-01

    Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/− transgenic for human CD46, is associated with survival of approximately 7–9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a ‘bridge’ to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application. PMID:23078060

  15. [Probiotics in liver diseases].

    PubMed

    Soriano, Germán; Sánchez, Elisabet; Guarner, Carlos

    2013-01-01

    Alterations in intestinal microbiota and inflammatory response play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and non-alcoholic steatohepatitis. Probiotics can be useful to delay disease progression and to prevent development of complications due to their ability to modulate intestinal flora, intestinal permeability and inflammatory response. Several studies have shown the efficacy of probiotics in the treatment of minimal hepatic encephalopathy and the prevention of episodes of overt hepatic encephalopathy. Probiotics have also been observed to prevent postoperative bacterial infections and to improve liver damage in non-alcoholic steatohepatitis. However, more studies are needed in order to confirm the efficacy and safety of probiotics in patients with liver diseases, and to better understanding of the mechanisms implicated in their effects.

  16. Alcoholic liver disease: Treatment

    PubMed Central

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

    2014-01-01

    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

  17. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  18. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. PMID:27082951

  19. Living related liver transplantation.

    PubMed

    Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M

    1992-01-01

    Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

  20. Eosinophilic Liver Infiltration

    PubMed Central

    Figueroa Rivera, Ivonne; Toro, Doris H.; Gutierrez, Jose; Acosta, Eduardo

    2015-01-01

    Eosinophilic liver infiltration is a commonly encountered focal eosinophil-related inflammation with or without necrosis, which can be seen on computed tomography (CT) in the presence of peripheral eosinophilia. Although this entity has a relatively benign course, it is related to numerable conditions for which diagnosis may be challenging and requires substantial diagnostic work-up for proper management and care of the underlying disease. We report a case of a 60-year-old man who presented with a 1-week history of right upper quadrant abdominal pain with multiple ill-defined liver hypodensities associated with significant eosinophilia. PMID:26504883

  1. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  2. Neoplasms of the liver

    SciTech Connect

    Okuda, K.; Ishak, K.G.

    1987-01-01

    Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy.

  3. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  4. 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...

  5. Plants Consumption and Liver Health

    PubMed Central

    Guan, Yong-Song; He, Qing

    2015-01-01

    The liver is a very important organ with a lot of functions for the host to survive. Dietary components are essential for and can be beneficial or detrimental to the healthy or diseased liver. Plants food is an essential part of the human diet and comprises various compounds which are closely related to liver health. Selected food plants can provide nutritional and medicinal support for liver disease. At the present, the knowledge of the effects of plants on the liver is still incomplete. The most urgent task at the present time is to find the best dietary and medicinal plants for liver health in an endless list of candidates. This review article updates the knowledge about the effects of plants consumption on the health of the liver, putting particular emphasis on the potential beneficial and harmful impact of dietary and medicinal plants on liver function. PMID:26221179

  6. Interventional Treatments for Liver Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Interventional Treatments for Liver Disease There are a ... liver that can be treated with nonsurgical, interventional radiology techniques. Portal Hypertension Seen most frequently in patients ...

  7. Endocannabinoids in Liver Disease

    PubMed Central

    Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

    2010-01-01

    Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

  8. Glycosylation and Liver Cancer

    PubMed Central

    Mehta, Anand; Herrera, Harmin; Block, Timothy

    2015-01-01

    Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. PMID:25727150

  9. 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 (...

  10. Ton That Tung's livers.

    PubMed

    Helling, Thomas S; Azoulay, Daniel

    2014-06-01

    Born in the early 20th century, the Vietnamese surgeon Ton That Tung received his medical education in French colonial Indochina at the fledgling l'Ecole de Médecine de Hanoi, the first indigenous medical school in Southeast Asia. The benefactor of a postgraduate position at the medical school, Ton That Tung subsequently obtained his surgical training at the Phù Doãn Hospital in Hanoi and concurrently developed a passion for the study of liver anatomy, pathology, and surgery. His contributions to an understanding of liver anatomy based on meticulous dissection of autopsy specimens antedated and rivaled later work by the famous Western anatomists Couinaud, Healey, Schroy, and others. Ton That Tung's contributions, however, were overshadowed by the intense national struggles of the Vietnamese to establish independent rule and self-governance from the French and by eventual alignment with eastern bloc Communist countries, thus isolating much of his work behind the "Iron Curtain" until well after the end of the Cold War. Nevertheless, Ton That Tung remains a pioneer in liver anatomy and liver surgery. His commitment to surgical science and, more importantly, to the Vietnamese people stands as a tribute to the tireless pursuit of his ideals. PMID:24335785

  11. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  12. The liver in haemochromatosis.

    PubMed

    Ulvik, Rune J

    2015-01-01

    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.

  13. Liver transplantation in Spain.

    PubMed

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  14. 3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by Opisthorchis felineus

    PubMed Central

    Demin, Alexander M; Pershina, Alexandra G; Ivanov, Vladimir V; Nevskaya, Kseniya V; Shevelev, Oleg B; Minin, Artyom S; Byzov, Iliya V; Sazonov, Alexey E; Krasnov, Victor P; Ogorodova, Ludmila M

    2016-01-01

    Purpose Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites. Materials and methods Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe3+ and Fe2+ salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic resonance properties of MNPs were investigated in vitro and in vivo. Results The amount of APS grafted on the surface of nanoparticles (0.60±0.06 mmol g−1) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity r2 was 271 mmol−1 s−1. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1±4.5 and 10.0±3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast-enhanced MRI of liver lesions induced by Opisthorchis felineus. Conclusion The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage.

  15. 3-Aminopropylsilane-modified iron oxide nanoparticles for contrast-enhanced magnetic resonance imaging of liver lesions induced by Opisthorchis felineus

    PubMed Central

    Demin, Alexander M; Pershina, Alexandra G; Ivanov, Vladimir V; Nevskaya, Kseniya V; Shevelev, Oleg B; Minin, Artyom S; Byzov, Iliya V; Sazonov, Alexey E; Krasnov, Victor P; Ogorodova, Ludmila M

    2016-01-01

    Purpose Liver fluke causes severe liver damage in an infected human. However, the infection often remains neglected due to the lack of pathognomonic signs. Nanoparticle-enhanced magnetic resonance imaging (MRI) offers a promising technique for detecting liver lesions induced by parasites. Materials and methods Surface modification of iron oxide nanoparticles produced by coprecipitation from a solution of Fe3+ and Fe2+ salts using 3-aminopropylsilane (APS) was carried out. The APS-modified nanoparticles were characterized by transmission electron microscopy, fourier transform infrared spectroscopy, and thermogravimetric analysis. Magnetic resonance properties of MNPs were investigated in vitro and in vivo. Results The amount of APS grafted on the surface of nanoparticles (0.60±0.06 mmol g−1) was calculated based on elemental analysis and infrared spectroscopy data. According to transmission electron microscopy data, there were no essential changes in the structure of nanoparticles during the modification. The APS-modified nanoparticles exhibit high magnetic properties; the calculated relaxivity r2 was 271 mmol−1 s−1. To obtain suspension with optimal hydrodynamic characteristics, amino groups on the surface of nanoparticles were converted into an ionic form with HCl. Cellular uptake of modified nanoparticles by rat hepatoma cells and human monocytes in vitro was 74.1±4.5 and 10.0±3.7 pg [Fe] per cell, respectively. Low cytotoxicity of the nanoparticles was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Annexin V/7-aminoactinomycin D flow cytometry assays. For the first time, magnetic nanoparticles were applied for contrast-enhanced MRI of liver lesions induced by Opisthorchis felineus. Conclusion The synthesized APS-modified iron oxide nanoparticles showed high efficiency as an MRI contrast agent for the evaluation of opisthorchiasis-related liver damage. PMID:27660439

  16. [Running through the liver transplantation].

    PubMed

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  17. Clonorchis sinensis lysophospholipase inhibits TGF-β1-induced expression of pro-fibrogenic genes through attenuating the activations of Smad3, JNK2, and ERK1/2 in hepatic stellate cell line LX-2.

    PubMed

    Zhou, Lina; Shang, Mei; Shi, Mengchen; Zhao, Lu; Lin, Zhipeng; Chen, Tingjin; Wu, Yinjuan; Tang, Zeli; Sun, Hengchang; Yu, Jinyun; Huang, Yan; Yu, Xinbing

    2016-02-01

    Liver fibrosis is a wound healing response associated with chronic liver injury. Hepatic stellate cells (HSCs) activation is a key event in the development of liver fibrosis. Since helminths have the ability to live for decades in the host by establishing an adaptive relationship in the interplay with its hosts, we hypothesize that whether Clonochis sinensis LysophospholipaseA (CsLysoPLA), a component of excretory/secretory proteins, can attenuate the fibrogenic response by inhibiting activation of LX-2 cells, thereby balancing the pro-fibrotic and anti-fibrotic response during the Clonochis sinensis (C. sinensis) infection. In the present study, LX-2 cells were stimulated with CsLysoPLA in the presence of TGF-β1, and the expressions of collagen type I (COL1A1), α-smooth muscle actin (α-SMA), and matrix metalloproteinase 2 (MMP2) were decreased. In addition, CsLysoPLA significantly inhibited the proliferation and migration of LX-2 cells stimulated by TGF-β1. Pretreatment of LX-2 cells with CsLysoPLA attenuated the phosphorylation of Smad3 as well as JNK2 and ERK1/2 in response to the stimulation of TGF-β1. For the first time, our results showed an anti-fibrogenic effect of CsLysoPLA by attenuating the response of LX-2 cells to TGF-β1 through inhibiting the activations of Smad3, ERK1/2, and JNK2. PMID:26486942

  18. Lipids changes in liver cancer*

    PubMed Central

    Jiang, Jing-ting; Xu, Ning; Zhang, Xiao-ying; Wu, Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism. Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver. It depends on the integrity of liver cellular function, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs, these processes are impaired and the plasma lipid and lipoprotein patterns may be changed. Liver cancer is the fifth common malignant tumor worldwide, and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). HBV and HCV infections are quite common in China and other Southeast Asian countries. In addition, liver cancer is often followed by a procession of chronic hepatitis or cirrhosis, so that hepatic function is damaged obviously on these bases, which may significantly influence lipid and lipoprotein metabolism in vivo. In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer. PMID:17565510

  19. Endoderm specification and liver development.

    PubMed

    Goessling, W; Stainier, D Y

    2016-01-01

    The endoderm is the innermost embryonic germ layer, and in zebrafish, it gives rise to the lining of the gut, the gills, liver, pancreas, gallbladder, and derivatives of the pharyngeal pouch. These organs form the gastrointestinal tract and are involved with the absorption, delivery, and metabolism of nutrients. The liver has a central role in regulating these processes because it controls carbohydrate and lipid metabolism, protein synthesis, and breakdown of endogenous and xenobiotic products. Liver dysfunction frequently leads to significant morbidity and mortality; however, in most settings of organ injury, the liver exhibits remarkable regenerative capacity. In this chapter, we review the principal mechanisms of endoderm and liver formation and provide protocols to assess liver formation and liver regeneration. PMID:27312502

  20. [Iron and liver disease].

    PubMed

    Miyanishi, Koji; Kato, Junji

    2016-07-01

    Free iron in the liver is believed to facilitate the formation of reactive oxygen species (ROS), including hydroxyl radicals (*OH), which cause oxidative damage of numerous cellular components such as lipids, proteins, and nucleic acids, and also upregulate collagen synthesis. The *OH radical is known to generate promutagenic bases such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In cases with chronic hepatitis C, long-term iron reduction therapy reduced the activity of hepatitis, suppressed fibrosis, and prevented hepatocarcinogenesis. In nonalcoholic steatohepatitis (NASH) livers, hepatic iron accumulation as well as oxidative DNA damage significantly increased. Humoral factor(s) in NASH serum may upregulate DMT1 expression in small intestine. Iron reduction therapy for NASH patients has a potential to reduce disease activity as well as hepatic oxidative damage. PMID:27455806

  1. Liver scintigraphy in ponies

    SciTech Connect

    Theodorakis, M.C.; Bermudez, A.J.; Manning, J.P.; Koritz, G.D.; Hillidge, C.J.

    1982-09-01

    Six derivatives of ethylenediamine-N,N'-bis (alpha-2-hydroxy phenyl) acetic acid labeled with /sup 99m/Tc were prepared and their imaging qualities evaluated in ponies. The 6 agents produced good scintigraphic images of certain structures of the liver in the pony. For each agent, 13 different scans were taken. Dorsal views of the left lateral, right lateral, and quadrate lobe were obtained with dorsal scans. Left lateral and left lateral oblique (45 degrees) scans provided a left lateral view of the left lobe and a medial view of the right lateral lobe. Right lateral scans revealed the right lateral and quadrate lobes. Administration of /sup 99m/Tc-labeled colloids which are commonly used in other species for liver scintigraphy resulted in extensive lung uptake in the pony.

  2. Iron and the liver.

    PubMed

    Pietrangelo, Antonello

    2016-01-01

    Humans have evolved to retain iron in the body and are exposed to a high risk of iron overload and iron-related toxicity. Excess iron in the blood, in the absence of increased erythropoietic needs, can saturate the buffering capacity of serum transferrin and result in non-transferrin-bound highly reactive forms of iron that can cause damage, as well as promote fibrogenesis and carcinogenesis in the parenchymatous organs. A number of hereditary or acquired diseases are associated with systemic or local iron deposition or iron misdistribution in organs or cells. Two of these, the HFE- and non-HFE hemochromatosis syndromes represent the paradigms of genetic iron overload. They share common clinical features and the same pathogenic basis, in particular, a lack of synthesis or activity of hepcidin, the iron hormone. Before hepcidin was discovered, the liver was simply regarded as the main site of iron storage and, as such, the main target of iron toxicity. Now, as the main source of hepcidin, it appears that the loss of the hepcidin-producing liver mass or genetic and acquired factors that repress hepcidin synthesis in the liver may also lead to iron overload. Usually, there is low-grade excess iron which, through oxidative stress, is sufficient to worsen the course of the underlying liver disease or other chronic diseases that are apparently unrelated to iron, such as chronic metabolic and cardiovascular diseases. In the future, modulation of hepcidin synthesis and activity or hepcidin hormone-replacing strategies may become therapeutic options to cure iron-related disorders.

  3. [Cytokines and the liver].

    PubMed

    Kershenobich, D; Borovoy, J; Guevara, L; Male, R; Alcocer, J

    1990-07-01

    The cytokines are proteins synthetized by lymphoid and monocyte/macrophage system cells in response to a wide variety of infectious stimulus, featuring bacterial endotoxins. These proteins have immunoregulatory effects and have been implicated in inflammation and fibrosis. In this review we refer to the interleukin-1, interleukin-6 and tumor necrosis factor because of their elevated basal levels in acute and chronic hepatopaties and in response to lipopolisacharide mainly in alcoholic liver disease. PMID:19256129

  4. Liver transplantation for malignancies.

    PubMed

    Eghtesad, Bijan; Aucejo, Federico

    2014-09-01

    Liver transplantation (LT) has become an acceptable and effective treatment for selected patients with hepatocellular carcinoma with excellent outcomes. More recently, LT has been tried in different primary and secondary malignancies of the liver. The outcomes of LT for very selected group of patients with hilar cholangiocarcinoma (CCA) have been promising. Excellent results have been reported in LT for patients with unresectable hepatic epithelioid hemangioendothelioma (HEHE). In contrast to excellent results after LT for HEHE, results of LT for angiosarcoma have been disappointing with no long-term survivors. Hepatoblastoma (HB) is the most common primary liver cancer in pediatric age group. Long-term outcomes after LT in patients with unresectable tumor and good response to chemotherapy have been promising. Indication for LT for hepatic metastasis from neuroendocrine tumors (NETs) is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. More recent limited outcomes data on LT for unresectable hepatic metastases from colorectal cancer have claimed some survival benefit compared to the previous reports. However, due to the high rate of tumor recurrence in a very short time after LT, especially in the era of organ shortage, this indication has not been favored by the transplant community. PMID:24604263

  5. Transplantable liver production plan: "Yamaton"--liver project, Japan.

    PubMed

    Hata, Toshiyuki; Uemoto, Shinji; Kobayashi, Eiji

    2013-10-01

    Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called "Yamaton" projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat-mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future. PMID:23896578

  6. [Liver damage caused by drugs].

    PubMed

    Strohmeyer, G; Weik, C

    1999-05-01

    The liver has a central role in the metabolism of many drugs, since this organ is the main site of biotransformation of endo- and xenobiotics. Water-soluble drugs have a small volume of distribution and can be eliminated unchanged in the urine. By contrast, lipid-soluble drugs have a larger volume of distribution and require conversion to water-soluble metabolites for their elimination in urine or bile. The liver with its specific receptors, transporters and enzymes is responsible for the uptake, transformation and excretion of the lipophilic drugs. While most of the drugs are transformed into stable metabolites, other drugs form reactive, potentially toxic, metabolites producing liver cell damage. Liver injury caused by drugs may mimic almost any kind of liver disease. Clinical findings are gastrointestinal symptoms with nausea, vomiting and abdominal pain, cholestatic liver injury with jaundice and pruritus of severe inflammatory and cirrhotic liver damage with signs of liver failure, encephalopathy and cerebral edema. The morphological changes vary from hepatitis, cholestasis, fatty liver, granulomatous hepatitis, peri-/portal inflammation, to fibrosis with cirrhotic alterations and vascular lesions and tumors. The most commonly used drugs causing severe liver injury are discussed in detail. These are anabolics, oral contraceptives, antituberculous and antifungal agents, nonsteroidal anti-inflammatory drugs, ring substituted amphetamins ("designer drugs"), antiarrhythmics and antibiotics.

  7. Role of liver progenitors in acute liver injury

    PubMed Central

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

    2013-01-01

    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

  8. Liver transplantation in acute liver failure: A challenging scenario

    PubMed Central

    Mendizabal, Manuel; Silva, Marcelo Oscar

    2016-01-01

    Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation. PMID:26819519

  9. Liver transplantation for Wilson's disease.

    PubMed

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  10. Intestinal microbiota in liver disease.

    PubMed

    Haque, Tanvir R; Barritt, A Sidney

    2016-02-01

    The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.

  11. Pregnancy-related liver disorders.

    PubMed

    Goel, Ashish; Jamwal, Kapil D; Ramachandran, Anup; Balasubramanian, Kunissery A; Eapen, Chundamannil E

    2014-06-01

    Pregnancy-related liver disorders accounted for 8% of all maternal deaths at our center from 1999 to 2011. Of the three pregnancy-related liver disorders (acute fatty liver of pregnancy (AFLP), HELLP (Hemolysis, elevated liver enzymes, low platelets) syndrome and pre-eclamptic liver dysfunction, which can lead to adverse maternal and fetal outcome, AFLP is most typically under - diagnosed. Risk of maternal death can be minimised by timely recognition and early/aggressive multi-specialty management of these conditions. Urgent termination of pregnancy remains the cornerstone of therapy for some of these life threatening disorders, but recent advancements in our understanding help us in better overall management of these patients. This review focuses on various aspects of pregnancy-related liver disorders. PMID:25755551

  12. Folate, Alcohol, and Liver Disease

    PubMed Central

    Medici, Valentina; Halsted, Charles H.

    2013-01-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  13. Experimental models of liver fibrosis

    PubMed Central

    Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2015-01-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research. PMID:26047667

  14. Obesity, inflammation, and liver cancer.

    PubMed

    Sun, Beicheng; Karin, Michael

    2012-03-01

    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  15. Radiation-Associated Liver Injury

    SciTech Connect

    Pan, Charlie C.; Kavanagh, Brian D.; Dawson, Laura A.; Li, X. Allen; Das, Shiva K.; Miften, Moyed; Ten Haken, Randall K.

    2010-03-01

    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.

  16. HBV and liver cancer.

    PubMed

    Leung, Nancy

    2005-07-01

    The association of hepatitis B virus (HBV) infection and liver cancer is well documented in epidemiological study. Patients with chronic hepatitis B have increased risk of hepatocelluar carcinoma (HCC), in particular those with active liver disease and cirrhosis. The incidence of HCC increases with age and is more common among male patients. The introduction of universal HBV vaccination program for the newborn in endemic regions has started to show beneficial impact. Taiwan introduced this program two decades ago and the incidence of liver cancer among infants and young children have declined significantly. The carcinogenic events leading to HCC are under intense research. A number of hypotheses have been proposed. HBV is not directly hepatotoxic but its interaction with the host immune system creates opportunity for HBV DNA integration into the host genome. One of the main foci of research is the HBX-encoded X protein. Its integration and protein expression impose alteration in cell proliferation cycle and apoptosis process. Many other factors may be involved including viral-induced alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta agents, patient's lifestyle such as smoking, alcohol excesses, and genetic factors of the host patient. The processes of necroinflammation, cell proliferation and fibrosis facilitate the initial carcinogenic development. HCC surveillance with tumor markers such as alpha-foetal protein, decarboxylated prothrombin, in conjunction with imaging techniques has identified early small HCC that is amenable to curative therapy. Viral load has been correlated with increase risk of HCC. The available anti-viral agents have demonstrated clinical benefit among those with maintained and sustained response. Interferon and lamivudine therapy have demonstrated reduction of HCC among responders. However, they only constitute a minority proportion of treated patients. The mainstay of prevention should lie in prevention of

  17. Heavy smoking and liver.

    PubMed

    El-Zayadi, Abdel-Rahman

    2006-10-14

    Smoking causes a variety of adverse effects on organs that have no direct contact with the smoke itself such as the liver. It induces three major adverse effects on the liver: direct or indirect toxic effects, immunological effects and oncogenic effects. Smoking yields chemical substances with cytotoxic potential which increase necro-inflammation and fibrosis. In addition, smoking increases the production of pro-inflammatory cytokines (IL-1, IL-6 and TNF- alpha) that would be involved in liver cell injury. It contributes to the development of secondary polycythemia and in turn to increased red cell mass and turnover which might be a contributing factor to secondary iron overload disease promoting oxidative stress of hepatocytes. Increased red cell mass and turnover are associated with increased purine catabolism which promotes excessive production of uric acid. Smoking affects both cell-mediated and humoral immune responses by blocking lymphocyte proliferation and inducing apoptosis of lymphocytes. Smoking also increases serum and hepatic iron which induce oxidative stress and lipid peroxidation that lead to activation of stellate cells and development of fibrosis. Smoking yields chemicals with oncogenic potential that increase the risk of hepatocellular carcinoma (HCC) in patients with viral hepatitis and are independent of viral infection as well. Tobacco smoking has been associated with suppression of p53 (tumour suppressor gene). In addition, smoking causes suppression of T-cell responses and is associated with decreased surveillance for tumour cells. Moreover, it has been reported that heavy smoking affects the sustained virological response to interferon (IFN) therapy in hepatitis C patients which can be improved by repeated phlebotomy. Smoker's syndrome is a clinico-pathological condition where patients complain of episodes of facial flushing, warmth of the palms and soles of feet, throbbing headache, fullness in the head, dizziness, lethargy, prickling

  18. Trout-liver histones

    PubMed Central

    Palau, J.; Butler, J. A. V.

    1966-01-01

    1. The histones of trout liver were examined and four main fractions (f1, f2b, f2a and f3) were isolated and characterized. 2. The amino acid analyses, N-terminal group analyses and starch-gel electrophoresis patterns are remarkably similar to the corresponding fractions of calf thymus. 3. The group f2a was also separated into two subfractions, f2al and f2a2, which are similar to those of calf thymus. ImagesFig. 1. PMID:5969291

  19. Getting a New Liver: Facts about Liver Transplants

    MedlinePlus

    ... liver does several things: • It helps digest your food. • It clears wastes from your blood. • It makes proteins that help your blood to clot. • It stores the sugars (glycogen) that are used for ... liver also controls the way your body uses food and the way it works with your immune ...

  20. [Liver gunshot wounds].

    PubMed

    Botoi, G; Blăjan, I; Nemeş, S

    2000-01-01

    The paper presents the 6 cases of liver shot wounds that were in supervision of the general surgery unit, County Hospital of Baia Mare, between the years 1990-1997. The patients were males, most of them being 20 to 30 years old. In 3 situations hunting rifles were involved, all followed by retention of metal foreign body. The wounds were plurivisceral in 5 of the 6 cases, the most frequently wounded was the right liver lobe. All the patients presented serious traumatic shock and haemorrhagic shock. Livertectomy was used in 40% of the cases being imposed by the dilacerant and transfixiant character of the wounds and also by the retention of foreign bodies in parenchime. We registered 2 demises, both in the first postoperatory hours. The paper proposes a few criteria that allow the application of a conservatory treatment:rapid favourable answer at deshocking therapy; hemodynamic stability; minimal hemoperitoneus (echographical and tomographical); absence of associated visceral wounds or, when they exist, of serious physiopathological consequences; access to performant means of imagistics.

  1. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  2. Five cases of ectopic liver and a case of accessory lobe of the liver.

    PubMed

    Watanabe, M; Matsura, T; Takatori, Y; Ueki, K; Kobatake, T; Hidaka, M; Hirakawa, H; Fukukmoto, S; Shimada, Y

    1989-01-01

    Five cases of ectopic liver, two of retro-peritoneal cavity and three of gallbladder, and a case of accessory lobe of the liver, are reported. One of these cases with ectopic liver was accompanied by multiple cysts of the liver and kidney, and biliary microhamartoma, which was observed laparoscopically on the surface of the main liver and histologically proven in the ectopic liver.

  3. 25 Ways to Love Your Liver

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  4. Chronic Liver Disease and Hispanic Americans

    MedlinePlus

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While the ...

  5. Vascular emergencies in liver trauma.

    PubMed

    Taourel, P; Vernhet, H; Suau, A; Granier, C; Lopez, F M; Aufort, S

    2007-10-01

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of complication and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications. PMID:17851012

  6. Current Issues in Liver Transplantation

    PubMed Central

    2016-01-01

    The state of liver transplantation continues to evolve. This article focuses on 3 separate yet important issues within this field. First, there is a proposal to change the allocation of donor livers in the United States. The fundamental premise of this proposal is to equalize access to donor livers across the country. To accomplish this goal, the proposal is to increase the geographic area of liver allocation. As might be expected, there is a great deal of controversy surrounding the possibility of a major change in liver allocation and distribution. A second area of interest, and perhaps the most important therapeutic breakthrough in the field of hepatology, is the introduction of direct-acting antiviral agents against hepatitis C virus (HCV) infection. With cure rates up to 100%, an increasing proportion of liver transplant candidates and recipients are being cured of HCV infection with therapies that have minimal side effects. Consequently, the impact of HCV infection on patient and graft survival will likely improve substantially over the next few years. Finally, this article reviews the role of donor-specific antibodies (DSAs) in antibody-mediated rejection. Long recognized as an important factor in graft survival in renal transplantation, DSAs have recently been shown to be a strong predictor of graft and patient survival in liver transplantation. However, the importance of DSAs in liver transplantation is uncertain, in large part due to the absence of proven therapies. PMID:27231452

  7. The Liver, Regulator of Nutrition.

    ERIC Educational Resources Information Center

    Dillon, J. C.

    1995-01-01

    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…

  8. Biliary Complications After Liver Transplantation.

    PubMed

    Jagannath, Sanjay; Kalloo, Anthony N.

    2002-04-01

    The incidence of biliary complications after liver transplant is estimated to be 8% to 20%. Post-liver transplant biliary complications may lead to acute and chronic liver injury. The early recognition and prompt treatment of such complications improves the long-term survival of the patient and graft. An understanding of the type of biliary reconstruction, the rationale for creating a particular anastomosis, and the technical difficulties in reconstructing the biliary tract are important in assessing and managing complications after liver transplant. Because the clinical presentation of these patients may be subtle, the physician must be aggressive and thoughtful in ordering and interpreting the diagnostic tests. Important points to remember are 1) that noninvasive examinations may fail to detect small obstructions or leaks, 2) a liver biopsy often is performed prior to cholangiography to exclude rejection and ischemia, and 3) the liver biopsy can miss an extrahepatic obstruction by misinterpreting portal inflammation as rejection. Biliary leaks and strictures are the most common biliary complications following liver transplant. Less common complications include ampullary dysfunction and stone/sludge formation. The effective management of biliary complications following a liver transplant depends on understanding the natural history, the prognosis, and the available therapeutic options for each type of complication.

  9. Nitric oxide in liver diseases.

    PubMed

    Iwakiri, Yasuko; Kim, Moon Young

    2015-08-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - and conclude with suggestions for future directions in NO-related studies on the liver. PMID:26027855

  10. NITRIC OXIDE IN LIVER DISEASES

    PubMed Central

    Iwakiri, Yasuko; Kim, Moon Young

    2015-01-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling, nitrated fatty acids and S-guanylation, and conclude with suggestions on future directions of NO-related studies on the liver. PMID:26027855

  11. Artificial and Bioartificial Liver Support

    PubMed Central

    2007-01-01

    The fact that liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation, lead to the development of various artificial and bioartificial liver support devices. While artificial systems are based on the principles of adsorption and filtration, the more complex concept of bioartificial devices includes the provision of liver cells. Instead of solely focussing on detoxification, these concepts also support the failing organ concerning synthetic and regulative functions. The systems were evaluated in a variety of clinical studies, demonstrating their safety and investigating the impact on the patient's clinical condition. This review gives an overview over the most common artificial and bioartificial liver support devices and summarizes the results of the clinical studies. PMID:19279696

  12. [Organ replacement therapy - extracorporeal liver assist devices].

    PubMed

    Sinner, Barbara; Kirchner, Gabriele I

    2016-09-01

    Liver failure is a disease with a high mortality rate. Often liver transplantation is the sole therapeutic option. On the one hand, liver support systems probably support the liver to allow regeneration, on the other hand they are an option to bridge for transplantation. This article gives an overview on the clinically used liver assist devices (molecular adsorbent recirculating system [MARS], Prometheus system, single-pass albumin dialysis [SPAD], plasmapheresis) and discusses the applications in liver failure. PMID:27631450

  13. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    PubMed

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  14. When Your Child Needs a Liver Transplant

    MedlinePlus

    ... Your Child for Surgery Hepatitis Hereditary Hemochromatosis Digestive System Blood Test: Hepatic (Liver) Function Panel What Happens in the Operating Room? Hepatitis Your Liver Your Digestive System Anesthesia - ...

  15. Screening in liver disease

    PubMed Central

    Poggio, Paolo Del; Mazzoleni, Marzio

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  16. Screening in liver disease.

    PubMed

    Del Poggio, Paolo; Mazzoleni, Marzio

    2006-09-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  17. Clonorchiasis.

    PubMed

    Qian, Men-Bao; Utzinger, Jürg; Keiser, Jennifer; Zhou, Xiao-Nong

    2016-02-20

    On Aug 21, 1875, James McConnell published in The Lancet his findings from a post-mortem examination of a 20-year-old Chinese man--undertaken at the Medical College Hospital in Calcutta, India--in whom he found Clonorchis sinensis in the bile ducts. Now, exactly 140 years later, we have a sound understanding of the lifecycle of this liver fluke, including key clinical, diagnostic, and epidemiological features. Developments in the so-called -omics sciences have not only advanced our knowledge of the biology and pathology of the parasite, but also led to the discovery of new diagnostic, drug, and vaccine targets. C sinensis infection is primarily related to liver and biliary disorders, especially cholangiocarcinoma. Clonorchiasis mainly occurs in east Asia, as a result of the region's social-ecological systems and deeply rooted cultural habit of consuming raw freshwater fish. The Kato-Katz technique, applied on fresh stool samples, is the most widely used diagnostic approach. Praziquantel is the treatment of choice and has been considered for preventive chemotherapy. Tribendimidine showed good safety and therapeutic profiles in phase 2 trials and warrants further investigation. Still today, the precise distribution, the exact number of infected people, subtle morbidities and pathogenesis, and the global burden of clonorchiasis are unknown. Integrated control strategies, consisting of preventive chemotherapy; information, education, and communication; environmental management; and capacity building through intersectoral collaboration should be advocated. PMID:26299184

  18. Liver Transplantation after Exertional Heatstroke-Induced Acute Liver Failure

    PubMed Central

    Virk, Hafeez Ul Hasan

    2016-01-01

    Exertional heatstroke (EHS) is a life-threatening disease characterized clinically by central nervous system dysfunction and severe hyperthermia. It frequently occurs among athletes, soldiers, and laborers. While cardiopulmonary symptoms are common in patients undergoing EHS, irreversible acute liver failure is a rarely described phenomenon. When managing cases of EHS complicated by acute liver failure, it is crucial to act promptly with aggressive total body cooling in order to prevent progression of the clinical syndrome. However, an urgent liver transplantation can be a therapeutic strategy when patients fail to improve with supportive measures. PMID:27738568

  19. Detection of antibodies in wild ruminants to evaluate exposure to liver trematodes.

    PubMed

    Arias, María Sol; Martínez-Carrasco, Carlos; León-Vizcaíno, Luis; Paz-Silva, Adolfo; Díez-Baños, Pablo; Morrondo, Patrocinio; Alonso, Francisco

    2012-08-01

    Wild ruminants sharing pastures with domestic livestock are at risk of infection by liver trematodes. Detection of antibodies provides a very useful tool to gain more knowledge about the distribution of these parasites. Non-lethal methods are strongly encouraged for the analysis of the risk of infection among wild ruminants. A seroepidemiological survey was conducted to analyze exposure to hepatic trematodes ( Fasciola hepatica and Dicrocoelium dendriticum ) in wild ruminants from southern Spain. Blood samples were collected from 69 bovids (Mouflon + Spanish ibex) and 143 cervids (red deer + fallow deer) from Sierra de Cazorla, Segura and Las Villas Natural Park. The samples were analyzed using the excretory/secretory antigens of each trematode to determine the IgG response. All the animals were examined at necropsy for the presence of flukes, and the species, age, and gender of the animals were recorded. Fasciola hepatica were only observed in cervids (3%; 95% confidence interval [CI]  =  2-8), while D. dendriticum specimens were recorded in 1% (0-8) of bovids and 4% (CI  =  2-9) of the cervids. The IgG-seroprevalence against F. hepatica was significantly higher in the cervids. Statistical differences according to gender were observed. The bovids exhibited the greatest percentages of positive cases to D. dendriticum antigens, and the DdES-seroprevalence was related to age of the animals. When considering all the factors, the FhES-seroprevalence was initially distributed according to the type of ruminant (cervids), gender (male), and age (>2 yr).

  20. Extracellular Matrix and Liver Disease

    PubMed Central

    Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

    2014-01-01

    Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

  1. Size mismatch in liver transplantation.

    PubMed

    Fukazawa, Kyota; Nishida, Seigo

    2016-08-01

    Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. PMID:27474079

  2. Nutritional Status and Liver Transplantation

    PubMed Central

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2012-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as ‘metabolic syndrome’, may play a negative role on the overall survival of liver transplant patients. In this report we

  3. [Occupational liver diseases: (author's transl)].

    PubMed

    Kuntz, H D; May, B

    1980-07-18

    A large number of exogenous substances with potential liver toxicity are to be found in work places and in the environment. Decisive importance is ascribed to regular supervision of exposed persons and adhering to the appropriate safety provisions without being able to ensure reliable prevention of toxic liver damage thereby. The prognosis of occupational toxic liver damage is good if recognition is timely and the causal noxae are eliminated. The aim of all diagnostic and prophylactic efforts must be rehabilitation, in addition to specific occupational medical and hygienic measures.

  4. Interventional Radiology in Liver Transplantation

    SciTech Connect

    Karani, John B. Yu, Dominic F.Q.C.; Kane, Pauline A.

    2005-04-15

    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.

  5. Post-hepatectomy liver failure

    PubMed Central

    Kauffmann, Rondi

    2014-01-01

    Hepatectomies are among some of the most complex operative interventions performed. Mortality rates after major hepatectomy are as high as 30%, with post-hepatic liver failure (PHLF) representing the major source of morbidity and mortality. We present a review of PHLF, including the current definition, predictive factors, pre-operative risk assessment, techniques to prevent PHLF, identification and management. Despite great improvements in morbidity and mortality, liver surgery continues to demand excellent clinical judgement in selecting patients for surgery. Appropriate choice of pre-operative techniques to improve the functional liver remnant (FLR), fastidious surgical technique, and excellent post-operative management are essential to optimize patient outcomes. PMID:25392835

  6. [Dissection techniques in liver surgery].

    PubMed

    Rau, H G; Schauer, R; Pickelmann, S; Beyer, B C; Angele, M K; Zimmermann, A; Meimarakis, G; Heizmann, O; Schildberg, F W

    2001-02-01

    The first liver resection was performed in 1888. Since then a wide variety of dissection techniques have been introduced. The blunt dissection was replaced by novel methods, i.e. the CUSA technique and the Jet Cutter for major liver resections. These methods represent selective dissection techniques; whereas non-selective methods include the scalpel, scissors, linear stapling cutter, high-frequency coagulation, and the laser technique. The aim of this review article is the comparison of the different resection techniques in liver surgery, focussing on blood loss and resection time. PMID:11253668

  7. Autoantibodies in autoimmune liver diseases.

    PubMed

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  8. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    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)

  9. Gut-Liver Axis in Alcoholic Liver Disease

    PubMed Central

    Szabo, Gyongyi

    2014-01-01

    Alcoholic liver disease (ALD) has been amongst the leading causes of liver cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation suggesting a role for gut-derived “toxins” in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that is increasingly recognized as a major factor in ALD. Bacterial endotoxin, LPS, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4 (TLR4). Recent studies also demonstrated that alcohol consumption is associated with alterations in the gut microbiome and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. PMID:25447847

  10. Liver disease in vineyard sprayers.

    PubMed

    Pimentel, J C; Menezes, A P

    1977-02-01

    Liver disease with inclusions of copper was recognized among 30 rural workers with "vineyard sprayer's lung." The pathological findings were varied: focal or diffuse swelling and proliferation of Kupffer cells; histiocytic and sarcoid-like granulomata; fibrosis of variable degree in the perisinusoidal, portal, and subcapsular areas, accompanied by atypical proliferation of the sinusoidal lining cells; micronodular cirrhosis; angiosarcoma of the liver; idiopathic portal hypertension. Abundant deposits of copper were revealed by histochemical techniques within hepatic and pulmonary lesions in these patients. The observations on the human and experimental material suggest an etiological relationship between exposure to copper sulfate and the lesions described. A morphological resemblance was noted between the "liver disease of vineyard sprayers" and the hepatic lesions reported in workers exposed to inorganic arsenic and to vinyl chloride. The identification of the inhaled foreign material within the liver lesions raises important etiological considerations.

  11. Calcium Signaling in the Liver

    PubMed Central

    Amaya, Maria Jimena; Nathanson, Michael H.

    2014-01-01

    Intracellular free Ca2+ ([Ca2+]i) is a highly versatile second messenger that regulates a wide range of functions in every type of cell and tissue. To achieve this versatility, the Ca2+ signaling system operates in a variety of ways to regulate cellular processes that function over a wide dynamic range. This is particularly well exemplified for Ca2+ signals in the liver, which modulate diverse and specialized functions such as bile secretion, glucose metabolism, cell proliferation, and apoptosis. These Ca2+ signals are organized to control distinct cellular processes through tight spatial and temporal coordination of [Ca2+]i signals, both within and between cells. This article will review the machinery responsible for the formation of Ca2+ signals in the liver, the types of subcellular, cellular, and intercellular signals that occur, the physiological role of Ca2+ signaling in the liver, and the role of Ca2+ signaling in liver disease. PMID:23720295

  12. Epigenetic biomarkers in liver cancer.

    PubMed

    Banaudha, Krishna K; Verma, Mukesh

    2015-01-01

    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  13. Biomarkers in Pediatric Liver Disease.

    PubMed

    Kyrana, Eirini; Fitzpatrick, Emer; Dhawan, Anil

    2016-01-01

    The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

  14. Folate, alcohol, and liver disease.

    PubMed

    Medici, Valentina; Halsted, Charles H

    2013-04-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  15. Isolation of methylglyoxal from liver.

    PubMed Central

    Fodor, G; Mujumdar, R; Szent-Gyorgyi, A

    1978-01-01

    Acetaldehyde and methylglyoxal were shown to be present in liver bound to protein. They were isolated in the form of 2,4-dinitrophenylhydrazones and osazones, respectively. The NMR spectrum of pure methylglyoxal was recorded. PMID:279916

  16. MedlinePlus: Liver Transplantation

    MedlinePlus

    ... and Research Clinical Trials Journal Articles Resources Reference Desk Find an Expert For You Children Patient Handouts Summary Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove ...

  17. The liver in tuberculous peritonitis.

    PubMed

    Sanai, Faisal M

    2006-01-01

    Tuberculous peritonitis is a common form of abdominal tuberculosis and is frequently associated with liver disease. Diagnosis of this disease presents a diagnostic dilemma and the presence of liver cirrhosis further confounds the clinical picture. Moreover, the co-existence of these two diseases casts doubt on the validity of various diagnostic tests available. The interpretation of tests of ascitic fluid analysis becomes questionable despite the fact that peritoneal tuberculosis and liver disease cause ascites to develop through separate mechanisms. In addition, the treatment of tuberculosis mandates a better understanding of the co-existent disease in view of the potential hepatotoxicity of anti-tuberculous medication. This review aims to address the prevalence of coexistent liver disease in patients with tuberculous peritonitis, the diagnostic difficulties posed by such and the various treatment approaches to be adopted.

  18. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  19. Split liver transplantation: What's unique?

    PubMed

    Dalal, Aparna R

    2015-09-24

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  20. 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.

  1. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePlus

    Non-Alcoholic Fatty Liver Disease What is Non-alcoholic fatty liver disease (NAFLD)? FAT N AFLD is a name that is given to a ... and under “Liver Health Information view ‘Nonalcoholic fatty liver Disease (NAFLD/NASH)’ IMPORTANT REMINDER: This information from the ...

  2. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  3. Energy Metabolism in the Liver

    PubMed Central

    Rui, Liangyou

    2014-01-01

    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 β 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-1α, 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

  4. Experience with transjugular liver biopsy.

    PubMed Central

    Bull, H J; Gilmore, I T; Bradley, R D; Marigold, J H; Thompson, R P

    1983-01-01

    The results of 193 transjugular liver biopsies performed with a modified needle are described. An adequate specimen was obtained in 97%, and complications were rare, although puncture of the liver capsule does occur and caused bleeding in two patients. Fever after the procedure was reduced by ultrasonic cleaning of the needle. Although not easy, this technique is safe and preferable in the management of selected patients, but in most patients percutaneous biopsy is to be preferred. PMID:6629116

  5. [Liver ultrasound: focal lesions and diffuse diseases].

    PubMed

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed.

  6. Blood flukes (Digenea: Aporocotylidae) infecting body cavity of South American catfishes (Siluriformes: Pimelodidae): two new species from rivers in Bolivia, Guyana and Peru with a re-assessment of Plehniella Szidat, 1951.

    PubMed

    Orelis-Ribeiro, Raphael; Bullard, Stephen A

    2015-01-01

    Plehniella Szidat, 1951 is emended based on new collections from South American long-whiskered catfishes. It is clearly differentiated from Sanguinicola Plehn, 1905 by lacking lateral tegumental body spines and by having 6 asymmetrical caeca. Plehniella sabajperezi sp. n. infects body cavity of Pimelodus albofasciatus (Mees) from the Demerara and Rupununi Rivers (Guyana) and Pimelodus blochii (Valenciennes) from Lake Tumi Chucua (Bolivia) and Napo River (Peru). It differs from Plehniella coelomicola Szidat, 1951 (type species) by having a thin-walled vas deferens that greatly exceeds the length of cirrus-sac and that joins the cirrus-sac at level of ovovitelline duct and ootype, an internal seminal vesicle that is absent or diminutive, and a cirrus-sac that is spheroid, nearly marginal, and envelops the laterally-directed distal portion of the male genitalia. Plehniella armbrusteri sp. n. infects body cavity of P. blochii from Lake Tumi Chucua (Bolivia). It differs from P. coelomicola and P. sabajperezi by having a relatively ovoid body, a massive intestine comprising caeca that are deeply-lobed to diverticulate and terminate in the posterior half of the body, a testis that flanks the distal tips of the posteriorly-directed caeca, and a proximal portion of the vas deferens that loops ventral to the testis. Small adults (Plehniella sp.) collected from body cavity of Pimelodus grosskopfii (Steindachner) from Cienega de Jobo and Canal del Dique (Colombia) differ from congeners by having a posteriorly-constricted body region, an anterior sucker with concentric rows of minute spines, an elongate anterior oesophageal swelling, short and wide caeca, and a male genital pore that opens proportionally more anteriad. This study nearly doubles the number of aporocotylids documented from South America Rivers and comprises the first record of a fish blood fluke from P. blochii, P. albofasciatus and P. grosskopfii as well as from Bolivia, Colombia, Guyana or Peru. PMID:26373332

  7. EGFR Signaling in Liver Diseases

    PubMed Central

    Komposch, Karin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC) highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs). PMID:26729094

  8. Neurologic complications after liver transplantation

    PubMed Central

    Živković, Saša A

    2013-01-01

    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

  9. Lipids in liver transplant recipients

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-01-01

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  10. Lipids in liver transplant recipients.

    PubMed

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-03-28

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  11. Serum Liver Enzyme Pattern in Birth Asphyxia Associated Liver Injury

    PubMed Central

    Chhavi, Nanda; Zutshi, Kiran; Singh, Niranjan Kumar; Awasthi, Ashish

    2014-01-01

    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

  12. Orthotopic liver transplantation in liver-based metabolic disorders.

    PubMed

    Mowat, A P

    1992-01-01

    The efficacy of orthotopic liver transplantation (OLT) in the management of more common liver-based metabolic disorders associated with severe liver damage, alpha-1-antitrypsin deficiency (PIZZ), Wilson disease and tyrosinaemia has been demonstrated and indications defined. An early mortality in excess of 15% and finite resources limit its use. Phenotypic heterogeneity make the precise indication in other disorders less certain. In disorders in which endstage liver disease is less frequent such as cystic fibrosis, haemochromatosis and galacosaemia it has been a very effective therapy. It has been used with encouraging results in disorders in which the liver is structurally normal such as Crigler-Najjar type I, primary hyperoxaluria type I and primary hypercholesterolaemia. In these it should be performed before there is permanent damage to brain, kidneys or heart. OLT in the short term prevents hyperammonaemic coma in urea cycle defects and may prevent extrahepatic disease in glycogen storage disease type IV. Its limitation in reversing all metabolic effects in these and other disorders is discussed. It is ineffective in protoporphyria or Niemann Pick disease type II (Sea Blue Histiocyte syndrome) in which the transplanted liver acquires the lesions of the initial disorder and extrahepatic features progress. Early referral provides optimum circumstances to assess the benefits of OLT as compared with those of other forms of management and to achieve transplantation at the ideal time. The place of OLT in management will require constant review as metabolic disorders are better defined, new forms of therapy evolve and as techniques of liver transplantation and modes of immunosuppression improve.

  13. Liver-Regenerative Transplantation: Regrow and Reset

    PubMed Central

    de l’Hortet, A. Collin; Takeishi, K.; Guzman-Lepe, J.; Handa, K.; Matsubara, K.; Fukumitsu, K.; Dorko, K.; Presnell, S. C.; Yagi, H.; Soto-Gutierrez, A.

    2016-01-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)–derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  14. Toward surface quantification of liver fibrosis progression

    NASA Astrophysics Data System (ADS)

    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

    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.

  15. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection

    PubMed Central

    Ackermann, Hanns; Bechstein, Wolf O.; Grünwald, Frank

    2016-01-01

    Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n = 13) or hepatic resection (n = 26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p = 0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS's time-activity-curve (p = 0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. PMID:27563464

  16. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection.

    PubMed

    Eckenschwiller, Manuel; Ackermann, Hanns; Bechstein, Wolf O; Grünwald, Frank

    2016-01-01

    Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n = 13) or hepatic resection (n = 26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p = 0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS's time-activity-curve (p = 0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. PMID:27563464

  17. Liver abnormalities and liver membrane autoantibodies in systemic lupus erythematosus.

    PubMed Central

    Kushimoto, K; Nagasawa, K; Ueda, A; Mayumi, T; Ishii, Y; Yamauchi, Y; Tada, Y; Tsukamoto, H; Kusaba, T; Niho, Y

    1989-01-01

    The hepatic involvement of 57 patients with systemic lupus erythematosus (SLE) was studied with special reference to liver membrane autoantibody (LMA). Liver abnormalities were found predominantly in patients with active SLE (27/48 (56%) in active SLE v 3/20 (15%) in inactive SLE). They were, however, rather mild or moderate and tended to disappear as the disease activity of SLE decreased. In this respect the liver abnormalities observed in this study differed from those in patients with lupoid hepatitis. The incidence of LMA in active SLE (8/11 (73%] was significantly greater than that in inactive SLE (4/12 (33%)). The mean LMA index value in active SLE was 8.3, which was also greater than the 2.9 in inactive SLE. Furthermore, in active SLE the mean LMA titre was significantly higher in patients with liver abnormalities than in those without. These results suggest that LMA may be associated with the activity of SLE and may be one of the factors which cause transient liver abnormalities. Images PMID:2596885

  18. Liver Autophagy in Anorexia Nervosa and Acute Liver Injury

    PubMed Central

    Kheloufi, Marouane; Boulanger, Chantal M.; Durand, François

    2014-01-01

    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

  19. Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation.

    PubMed

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-05-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  20. Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

    PubMed Central

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-01-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  1. Liver transplantation in small babies.

    PubMed

    Vázquez, J; Gámez, M; Santamaría, M L; Murcia, J; Díaz, M C; Camarena, C; Jara, P; Tovar, J A

    1993-08-01

    Pediatric liver transplantation is an effective treatment for end-stage liver disease with 1- and 5-year survivals approaching 90% and 70%, respectively. Survival is influenced by the recipient's age, weight, primary disease, vascular malformations, and nutritional status. Younger patients weighing less than 13 kg are considered to be a high-risk group. The aim of this article is to evaluate the impact of this group of patients on the overall results of our pediatric liver transplant program. From January 1986 through January 1992 we performed 76 liver transplants in 59 pediatric patients. Sixteen received a second graft and a third was required in one. Fourteen patients weighed less than 13 kg (mean, 11 kg; range, 6 to 13 kg). Their mean age was 12 months, with a range of 8 to 36 months. Indications for transplantation were: biliary atresia (9), Byler's disease (1), tyrosinemia (3), and alpha 1-antitrypsin deficiency (1). The incidence of rejection in this group (52%) was not significantly different from that in other patients (61%). Ten episodes of acute rejection required only steroids: in one monoclonal antibodies were added. Five patients had a new graft implanted, four for hepatic artery thrombosis and one for primary liver nonfunction. Nine patients are alive (64%) with the follow-up time ranging from 2 to 56 months (mean, 31). Five patients died of multiorgan failure (3), portal vein thrombosis (1), and primary liver nonfunction (1). Four-year graft and patient survival rates were 47% and 64%, respectively. Small babies are a high-risk group in a pediatric liver transplant program.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  3. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease.

    PubMed

    Lucero, Catherine; Brown, Robert S

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  4. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    PubMed Central

    Czaja, Albert J

    2014-01-01

    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

  5. Autophagy regulates sphingolipid levels in the liver[S

    PubMed Central

    Alexaki, Aikaterini; Gupta, Sita D.; Majumder, Saurav; Kono, Mari; Tuymetova, Galina; Harmon, Jeffrey M.; Dunn, Teresa M.; Proia, Richard L.

    2014-01-01

    Sphingolipid levels are tightly regulated to maintain cellular homeostasis. During pathologic conditions such as in aging, inflammation, and metabolic and neurodegenerative diseases, levels of some sphingolipids, including the bioactive metabolite ceramide, are elevated. Sphingolipid metabolism has been linked to autophagy, a critical catabolic process in both normal cell function and disease; however, the in vivo relevance of the interaction is not well-understood. Here, we show that blocking autophagy in the liver by deletion of the Atg7 gene, which is essential for autophagosome formation, causes an increase in sphingolipid metabolites including ceramide. We also show that overexpression of serine palmitoyltransferase to elevate de novo sphingolipid biosynthesis induces autophagy in the liver. The results reveal autophagy as a process that limits excessive ceramide levels and that is induced by excessive elevation of de novo sphingolipid synthesis in the liver. Dysfunctional autophagy may be an underlying mechanism causing elevations in ceramide that may contribute to pathogenesis in diseases. PMID:25332431

  6. The International Liver Transplant Society Guideline on Living Liver Donation.

    PubMed

    Miller, Charles M; Durand, Francois; Heimbach, Julie K; Kim-Schluger, Leona; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Quintini, Cristiano; Pomfret, Elizabeth Anne

    2016-06-01

    The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

  7. Bile acid signaling and liver regeneration.

    PubMed

    Fan, Mingjie; Wang, Xichun; Xu, Ganyu; Yan, Qingfeng; Huang, Wendong

    2015-02-01

    The liver is able to regenerate itself in response to partial hepatectomy or liver injury. This is accomplished by a complex network of different cell types and signals both inside and outside the liver. Bile acids (BAs) are recently identified as liver-specific metabolic signals and promote liver regeneration by activating their receptors: Farnesoid X Receptor (FXR) and G-protein-coupled BA receptor 1 (GPBAR1, or TGR5). FXR is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. FXR promotes liver regeneration after 70% partial hepatectomy (PHx) or liver injury. Moreover, activation of FXR is able to alleviate age-related liver regeneration defects. Both liver- and intestine-FXR are activated by BAs after liver resection or injury and promote liver regeneration through distinct mechanism. TGR5 is a membrane-bound BA receptor and it is also activated during liver regeneration. TGR5 regulates BA hydrophobicity and stimulates BA excretion in urine during liver regeneration. BA signaling thus represents a novel metabolic pathway during liver regeneration. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

  8. Liver transplantation at Mount Sinai.

    PubMed

    Kim-Schluger, L; Florman, S S; Gondolesi, G; Emre, S; Sheiner, P A; Fishbein, T M; Schwartz, M E; Miller, C M

    2000-01-01

    Nearly 2000 liver transplants have been performed over the past 12 years at Mount Sinai, with a recent exponential growth in living donor surgeries. Living-donor liver transplantation has emerged as an important option for our patients with end-stage liver disease. We are only beginning to recognize fully the advantages that 'scheduled' liver transplantation can offer. In this era of severe cadaver organ shortages, living donation offers patients the option of liver replacement in a timely fashion, before life-threatening complications of hepatic failure and/or carcinoma progression prohibit transplantation. The next era of transplantation at Mount Sinai will bring significant increases in the number of transplants performed with living donors, with projections of over 50% of the total transplants each year expected to involve living donations. We are committed to offering this option while recognizing that donor safety remains paramount and cannot be overemphasized. Proper donor and recipient selection, as well as surgical experience are imperative to success with this technically demanding procedure. Recurrent disease after transplantation, particularly with hepatitis C, remains a challenge clinically. Further investigations into the pathogenesis of the rapid progression of recurrent hepatitis C need to be addressed. Living donor transplantation could be an important option for these patients and would allow timely transplantation and the potential for improved survival in patients with hepatocellular carcinoma. PMID:11512318

  9. Hydroxycut-induced Liver Toxicity

    PubMed Central

    Kaswala, DH; Shah, S; Patel, N; Raisoni, S; Swaminathan, S

    2014-01-01

    In the recent era, use of various nutritional supplements is highly encouraged amongst the people of United States. Weight loss supplements are major part of the nutritional supplements and their usage is unregulated in the US. Obesity is a major health concern in the US and Americans spend around $30 billion a year for weight loss supplements. At times, these supplements can be responsible for documented or undocumented adverse drug effects. The health consequences related to these supplements are often overlooked by the general public, even though FDA issues advisories regarding them. One common supplement used for weight loss was Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada). Hydroxycut was recalled from the market after a FDA warning in May 2009 because of 23 reports of serious health problems ranging from jaundice and elevated liver enzymes to liver damage. 1 This case report adds evidence for Hydroxycut - induced hepatotoxicity. A 27 year old man with right upper quadrant pain and jaundice was found to have elevated liver enzymes and was taking Hydroxycut along with other supplements. Liver biopsy showed drug induced hepatotoxicity. Discontinuation of Hydroxycut dramatically improved liver functions and related symptoms. PMID:24669349

  10. Learning to program the liver.

    PubMed

    Klaassen, Curtis D

    2014-01-01

    Half a century ago, people were learning to program computers. Similarly, we have been trying to learn how to program the liver to protect us from chemicals. We have given various chemicals that activate transcription factors such as the nuclear receptors: These ligand-activated nuclear receptors enter the nucleus of liver cells (hepatocytes) and bind to their specific motifs in DNA to increase the transcription of various genes that protect against chemical-induced injury. Several examples from our laboratory are given to demonstrate this detoxification process: (a) a steroid chemical that increases the expression of a hepatic transporter to enhance the elimination of other chemicals and thus decrease their toxicity, (b) a metal that decreases its own toxicity by increasing the production of a protein to which it binds, and (c) an herbal chemical that activates a transcription factor that serves as a sensor of oxidative stress and electrophiles to protect against cytotoxicity by increasing the expression of numerous antioxidant proteins. In addition, at the present time, we are investigating which bile acids that are synthesized in the liver and altered by bacteria in the intestine may be used to alter the programming of the liver, as well as how the liver reprograms itself after birth in the transition from a hematopoietic organ to one that decreases the toxicity of chemicals.

  11. Malnutrition, liver damage, and cancer.

    PubMed

    Grasso, P

    1981-01-01

    There is no clear indication that malnutrition, per se, is a principal cause of cancer in man, but the prevalence of liver cancer in areas where malnutrition exists supports this hypothesis. Liver damage and liver cancer have been induced in laboratory rats by diets consisting of peanut meal and proteins deficient in some essential amino acids. However, liver damage, but not cancer, was produced when the diets contained no peanut meal but consisted of a mixture of amino acids deficient in methionine and cysteine, so that it is possible that aflatoxin, a contaminant of peanut meal, may have been responsible for the malignancies seen in the earlier experiments. Liver cancer developes in a high proportion of mice allowed to feed ad libitum or given a diet containing a high proportion of fat (groundnut oil) or protein (casein). Dietary restriction reduced the incidences of this cancer. This findings lends some support to current thinking that diet may be a factor in the development of cancer in man.

  12. Infections in liver transplant recipients.

    PubMed

    Romero, Fabian A; Razonable, Raymund R

    2011-04-27

    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.

  13. Cholangiocyte proliferation and liver fibrosis

    PubMed Central

    Glaser, Shannon S.; Gaudio, Eugenio; Miller, Tim; Alvaro, Domenico; Alpini, Gianfranco

    2009-01-01

    Cholangiocyte proliferation is triggered during extrahepatic bile duct obstruction induced by bile duct ligation, which is a common in vivo model used for the study of cholangiocyte proliferation and liver fibrosis. The proliferative response of cholangiocytes during cholestasis is regulated by the complex interaction of several factors, including gastrointestinal hormones, neuroendocrine hormones and autocrine or paracrine signalling mechanisms. Activation of biliary proliferation (ductular reaction) is thought to have a key role in the initiation and progression of liver fibrosis. The first part of this review provides an overview of the primary functions of cholangiocytes in terms of secretin-stimulated bicarbonate secretion – a functional index of cholangiocyte growth. In the second section, we explore the important regulators, both inhibitory and stimulatory, that regulate the cholangiocyte proliferative response during cholestasis. We discuss the role of proliferating cholangiocytes in the induction of fibrosis either directly via epithelial mesenchymal transition or indirectly via the activation of other liver cell types. The possibility of targeting cholangiocyte proliferation as potential therapy for reducing and/or preventing liver fibrosis, and future avenues for research into how cholangiocytes participate in the process of liver fibrogenesis are described. PMID:19239726

  14. Focal liver lesions found incidentally.

    PubMed

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-03-28

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  15. Development of a PCR assay and pyrosequencing for identification of important human fish-borne trematodes and its potential use for detection in fecal specimens

    PubMed Central

    2014-01-01

    Background Small liver and minute intestinal flukes are highly prevalent in Southeast Asia. Definitive diagnosis of parasite infection is usually achieved parasitologically by finding the fluke eggs in feces. However, their eggs are difficult to differentiate morphologically in fecal samples, even for experienced technicians. The present study developed a PCR assay coupled with DNA pyrosequencing for identification of the fish-borne trematodes (FBT), Opisthorchis viverrini, Clonorchis sinensis, Haplorchis taichui, H. pumilio and Stellantchasmus falcatus, and to evaluate potential detection in fecal specimens, and identification and differentiation of cercarial and metacercarial stages. Methods Primers targeting the partial 28S large subunit ribosomal RNA gene were designed and about 46–47 nucleotides were selected as the target region for species identification by a PCR assay coupled with a pyrosequencing technique. Results The nucleotide variations at 24 positions, which is sufficient for the identification of the five species of FBT were selected. The method could identify O. viverrini and C. sinensis eggs in feces, cercarial and metacercarial stages of O. viverrini, and metacercarial stage of H. pumilio and H. taichui. The detection limit was as little as a single O. viverrini or C. sinensis egg artificially inoculated in 100 mg of non-infected fecal sample (equivalent to 10 eggs per gram), indicating highly sensitivity. The method was found to be superior to the traditional microscopy method and was more rapid than Sanger DNA sequencing. Conclusions DNA pyrosequencing-based identification is a valuable tool for differentiating O. viverrini and other Opisthorchis-like eggs, and can be applied to epidemiological studies and for molecular taxonomic investigation of FBT in endemic areas. PMID:24589167

  16. Exacerbation of pulmonary sarcoidosis after liver transplantation.

    PubMed

    Shibolet, Oren; Kalish, Yossi; Wolf, Dana; Pappo, Orit; Laxer, Uri; Berkman, Neville; Shaham, Dorit; Ashur, Yaffa; Ilan, Yaron

    2002-10-01

    Patients with hepatic sarcoidosis rarely require orthotopic liver transplantation (OLT). Progression of granulomatous activity involving other organs after OLT has rarely been described. We describe a 32-year-old woman who underwent liver transplantation for sarcoidosis-associated end-stage liver disease. She presented 4 years later with shortness of breath, hilar lymphadenopathy, and interstitial lung abnormalities. Liver functions were normal. Open lung biopsy results revealed granulomata compatible with sarcoidosis. The patient made a complete recovery after corticosteroid treatment. To the best of our knowledge, this is a first description of severe exacerbation of pulmonary sarcoidosis in an immunosuppressed patient who underwent liver transplantation for sarcoidosis-associated liver disease.

  17. Liver isolation in abdominal MRI.

    PubMed

    Rajasvaran, Logeswaran; Haw, Tan Wooi; Sarker, Shakowat Zaman

    2008-08-01

    This work presents a method for liver isolation in magnetic resonance imaging (MRI) abdomen images. It is based on a priori statistical information about the shape of the liver obtained from a training set using the segmentation approach. Morphological watershed algorithm is used as a key technique as it is a simple and intuitive method, producing a complete division of the image in separated regions even if the contrast is poor, and it is fast, with possibility for parallel implementation. To overcome the over-segmentation problem of the watershed process, image preprocessing and postprocessing are applied. Morphological smoothing, Gaussian smoothing, intensity thresholding, gradient computation and gradient thresholding are proposed for preprocessing with morphological and graph based region adjacent list constructed for region merging. A new integrated region similarity function is also defined for region merging control. The proposed method produces good isolation of liver in axial MRI images of the abdomen, as is shown in this paper.

  18. Microbiota, immunity and the liver.

    PubMed

    Vaikunthanathan, T; Safinia, N; Lombardi, G; Lechler, R I

    2016-03-01

    The gut harbors a complex community of over 100 trillion microbial cells known to exist in symbiotic harmony with the host influencing human physiology, metabolism, nutrition and immune function. It is now widely accepted that perturbations of this close partnership results in the pathogenesis of several major diseases with increasing evidence highlighting their role outside of the intestinal tract. The intimate proximity and circulatory loop of the liver and the gut has attracted significant attention regarding the role of the microbiota in the development and progression of liver disease. Here we give an overview of the interaction between the microbiota and the immune system and focus on their convincing role in both the propagation and treatment of liver disease. PMID:26835593

  19. Liver transplantation for hilar cholangiocarcinoma.

    PubMed

    Robles, Ricardo; Sánchez-Bueno, Francisco; Ramírez, Pablo; Brusadin, Roberto; Parrilla, Pascual

    2013-12-28

    The most appropriate treatment for Klatskin tumor (KT) with a curative intention is multimodal therapy based on achieving resection with tumour-free margins (R0 resections) combined with other types of neoadjuvant or adjuvant treatment (the most important factor affecting KT survival is the possibility of R0 resections, achieving 5-year survival rate of 40%-50%). Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%. In irresectable non-disseminated KT patients, using liver transplantation without neoadjuvant treatment, the 5-year survival rate increase to 38%, reaching 50% survival in early stage. In selected cases, with liver transplantation and neoadjuvant treatment (chemotherapy and radiotherapy), the actuarial survival rate is 65% at 5 years and 59% at 10 years. In conclusion, correct staging, neoadjuvant treatment, living donor and priority on the liver transplant waiting list may lead to improved results. PMID:24409049

  20. Diagnosis of alcoholic liver disease.

    PubMed

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-09-01

    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