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Sample records for liver fluke clonorchis

  1. Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis

    PubMed Central

    Cho, Pyo Yun; Kim, Tae Im; Cho, Shin-Hyeong; Choi, Sang-Haeng; Park, Hong-Seog; Kim, Tong-Soo; Hong, Sung-Jong

    2011-01-01

    Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and

  2. 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

  3. [Genomics and transcriptomics of the Chinese liver fluke Clonorchis sinensis (Opisthorchiidae, Trematoda)].

    PubMed

    Chelomina, G N

    2017-01-01

    The review summarizes the results of first genomic and transcriptomic investigations of the liver fluke Clonorchis sinensis (Opisthorchiidae, Trematoda). The studies mark the dawn of the genomic era for opisthorchiids, which cause severe hepatobiliary diseases in humans and animals. Their results aided in understanding the molecular mechanisms of adaptation to parasitism, parasite survival in mammalian biliary tracts, and genome dynamics in the individual development and the development of parasite-host relationships. Special attention is paid to the achievements in studying the codon usage bias and the roles of mobile genetic elements (MGEs) and small interfering RNAs (siRNAs). Interspecific comparisons at the genomic and transcriptomic levels revealed molecular differences, which may contribute to understanding the specialized niches and physiological needs of the respective species. The studies in C. sinensis provide a basis for further basic and applied research in liver flukes and, in particular, the development of efficient means to prevent, diagnose, and treat clonorchiasis.

  4. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review.

    PubMed

    Kim, Tong-Soo; Pak, Jhang Ho; Kim, Jong-Bo; Bahk, Young Yil

    2016-11-01

    Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier 8th National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA. [BMB Reports 2016; 49(11): 590-597].

  5. Clonorchis sinensis, an oriental liver fluke, as a human biological agent of cholangiocarcinoma: a brief review

    PubMed Central

    Kim, Tong-Soo; Pak, Jhang Ho; Kim, Jong-Bo; Bahk, Young Yil

    2016-01-01

    Parasitic diseases remain an unarguable public health problem worldwide. Liver fluke Clonorchis sinensis is a high risk pathogenic parasitic helminth which is endemic predominantly in Asian countries, including Korea, China, Taiwan, Vietnam, and the far eastern parts of Russia, and is still actively transmitted. According to the earlier 8th National Survey on the Prevalence of Intestinal Parasitic Infections in 2012, C. sinensis was revealed as the parasite with highest prevalence of 1.86% in general population among all parasite species surveyed in Korea. This fluke is now classified under one of the definite Group 1 human biological agents (carcinogens) by International Agency of Research on Cancer (IARC) along with two other parasites, Opisthorchis viverrini and Schistosoma haematobium. C. sinensis infestation is mainly linked to liver and biliary disorders, especially cholangiocarcinoma (CCA). For the purposes of this mini-review, we will only focus on C. sinensis and review pathogenesis and carcinogenesis of clonorchiasis, disease condition by C. sinensis infestation, and association between C. sinensis infestation and CCA. In this presentation, we briefly consider the current scientific status for progression of CCA by heavy C. sinensis infestation from the food-borne trematode and development of CCA. PMID:27418285

  6. 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

  7. 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.

  8. 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. Copyright © 2014 Australian Society for

  9. Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for histochemical analysis and serodiagnosis of clonorchiasis.

    PubMed

    Kwon, Soon Bin; Kim, Paul; Woo, Hae Sun; Kim, Tae Yun; Kim, Ju Yeong; Lee, Hye Min; Jang, Yun Soo; Kim, Eun-Min; Yong, Tai-Soon; Seong, Baik Lin

    2018-03-27

    Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.

  10. 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.

  11. Parasite-Associated Cancers (Blood Flukes/Liver Flukes).

    PubMed

    Feng, Meng; Cheng, Xunjia

    2017-01-01

    Parasitic infection remains as a persistent public health problem and can be carcinogenic. Three helminth parasites, namely, Clonorchis sinensis (liver fluke) and Opisthorchis viverrini as well as Schistosoma haematobium (blood fluke), are classified as Group 1 carcinogens by the World Health Organization's International Agency for Research on Cancer (IARC Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), World Health Organization, International Agency for Research on Cancer, 2011). Infection by these parasites is frequently asymptomatic and is thus rarely diagnosed at early exposure. Persistent infection can cause severe cancer complications. Until now, the cellular and molecular mechanisms linking fluke infections to cancer formation have yet to be defined, although many studies have focused on these mechanisms in recent years, and numerous findings were made in various aspects of parasite-associated cancers. Herein, we only introduce the fluke-induced cholangiocarcinoma (CCA) and bladder carcinoma and mainly focus on key findings in the last 5 years.

  12. Molecular and structural characteristics of multidrug resistance-associated protein 7 in Chinese liver fluke Clonorchis sinensis.

    PubMed

    Dai, Fuhong; Yoo, Won Gi; Lee, Ji-Yun; Lu, Yanyan; Pak, Jhang Ho; Sohn, Woon-Mok; Hong, Sung-Jong

    2017-03-01

    Multidrug resistance-associated protein 7 (MRP7, ABCC10) is a C subfamily member of the ATP-binding cassette (ABC) superfamily. MRP7 is a lipophilic anion transporter that pumps endogenous and xenobiotic substrates from the cytoplasm to the extracellular milieu. Here, we cloned and characterized CsMRP7 as a novel ABC transporter from the Chinese liver fluke, Clonorchis sinensis. Full-length cDNA of CsMRP7 was 5174 nt, encoded 1636 amino acids (aa), and harbored a 147-bp 5'-untranslated region (5'-UTR) and 116-bp 3'-UTR. Phylogenetic analysis confirmed that CsMRP7 was closer to the ABCC subfamily than the ABCB subfamily. Tertiary structures of the N-terminal region (1-322 aa) and core region (323-1621 aa) of CsMRP7 were generated by homology modeling using glucagon receptor (PDB ID: 5ee7_A) and P-glycoprotein (PDB ID: 4f4c_A) as templates, respectively. CsMRP7 nucleotide-binding domain 2 (NBD2) was conserved more than NBD1, which was the sites of ATP binding and hydrolysis. Like typical long MRPs, CsMRP7 has an additional membrane-spanning domain 0 (MSD0) and cytoplasmic loop, along with a common structural fold consisting of MSD1-NBD1-MSD2-NBD2 as a single polypeptide assembly. MSD0, MSD1, and MSD2 consisted of TM1-7, TM8-13, and TM14-19, respectively. The CsMRP7 transcript was more abundant in the metacercariae than in the adult worms. Truncated NBD1 (39 kDa) and NBD2 (44 kDa) were produced in bacteria and mouse immune sera were raised. CsMRP7 was localized in the apical side of the intestinal epithelium, sperm in the testes and seminal receptacle, receptacle membrane, and mesenchymal tissue around intestine in the adult worm. These results provide molecular information and insights into structural and functional characteristics of CsMRP7 and homologs of flukes.

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

    PubMed

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

    2014-09-01

    Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P < 0.01) and EPG (P < 0.01) in CsCB2 and CsCB3 groups were significantly lower than in control group. In conclusion, we profiled secreted cathepsin B cysteine proteases family for the first time and demonstrated that all CsCB family were C. sinensis excretory/secretory products that may regulate host immune responses.

  14. The Carcinogenic Liver Fluke, Clonorchis sinensis: New Assembly, Reannotation and Analysis of the Genome and Characterization of Tissue Transcriptomes

    PubMed Central

    Wang, Xiaoyun; Liu, Hailiang; Chen, Yangyi; Guo, Lei; Luo, Fang; Sun, Jiufeng; Mao, Qiang; Liang, Pei; Xie, Zhizhi; Zhou, Chenhui; Tian, Yanli; Lv, Xiaoli; Huang, Lisi; Zhou, Juanjuan; Hu, Yue; Li, Ran; Zhang, Fan; Lei, Huali; Li, Wenfang; Hu, Xuchu; Liang, Chi; Xu, Jin; Li, Xuerong; Yu, Xinbing

    2013-01-01

    Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis. PMID:23382950

  15. Lineage-specific expansion and loss of tyrosinase genes across platyhelminths and their induction profiles in the carcinogenic oriental liver fluke, Clonorchis sinensis.

    PubMed

    Kim, Seon-Hee; Bae, Young-An

    2017-09-01

    Tyrosinase provides an essential activity during egg production in diverse platyhelminths by mediating sclerotization of eggshells. In this study, we investigated the genomic and evolutionary features of tyrosinases in parasitic platyhelminths whose genomic information is available. A pair of paralogous tyrosinases was detected in most trematodes, whereas they were lost in cyclophyllidean cestodes. A pseudophyllidean cestode displaying egg biology similar to that of trematodes possessed an orthologous gene. Interestingly, one of the paralogous tyrosinases appeared to have been multiplied into three copies in Clonorchis sinensis and Opisthorchis viverrini. In addition, a fifth tyrosinase gene that was minimally transcribed through all developmental stages was further detected in these opisthorchiid genomes. Phylogenetic analyses demonstrated that the tyrosinase gene has undergone duplication at least three times in platyhelminths. The additional opisthorchiid gene arose from the first duplication. A paralogous copy generated from these gene duplications, except for the last one, seemed to be lost in the major neodermatans lineages. In C. sinensis, tyrosinase gene expressions were initiated following sexual maturation and the levels were significantly enhanced by the presence of O2 and bile. Taken together, our data suggest that tyrosinase has evolved lineage-specifically across platyhelminths related to its copy number and induction mechanism.

  16. Recurrent emergence of structural variants of LTR retrotransposon CsRn1 evolving novel expression strategy and their selective expansion in a carcinogenic liver fluke, Clonorchis sinensis.

    PubMed

    Kim, Seon-Hee; Kong, Yoon; Bae, Young-An

    2017-06-01

    Autonomous retrotransposons, in which replication and transcription are coupled, encode the essential gag and pol genes as a fusion or separate overlapping form(s) that are expressed in single transcripts regulated by a common upstream promoter. The element-specific expression strategies have driven development of relevant translational recoding mechanisms including ribosomal frameshifting to satisfy the protein stoichiometry critical for the assembly of infectious virus-like particles. Retrotransposons with different recoding strategies exhibit a mosaic distribution pattern across the diverse families of reverse transcribing elements, even though their respective distributions are substantially skewed towards certain family groups. However, only a few investigations to date have focused on the emergence of retrotransposons evolving novel expression strategy and causal genetic drivers of the structural variants. In this study, the bulk of genomic and transcribed sequences of a Ty3/gypsy-like CsRn1 retrotransposon in Clonorchis sinensis were analyzed for the comprehensive examination of its expression strategy. Our results demonstrated that structural variants with single open reading frame (ORF) have recurrently emerged from precedential CsRn1 copies encoding overlapping gag-pol ORFs by a single-nucleotide insertion in an upstream region of gag stop codon. In the parasite genome, some of the newly evolved variants appeared to undergo proliferative burst as active master lineages together with their ancestral copies. The genetic event was similarly observed in Opisthorchis viverrini, the closest neighbor of C. sinensis, whereas the resulting structural variants might have failed to overcome purifying selection and comprised minor remnant copies in the Opisthorchis genome. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Identification of the rumen fluke, Calicophoron daubneyi, in GB livestock: possible implications for liver fluke diagnosis.

    PubMed

    Gordon, D K; Roberts, L C P; Lean, N; Zadoks, R N; Sargison, N D; Skuce, P J

    2013-07-01

    The liver fluke, Fasciola hepatica, is common in many parts of Great Britain. To detect liver fluke infection and to assess whether fasciolicide treatment has been successful, the faecal egg count (FEC) and faecal egg count reduction test (FECRT) are widely used. Rumen fluke is also increasingly reported from Great Britain, but its species identity is yet to be determined. Liver fluke and rumen fluke eggs are morphologically similar, which may lead to erroneous diagnoses of liver fluke infection or treatment failure. As an alternative to FEC, a coproantigen ELISA (cELISA) can be used. The potential for this test to cross-react with rumen fluke species from Great Britain has not been evaluated. Rumen fluke specimens from cattle and sheep in Scotland were identified to species level using DNA sequencing of the ITS-2 region. Subsequently, rumen and liver fluke obtained from naturally co-infected sheep were subjected to immunohistochemistry using antibodies from a commercially available cELISA kit for F. hepatica. Finally, faecal samples from naturally co-infected sheep flocks were examined by FEC and cELISA. Rumen fluke from imported and home-bred cattle and sheep in Scotland belonged to the species Calicophoron daubneyi, rather than Paramphistomum cervi, the species presumed to be most common in Great Britain. Intense staining of the gastrodermis was observed in F. hepatica but cross-reactivity with C. daubneyi was not seen. Faecal samples that contained rumen fluke eggs but not liver fluke eggs were all negative by cELISA. We conclude that C. daubneyi is the most common rumen fluke of domestic ruminants in Scotland and that cELISA reduction testing may be a valuable alternative to FECRT in herds or flocks that are co-infected with liver and rumen fluke. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 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.

  19. The Battle of Worldviews: A Case Study of Liver Fluke Infection in Khon Kaen, Thailand.

    PubMed

    Samiphak, Sara; Syme, S Leonard

    2017-10-01

    Control efforts to reduce infection from the parasitic flatworm Opisthorchis viverrini have progressed through understanding the epidemiology of Opisthorchis viverrini, antiparasitic drug developments, technological innovations, health education promoting cooking of fish, and improved hygienic defecation. Yet the problem persists. The case study method was used to examine the fundamental cause of the liver fluke infection problem. Evidence shows that the liver fluke-infected population does not care about living a long life. For them, suffering and death are simply a part of life, and expected. Thus, the cause(s) leading to death is not important. They believe morally bad actions, and predetermined fate associated with kamma in Buddhism, play a big role whether or not one is infected with the liver fluke. Health interventions may be made more effective if they take into account the liver fluke-infected population's worldviews about ethics, morality, life, and death. We researchers should not feel concerned only about medically determined causes of death.

  20. The role of evolutionary biology in research and control of liver flukes in Southeast Asia.

    PubMed

    Echaubard, Pierre; Sripa, Banchob; Mallory, Frank F; Wilcox, Bruce A

    2016-09-01

    Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology-based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The Role of Evolutionary Biology in Research and Control of Liver Flukes in Southeast Asia

    PubMed Central

    Echaubard, Pierre; Sripa, Banchob; Mallory, Frank F.; Wilcox, Bruce A.

    2016-01-01

    Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology-based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework. PMID:27197053

  2. 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.

  3. Liver fluke prevention and control in the northeast of Thailand through action research.

    PubMed

    Wongba, N; Thaewnongiew, K; Phathee, K; Laithavewat, L; Duangsong, R; Promthet, S; Tangsawad, S

    2011-01-01

    The aim of this action research was to enhance people's potential to prevent and control liver fluke infestation. The subjects were a total of 96 participants comprising 20 community leaders, 74 individuals handling and preparing food, and 2 officials from the Local Administration. Quantitative data were collected through questionnaire and the results of stool examination of the participants were recorded. The main methods used to collect qualitative data were focus group discussions and in-depth interviews. For qualitative data analysis, the researchers undertook a qualitative content analysis. For quantitative data, conventional descriptive statistics were used and the mean differences with the 95% CI before and after the study were compared. The results in the early stage found that the participants were not aware of the fact that eating raw fish might be the cause of developing cholangiocarcinoma. 94.8% of participants however knew that eating raw fish might be cause having liver fluke infection which can be treated be taking an antihelminthic drug. They perceived that it is way of life since their ancestors already consumed raw fish because they found it to be delicious. However, through participating in this study, it was realized how dangerous it is to get infected with the liver fluke. Participants also learned the life cycle of liver fluke. They talked about this within their families, and communicated as well as cooperated with others to strengthen a network of a club concentrating on not eating raw fish. The communities and the Sub-district Administrative Organization supported the project. In conclusion, it is advisable to improve the behavior of participants in villages so that they became aware how to prevent and control liver fluke infection and therefore the development of cholangiocarcinoma.

  4. 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

  5. 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

  6. 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

  7. Prevalence of liver fluke infection in Irish horses and assessment of a serological test for diagnosis of equine fasciolosis.

    PubMed

    Quigley, A; Sekiya, M; Egan, S; Wolfe, A; Negredo, C; Mulcahy, G

    2017-03-01

    There is little information on the prevalence of Fasciola hepatica infection in the horse population in Ireland or the potential impact of fluke infection on animal health. To investigate F. hepatica infection in the Irish horse population and to assess the diagnostic potential of an indirect enzyme-linked immunosorbent assay (ELISA) based on the F. hepatica recombinant cathepsin L1 (CL1) antigen. Cross-sectional abattoir survey of horses for liver fluke status. Animals (n = 200) were examined at an abattoir between May 2013 and April 2014. Horses were graded ante mortem for body condition score. Blood and faeces were collected and livers were examined post mortem by gross morphology. A cohort (n = 35) of livers were also examined histologically. Haematology and blood biochemistry, including serum liver enzyme activities, were measured and faeces were sedimented for egg counts. Serum was assayed by indirect ELISA using a recombinant CL1. The prevalence of liver fluke infection was 9.5%. There was no correlation between liver fluke status and time of year, breed classification, age group, sex, body condition score, ante mortem assessment, strongyle infection status, serum liver enzyme activities or CL1 concentration. A comparison of the CL1 ELISA in horse sera compared with a reference standard diagnosis showed high specificity of 95.6% (95% confidence interval [CI] 91.5-98.0%), but low sensitivity of 42.1% (95% CI 20.2-66.5%). This study is limited by its nature as an abattoir study, the relatively small number of animals examined (n = 200), and the absence of a known negative group of horses. Blood biomarkers are not good indicators of liver fluke infection and the CL1 ELISA is not a sensitive tool for diagnosis of fluke infection in the horse. The prevalence of F. hepatica in horses indicates that further research is required to assess the potential impact of liver fluke on equine liver health. © 2016 EVJ Ltd.

  8. Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis.

    PubMed

    Zhou, Lina; Shi, Mengchen; Zhao, Lu; Lin, Zhipeng; Tang, Zeli; Sun, Hengchang; Chen, Tingjin; Lv, Zhiyue; Xu, Jin; Huang, Yan; Yu, Xinbing

    2017-06-17

    Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C. sinensis lysophospholipase A (CsLysoPLA) in C. sinensis-induced liver fibrosis remain unknown. A mouse macrophage cell line (RAW264.7) was cultured and treated with CsLysoPLA. IL-25 and members of its associated signaling pathway were detected by performing quantitative real-time PCR, Western blotting and immunofluorescent staining. A human hepatic stellate cell line (LX-2) was cultured and exposed to IL-25. LX-2 cell activation markers were examined via quantitative real-time PCR, Western blotting and immunofluorescent staining. Migration was analyzed in transwell plates. Treating RAW264.7 cells with CsLysoPLA significantly induced IL-25 expression. Elevated PKA, B-Raf, and ERK1/2 mRNA levels and phosphorylated B-Raf and ERK1/2 were detected in CsLysoPLA-stimulated RAW264.7 cells. The PKA inhibitor H-89 weakened B-Raf and ERK1/2 phosphorylation whereas the AKT activator SC79 attenuated ERK1/2 phosphorylation in RAW264.7 cells. Both H-89 and SC79 inhibited CsLysoPLA-induced IL-25 upregulation. In addition, stimulation of LX-2 cells with IL-25 upregulated the expression of mesenchymal cell markers, including α-smooth muscle actin (α-SMA) and collagen type I (Collagen-I), and promoted cell migration. CsLysoPLA activates HSCs by upregulating IL-25 in macrophages through the PKA-dependent B-Raf/ERK1/2 pathway and potentially promotes hepatic fibrosis during C. sinensis infection.

  9. 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.

  10. 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

  11. CpG-island methylation study of liver fluke-related cholangiocarcinoma

    PubMed Central

    Sriraksa, R; Zeller, C; El-Bahrawy, M A; Dai, W; Daduang, J; Jearanaikoon, P; Chau-in, S; Brown, R; Limpaiboon, T

    2011-01-01

    Background: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. Methods: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. Results: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. Conclusion: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP. PMID:21448164

  12. Specific and common antigens of Clonorchis sinensis and Opisthorchis viverrini (Opisthorchidae, Trematoda)

    PubMed Central

    Choi, Min-Ho; Ryu, Jin-Sook; Lee, Mejeong; Li, Shunyu; Chung, Byung-Suk; Chai, Jong-Yil; Sithithaworn, Paiboon; Tesana, Smarn

    2003-01-01

    The antigenic characterizations and serological reactions of human liver flukes, Clonorchis sinensis and Opisthorchis viverrini, were analyzed by immunoblot. The antigenic profiles of the crude extract of Clonorchis contained major proteins of 8, 26-28, 34-37, 43, and 70 kDa, and those of Opisthorchis 34-37, 43, 70, and 100 kDa. Of these, the 8, 26-28 and 34-37 kDa bands of Clonorchis and the 100 kDa of Opisthorchis were major components of each excretory-secretory antigen. The 8 and 26-28 kDa bands were specific to Clonorchis but the 100 kDa of Opisthorchis cross-reacted with the sera of clonorchiasis, and the 34-37, 70 and 100 kDa bands cross-reacted with sera of other helminthiases. The frequency and intensity of the immunoblot reactions were positively correlated with the intensity of the liver fluke infection. PMID:12972729

  13. DIAGNOSIS AND THERAPY OF LIVER FLUKE (FASCIOLOIDES MAGNA) INFECTION IN FALLOW DEER (DAMA DAMA) IN SERBIA.

    PubMed

    Trailović, Saša M; Marinković, Darko; Kulišić, Zoran

    2016-04-28

    Giant liver fluke ( Fascioloides magna ) infection is an important health problem of cervids in southeastern Europe. We measured the prevalence and intensity of infection with F. magna in a fenced area near the Danube River in the South Bačka District of Serbia. Parasitologic, pathomorphologic, and histopathologic examinations were conducted from November 2007 to February 2008, beginning with a population of 127 adult fallow deer ( Dama dama ). After a positive diagnosis, therapy with triclabendazole-medicated corn was applied. Deer were treated at four baiting stations, using medicated feed providing triclabendazole at an estimated dose of 10-14 mg/kg of body weight per deer. Treatment lasted for 7 d in early February 2008 and an additional 7 d 2 wk later. For the complete success of pharmacotherapy it was necessary to prevent any contact of deer with the snail intermediate host ( Galba truncatula ). Intervention in the habitat, removing grass and low vegetation, and draining ponds reduces the possibility of contact. Six months after the treatment, livers of hunted deer were reddish, with fibrous tracks; pigmentation and cysts in the parenchyma were surrounded by a fibrous capsule and their fecal samples contained no eggs of F. magna . Over the following years, livers of hunted deer were negative, and the last control cull in March 2015 confirmed complete absence of infection. We reconfirmed the presence of giant liver flukes in fallow deer in Serbia, apparently the result of natural spread across the Danube from Hungary and Croatia. We also report that the treatment of deer with triclabendazole-medicated corn is an effective method for administration of therapeutic doses of drug in semicaptive deer. Interventions in the environment are necessary to prevent recontact of deer with habitats used by the snail intermediate host, and enable the success of the therapy.

  14. Detection of major climatic and environmental predictors of liver fluke exposure risk in Ireland using spatial cluster analysis.

    PubMed

    Selemetas, Nikolaos; de Waal, Theo

    2015-04-30

    Fasciolosis caused by Fasciola hepatica (liver fluke) can cause significant economic and production losses in dairy cow farms. The aim of the current study was to identify important weather and environmental predictors of the exposure risk to liver fluke by detecting clusters of fasciolosis in Ireland. During autumn 2012, bulk-tank milk samples from 4365 dairy farms were collected throughout Ireland. Using an in-house antibody-detection ELISA, the analysis of BTM samples showed that 83% (n=3602) of dairy farms had been exposed to liver fluke. The Getis-Ord Gi* statistic identified 74 high-risk and 130 low-risk significant (P<0.01) clusters of fasciolosis. The low-risk clusters were mostly located in the southern regions of Ireland, whereas the high-risk clusters were mainly situated in the western part. Several climatic variables (monthly and seasonal mean rainfall and temperatures, total wet days and rain days) and environmental datasets (soil types, enhanced vegetation index and normalised difference vegetation index) were used to investigate dissimilarities in the exposure to liver fluke between clusters. Rainfall, total wet days and rain days, and soil type were the significant classes of climatic and environmental variables explaining the differences between significant clusters. A discriminant function analysis was used to predict the exposure risk to liver fluke using 80% of data for modelling and the remaining subset of 20% for post hoc model validation. The most significant predictors of the model risk function were total rainfall in August and September and total wet days. The risk model presented 100% sensitivity and 91% specificity and an accuracy of 95% correctly classified cases. A risk map of exposure to liver fluke was constructed with higher probability of exposure in western and north-western regions. The results of this study identified differences between clusters of fasciolosis in Ireland regarding climatic and environmental variables and

  15. Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice.

    PubMed

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

    2016-07-01

    Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, α-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression.

  16. The secreted and surface proteomes of the adult stage of the carcinogenic human liver fluke Opisthorchis viverrini

    PubMed Central

    Mulvenna, Jason; Sripa, Banchob; Brindley, Paul J.; Gorman, Jeffrey; Jones, Malcolm K.; Colgrave, Michelle L.; Jones, Alun; Nawaratna, Sujeevi; Laha, Thewarach; Suttiprapa, Sutas; Smout, Michael J.; Loukas, Alex

    2011-01-01

    Infection with the human liver fluke, Opisthorchis viverrini, is a serious public health problem in Thailand, Laos and nearby locations in Southeast Asia. Both experimental and epidemiological evidence strongly implicate liver fluke infection in the etiology of one of the liver cancer subtypes, cholangiocarcinoma (CCA). To identify parasite proteins critical for liver fluke survival and the etiology of CCA, OFFGEL electrophoresis and Multiple reaction monitoring were employed to characterize 300 parasite proteins from the O. viverrini excretory/secretory products (ES) and, utilizing selective labeling and sequential solubilization, from the host-exposed tegument. The ES included a complex mixture of proteins that have been associated with cancers, including proteases of different mechanistic classes and orthologues of mammalian growth factors and anti-apoptotic proteins. Also identified was a cysteine protease inhibitor which, in other helminth pathogens, induces nitric oxide production by macrophages, and, hence may contribute to malignant transformation of inflamed cells. Proteases in ES included cathepsins, calpain and a protein with homology to autoimmune prostatitis antigen 2. More than 160 tegumental proteins were identified using sequential solubilization of isolated teguments, and a subset of these was localized to the surface membrane of the tegument by labeling living flukes with biotin and confirming surface localization with fluorescence microscopy. These included annexins, which are potential immuno-modulators, and orthologues of the schistosomiasis vaccine antigens Sm29 and tetraspanin-2. Novel roles in pathogenesis were suggested for the tegument-host interface since more than ten biotinylated surface proteins had no homologues in the public databases. The O. viverrini proteins identified here provide an extensive catalogue of novel leads for research on the pathogenesis of opisthorchiasis and the development of novel interventions for this disease

  17. Oxidative stress-mediated mouse liver lesions caused by Clonorchis sinensis infection.

    PubMed

    Maeng, Sejung; Lee, Hye Won; Bashir, Qudsia; Kim, Tae Im; Hong, Sung-Jong; Lee, Tae Jin; Sohn, Woon-Mok; Na, Byoung-Kuk; Kim, Tong-Soo; Pak, Jhang Ho

    2016-03-01

    Clonorchis sinensis is a high-risk pathogenic helminth that strongly provokes inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma in chronically infected individuals. Chronic inflammation is associated with an increased risk of various cancers due to the disruption of redox homeostasis. Accordingly, the present study was conducted to examine the time course relationship between histopathological changes and the appearance of oxidative stress markers, including lipid peroxidation, enzymes involved in lipid peroxidation, and mutagenic DNA adducts in the livers of mice infected with C. sinensis, as well as proinflammatory cytokines in infected mouse sera. Histopathological phenotypes such as bile duct epithelial hyperplasia, periductal fibrosis, edema and inflammatory infiltration increased in infected livers in a time-dependent manner. Intense immunoreactivity of lipid peroxidation products (4-hydroxy-2-nonenal; malondialdehyde), cyclooxygenase-2, 5-lipoxygenase and 8-oxo-7,8-dihydro-2'-deoxyguanosine were concomitantly observed in these injured regions. We also found elevated expressions of cyclooxygenase-2 and 5-lipoxygenase in C. sinensis excretory-secretory product-treated cholangiocarcinoma cells. Moreover, the levels of proinflammatory cytokines such as TNF-α, ILβ-1 and IL-6 were differentially upregulated in infected sera. With regard to oxidative stress-mediated carcinogenesis, our findings suggest that C. sinensis infestation may disrupt host redox homeostasis, creating a damaging environment that favors the development of advanced hepatobiliary diseases such as clonorchiasis-associated cholangiocarcinoma. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  18. A combination of liver fluke infection and traditional northeastern Thai foods associated with cholangiocarcinoma development.

    PubMed

    Sriraj, Pranee; Boonmars, Thidarut; Aukkanimart, Ratchadawan; Songsri, Jiraporn; Sripan, Panupan; Ratanasuwan, Panaratana; Boonjaraspinyo, Sirintip; Wongchalee, Nadchanan; Laummaunwai, Porntip

    2016-10-01

    Opisthorchis viverrini infection is one of the risk factors for cholangiocarcinoma (CCA) in northeast Thailand, a region with one of the highest reported incidence rates of CCA. The traditional practice of eating raw fish, repeated exposure to liver flukes, and consumption of nitrosamine-contaminated food are major risk factors for CCA. So far, there have been no reports about which northeastern traditional dishes may be involved in CCA development. The present study, thus, investigated the effects of traditional foods. It focused specifically on the consumption of fermented foods in combination with O. viverrini infection in hamsters. Syrian hamsters were divided into six groups: (i) normal hamsters, (ii) O. viverrini infection only and (iii)-(vi) O. viverrini infection plus fermented foods (pla som-fish fermented for 1 day), som wua-fermented beef, som phag-fermented vegetables, and pla ra-fish fermented for 6 months. Syrian hamster livers were used for analysis of histopathological changes through hematoxylin and eosin; Sirius Red; and immunohistostaining for cytokeratin-19, proliferating cell nuclear antigen, and CA19-9. Hamster sera were used for liver and kidney function tests. Results of all O. viverrini-infected groups and fermented food groups showed that histopathological changes consisted primarily of aggregations of inflammatory cells surrounding the hepatic bile duct, especially at the hilar region. However, there was a difference in virulence. Interestingly, aggregations of inflammatory cells, new bile duct formation, and fibrosis were observed in subcapsular hepatic tissue, which correlated to positive immunohistochemical staining and increased liver function test. The present study suggests that fermented food consumption can exacerbate cholangitis and cholangiofibrosis, which are risk factors for cholangiocarcinoma-associated opisthorchiasis.

  19. Population-Based Intervention for Liver Fluke Prevention and Control in Meuang Yang District, Nakhon Ratchasima Province, Thailand.

    PubMed

    Kompor, Pontip; Muang Karn, Rattikarn; Norkaew, Jun; Kujapun, Jirawoot; Photipim, Mali; Ponphimai, Sukanya; Chavengkun, Wasugree; Phong Paew, Somkiat; Kaewpitoon, Soraya; Rujirakul, Ratana; Wakhuwathapong, Parichart; Phatisena, Tanida; Eaksanti, Thawatchai; Joosiri, Apinya; Polsripradistdist, Poowadol; Padchasuwan, Natnapa; Kaewpitoon, Natthawut

    2016-01-01

    Opisthorchiasis is still a major health problem in rural communities of Thailand. Infection is associated with cholangiocarcinoma (CCA), which is found frequently in Thailand, particularly in the northeastern. Therefore, this study aimed to evaluate the effectiveness of health intervention in the population at risk for opisthorchiasis and CCA. A quasi-experimental study was conducted in Meuang Yang district, Nakhon Ratchasima province, northeastern Thailand, between June and October 2015. Participants were completed health intervention comprising 4 stations; 1, VDO clip of moving adult worm of liver fluke; 2, poster of life cycle of liver fluke; 3, microscopy with adult and egg liver fluke; and 4, brochure with the knowledge of liver fluke containing infection, signs, symptoms, related disease, diagnosis, treatment, prevention, and control. Pre-and-post-test questionnaires were utilized to collect data from all participants. Students paired t-tests were used to analyze differences between before and after participation in the health intervention. Knowledge (mean difference=-7.48, t=-51.241, 95% CI, -7.77, -7.19, p-value =0.001), attitude (mean difference=-9.07, t=-9.818, 95% CI=-10.9, -7.24, p-value=0.001), and practice (mean difference=-2.04, t=-2.688, 95% CI=-3.55, -0.53, p-value=0.008), changed between before and after time points with statistical significance. Community rules were concluded regarding: (1) cooked cyprinoid fish consumption; (2) stop under cooked cyprinoid fish by household cooker; (3) cooked food consumption; (4) hygienic defecation; (5) corrected knowledge campaign close to each household; (6) organizing a village food safety club; (7) and annual health check including stool examination featuring monitoring by village health volunteers and local public health officers. The results indicates that the present health intervention program was effective and easy to understand, with low cost and taking only a short time. Therefore, this program may

  20. Large numbers of interleukins-22- and -17A-producing T helper cells in cholangiocarcinoma related to liver fluke infection.

    PubMed

    Su, Si-Biao; Zhang, Jian-Feng; Huang, Fei-Fei; Cen, Yu; Jiang, Hai-Xing

    2017-08-01

    Cholangiocarcinoma (CCA) associated with liver fluke infection involves inflammatory and immune processes; however, whether these involve the proinflammatory cytokine IL-17A and proliferative cytokine IL-22 remains unclear. Here, numbers of IL-22- and IL-17A-producing Th cells and cytokine concentrations in 30 patients with CCA and long-term liver fluke infection, 40 patients with liver-fluke infection but not CCA, and 16 healthy controls were compared. Analyses were performed using immunohistochemistry, flow cytometry, ELISA and RT-PCR. Immunohistochemical staining showed weaker expression of IL-22 and IL-17A in patients with CCA with than in those without liver fluke infection (P < 0.01). Flow cytometry revealed significantly greater median proportions of IL-22-producing T helper cells in patients with CCA (2.2%) than in those without it (0.69%) or controls (0.4%, P < 0.001). Similar results were obtained for IL-17A-producing T helper cells. ELISA revealed plasma concentrations of IL-22 were 1.3-fold higher in patients with CCA than in those without it and 4.6-fold higher than in controls (P < 0.001). Plasma concentrations of IL-17A were 2.5-fold higher in patients with CCA than in those without it, and 21-fold higher than in controls (P < 0.001). Amounts of IL-22 and IL-17A mRNAs in blood were significantly higher in patients with CCA than in the other two groups. Proportions of CD4 + CD45RO + T cells producing IL-22 correlated with proportions producing IL-17A (r = 0.759; P < 0.001), and plasma concentrations of IL-22 correlated with those of IL-17A (r = 0.726; P < 0.001). These results suggest that both IL-17A and IL-22 affect development of CCA related to liver fluke infection. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  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. Enzyme-linked immunosorbent assay for diagnosis of Amphimerus spp. liver fluke infection in Humans

    PubMed Central

    Cevallos, William; Calvopiña, Manuel; Nipáz, Victoria; Vicente-Santiago, Belén; López-Albán, Julio; Fernández-Soto, Pedro; Guevara, Ángel; Muro, Antonio

    2017-01-01

    BACKGROUND Amphimerus spp. is a liver fluke that infects humans and domestic animals. It is highly prevalent in some Ecuadorian communities. Currently, diagnosis is based on the microscopic observation of eggs in faeces, but this has variable sensitivity. More sensitive methods are needed for diagnostic testing. OBJECTIVE The main objective of this work was to develop an enzyme-linked immunosorbent assay (ELISA) using crude antigens from Amphimerus spp. adult worms to detect anti-Amphimerus IgG in human sera. METHODS Crude somatic antigens were obtained from adult Amphimerus spp. worms. Human sera from 119 patients were tested: 48 from individuals with a confirmed Amphimerus spp. infection, 78 from non-infected Ecuadorians living in the endemic region, 60 from persons living in non-endemic areas (20 Ecuadorians, 20 Europeans, and 20 Africans), and 33 who had other parasitic and non-parasitic infections. PRINCIPAL FINDINGS Results were analysed using the receiver-operator characteristic (ROC) curve analysis with an area under curve (AUC) value of 0.967. The accuracy of the ELISA was high. The sensitivity was 85.0% [95% confidence interval (CI): 80.3-89.7%] and the specificity was 71.0% (95% CI: 65.2-76.8%). Some cross reactivity was detected against Paragonimus mexicanus, Fasciola hepatica, Schistosomiasis, Taenia solium, Strongyloides stercoralis, Mansonella spp., and Vampirolepis nana. MAIN CONCLUSIONS We have developed the first ELISA technique that detects anti-Amphimerus IgG in human sera with good sensitivity, repeatability and reproducibility. However, more specific antigens are needed to further enhance performance of this assay. Regardless, this ELISA test could be useful for early diagnosis and prompt treatment of human Amphimerus spp. infections. PMID:28443982

  3. Assessing the Role of Climate Variability on Liver Fluke Risk in the UK Through Mechanistic Hydro-Epidemiological Modelling

    NASA Astrophysics Data System (ADS)

    Beltrame, L.; Dunne, T.; Rose, H.; Walker, J.; Morgan, E.; Vickerman, P.; Wagener, T.

    2016-12-01

    Liver fluke is a flatworm parasite infecting grazing animals worldwide. In the UK, it causes considerable production losses to cattle and sheep industries and costs farmers millions of pounds each year due to reduced growth rates and lower milk yields. Large part of the parasite life-cycle takes place outside of the host, with its survival and development strongly controlled by climatic and hydrologic conditions. Evidence of climate-driven changes in the distribution and seasonality of fluke disease already exists, as the infection is increasingly expanding to new areas and becoming a year-round problem. Therefore, it is crucial to assess current and potential future impacts of climate variability on the disease to guide interventions at the farm scale and mitigate risk. Climate-based fluke risk models have been available since the 1950s, however, they are based on empirical relationships derived between historical climate and incidence data, and thus are unlikely to be robust for simulating risk under changing conditions. Moreover, they are not dynamic, but estimate risk over large regions in the UK based on monthly average climate conditions, so they do not allow investigating the effects of climate variability for supporting farmers' decisions. In this study, we introduce a mechanistic model for fluke, which represents habitat suitability for disease development at 25m resolution with a daily time step, explicitly linking the parasite life-cycle to key hydro-climate conditions. The model is used on a case study in the UK and sensitivity analysis is performed to better understand the role of climate variability on the space-time dynamics of the disease, while explicitly accounting for uncertainties. Comparisons are presented with experts' knowledge and a widely used empirical model.

  4. 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

    2014-12-01

    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.

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

    PubMed Central

    Mansour, T. E.

    1957-01-01

    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. PMID:13489165

  6. High Prevalence of Human Liver Infection by Amphimerus spp. Flukes, Ecuador

    PubMed Central

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

    2011-01-01

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

  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. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. 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

  9. 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

  10. Clonorchis sinensis and Clonorchiasis: The Relevance of Exploring Genetic Variation.

    PubMed

    Wang, Daxi; Young, Neil D; Korhonen, Pasi K; Gasser, Robin B

    2018-01-01

    Parasitic trematodes (flukes) cause substantial mortality and morbidity in humans. The Chinese liver fluke, Clonorchis sinensis, is one of the most destructive parasitic worms in humans in China, Vietnam, Korea and the Russian Far East. Although C. sinensis infection can be controlled relatively well using anthelmintics, the worm is carcinogenic, inducing cholangiocarcinoma and causing major suffering in ~15 million people in Asia. This chapter provides an account of C. sinensis and clonorchiasis research-covering aspects of biology, epidemiology, pathogenesis and immunity, diagnosis, treatment and control, genetics and genomics. It also describes progress in the area of molecular biology (genetics, genomics, transcriptomics and proteomics) and highlights challenges associated with comparative genomics and population genetics. It then reviews recent advances in the sequencing and characterisation of the mitochondrial and nuclear genomes for a Korean isolate of C. sinensis and summarises salient comparative genomic work and the implications thereof. The chapter concludes by considering how advances in genomic and informatics will enable research on the genetics of C. sinensis and related parasites, as well as the discovery of new fluke-specific intervention targets. © 2018 Elsevier Ltd All rights reserved.

  11. 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. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Potential risk of a liver fluke Opisthorchis viverrini infection brought by immigrants from prevalent areas: A case study in the lower Northern Thailand.

    PubMed

    Pumidonming, Wilawan; Katahira, Hirotaka; Igarashi, Makoto; Salman, Doaa; Abdelbaset, Abdelbaset E; Sangkaeo, Khamphon

    2018-02-01

    Considering the long lifespan of the liver fluke Opisthorchis viverrini, human mobility from prevalent regions to other neighboring areas has the possibility to disperse carriers and complicate the opisthorchiasis problem. To evaluate this, mass screening of the fluke infection was conducted in nine communities of lower Northern Thailand, combined with a questionnaire survey to distinguish the participant's origin. The liver fluke infection was found in 70 individuals (7.2%) of the examined 971 stool samples from seven communities, with light intensity providing small numbers of eggs in the examined stool. Prevalence in the positive communities varied from 2.1% to 28.7%. As a result of generalized linear mixed models fitting, regional origin and raw-fish eating habits were stably selected as variables affecting the parasite infection while occupation and educational background were secondary ones. Majority of the infected cases (64.3%) were found from the immigrants of northeastern Thailand (the fluke prevalent region), providing 2.28-2.42 times higher infectious risk on average against the local residents. Daily consumption of raw fish averaged a 3.12-3.60 times higher risk compared to those with no raw-fish eating habit. Our findings suggest that people's origin and moving history deserve further attentions in health promotion programs including education for safe eating. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Genetic and infective diversity of the liver fluke Fasciola hepatica (Trematoda: Digenea) from Cuba.

    PubMed

    Vázquez, A A; Lounnas, M; Sánchez, J; Alba, A; Milesi, A; Hurtrez-Boussès, S

    2016-11-01

    In this study we present the first approach to exploration of the genetic diversity of Cuban Fasciola hepatica populations using microsatellite markers, coupled with observed prevalence in slaughterhouses. Nine populations of flukes recovered from cows and buffalos were studied in the central-western region of Cuba. The observed infection rates of definitive hosts (bovines) were 70-100% in most cases. An important amount of polymorphism was found in the four loci explored. However, no apparent genetic differences were found between populations from different provinces or bovine species. The absence of deviations from Hardy-Weinberg equilibrium suggests a high rate of cross-fertilization between F. hepatica individuals. This result was confirmed when all multilocus genotypes were tested for clonal reproduction and only four individuals differed statistically (P sex< 0.05). High values of expected heterozygosity coupled with highly probable mixing among strains make the metapopulation genetically diversified but similar in terms of certain alleles (low F ST values). These results suggest a close relationship between parasite diversity and cattle management in Cuba. Our findings should be taken into consideration by veterinary authorities to help mitigate fasciolosis transmission.

  15. 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

  16. Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand.

    PubMed

    Saensa-Ard, Sunitta; Leuangwattanawanit, Saman; Senggunprai, Laddawan; Namwat, Nisana; Kongpetch, Sarinya; Chamgramol, Yaovalux; Loilome, Watcharin; Khansaard, Walaiporn; Jusakul, Apinya; Prawan, Auemduan; Pairojkul, Chawalit; Khantikeo, Narong; Yongvanit, Puangrat; Kukongviriyapan, Veerapol

    2017-11-01

    Cholangiocarcinoma is a rare type of cancer which is an increasingly discernible health threat. The disease is usually very difficult in diagnosis and various treatment modalities are typically not effective. Cholangiocarcinoma is a complex and very heterogeneous malignancy characterized by tumor location, different risk factors, molecular profiling, and prognosis. Cancer cell lines represent an important tool for investigation in various aspects of tumor biology and molecular therapeutics. We established two cell lines, KKU-452 and KKU-023, which were derived from patients residing in the endemic area of liver fluke infection in Thailand. Both of tumor tissues have gross pathology of perihilar and intrahepatic mass-forming cholangiocarcinoma. Two cell lines were characterized for their biological, molecular and genetic properties. KKU-452 and KKU-023 cells are both adherent cells with epithelium morphology, but have some differences in their growth pattern (a doubling time of 17.9 vs 34.8 h, respectively) and the expression of epithelial bile duct markers, CK7 and CK19. Cytogenetic analysis of KKU-452 and KKU-023 cells revealed their highly complex karyotypes; hypertriploid and hypotetraploid, respectively, with multiple chromosomal aberrations. Both cell lines showed mutations in p53 but not in KRAS. KKU-452 showed a very rapid migration and invasion properties in concert with low expression of E-cadherin and high expression of N-cadherin, whereas KKU-023 showed opposite characters. KKU-023, but not KKU-452, showed in vivo tumorigenicity in xenografted nude mice. Those two established cholangiocarcinoma cell lines with unique characters may be valuable for better understanding the process of carcinogenesis and developing new therapeutics for the patients.

  17. Modeling impacts of climate change on the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand.

    PubMed

    Suwannatrai, A; Pratumchart, K; Suwannatrai, K; Thinkhamrop, K; Chaiyos, J; Kim, C S; Suwanweerakamtorn, R; Boonmars, T; Wongsaroj, T; Sripa, B

    2017-01-01

    Global climate change is now regarded as imposing a significant threat of enhancing transmission of parasitic diseases. Maximum entropy species distribution modeling (MaxEnt) was used to explore how projected climate change could affect the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand. A range of climate variables was used: the Hadley Global Environment Model 2-Earth System (HadGEM2-ES) climate change model and also the IPCC scenarios A2a for 2050 and 2070. Occurrence data from surveys conducted in 2009 and 2014 were obtained from the Department of Disease Control, Ministry of Public Health, Thailand. The MaxEnt model performed better than random for O. viverrini with training AUC values greater than 0.8 under current and future climatic conditions. The current distribution of O. viverrini is significantly affected by precipitation and minimum temperature. According to current conditions, parts of Thailand climatically suitable for O. viverrini are mostly in the northeast and north, but the parasite is largely absent from southern Thailand. Under future climate change scenarios, the distribution of O. viverrini in 2050 should be significantly affected by precipitation, maximum temperature, and mean temperature of the wettest quarter, whereas in 2070, significant factors are likely to be precipitation during the coldest quarter, maximum, and minimum temperatures. Maps of predicted future distribution revealed a drastic decrease in presence of O. viverrini in the northeast region. The information gained from this study should be a useful reference for implementing long-term prevention and control strategies for O. viverrini in Thailand.

  18. A case of probable mixed-infection with Clonorchis sinensis and Fasciola sp.: CT and parasitological findings.

    PubMed

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

    2010-06-01

    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.

  19. 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.

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

    PubMed

    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.

  1. 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

  2. Influence of levamisole and Freund's adjuvant on mouse immunisation with antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758.

    PubMed

    Gutierrez-Sanchez, Maria de Los Angeles; Luna-Herrera, Julieta; Trejo-Castro, Lauro; Montenegro-Cristino, Natividad; Almanza-Gonzalez, Alfredo; Escobar-Gutierrez, Alejandro; de la Rosa-Arana, Jorge Luis

    2015-08-28

    We have studied the influence of both levamisole (AL) and Freund's adjuvant (AF) on the immunisation of mice with the secretory antigens of adults of the liver fluke Fasciola hepatica Linnaeus, 1758. Total IgG antibodies were detected in all groups where the F. hepatica antigen was administered, been levels of IgG1 increased respect to IgG2a antibodies. During immunisation, IL-4 and IFN-γ were only detected in AL and AF groups, but after infection, IL-4 boosted in all groups. IFN-γ increased two fold in AF and AL groups compared to the saline solution (AS) group. Worm recovering was of 32-35% in groups administered without antigen whereas in AS, AL and AF groups recovering was of 25%, 12% and 8%, respectively. Macroscopical lesions in the liver were scarce in AL and AF groups. Our data suggest that immunisation of mice with antigens of F. hepatica enhances the immune response avoiding both liver damage and worm establishment after challenge infection. The murine model of fasciolosis has appeared to be useful to elucidate the mechanism by which the parasite modulates immune responses toward a Th2 type but also the development of Th1 type-inducing vaccines.

  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. Upregulation of 14-3-3 eta in chronic liver fluke infection is a potential diagnostic marker of cholangiocarcinoma.

    PubMed

    Haonon, Ornuma; Rucksaken, Rucksak; Pinlaor, Porntip; Pairojkul, Chawalit; Chamgramol, Yaovalux; Intuyod, Kitti; Onsurathum, Sudarat; Khuntikeo, Narong; Pinlaor, Somchai

    2016-03-01

    To discover protein markers in chronic/advanced opisthorchiasis for the early detection of Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA). Liver tissues derived from normal hamsters and those with chronic/advanced opisthorchiasis (n = 5 per group) were subjected to 2DE and LC-MS/MS. Candidate protein expression was confirmed in hamster models and human CCA tissue microarray (TMA) using immunohistochemistry and Western blot. Proteomics analysis detected 14-3-3 eta only in infected hamsters, not in uninfected controls. Immunohistochemistry and Western blot analysis confirmed low expression of 14-3-3 eta in normal hamster livers and demonstrated increased expression through time in infected livers. This protein was also observed in parasite organs, especially during the chronic phase of opisthorchiasis. Moreover, increased expression of 14-3-3 eta, relative to normal hamster livers, was observed during the early stage of CCA induced by OV infection and administration of N-nitrosodimethylamine. Immunohistochemical analysis of human TMA revealed that 14-3-3 eta was highly expressed in CCA (84.23%, 187/222 cases) but was not found in hepatocellular carcinoma or healthy liver tissues. 14-3-3 eta protein has potential as a screening and early diagnostic marker for CCA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. EGG-HATCHING MECHANISM OF HUMAN LIVER FLUKE, OPISTHORCHIS VIVERRINI: A ROLE FOR LEUCINE AMINOPEPTIDASES FROM THE SNAIL HOST, BITHYNIA SIAMENSIS GONIOMPHALOS.

    PubMed

    Tesana, Smarn; Khampoosa, P; Piratae, S; Prasopdee, S; Sripanidkulchai, B

    2018-05-08

    The human liver fluke Opisthorchis viverrini (Platyhelminthes, Trematoda, Digenea) uses snails of the genus Bithynia as first intermediate host. Peculiarly among trematodes, the eggs of O. viverrini hatch within the digestive tract of its snail host. It remains uncertain whether hatching in this species is mediated through mechanical fracture of the eggshell or by digestion with specific digestive enzymes. This study aimed to characterize enzymes with specific inhibitor and factors involved in the hatching activity of O. viverrini eggs. For measuring egg hatching in vivo, 50 O. viverrini mature eggs were fed to individual Bithynia siamensis goniomphalos snail at various temperature conditions for 24 hrs. Ex vivo, mature eggs were incubated with crude snail extract and commercial leucine aminopeptidase (LAP). Egg-hatching of O. viverrini was temperature dependent, with optimal hatching occurring at 24-28 C, with a peak of hatching of 93.54% in vivo and 30.55% ex vivo occurring at these temperatures. Ex vivo hatching rates increased to 45.87% under anaerobic conditions at 28 C. Some 22.70% and 16.21% of heat-killed eggs also hatched within the snail digestive tract and snail extract, respectively, indicating that host molecules are involved in the hatching response. Most eggs hatch in the anterior regions of the digestive tract. Hatching was completely inhibited in the presence of bestatin, an inhibitor of leucine aminopeptidase (LAP), but not in the presence of phosphatase inhibitors. Bestatin inhibition of hatching was reversible. Finally, egg hatching could be induced by addition of a porcine LAP. The results indicate that this digenean utilizes both LAP of the snail host and movement of miracidia for hatching.

  6. 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

  7. Peroxiredoxin 6 expression is inversely correlated with nuclear factor-κB activation during Clonorchis sinensis infestation.

    PubMed

    Pak, Jhang Ho; Son, Woo Chan; Seo, Sang-Beom; Hong, Sung-Jong; Sohn, Woon-Mok; Na, Byoung-Kuk; Kim, Tong-Soo

    2016-10-01

    Clonorchis sinensis is a carcinogenic human liver fluke. Its infection promotes persistent oxidative stress and chronic inflammation environments in the bile duct and surrounding liver tissues owing to direct contact with worms and their excretory-secretory products (ESPs), provoking epithelial hyperplasia, periductal fibrosis, and cholangiocarcinogenesis. We examined the reciprocal regulation of two ESP-induced redox-active proteins, NF-κB and peroxiredoxin 6 (Prdx6), during C. sinensis infection. Prdx6 overexpression suppressed intracellular free-radical generation by inhibiting NADPH oxidase2 and inducible nitric oxide synthase activation in the ESP-treated cholangiocarcinoma cells, substantially attenuating NF-κB-mediated inflammation. NF-κB overexpression decreased Prdx6 transcription levels by binding to two κB sites within the promoter. This transcriptional repression was compensated for by other ESP-induced redox-active transcription factors, including erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor 1α (HIF1α), and CCAAT/enhancer-binding protein β (C/EBPβ). Distribution of immunoreactive Prdx6 and NF-κB was distinct in the early stages of infection in mouse livers but shared concomitant localization in the later stages. The intensity and extent of their immunoreactive staining in infected mouse livers are proportional to lesion severity and infection duration. The constitutive elevations of Prdx6 and NF-κB during C. sinensis infection may be associated with more severe persistent hepatobiliary abnormalities mediated by clonorchiasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Clonorchis sinensis omega-class glutathione transferases are reliable biomarkers for serodiagnosis of clonorchiasis and opisthorchiasis.

    PubMed

    Kim, J-G; Ahn, C-S; Sripa, B; Eom, K S; Kang, I; Sohn, W-M; Nawa, Y; Kong, Y

    2018-04-09

    To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87) and clonorchiasis (n = 120), as well as those in sera from patients with other helminthic infections (n = 252) and healthy controls (n = 40) were retrospectively analysed by ELISA. We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts (<100, n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Prevalence of fascioliasis (liver flukes) infection in cattle and buffaloes slaughtered at the municipal abattoir of El-Kharga, Egypt

    PubMed Central

    Elshraway, Nagwa T.; Mahmoud, Wafaa G.

    2017-01-01

    Aim: The main objectives of this study were to determine the prevalence of fascioliasis infections in cattle and buffaloes, slaughtered in El-Kharga city slaughterhouse at New Valley Governorate. Materials and Methods: The slaughtered animals were daily inspected for liver fascioliasis allover 2016. Macroscopic fascioliasis was detected from a total of 2251 basing on animals specie, sex, season, and Fasciola spp. in addition to microscopic examination of blood, fecal samples which collected from female cattle and buffalo (50 each). Results: The total prevalence rate of Fasciola sp. infection occurs in the study area were about 695/2251 (30.88%) from the total cattle and bovine slaughtered carcasses. The incidence of fascioliasis was 4/12 (33.33%) and 678/2200 (30.82%) for females and males cattle carcasses, respectively, while the infection rate in buffalo carcasses was 1/4 (25.00%) and 12/35 (34.29%) for females and males buffalo carcasses, respectively. Conclusion: The moderate fasciolosis infection in cattle and buffaloes slaughtered at the municipal abattoir of El-Kharga, Egypt. The highest fascioliasis infection was recorded during winter and autumn. It constitutes a major cause of economic losses at El-Kharga abattoir and threat public health. PMID:28919682

  10. Characterization of a novel organic solute transporter homologue from Clonorchis sinensis

    PubMed Central

    Dai, Fuhong; Lee, Ji-Yun; Pak, Jhang Ho; Sohn, Woon-Mok

    2018-01-01

    Clonorchis sinensis is a liver fluke that can dwell in the bile ducts of mammals. Bile acid transporters function to maintain the homeostasis of bile acids in C. sinensis, as they induce physiological changes or have harmful effects on C. sinensis survival. The organic solute transporter (OST) transports mainly bile acid and belongs to the SLC51 subfamily of solute carrier transporters. OST plays a critical role in the recirculation of bile acids in higher animals. In this study, we cloned full-length cDNA of the 480-amino acid OST from C. sinensis (CsOST). Genomic analysis revealed 11 exons and nine introns. The CsOST protein had a ‘Solute_trans_a’ domain with 67% homology to Schistosoma japonicum OST. For further analysis, the CsOST protein sequence was split into the ordered domain (CsOST-N) at the N-terminus and disordered domain (CsOST-C) at the C-terminus. The tertiary structure of each domain was built using a threading-based method and determined by manual comparison. In a phylogenetic tree, the CsOST-N domain belonged to the OSTα and CsOST-C to the OSTβ clade. These two domains were more highly conserved with the OST α- and β-subunits at the structure level than at sequence level. These findings suggested that CsOST comprised the OST α- and β-subunits. CsOST was localized in the oral and ventral suckers and in the mesenchymal tissues abundant around the intestine, vitelline glands, uterus, and testes. This study provides fundamental data for the further understanding of homologues in other flukes. PMID:29702646

  11. [A domestic cat infected with a large number of Clonorchis sinensis].

    PubMed

    Qiang, Chai; Xiao-Dong, Zhan; Chao-Pin, Li

    2016-07-18

    Adult Clonorchis sinensis not only occurs in human hepatic duct, but also in the liver, gallbladder and bile ducts of animals, including dogs and cats, thus causing clonorchiasis-one of important parasitic zoonoses. In present study, we dissected a domestic cat in which a total of 736 pieces of trematodes, identified as Clonorchis sinensis , were detected in the liver and cholecyst. The findings indicate that Clonorchis sinensis may be endemic in domestic animals in Wuhu area, and observe our awareness in prevention of the parasites in house pets.

  12. Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis

    PubMed Central

    Jamnongkan, Wassana; Thanee, Malinee; Yongvanit, Puangrat; Loilome, Watcharin; Thanan, Raynoo; Kimawaha, Phongsaran; Boonmars, Tidarat; Silakit, Runglawan; Namwat, Nisana

    2018-01-01

    Cholangiocarcinoma (CCA) caused by infection of the liver fluke Opisthorchis viverrini, (Ov) is the major public health problem in northeast Thailand. Following Ov infection the subsequent molecular changes can be associated by reactive oxygen species (ROS) induced chronic inflammation, advanced periductal fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of cell death in prolonged oxidative stress conditions can occur but some damaged/mutated cells could survive and enable clonal expansion. Our study used a natural product, xanthohumol (XN), which is an anti-oxidant and anti-inflammatory compound, to examine whether it could prevent Ov-associated CCA carcinogenesis. We measured the effect of XN with or without praziquantel (PZ), an anti-helminthic treatment, on DNA damage, redox status change including iron accumulation and periductal fibrosis during CCA genesis induced by administration of Ov and N-dinitrosomethylamine (NDMA) in hamsters. Animals were randomly divided into four groups: group I, Ov infection and NDMA administration (ON); group II, Ov infection and NDMA administration and PZ treatment (ONP); the latter 2 groups were similar to group I and II, but group III received additional XN (XON) and group IV received XN plus PZ (XONP). The results showed that high 8-oxodG (a marker of DNA damage) was observed throughout cholangiocarcinogenesis. Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the ROS defense system), whereas decreased expression of phospho-p38MAPK (a major ROS target), was found during the progression of the bile duct cell transformation. In addition, high accumulation of iron and expression of transferrin receptor-1 (TfR-1) in both malignant bile ducts and inflammatory cells were detected. Furthermore, fibrosis also increased with the highest level being on day 180. On the other hand, the groups of XN with or without PZ supplementations showed an effective reduction in all the markers

  13. Development of a TaqMan based real-time PCR assay for detection of Clonorchis sinensis DNA in human stool samples and fishes.

    PubMed

    Cai, Xian-Quan; Yu, Hai-Qiong; Bai, Jian-Shan; Tang, Jian-Dong; Hu, Xu-Chu; Chen, Ding-Hu; Zhang, Ren-Li; Chen, Mu-Xin; Ai, Lin; Zhu, Xing-Quan

    2012-03-01

    Clonorchiasis caused by the oriental liver fluke Clonorchis sinensis is a fish-borne zoonosis endemic in a number of countries. This article describes the development of a TaqMan based real-time PCR assay for detection of C. sinensis DNA in human feces and in fishes. Primers targeting the first internal transcribed spacer (ITS-1) sequence of the fluke were highly specific for C. sinensis, as evidenced by the negative amplification of closely related trematodes in the test with the exception of Opisthorchis viverrini. The detection limit of the assay was 1pg of purified genomic DNA, 5EPG (eggs per gram feces) or one metacercaria per gram fish filet. The assay was evaluated by testing 22 human fecal samples and 37 fish tissues microscopically determined beforehand, and the PCR results were highly in agreement with the microscopic results. This real-time PCR assay provides a useful tool for the sensitive detection of C. sinensis DNA in human stool and aquatic samples in China and other endemic countries where O. viverrini and Opisthorchis felineus are absent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. The Fluke Security Project

    DTIC Science & Technology

    2000-04-01

    be an extension of Utah’s nascent Quarks system, oriented to closely coupled cluster environments. However, the grant did not actually begin until... Intel x86, implemented ten virtual machine monitors and servers, including a virtual memory manager, a checkpointer, a process manager, a file server...Fluke, we developed a novel hierarchical processor scheduling frame- work called CPU inheritance scheduling [5]. This is a framework for scheduling

  15. Mitochondrial genomic comparison of Clonorchis sinensis from South Korea with other isolates of this species.

    PubMed

    Wang, Daxi; Young, Neil D; Koehler, Anson V; Tan, Patrick; Sohn, Woon-Mok; Korhonen, Pasi K; Gasser, Robin B

    2017-07-01

    Clonorchiasis is a neglected tropical disease that affects >35 million people mainly in China, Vietnam, South Korea and some parts of Russia. The disease-causing agent, Clonorchis sinensis, is a liver fluke of humans and other piscivorous animals, and has a complex aquatic life cycle involving snails and fish intermediate hosts. Chronic infection in humans causes liver disease and associated complications including malignant bile duct cancer. Central to control and to understanding the epidemiology of this disease is knowledge of the specific identity of the causative agent as well as genetic variation within and among populations of this parasite. Although most published molecular studies seem to suggest that C. sinensis represents a single species and that genetic variation within the species is limited, karyotypic variation within C. sinensis among China, Korea (2n=56) and Russian Far East (2n=14) suggests that this taxon might contain sibling species. Here, we assessed and applied a deep sequencing-bioinformatic approach to sequence and define a reference mitochondrial (mt) genome for a particular isolate of C. sinensis from Korea (Cs-k2), to confirm its specific identity, and compared this mt genome with homologous data sets available for this species. Comparative analyses revealed consistency in the number and structure of genes as well as in the lengths of protein-coding genes, and limited genetic variation among isolates of C. sinensis. Phylogenetic analyses of amino acid sequences predicted from mt genes showed that representatives of C. sinensis clustered together, with absolute nodal support, to the exclusion of other liver fluke representatives, but sub-structuring within C. sinensis was not well supported. The plan now is to proceed with the sequencing, assembly and annotation of a high quality draft nuclear genome of this defined isolate (Cs-k2) as a basis for a detailed investigation of molecular variation within C. sinensis from disparate

  16. 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.

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

    PubMed

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

    2013-12-01

    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.

  18. Molecular characterization of an α-N-acetylgalactosaminidase from Clonorchis sinensis.

    PubMed

    Lee, Myoung-Ro; Yoo, Won Gi; Kim, Yu-Jung; Kim, Dae-Won; Cho, Shin-Hyeong; Hwang, Kwang Yeon; Ju, Jung-Won; Lee, Won-Ja

    2012-11-01

    The α-N-acetylgalactosaminidase (α-NAGAL) is an exoglycosidase that selectively cleaves terminal α-linked N-acetylgalactosamines from a variety of sugar chains. A complementary DNA (cDNA) clone encoding a novel Clonorchis sinensis α-NAGAL (Cs-α-NAGAL) was identified in the expressed sequence tags database of the adult C. sinensis liver fluke. The complete coding sequence was 1,308 bp long and encoded a 436-residue protein. The selected glycosidase was manually curated as α-NAGAL (EC 3.2.1.49) based on a composite bioinformatics analysis including a search for orthologues, comparative structure modeling, and the generation of a phylogenetic tree. One orthologue of Cs-α-NAGAL was the Rattus norvegicus α-NAGAL (accession number: NP_001012120) that does not exist in C. sinensis. Cs-α-NAGAL belongs to the GH27 family and the GH-D clan. A phylogenetic analysis revealed that the GH27 family of Cs-α-NAGAL was distinct from GH31 and GH36 within the GH-D clan. The putative 3D structure of Cs-α-NAGAL was built using SWISS-MODEL with a Gallus gallus α-NAGAL template (PDB code 1ktb chain A); this model demonstrated the superimposition of a TIM barrel fold (α/β) structure and substrate binding pocket. Cs-α-NAGAL transcripts were detected in the adult worm and egg cDNA libraries of C. sinensis but not in the metacercaria. Recombinant Cs-α-NAGAL (rCs-α-NAGAL) was expressed in Escherichia coli, and the purified rCs-α-NAGAL was recognized specifically by the C. sinensis-infected human sera. This is the first report of an α-NAGAL protein in the Trematode class, suggesting that it is a potential diagnostic or vaccine candidate with strong antigenicity.

  19. 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.

  20. Clonorchis sinensis excretory-secretory products promote the migration and invasion of cholangiocarcinoma cells by activating the integrin β4-FAK/Src signaling pathway.

    PubMed

    Pak, Jhang Ho; Bashir, Qudsia; Kim, In Ki; Hong, Sung-Jong; Maeng, Sejung; Bahk, Young Yil; Kim, Tong-Soo

    2017-06-01

    Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion. In particular, the expression levels of integrin α isoforms and β4 were upregulated in response to ESPs. Increased expression of integrin β4 was probably correlated with activation of focal adhesion kinase (FAK) and the steroid receptor coactivator (Src) family kinase and the subsequent activation of two downstream focal adhesion molecules, paxillin and vinculin. Moreover, inhibition of FAK/Src activation reduced paxillin and vinculin phosphorylation and attenuated ESP-induced CCA cell migration and invasion. These findings suggest that the integrin β4-FAK/Src signaling axis may play a crucial role in clonorchiasis-associated CCA metastasis during tumor progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Molecular and Structural Characterization of the Tegumental 20.6-kDa Protein in Clonorchis sinensis as a Potential Druggable Target.

    PubMed

    Kim, Yu-Jung; Yoo, Won Gi; Lee, Myoung-Ro; Kang, Jung-Mi; Na, Byoung-Kuk; Cho, Shin-Hyeong; Park, Mi-Yeoun; Ju, Jung-Won

    2017-03-04

    The tegument, representing the membrane-bound outer surface of platyhelminth parasites, plays an important role for the regulation of the host immune response and parasite survival. A comprehensive understanding of tegumental proteins can provide drug candidates for use against helminth-associated diseases, such as clonorchiasis caused by the liver fluke Clonorchis sinensis . However, little is known regarding the physicochemical properties of C. sinensis teguments. In this study, a novel 20.6-kDa tegumental protein of the C. sinensis adult worm (CsTegu20.6) was identified and characterized by molecular and in silico methods. The complete coding sequence of 525 bp was derived from cDNA clones and encodes a protein of 175 amino acids. Homology search using BLASTX showed CsTegu20.6 identity ranging from 29% to 39% with previously-known tegumental proteins in C. sinensis . Domain analysis indicated the presence of a calcium-binding EF-hand domain containing a basic helix-loop-helix structure and a dynein light chain domain exhibiting a ferredoxin fold. We used a modified method to obtain the accurate tertiary structure of the CsTegu20.6 protein because of the unavailability of appropriate templates. The CsTegu20.6 protein sequence was split into two domains based on the disordered region, and then, the structure of each domain was modeled using I-TASSER. A final full-length structure was obtained by combining two structures and refining the whole structure. A refined CsTegu20.6 structure was used to identify a potential CsTegu20.6 inhibitor based on protein structure-compound interaction analysis. The recombinant proteins were expressed in Escherichia coli and purified by nickel-nitrilotriacetic acid affinity chromatography. In C. sinensis , CsTegu20.6 mRNAs were abundant in adult and metacercariae, but not in the egg. Immunohistochemistry revealed that CsTegu20.6 localized to the surface of the tegument in the adult fluke. Collectively, our results contribute to a

  2. Risk factors for Clonorchis sinensis infection transmission in humans in northern Vietnam: A descriptive and social network analysis study.

    PubMed

    Vinh, Hoang Quang; Phimpraphai, Waraphon; Tangkawattana, Sirikachorn; Smith, John F; Kaewkes, Sasithorn; Dung, Do Trung; Duong, Tran Thanh; Sripa, Banchob

    2017-04-01

    Clonorchis sinensis is major fish-borne trematode, endemic in North Vietnam. Risk factors described so far include individual eating behaviors and environmental factors. Here, additional to conventional risk factors, we report on socially influenced liver fluke transmission in endemic communities. A cross-sectional study on risk factors and fish sharing networks was conducted in 4 villages of Gia Thinh Commune, Ninh Binh Province. A total of 510 residents in 272 households were recruited for risk factor analysis while 220 households, 28 fishermen and 10 fish-sellers were enrolled for social network study. Fecal examination for C. sinensis eggs was performed. Average C. sinensis infection rate at Gia Thinh commune was 16.5% (range 2% to 34.4%). Higher infection rates were significantly associated with males, lower educational levels, eating raw fish, and location of the villages. Social network analysis (SNA) showed a strong positive correlation between ego network size (number of households in fish sharing network) and quantity of raw fish consumed (r=0.603, P<0.05). The infection rate in people who ate raw-fish caught from a nearby river was significantly higher than those who consumed fish taken from farmed ponds (P<0.05). The amount of raw-fish meal consumed per resident/year was significantly higher in villages that had a strong network of sharing raw-fish food (P<0.001). This study reports for the first time on fish-food sharing among neighbors, proximity to water bodies, frequency of eating raw fish from natural water bodies and low education were key risk factors in C. sinensis infection transmission in northern Vietnam. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Phylogenetic characterization of Clonorchis sinensis proteins homologous to the sigma-class glutathione transferase and their differential expression profiles.

    PubMed

    Bae, Young-An; Kim, Jeong-Geun; Kong, Yoon

    2016-01-01

    Glutathione transferase (GST) is one of the major antioxidant proteins with diverse supplemental activities including peroxidase, isomerase, and thiol transferase. GSTs are classified into multiple classes on the basis of their primary structures and substrate/inhibitor specificity. However, the evolutionary routes and physiological environments specific to each of the closely related bioactive enzymes remain elusive. The sigma-like GSTs exhibit amino acid conservation patterns similar to the prostaglandin D synthases (PGDSs). In this study, we analyzed the phylogenetic position of the GSTs of the biocarcinogenic liver fluke, Clonorchis sinensis. We also observed induction profile of the GSTs in association with the parasite's maturation and in response to exogenous oxidative stresses, with special attention to sigma-class GSTs and PGDSs. The C. sinensis genome encoded 12 GST protein species, which were separately assigned to cytosolic (two omega-, one zeta-, two mu-, and five sigma-class), mitochondrial (one kappa-class), and microsomal (one membrane-associated proteins in eicosanoid and glutathione metabolism-like protein) GST families. Multiple sigma GST (or PGDS) orthologs were also detected in Opisthorchis viverrini. Other trematode species possessed only a single sigma-like GST gene. A phylogenetic analysis demonstrated that one of the sigma GST lineages duplicated in the common ancestor of trematodes were specifically expanded in the opisthorchiids, but deleted in other trematodes. The induction profiles of these sigma GST genes along with the development and aging of C. sinensis, and against various exogenous chemical stimuli strongly suggest that the paralogous sigma GST genes might be undergone specialized evolution to cope with the diverse hostile biochemical environments within the mammalian hepatobiliary ductal system. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Risk factors for Clonorchis sinensis infection transmission in humans in northern Vietnam: A descriptive and social network analysis study

    PubMed Central

    Vinh, Hoang Quang; Phimpraphai, Waraphon; Tangkawattana, Sirikachorn; Smith, John F.; Kaewkes, Sasithorn; Dung, Do Trung; Duong, Tran Thanh; Sripa, Banchob

    2016-01-01

    Clonorchis sinensis is major fish-borne trematode, endemic in North Vietnam. Risk factors described so far include individual eating behaviors and environmental factors. Here, additional to conventional risk factors, we report on socially influenced liver fluke transmission in endemic communities. A cross-sectional study on risk factors and fish sharing networks was conducted in 4 villages of Gia Thinh Commune, Ninh Binh Province. A total of 510 residents in 272 households were recruited for risk factor analysis while 220 households, 28 fishermen and 10 fish-sellers were enrolled for social network study. Fecal examination for C. sinensis eggs was performed. Average C. sinensis infection rate at Gia Thinh commune was 16.5% (range 2% to 34.4%). Higher infection rates were significantly associated with males, lower educational levels, eating raw fish, and location of the villages. Social network analysis (SNA) showed a strong positive correlation between ego network size (number of households in fish sharing network) and quantity of raw fish consumed (r=0.603, P< 0.05). The infection rate in people who ate raw-fish caught from a nearby river was significantly higher than those who consumed fish taken from farmed ponds (P<0.05). The amount of raw-fish meal consumed per resident/year was significantly higher in villages that had a strong network of sharing raw-fish food (P<0.001). This study reports for the first time on fish-food sharing among neighbors, proximity to water bodies, frequency of eating raw fish from natural water bodies and low education were key risk factors in C. sinensis infection transmission in northern Vietnam. PMID:27939296

  5. Cholecystolithiasis Is Associated with Clonorchis sinensis Infection

    PubMed Central

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

    2012-01-01

    Background The objective of this study was to analyze gallbladder stones for direct evidence of a relationship between Clonorchis sinensis infection and gallbladder stones formation. Methodology We investigated one hundred eighty-three gallbladder stones for the presence of Clonorchis sinensis eggs using microscopy, and analyzed their composition using Fourier transform infrared spectroscopy. We confirmed the presence of Clonorchis sinensis eggs in the gallbladder stones using real-time fluorescent PCR and scanning electron microscopy. Principal Findings Clonorchis sinensis eggs were detected in 122 of 183 gallbladder stones based on morphologic characteristics and results from real-time fluorescent PCR. The proportion of pigment stones, cholesterol stones and mixed gallstones in the egg-positive stones was 79.5% (97/122), 3.3% (4/122) and 17.2% (21/122), respectively, while 29.5% (18/61), 31.1% (19/61) and 39.3% (24/61) in the egg-negative stones. The proportion of pigment stone in the Clonorchis sinensis egg-positive stones was higher than in egg-negative stones (P<0.0001). In the 30 egg-positive stones examined by scanning electron microscopy, dozens or even hundreds of Clonorchis sinensis eggs were visible (×400) showing a distinct morphology. Many eggs were wrapped with surrounding particles, and in some, muskmelon wrinkles was seen on the surface of the eggs. Also visible were pieces of texture shed from some of the eggs. Some eggs were depressed or without operculum while most eggs were adhered to or wrapped with amorphous particles or mucoid matter (×3000). Conclusion Clonorchis sinensis eggs were detected in the gallbladder stones which suggests an association between Clonorchis sinensis infection and gallbladder stones formation, especially pigment stones. PMID:22905137

  6. Cholecystolithiasis is associated with Clonorchis sinensis infection.

    PubMed

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

    2012-01-01

    The objective of this study was to analyze gallbladder stones for direct evidence of a relationship between Clonorchis sinensis infection and gallbladder stones formation. We investigated one hundred eighty-three gallbladder stones for the presence of Clonorchis sinensis eggs using microscopy, and analyzed their composition using Fourier transform infrared spectroscopy. We confirmed the presence of Clonorchis sinensis eggs in the gallbladder stones using real-time fluorescent PCR and scanning electron microscopy. Clonorchis sinensis eggs were detected in 122 of 183 gallbladder stones based on morphologic characteristics and results from real-time fluorescent PCR. The proportion of pigment stones, cholesterol stones and mixed gallstones in the egg-positive stones was 79.5% (97/122), 3.3% (4/122) and 17.2% (21/122), respectively, while 29.5% (18/61), 31.1% (19/61) and 39.3% (24/61) in the egg-negative stones. The proportion of pigment stone in the Clonorchis sinensis egg-positive stones was higher than in egg-negative stones (P<0.0001). In the 30 egg-positive stones examined by scanning electron microscopy, dozens or even hundreds of Clonorchis sinensis eggs were visible (×400) showing a distinct morphology. Many eggs were wrapped with surrounding particles, and in some, muskmelon wrinkles was seen on the surface of the eggs. Also visible were pieces of texture shed from some of the eggs. Some eggs were depressed or without operculum while most eggs were adhered to or wrapped with amorphous particles or mucoid matter (×3000). Clonorchis sinensis eggs were detected in the gallbladder stones which suggests an association between Clonorchis sinensis infection and gallbladder stones formation, especially pigment stones.

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

    PubMed

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

    2014-12-01

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

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

    SciT

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won

    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 ofmore » 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

  9. 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

  10. 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

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

    PubMed Central

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

    2012-01-01

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

  12. Heat shock proteins 70 and 90 from Clonorchis sinensis induce Th1 response and stimulate antibody production.

    PubMed

    Chung, Eun Joo; Jeong, Young-Il; Lee, Myoung-Ro; Kim, Yu Jung; Lee, Sang-Eun; Cho, Shin-Hyeong; Lee, Won-Ja; Park, Mi-Yeoun; Ju, Jung-Won

    2017-03-01

    Heat shock proteins (HSPs) are found in all prokaryotes and most compartments of eukaryotic cells. Members of the HSP family mediate immune responses to tissue damage or cellular stress. However, little is known about the immune response induced by the oriental liver fluke, Clonorchis sinensis, even though this organism is carcinogenic to humans. We address this issue in the present study in mouse bone marrow dendritic cells (mBMDCs), using recombinant HSP70 and 90 from C. sinensis (rCsHSP70 and rCsHSP90). rCsHSP70 and rCsHSP90 were produced in an E. coli system. Purified recombinant proteins were treated in BMDCs isolated from C57BL/6 mice. T cells were isolated from Balb/c mice and co-cultured with activated mBMDCs. Expression of surface molecules was measured by flow cytometry and cytokine secretion was quantified using ELISA. C57BL/6 mice were divided into four groups, including peptide alone, peptide/Freund's adjuvant, peptide/CsHSP70, peptide/CsHSP90, and were immunized intraperitoneally three times. Two weeks after final immunization, antibodies against peptide were measured using ELISA. Both proteins induced a dose-dependent upregulation in major histocompatibility complex and co-stimulatory molecule expression and increased secretion of pro-inflammatory cytokines including interleukin (IL)-1β, -6, and -12p70 and tumor necrosis factor-α in mBMDCs. Furthermore, when allogenic T cells were incubated with mBMDCs activated by rCsHSP70 and rCsHSP90, the helper T cell (Th)1 cytokine interferon-γ was up-regulated whereas the level of the Th2 cytokine IL-4 was unchanged. These results indicate that rCsHSPs predominantly induce a Th1 response. Over and above these results, we also demonstrated that the production of peptide-specific antibodies can be activated after immunization via in vitro peptide binding with rCsHSP70 or rCsHSP90. This study showed for the first time that the HSP or HSP/peptide complexes of C. sinensis could be considered as a more effective

  13. Epidemiological investigation of a severe rumen fluke outbreak on an Irish dairy farm.

    PubMed

    O'Shaughnessy, James; Garcia-Campos, Andres; McAloon, Conor G; Fagan, Seamus; de Waal, Theo; McElroy, Maire; Casey, Micheal; Good, Barbara; Mulcahy, Grace; Fagan, John; Murphy, Denise; Zintl, Annetta

    2017-11-16

    Although the rumen fluke, Calicophoron daubneyi is now very common and widespread throughout Western Europe, reports of clinical cases are still rare. This study explores the epidemiological background to a severe rumen fluke outbreak in 6-month-old heifers on a dairy farm in Ireland. Sequence analysis of the cytochrome oxidase subunit 1 (Cox1) gene of the rumen fluke metacercariae on pasture failed to identify predominant, possibly pathogenic subtypes. However, estimates of metacercarial load indicated that the animals were exposed to a daily dose of about 5334 C. daubneyi metacercariae for a period of 3 weeks resulting in the build-up of very large numbers of immature worms in the small intestine. It is hypothesized that specific environmental conditions may favour this parasite over its competitor, the liver fluke, Fasciola hepatica, possibly by allowing it to emerge earlier. The possibility that C. daubneyi may be better adapted to the Irish climate than F. hepatica together with the fact that selective treatment against F. hepatica effectively frees the niche for C. daubneyi, may result in the gradual replacement of F. hepatica by C. daubneyi.

  14. Oral delivery of Bacillus subtilis spores expressing cysteine protease of Clonorchis sinensis to grass carp (Ctenopharyngodon idellus): Induces immune responses and has no damage on liver and intestine function.

    PubMed

    Tang, Zeli; Sun, Hengchang; Chen, TingJin; Lin, Zhipeng; Jiang, Hongye; Zhou, Xinyi; Shi, Cunbin; Pan, Houjun; Chang, Ouqin; Ren, Pengli; Yu, Jinyun; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

    2017-05-01

    Clonorchis sinensis (C. sinensis) is a fish-borne trematode. Human can be infected by ingestion of C. sinensis metacercariae parasitized in grass carp (Ctenopharyngodon idella). For induction of effective oral immune responses, spores of Bacillus subtilis (B. subtilis) WB600 were utilized as vehicle to delivery CsCP (cysteine protease of C. sinensis) cooperated with CotC (B.s-CotC-CP), one of coat proteins, to the gastrointestinal tract. After routine culture of 8-12 h in LB medium, B. subtilis containing CotC-CsCP was transferred into the sporulation culture medium. SDS-PAGE, western blotting and the growth curve indicated that the best sporulation time of recombinant WB600 was 24-30 h at 37 °C with continuous shaking (250 rpm). Grass carp were fed with three levels of B.s-CotC-CP (1 × 10 6 , 1 × 10 7 , and 1 × 10 8  CFU g -1 ) incorporated in the basal pellets diet. The commercial pellets or supplemented with spores just expressing CotC (1 × 10 7  CFU g -1 ) were served as control diet. Our results showed that grass carp orally immunized with the feed-based B.s-CotC-CP developed a strong specific immune response with significantly (P < 0.05) higher levels of IgM in samples of serum, bile, mucus of surface and intestinal compared to the control groups. Abundant colonization spores expressing CsCP were found in hindgut that is conducive to absorption and presentation of antigen. Moreover, B. subtilis spores appeared to show no sign of toxicity or damage in grass carp. Our cercariae challenge experiments suggested that oral administration of spores expressing CsCP could develop an effective protection against C. sinensis in fish body. Therefore, this study demonstrated that the feed-based recombinant spores could trigger high levels of mucosal and humoral immunity, and would be a promising candidate vaccine against C. sinensis metacercariae formation in freshwater fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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

  16. Virus-like particles vaccine containing Clonorchis sinensis tegumental protein induces partial protection against Clonorchis sinensis infection.

    PubMed

    Lee, Dong-Hun; Kim, Ah-Ra; Lee, Su-Hwa; Quan, Fu-Shi

    2017-12-29

    Human clonorchiasis, caused by the infection of Clonorchis sinensis, is one of the major health problems in Southeast Asia. However, vaccine efficacy against C. sinensis infection remains largely unknown. In this study, for the first time, we generated virus-like particles (VLPs) vaccine containing the C. sinensis tegumental protein 22.3 kDa (CsTP 22.3) and the influenza matrix protein (M1) as a core protein, and investigated the vaccine efficacy in Sprague-Dawley rats. Intranasal immunization of VLPs vaccine induced C. sinensis-specific IgG, IgG2a and IgG2c in the sera and IgA responses in the feces and intestines. Notably, upon challenge infection with C. sinensis metacercariae, significantly lower adult worm loads (70.2%) were measured in the liver of rats immunized with VLPs, compared to those of naïve rats. Furthermore, VLPs immunization induced antibody secreting cells (ASC) responses and CD4+/CD8+ T cell responses in the spleen. Our results indicated that VLPs vaccine containing C. sinensis CsTP 22.3 kDa provided partial protection against C. sisnensis infection. Thus, VLPs could be a potential vaccine candidate against C. sinensis.

  17. In vitro antihelmintic effect of fifteen tropical plant extracts on excysted flukes of Fasciola hepatica.

    PubMed

    Alvarez-Mercado, José Manuel; Ibarra-Velarde, Froylán; Alonso-Díaz, Miguel Ángel; Vera-Montenegro, Yolanda; Avila-Acevedo, José Guillermo; García-Bores, Ana María

    2015-02-27

    Fasciolosis due to Fasciola hepatica is the most important hepatic disease in veterinary medicine. Its relevance is important because of the major economical losses to the cattle industry such as: reduction in milk, meat and wool production; miscarriages, anemia, liver condemnation and occasionally deaths, are estimated in billons of dollars. The emergence of fluke resistance due to over or under dosing of fasciolides as well as environmental damage produced by the chemicals eliminated in field have stimulated the need for alternative methods to control Fasciola hepatica. The aim of this study was to evaluate the in vitro anthelmintic effect of fifteen tropical plant extracts used in tradicional Mexican medicine, on newly excysted flukes of Fasciola hepatica. The flukes were exposed in triplicate at 500, 250 and 125 mg/L to each extract. The efficacy was assessed as the mortality rate based on the number of live and dead flukes after 24, 48 and 72 h post-exposure. The plants with anthelmintic effect were evaluated once again with a concentration of 375 mg/L in order to confirm the results and to calculate lethal concentrations at 50%, 90% and 99% (LC(50), LC(90), and LC(99)). Plant extracts of Lantana camara, Bocconia frutescens, Piper auritum, Artemisia mexicana and Cajanus cajan had an in vitro anthelmintic effect (P <0.05). The LC(50), LC(90) and LC(99) to A. mexicana, C. cajan and B. frutescens were 92.85, 210.44 and 410.04 mg/L, 382.73, 570.09 and 788.9 mg/L and 369.96, 529.94 and 710.34 mg/L, respectively. It is concluded that five tropical plant extracts had promising anthelmintic effects against F. hepatica. Further studies on toxicity and in vivo biological evaluation in ruminant models might help to determine the anthelmintic potential of these plant extracts.

  18. Molecular phylogenetic identification of Fasciola flukes in Nepal.

    PubMed

    Shoriki, Takuya; Ichikawa-Seki, Madoka; Devkota, Bhuminand; Rana, Hari B; Devkota, Shiva P; Humagain, Sudeep K; Itagaki, Tadashi

    2014-12-01

    Eighty-one Fasciola flukes collected from 8 districts in Nepal were analyzed for their species identification on the basis of their spermatogenic status and nuclear ribosomal internal transcribed spacer 1 (ITS1) and for their phylogenetic relation with Fasciola flukes from other Asian countries on the basis of the mitochondrial NADH dehydrogenase subunit 1 (nad1) gene. Sixty-one flukes (75.3%) were aspermic Fasciola sp., and 20 flukes (24.7%) were identified as Fasciola gigantica. All of the aspermic flukes displayed the Fh/Fg type in ITS1, which was predominant in aspermic Fasciola sp. from China, and most (60 flukes) displayed the Fsp-ND1-N1 haplotype in the nad1, which had an identical nucleotide sequence to the major haplotype (Fg-C2) of the aspermic flukes from China. These results suggest that aspermic Fasciola sp. was introduced into Nepal from China. Furthermore, the results of the diversity indices, neutrality indices, and median-joining network analysis with reference haplotypes from Asian countries suggest that aspermic Fasciola sp. rapidly expanded its distribution. In contrasts, F. gigantica displayed 10 nad1 haplotypes, which showed higher population diversity indices than the haplotypes of aspermic flukes, indicating that the F. gigantica population was clearly distributed in Nepal earlier than the aspermic Fasciola population. Although the F. gigantica haplotypes from Nepal formed a star-like phylogeny consisting of a main founder haplotype (Fg-ND1-N1), together with some F. gigantica haplotypes from Myanmar and Thailand, the Nepal population differed genetically from F. gigantica populations of neighboring countries as each country had distinct founder haplotype(s). Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Unusual thiol-based redox metabolism of parasitic flukes.

    PubMed

    Tripathi, Timir; Suttiprapa, Sutas; Sripa, Banchob

    2017-08-01

    Parasitic flukes are exposed to free radicals and, to a greater extent, reactive oxygen species (ROS) during their life cycle. Despite being relentlessly exposed to ROS released by activated immune cells, these parasites can survive for many years in the host. Cellular thiol-based redox metabolism plays a crucial role in parasite survival within their hosts. Evidence shows that oxidative stress and redox homeostasis maintenance are important clinical and pathobiochemical as well as effective therapeutic principles in various diseases. The characterization of redox and antioxidant enzymes is likely to yield good target candidates for novel drugs and vaccines. The absence of active catalase in fluke parasites offers great potential for the development of chemotherapeutic agents that act by perturbing the redox equilibrium of the cell. One of the redox-sensitive enzymes, thioredoxin glutathione reductase (TGR), has been accepted as a drug target against blood fluke infections, and related clinical trials are in progress. TGR is the sole enzyme responsible for Trx and GSH reduction in parasitic flukes. The availability of helminth genomes has accelerated the research on redox metabolism of flukes; however, significant achievements have yet to be attained. The present review summarizes current knowledge on the redox and antioxidant system of the parasitic flukes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Improved genomic resources and new bioinformatic workflow for the carcinogenic parasite Clonorchis sinensis: Biotechnological implications.

    PubMed

    Wang, Daxi; Korhonen, Pasi K; Gasser, Robin B; Young, Neil D

    Clonorchis sinensis (family Opisthorchiidae) is an important foodborne parasite that has a major socioeconomic impact on ~35 million people predominantly in China, Vietnam, Korea and the Russian Far East. In humans, infection with C. sinensis causes clonorchiasis, a complex hepatobiliary disease that can induce cholangiocarcinoma (CCA), a malignant cancer of the bile ducts. Central to understanding the epidemiology of this disease is knowledge of genetic variation within and among populations of this parasite. Although most published molecular studies seem to suggest that C. sinensis represents a single species, evidence of karyotypic variation within C. sinensis and cryptic species within a related opisthorchiid fluke (Opisthorchis viverrini) emphasise the importance of studying and comparing the genes and genomes of geographically distinct isolates of C. sinensis. Recently, we sequenced, assembled and characterised a draft nuclear genome of a C. sinensis isolate from Korea and compared it with a published draft genome of a Chinese isolate of this species using a bioinformatic workflow established for comparing draft genome assemblies and their gene annotations. We identified that 50.6% and 51.3% of the Korean and Chinese C. sinensis genomic scaffolds were syntenic, respectively. Within aligned syntenic blocks, the genomes had a high level of nucleotide identity (99.1%) and encoded 15 variable proteins likely to be involved in diverse biological processes. Here, we review current technical challenges of using draft genome assemblies to undertake comparative genomic analyses to quantify genetic variation between isolates of the same species. Using a workflow that overcomes these challenges, we report on a high-quality draft genome for C. sinensis from Korea and comparative genomic analyses, as a basis for future investigations of the genetic structures of C. sinensis populations, and discuss the biotechnological implications of these explorations. Copyright © 2018

  1. 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.

  2. Clonorchis sinensis ova in bile juice cytology from a patient with severe hyperbilirubinemia and portal vein thrombosis.

    PubMed

    Fujiya, Keiichi; Ganno, Hideaki; Ando, Masayuki; Chong, Ja-Mun

    2016-03-01

    Infection with the trematode Clonorchis sinensis is the most common human fluke infection in East Asian populations. Although this infection is associated with obstructive jaundice or choledocholithiasis, portal vein thrombosis has not been reported. Here, we report the first case of a 60-year-old man who had both C. sinensis infection and portal vein thrombosis with severe hyperbilirubinemia (75.4 mg/dl). He initially presented with abdominal pain and jaundice. Computed tomography revealed gallstones, common bile duct calculus, and thrombus in the left main branch of the portal vein. A nasobiliary tube was inserted under endoscopic retrograde cholangiography. Cytology of the bile juice revealed many C. sinensis eggs. The abdominal pain and jaundice improved following choledocholithotomy and combination treatment with a chemotherapeutic agent and anti-coagulant. This case suggests that inflammation around the portal vein as a result of C. sinensis infection has the potential to evoke portal vein thrombosis. Such cases should be treated with both a chemotherapeutic agent and anti-coagulant therapy. In conclusion, the possibility of infection with C. sinensis should be considered in patients presenting with hyperbilirubinemia and portal vein thrombosis, particularly in East Asian populations. © 2015 Wiley Periodicals, Inc.

  3. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2012-07-01

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

  5. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo.

    PubMed

    Kim, Eun-Min; Kwak, You Shine; Yi, Myung-Hee; Kim, Ju Yeong; Sohn, Woon-Mok; Yong, Tai-Soon

    2017-05-01

    Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs) resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages) and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages). Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype), which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection.

  6. Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo

    PubMed Central

    Kim, Eun-Min; Kwak, You Shine; YI, Myung-Hee; Kim, Ju Yeong; Sohn, Woon-Mok

    2017-01-01

    Clonorchis sinensis infection elicits hepatic inflammation, which can lead to cholangitis, periductal hepatic fibrosis, liver cirrhosis, and even cholangiocarcinoma. Hepatic macrophages are an intrinsic element of both innate and acquired immunity. This study was conducted to demonstrate the dynamics of hepatic macrophage polarization during C. sinensis infection in mice and to identify factors regulating this polarization. Treatment of hepatic macrophages isolated from normal mice with C. sinensis excretory/secretory products (ESPs) resulted in the preferential generation of classically activated hepatic macrophages (M1 macrophages) and the production of pro-inflammatory cytokines. Additionally, cells stimulated with C. sinensis ESPs exhibited changes in cellular morphology. During the early stages of C. sinensis infection, hepatic macrophages preferentially differentiated into M1 macrophages; however, during the C. sinensis mature worm stage, when eggs are released, there were significant increases in the abundance of both M1 macrophages and alternatively activated hepatic macrophages (M2 macrophages). Moreover, there was a further increase in the M2 macrophage count during the fibrotic and cirrhotic stage of infection. Notably, this fibrotic and cirrhotic stage promoted a strong increase in the proportion of Arg-1-producing macrophages (M2 phenotype), which were associated with fibrosis and tissue repair in the liver. Our results suggest that the dynamic polarization of hepatic macrophages as C. sinensis infection progresses is related to the histological lesions present in liver tissue. Hepatic macrophages thus play an important role in local immunity during C. sinensis infection. PMID:28542159

  7. Hepatic iron overload is associated with hepatocyte apoptosis during Clonorchis sinensis infection.

    PubMed

    Han, Su; Tang, Qiaoran; Chen, Rui; Li, Yihong; Shu, Jing; Zhang, Xiaoli

    2017-08-01

    Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury. The Perls' Prussian staining and atomic absorption spectrometry methods were used to investigate the iron overload in hepatic sections of wistar rats and patients infected with C. sinensis. The hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL) methods. Spearman analysis was used for determining the correlation of the histological hepatic iron index and the apoptotic index. Blue iron particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial cells, around the liver portal and central vein area of both patients and rats. The total iron score was found to be higher in the infected groups than the respective control from 8 weeks. The hepatic iron concentration was also significantly higher in treatment groups than in control rats from 8 weeks. The hepatocyte apoptosis was found to be significantly higher in the portal area of the liver tissue and around the central vein. However, spearman's rank correlation coefficient revealed that there was a mildly negative correlation between the iron index and hepatocyte apoptosis. This present study confirmed that hepatic iron overload was found during C. sinensis infection. This suggests that iron overload may be associated with hepatocyte apoptosis and involved in liver injury during C. sinensis infection. Further studies are needed to investigate the molecular mechanism involved here.

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

    PubMed

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

    2014-10-01

    Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. © 2014 John Wiley & Sons Ltd.

  9. Immune responses induced by co-infection with Capillaria hepatica in Clonorchis sinensis-infected rats.

    PubMed

    Moon, E-K; Lee, S-H; Goo, T W; Quan, F-S

    2018-07-01

    Clonorchis sinensis and Capillaria hepatica are zoonotic parasites that mainly infect the liver and cause serious liver disorders. However, immunological parameters induced by co-infection with these parasites remain unknown. In this study, for the first time, we investigated immunological profiles induced by co-infection with C. hepatica (CH) in C. sinensis (CS)-infected rats (Sprague-Dawley). Rats were infected primarily with 50 metacercariae of C. sinensis; 4 weeks later, they were subsequently infected with 1000 infective C. hepatica eggs. Significantly higher levels of C. sinensis- or C. hepatica-specific IgG antibodies were found in the sera of rats. Interestingly, no cross-reacting antibody was observed between C. sinensis and C. hepatica infections. Significantly raised eosinophil levels were found in the blood of C. sinensis/C. hepatica co-infected rats (CS + CH) compared to the blood of rats infected singly with C. sinensis. Co-infected rats showed significantly higher levels of lymphocyte proliferation and cytokine production compared to a single C. sinensis infection. The worm burden of C. sinensis was significantly reduced in co-infected rats compared to the single C. sinensis infection. These results indicate that the eosinophils, lymphocyte proliferation and cytokine production induced by subsequent infection with C. hepatica in C. sinensis-infected rats might contribute to the observed C. sinensis worm reduction.

  10. Dysregulation of hepatic microRNA expression profiles with Clonorchis sinensis infection.

    PubMed

    Han, Su; Tang, Qiaoran; Lu, Xi; Chen, Rui; Li, Yihong; Shu, Jing; Zhang, Xiaoli; Cao, Jianping

    2016-11-30

    Clonorchiasis remains an important zoonotic parasitic disease worldwide. The molecular mechanisms of host-parasite interaction are not fully understood. Non-coding microRNAs (miRNAs) are considered to be key regulators in parasitic diseases. The regulation of miRNAs and host micro-environment may be involved in clonorchiasis, and require further investigation. MiRNA microarray technology and bioinformatic analysis were used to investigate the regulatory mechanisms of host miRNA and to compare miRNA expression profiles in the liver tissues of control and Clonorchis sinensis (C. sinensis)-infected rats. A total of eight miRNAs were downregulated and two were upregulated, which showed differentially altered expression profiles in the liver tissue of C. sinensis-infected rats. Further analysis of the differentially expressed miRNAs revealed that many important signal pathways were triggered after infection with C. sinensis, which were related to clonorchiasis pathogenesis, such as cell apoptosis and inflammation, as well as genes involved in signal transduction mechanisms, such as pathways in cancer and the Wnt and Mitogen-activated protein kinases (MAPK) signaling pathways. The present study revealed that the miRNA expression profiles of the host were changed by C. sinensis infection. This dysregulation in miRNA expression may contribute to the etiology and pathophysiology of clonorchiasis. These results also provide new insights into the regulatory mechanisms of miRNAs in clonorchiasis, which may present potential targets for future C. sinensis control strategies.

  11. Molecular characterization of Fasciola flukes obtained from wild sika deer and domestic cattle in Hokkaido, Japan.

    PubMed

    Ichikawa-Seki, Madoka; Shiroma, Tomoko; Kariya, Tatsuya; Nakao, Ryo; Ohari, Yuma; Hayashi, Kei; Fukumoto, Shinya

    2017-10-01

    The number of wild sika deer (Cervus nippon yesoensis) continues to increase in Hokkaido Prefecture, Japan. The major concern for the livestock industry is the transmission of pathogens between sika deer and cattle. Fasciolosis is an important disease that can occur in both animals. The aim of this study was to examine the possible mutual transmission of this disease in Hokkaido Prefecture. A total of 105 Fasciola flukes were obtained from sika deer and 96 from domestic cattle. The Fasciola flukes in Japan are reported to possess no mature sperm. However, in this study, 14 flukes from sika deer and eight flukes from cattle contained mature sperm in their seminal vesicles. All the Fasciola flukes from the two host animals had Fh/Fg type in nuclear phosphoenolpyruvate carboxykinase (pepck) gene, with a mixed fragment pattern derived from F. hepatica and F. gigantica, which are considered to be hybrid Fasciola flukes. However, almost all the flukes had Fsp1 haplotype in NADH dehydrogenase subunit 1 (nad1) gene, indicating that their maternal lineage was F. hepatica. A new haplotype, Fsp3, was detected in one fluke obtained from cattle and differed in one nucleotide from Fsp1. Therefore, the Fasciola flukes detected in both host species had almost identical molecular characteristics. These findings suggest the mutual transmission of Fasciola flukes between sika deer and domestic cattle in Hokkaido. Copyright © 2017. Published by Elsevier B.V.

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

    PubMed

    Li, Wenfang; Dong, Huimin; Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-06-01

    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. 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. 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.

  13. 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

  14. Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

    PubMed

    Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2017-08-01

    Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (P<0.001). Kupffer cells expressed Th2-related cytokines (IL-10 and IL-13) during primary infection. In addition, serum levels of C. sinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

  15. 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

  16. Identification and characterization of Clonorchis sinensis cathepsin B proteases in the pathogenesis of clonorchiasis.

    PubMed

    Chen, Wenjun; Ning, Dan; Wang, Xiaoyun; Chen, Tingjin; Lv, Xiaoli; Sun, Jiufeng; Wu, De; Huang, Yan; Xu, Jin; Yu, Xinbing

    2015-12-21

    Human clonorchiasis is a prevailing food-borne disease caused by Clonorchis sinensis infection. Functional characterizations of key molecules from C. sinensis could facilitate the intervention of C. sinensis associated diseases. In this study, immunolocalization of C. sinensis cathepsin B proteases (CsCBs) in C. sinensis worms was investigated. Four CsCBs were expressed in Pichia pastoris yeast cells. Purified yCsCBs were measured for enzymatic and hydrolase activities in the presence of various host proteins. Cell proliferation, wound-healing and transwell assays were performed to show the effect of CsCBs on human cells. CsCBs were localized in the excretory vesicle, oral sucker and intestinal tract of C. sinensis. Recombinant yCsCBs from yeast showed active enzymatic activity at pH 5.0-5.5 and at 37-42 °C. yCsCBs can degrade various host proteins including human serum albumin, human fibronectin, human hemoglobin and human IgG. CsCBs were detected in liver tissues of mice and cancer patients afflicted with clonorchiasis. Various bioassays collectively demonstrated that CsCBs could promote cell proliferation, migration and invasion of human cancer cells. Our results demonstrated that CsCBs can degrade various human proteins and we proved that the secreted CsCBs are involved in the pathogenesis of clonorchiasis.

  17. A natural focus of the blood fluke Orientobilharzia turkestanica (Skrjabin, 1913) (Trematoda: Schistosomatidae) in red deer (Cervus elaphus) in Hungary.

    PubMed

    Majoros, Gábor; Dán, Adám; Erdélyi, Károly

    2010-06-24

    The large American liver fluke, Fascioloides magna - introduced to Europe before 1875 - was the first non-indigenous trematode to be detected in Hungarian cervids in 1995. As the most precious deer population became infected in the Gemenc game reserve a study has been launched to assess the extent and the effect of F. magna infections and to examine the options for the treatment of infected deer populations. Livers of red deer shot during regular hunting were submitted for the survey and were investigated by necropsy for the presence of F. magna and other liver dwelling trematodes. Recovered parasites were counted, sorted and stored in 70% ethanol. Unexpectedly, blood flukes were found in liver blood vessels at necropsy. They were identified as Orientobilharzia turkestanica (Skrjabin, 1913) by their morphological features as well as by molecular methods. This parasite is widespread in the middle belt of Asia from Korea to the eastern part of Turkey and infects mainly bovids. It was never found in red deer until now and this is the first report of its occurrence in Hungary and Europe. A subsequent search for the local intermediate host of O. turkestanica in the Gemenc area identified only the pulmonate snail Radix auricularia (Linnaeus, 1758) [syn: Lymnaea auricularia] as a vector capable of producing cercariae of this trematode. Cercariae of O. turkestanica were examined morphologically and were confirmed to be the larvae of this trematode by PCR. O. turkestanica appears to be fairly common in red deer of the Gemenc area. No clinical or pathological effect of the infection could be identified in this study. A form of cercarial dermatitis locally called "water mange" was formerly attributed to the larvae of avian shistosomes. It regularly occurred among fishermen fishing in shallow ponds remaining after floods along the Danube in the Gemenc area. This isolated habitat of O. turkestanica presents an exceptional opportunity to study epidemical situations of typical

  18. Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia.

    PubMed

    Sissay, Menkir M; Uggla, Arvid; Waller, Peter J

    2007-10-01

    A 2-year abattoir survey was carried out to determine the prevalence, abundance and seasonal incidence of gastro-intestinal (GI) nematodes and trematodes (flukes) of sheep and goats in the semi-arid zone of eastern Ethiopia. During May 2003 to April 2005, viscera including liver, lungs and GI tracts were collected from 655 sheep and 632 goats slaughtered at 4 abattoirs located in the towns of Haramaya, Harar, Dire Dawa and Jijiga in eastern Ethiopia. All animals were raised in the farming areas located within the community boundaries for each town. Collected materials were transported within 24 h to the parasitology laboratory of Haramaya University for immediate processing. Thirteen species belonging to 9 genera of GI nematodes (Haemonchus contortus, Trichostrongylus axei, T. colubriformis, T. vitrinus, Nematodirus filicollis, N. spathiger Oesopha-gostomum columbianum, O. venulosum, Strongyloides papillosus, Bunostomum trigonocephalum, Trichuris ovis, Cooperia curticei and Chabertia ovina), and 4 species belonging to 3 genera of trematodes (Fasciola hepatica, F. gigantica, Paramphistomum {Calicohoron} microbothrium and Dicrocoelium dendriticum) were recorded in both sheep and goats. All animals in this investigation were infected with multiple species to varying degrees. The mean burdens of adult nematodes were generally moderate in both sheep and goats and showed patterns of seasonal abundance that corresponded with the bi-modal annual rainfall pattern, with highest burdens around the middle of the rainy season. In both sheep and goats there were significant differences in the mean worm burdens and abundance of the different nematode species between the four geographic locations, with worm burdens in the Haramaya and Harar areas greater than those observed in the Dire Dawa and Jijiga locations. Similar seasonal variations were also observed in the prevalence of flukes. But there were no significant differences in the prevalence of each fluke species between the

  19. 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 Central

    Biswal, Devendra Kumar; Ghatani, Sudeep; Shylla, Jollin A.; Sahu, Ranjana; Mullapudi, Nandita

    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

  20. Molecular analysis of aspermic Fasciola flukes from Korea on the basis of the nuclear ITS1 region and mitochondrial DNA markers and comparison with Japanese aspermic Fasciola flukes.

    PubMed

    Ichikawa, Madoka; Itagaki, Tadashi

    2012-07-01

    It has been speculated that populations of aspermic Fasciola flukes in Korea and Japan have a close phylogenetic relationship. To evaluate this, we analyzed 33 Korean aspermic Fasciola flukes on the basis of nuclear ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1) and cytochrome c oxidase 1 (cox1) sequences. Fh, Fg, and Fh/Fg types were detected in the ITS1 region and displayed the fragment patterns of F. hepatica, F. gigantica, and both species, respectively by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Additionally, three concatenated haplotypes of nad1 and cox1(nad1/cox1) were detected, and 2 of these, Kor1/Kor1 (Fsp1/Fsp1) haplotype and Kor2a/Kor2 (Fsp2/Fsp2) haplotype, were shared by Korean and Japanese aspermic flukes. The Fst value (0.019), calculated using the concatenated sequences, indicated that Korean and Japanese aspermic Fasciola populations were genetically undifferentiated. Interestingly, a combination of the Fh/Fg type and Kor1/Kor1 haplotype was found at the highest frequency in Korean aspermic flukes, whereas the Fg type and Fsp2/Fsp2 haplotype combination was found at a conspicuously high frequency in Japanese aspermic flukes. This indicates that a founder effect caused by the introduction of infected hosts may have played a key role in the introduction of aspermic Fasciola flukes from Korea into Japan.

  1. Random and systematic sampling error when hooking fish to monitor skin fluke (Benedenia seriolae) and gill fluke (Zeuxapta seriolae) burden in Australian farmed yellowtail kingfish (Seriola lalandi).

    PubMed

    Fensham, J R; Bubner, E; D'Antignana, T; Landos, M; Caraguel, C G B

    2018-05-01

    The Australian farmed yellowtail kingfish (Seriola lalandi, YTK) industry monitor skin fluke (Benedenia seriolae) and gill fluke (Zeuxapta seriolae) burden by pooling the fluke count of 10 hooked YTK. The random and systematic error of this sampling strategy was evaluated to assess potential impact on treatment decisions. Fluke abundance (fluke count per fish) in a study cage (estimated 30,502 fish) was assessed five times using the current sampling protocol and its repeatability was estimated the repeatability coefficient (CR) and the coefficient of variation (CV). Individual body weight, fork length, fluke abundance, prevalence, intensity (fluke count per infested fish) and density (fluke count per Kg of fish) were compared between 100 hooked and 100 seined YTK (assumed representative of the entire population) to estimate potential selection bias. Depending on the fluke species and age category, CR (expected difference in parasite count between 2 sampling iterations) ranged from 0.78 to 114 flukes per fish. Capturing YTK by hooking increased the selection of fish of a weight and length in the lowest 5th percentile of the cage (RR = 5.75, 95% CI: 2.06-16.03, P-value = 0.0001). These lower end YTK had on average an extra 31 juveniles and 6 adults Z. seriolae per Kg of fish and an extra 3 juvenile and 0.4 adult B. seriolae per Kg of fish, compared to the rest of the cage population (P-value < 0.05). Hooking YTK on the edge of the study cage biases sampling towards the smallest and most heavily infested fish in the population, resulting in poor repeatability (more variability amongst sampled fish) and an overestimation of parasite burden in the population. In this particular commercial situation these finding supported that health management program, where the finding of an underestimation of parasite burden could provide a production impact on the study population. In instances where fish populations and parasite burdens are more homogenous, sampling

  2. Morphology of the core fibrous layer of the cetacean tail fluke.

    PubMed

    Gough, William T; Fish, Frank E; Wainwright, Dylan K; Bart-Smith, Hilary

    2018-06-01

    The cetacean tail fluke blades are not supported by any vertebral elements. Instead, the majority of the blades are composed of a densely packed collagenous fiber matrix known as the core layer. Fluke blades from six species of odontocete cetaceans were examined to compare the morphology and orientation of fibers at different locations along the spanwise and chordwise fluke blade axes. The general fiber morphology was consistent with a three-dimensional structure comprised of two-dimensional sheets of fibers aligned tightly in a laminated configuration along the spanwise axis. The laminated configuration of the fluke blades helps to maintain spanwise rigidity while allowing partial flexibility during swimming. When viewing the chordwise sectional face at the leading edge and mid-chord regions, fibers displayed a crossing pattern. This configuration relates to bending and structural support of the fluke blade. The trailing edge core was found to have parallel fibers arranged more dorso-ventrally. The fiber morphology of the fluke blades was dorso-ventrally symmetrical and similar in all species except the pygmy sperm whale (Kogia breviceps), which was found to have additional core layer fiber bundles running along the span of the fluke blade. These additional fibers may increase stiffness of the structure by resisting tension along their long spanwise axis. © 2018 Wiley Periodicals, Inc.

  3. Echinostome Flukes Receovered from Humans in Khammouane Province, Lao PDR

    PubMed Central

    Sohn, Woon-Mok; Yong, Tai-Soon; Eom, Keeseon S.; Min, Duk-Young; Hoang, Eui-Hyug; Phammasack, Bounlay; Insisiengmay, Bounnaloth; Rim, Han-Jong

    2012-01-01

    Echinostome eggs were detected in 22 (1.1%) of 2,074 people residing in riparian villages along the Mekong River in Khammouane Province, Lao PDR. In order to recover the adult flukes, 9 persons were treated with praziquantel and purged with magnesium salts. A total of 55 echinostome specimens (4 species) were recovered from the 9 persons. Echinostoma revolutum (8 specimens) was recovered from 3 persons, Artyfechinostomum malayanum (8 specimens) was from 2 persons, Echinochasmus japonicus (33 specimens) was from 7 persons, and Euparyphium sp. (6 specimens) was from 1 person. In Lao PDR, only human infections with E. japonicus were previously known. Therefore, the present study describes human infections with E. revolutum, A. malayanum, and Euparyphium sp. for the first time in Lao PDR. These results indicate that the surveyed villages of Khammouane Province, Lao PDR are low-grade endemic foci of echinostomiasis. PMID:22949759

  4. Expression and potential roles of IL-33/ST2 in the immune regulation during Clonorchis sinensis infection.

    PubMed

    Yu, Qian; Li, Xiang-Yang; Cheng, Xiao-Dan; Shen, Li-Ping; Fang, Fan; Zhang, Bo; Hua, Hui; Yan, Chao; Tang, Ren-Xian; Zheng, Kui-Yang

    2016-06-01

    During clonorchiasis, immune responses of hosts are responsible for the removal of the worms and also are involved in the progress of the pathological damage caused by Clonorchis sinensis. Interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, has emerged as a potent inducer to bile duct proliferation and fibrosis; however, little is known of this signaling in the pathogen-caused periductal inflammation and fibrosis. In the present study, using immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay (ELISA), and flow cytometry, we studied the expression of IL-33/ST2 during C. sinensis infection, as well as their potential roles in C. sinensis-induced host immune responses. The results showed that a higher level of IL-33 was detected in the sera of patients of clonorchiasis (n = 45), compared with in those of healthy donors (n = 16). Similarly, in FVB mice experimentally infected with C. sinensis, a higher level of IL-33 was detected at latent stage both in the serum and in the liver, as well as the up-regulated expression of ST2 receptor on the inflammatory cells, especially on CD4(+) T cells in the liver of infected mice. Our results, for the first time, indicated that the increased IL-33/ST2 may be involved in the regulation of immunopathology induced by C. sinensis.

  5. The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease.

    PubMed

    Tang, Zeli; Shang, Mei; Chen, Tingjin; Ren, Pengli; Sun, Hengchang; Qu, Hongling; Lin, Zhipeng; Zhou, Lina; Yu, Jinyun; Jiang, Hongye; Zhou, Xinyi; Li, Xuerong; Huang, Yan; Xu, Jin; Yu, Xinbing

    2016-12-19

    Clonorchiasis, a food-borne zoonosis, is caused by Clonorchis sinensis. The intestinal tract and bile ducts are crucial places for C. sinensis metacercariae to develop into adult worms. The endospore of Bacillus subtilis is an ideal oral immunization vehicle for delivery of heterologous antigens to intestine. Cysteine protease of C. sinensis (CsCP) is an endogenous key component in the excystment of metacercariae and other physiological or pathological processes. We constructed a fusion gene of CotC (a coat protein)-CsCP and obtained B. subtilis spores with recombinant plasmid of pEB03-CotC-CsCP (B.s-CotC-CsCP). CotC-CsCP expressed on spores' surface was detected by Western blotting and immunofluorescence. Immunological characteristics of recombinant spore coat protein were evaluated in a mouse model. The levels of CsCP-specific antibodies were detected by ELISA. Effects of recombinant spores on mouse intestine were evaluated by histological staining. The activities of biochemical enzymes in serum were assayed by microplate. Liver sections of infected mice were evaluated by Ishak score after Masson's trichrome. The B.s-CotC-CsCP spores displayed CsCP on their coat. Specific IgG and isotypes were significantly induced by coat proteins of B.s-CotC-CsCP spores after subcutaneous immunization. IgA levels in intestinal mucus and bile of B.s-CotC-CsCP orally treated mice significantly increased. Additionally, more IgA-secreting cells were observed in enteraden and lamina propria regions of the mouse jejunum, and an increased amount of acidic mucins in intestines were also observed. There were no significant differences in enzyme levels of serum among groups. No inflammatory injury was observed in the intestinal tissues of each group. The degree of liver fibrosis was significantly reduced after oral immunization with B.s-CotC-CsCP spores. Bacillus subtilis spores maintained the original excellent immunogenicity of CsCP expressed on their surface. Both local and systemic

  6. 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.

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

    PubMed

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

    2016-06-01

    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.

  8. 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.

  9. Codon Usage Patterns of Tyrosinase Genes in Clonorchis sinensis.

    PubMed

    Bae, Young-An

    2017-04-01

    Codon usage bias (CUB) is a unique property of genomes and has contributed to the better understanding of the molecular features and the evolution processes of particular gene. In this study, genetic indices associated with CUB, including relative synonymous codon usage and effective numbers of codons, as well as the nucleotide composition, were investigated in the Clonorchis sinensis tyrosinase genes and their platyhelminth orthologs, which play an important role in the eggshell formation. The relative synonymous codon usage patterns substantially differed among tyrosinase genes examined. In a neutrality analysis, the correlation between GC 12 and GC 3 was statistically significant, and the regression line had a relatively gradual slope (0.218). NC-plot, i.e., GC 3 vs effective number of codons (ENC), showed that most of the tyrosinase genes were below the expected curve. The codon adaptation index (CAI) values of the platyhelminth tyrosinases had a narrow distribution between 0.685/0.714 and 0.797/0.837, and were negatively correlated with their ENC. Taken together, these results suggested that CUB in the tyrosinase genes seemed to be basically governed by selection pressures rather than mutational bias, although the latter factor provided an additional force in shaping CUB of the C. sinensis and Opisthorchis viverrini genes. It was also apparent that the equilibrium point between selection pressure and mutational bias is much more inclined to selection pressure in highly expressed C. sinensis genes, than in poorly expressed genes.

  10. Paramphistomum cervi: surface topography of the tegument of adult fluke.

    PubMed

    Panyarachun, Busaba; Sobhon, Prasert; Tinikul, Yotsawan; Chotwiwatthanakun, Charoonroj; Anupunpisit, Vipavee; Anuracpreeda, Panat

    2010-06-01

    Adult Paramphistomum cervi or rumen fluke are pear-shaped, slightly concave ventrally and convex dorsally. The worm measures about 5-13 mm in length and 2-5 mm in width across the mid-section. As observed by scanning electron microscopy (SEM), the tegumental surface in all part of the body, appears highly corrugated with transverse folds alternating with grooves and is spineless. At high magnification, the surface of the fold is composed of microfolds or ridges separated by microgrooves or pits. Corrugations and invaginations of the ventral surface are also more extensive than on the dorsal surface of the body. Both anterior and posterior suckers have thick rims covered with transverse folds without spine. The genital pore is situated at the anterior third of the body. There are two types of sensory papillae on the surface: type 1 is bulbous in shape, measuring 10-15 microm in diameter at the base with nipple-like tips, and type 2 has a similar shape and size and also a short cilia on top. These sensory papillae usually occur in large clusters, each having between 5 and 20 units depending on the region of the body. Clusters of papillae on the ventral surface and around the anterior suckers tend to be more numerous and larger in size. The dorsal surface of the body has the least number of papillae. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  11. 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

  12. Presence and species identity of rumen flukes in cattle and sheep in the Netherlands.

    PubMed

    Ploeger, H W; Ankum, L; Moll, L; van Doorn, D C K; Mitchell, G; Skuce, P J; Zadoks, R N; Holzhauer, M

    2017-08-30

    The purpose of the study was to gain knowledge about the prevalence and identity of rumen flukes (RF) in cattle and sheep in the Netherlands. Routine faecal examinations of diagnostic submissions between May 2009 and September 2014 showed a mean annual herd or flock RF prevalence of 15.8% for cattle and 8.0% for sheep. Prevalence in cattle was higher after 2012 than before, which may reflect a change in detection method as well as an increase in true prevalence. During November and December 2014, an abattoir survey was conducted to allow for scoring of rumen fluke burden and to obtain specimens for molecular species characterization. Over 8 visits to 5 abattoirs in areas deemed to pose a high risk for trematode infection, 116 cows and 41 sheep from 27 herds and 10 flocks were examined. Prevalence of RF was higher in beef cattle than in dairy cattle and higher in cattle than in sheep. Median fluke burden was >100 specimens per animal for most positive animals. Using a semi-quantitative RF density score as a gold standard, sensitivity and specificity of a modified quantitative Dorsman egg counting method were estimated at 82.6% and 83.3%, respectively. Of 14 collected adult rumen flukes, twelve (8 bovine and 4 ovine specimens) were identified as Calicophoron daubneyi. The other two, of bovine origin, were identified as Paramphistomum leydeni, which was unexpected as in other European countries all recently collected rumen flukes in both cattle and sheep were identified as C. daubneyi. The findings implicate that multiple rumen fluke species, intermediate host species and transmission cycles may play a role in rumen fluke infections in the Netherlands. Copyright © 2017. Published by Elsevier B.V.

  13. Characterization and identification of differentially expressed microRNAs during the process of the peribiliary fibrosis induced by Clonorchis sinensis.

    PubMed

    Yan, Chao; Shen, Li-Ping; Ma, Rui; Li, Bo; Li, Xiang-Yang; Hua, Hui; Zhang, Bo; Yu, Qian; Wang, Yu-Gang; Tang, Ren-Xian; Zheng, Kui-Yang

    2016-09-01

    Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C. sinensis-infected mice at 2, 8 or 16weeks post infection (p.i.), compared with those at 0week p.i., and there were 143 down-regulated and 206 up-regulated miRNAs among them. These all dysregulated miRNAs were potentially involved in the pathological processes of clonorchiasis by regulation of cancer-related signaling pathway, TGF-β signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, PI3K /AKT signaling pathway, etc. 169 of these dysregulated miRNAs were predicted to be involved in the TGF/Smads signaling pathway which plays an important role in the biliary fibrosis caused by C. sinensis. Additionally, miRNA-32, miRNA-34a, miRNA-125b and miRNA-497 were negatively correlated with Smad7 expression, indicating these miRNAs may specifically down-regulate Smad7 expression and participate in regulation of biliary fibrosis caused by C. sinensis. The results of the present study for the first time demonstrated that miRNAs were differentially expressed in the liver of mice infected by C. sinensis, and these miRNAs may play important roles in regulation of peribiliary fibrosis caused by C. sinensis, which may provide possible therapeutic targets for clonorchiasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Secreted phospholipase A2 of Clonorchis sinensis activates hepatic stellate cells through a pathway involving JNK signalling.

    PubMed

    Wu, Yinjuan; Li, Ye; Shang, Mei; Jian, Yu; Wang, Caiqin; Bardeesi, Adham Sameer A; Li, Zhaolei; Chen, Tingjin; Zhao, Lu; Zhou, Lina; He, Ai; Huang, Yan; Lv, Zhiyue; Yu, Xinbing; Li, Xuerong

    2017-03-16

    Secreted phospholipase A2 (sPLA2) is a protein secreted by Clonorchis sinensis and is a component of excretory and secretory products (CsESPs). Phospholipase A2 is well known for its role in liver fibrosis and inhibition of tumour cells. The JNK signalling pathway is involved in hepatic stellate cells (HSCs) activation. Blocking JNK activity with SP600125 inhibits HSCs activation. In a previous study, the protein CssPLA2 was expressed in insoluble inclusion bodies. Therefore, it's necessary to express CssPLA2 in water-soluble form and determine whether the enzymatic activity of CssPLA2 or cell signalling pathways is involved in liver fibrosis caused by clonorchiasis. Balb/C mice were given an abdominal injection of MBP-CssPLA2. Liver sections with HE and Masson staining were observed to detect accumulation of collagen. Western blot of mouse liver was done to detect the activation of JNK signalling pathway. In vitro, HSCs were incubated with MBP-CssPLA2 to detect the activation of HSCs as well as the activation of JNK signalling pathway. The mutant of MBP-CssPLA2 without enzymatic activity was constructed and was also incubated with HSCs to check whether activation of the HSCs was related to the enzymatic activity of MBP-CssPLA2. The recombinant protein MBP-CssPLA2 was expressed soluble and of good enzymatic activity. A mutant of CssPLA2, without enzymatic activity, was also constructed. In vivo liver sections of Balb/C mice that were given an abdominal injection of 50 μg/ml MBP-CssPLA2 showed an obvious accumulation of collagen and a clear band of P-JNK1 could be seen by western blot of the liver tissue. In vitro, MBP-CssPLA2, as well as the mutant, was incubated with HSCs and it was proved that activation of HSCs was related to activation of the JNK signalling pathway instead of the enzymatic activity of MBP-CssPLA2. Activation of HSCs by CssPLA2 is related to the activation of the JNK signalling pathway instead of the enzymatic activity of CssPLA2. This finding

  15. 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

  16. 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.

  17. 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.

  18. Protease Inhibitors of Parasitic Flukes: Emerging Roles in Parasite Survival and Immune Defence.

    PubMed

    Ranasinghe, Shiwanthi L; McManus, Donald P

    2017-05-01

    Protease inhibitors play crucial roles in parasite development and survival, counteracting the potentially damaging immune responses of their vertebrate hosts. However, limited information is currently available on protease inhibitors from schistosomes and food-borne trematodes. Future characterization of these molecules is important not only to expand knowledge on parasitic fluke biology but also to determine whether they represent novel vaccine and/or drug targets. Moreover, protease inhibitors from flukes may represent lead compounds for the development of a new range of therapeutic agents against inflammatory disorders and cancer. This review discusses already identified protease inhibitors of fluke origin, emphasizing their biological function and their possible future development as new intervention targets. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.

    PubMed

    Wang, Caiqin; Lei, Huali; Tian, Yanli; Shang, Mei; Wu, Yinjuan; Li, Ye; Zhao, Lu; Shi, Mengchen; Tang, Xin; Chen, Tingjin; Lv, Zhiyue; Huang, Yan; Tang, Xiaoping; Yu, Xinbing; Li, Xuerong

    2017-05-25

    Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools. Recombinant CsGRN (rCsGRN) protein was expressed in Escherichia coli BL21 (DE3). The localisation of CsGRN in adult worms and Balb/c mice infected with C. sinensis was investigated by immunofluorescence and immunohistochemistry, respectively. Stable CsGRN-overexpressed cell lines of hepatoma cells (PLC-GRN cells) and cholangiocarcinoma cells (RBE-GRN cells) were constructed by transfection of eukaryotic expression plasmid of pEGFP-C1-CsGRN. The effects on cell migration and invasion of CsGRN were assessed through the wound-healing assay and transwell assay. The levels of matrix metalloproteinase 2 and 9 (MMP2 and MMP9) in PLC-GRN or RBE-GRN cells were detected by real-time PCR (qRT-PCR). The levels of E-cadherin, vimentin, N-cadherin, zona occludens proteins (ZO-1), β-catenin, phosphorylated ERK (p-ERK) and phosphorylated AKT (p-AKT) were analysed by Western blotting. CsGRN, including the conserved GRN domains, was confirmed to be a member of the granulin family. CsGRN was identified as an ingredient of CsESPs. CsGRN was localised in the tegument and testes of the adult worm. Furthermore, it appeared in the cytoplasm of hepatocytes and biliary epithelium cells from infected Balb/c mouse. The enhancement of cell migration and invasion of PLC-GRN and RBE-GRN cells were observed. In addition, CsGRN upregulated the levels of vimentin, N-cadherin, β-catenin, MMP2 and MMP9, while it downregulated the level of ZO-1 in PLC-GRN/RBE-GRN cells. In total proteins of liver tissue

  20. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Application of Pineapple Juice in the Fish Digestion Process for Carcinogenic Liver Fluke Metacercaria Collection

    PubMed Central

    Sripan, Panupan; Aukkanimart, Ratchadawan; Boonmars, Thidarut; Pranee, Sriraj; Songsri, Jiraporn; Boueroy, Parichart; Khueangchaingkhwang, Sukhonthip; Pumhirunroj, Benjamabhorn; Artchayasawat, Atchara

    2017-01-01

    Pepsin is common digestive enzyme used for fish digestion in the laboratory to collect trematode metacercariae. In a field study, to survey the infected fish is needed a huge yield of pepsin and it is very expensive. Therefore, our purpose of this study was to investigate the candidate enzyme from pineapple juice which has a digestive enzyme called bromelain, a mixture of proteolytic enzymes, to digest fish in order to harvest metacercariae. Fish were divided into 2 groups: one group in which metacercariae were harvested using acid pepsin as a control and other groups in which the fish was digested using fresh pineapple juices. The results showed that pineapple juice is able to digest fish similarly to pepsin. The Pattavia pineapple juice had the highest number of metacercariae similar to the control. For Trat Si Thong pineapple juice, we found the number of metacercariae was less than control. This result suggests that the Pattavia pineapple juice was optimal juice for fish digestion to metacercaria collection and can be used instread of pepsin acid. PMID:28441786

  2. 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

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

    PubMed

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

    2016-06-01

    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 mm(3)) from the Cs group was a hepatocellular adenoma and the other (280.6 mm(3)) 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.

  4. Bacillus subtilis spore with surface display of paramyosin from Clonorchis sinensis potentializes a promising oral vaccine candidate.

    PubMed

    Sun, Hengchang; Lin, Zhipeng; Zhao, Lu; Chen, Tingjin; Shang, Mei; Jiang, Hongye; Tang, Zeli; Zhou, Xinyi; Shi, Mengchen; Zhou, Lina; Ren, Pengli; Qu, Honglin; Lin, Jinsi; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

    2018-03-07

    Clonorchiasis caused by Clonorchis sinensis has become increasingly prevalent in recent years. Effective prevention strategies are urgently needed to control this food-borne infectious disease. Previous studies indicated that paramyosin of C. sinensis (CsPmy) is a potential vaccine candidate. We constructed a recombinant plasmid of PEB03-CotC-CsPmy, transformed it into Bacillus subtilis WB600 strain (B.s-CotC-CsPmy), and confirmed CsPmy expression on the spore surface by SDS-PAGE, Western blotting and immunofluorescence assay. The immune response and protective efficacy of the recombinant spore were investigated in BALB/c mice after intragastrical or intraperitoneal immunization. Additionally, biochemical enzyme activities in sera, the intestinal histopathology and gut microflora of spore-treated mice were investigated. CsPmy was successfully expressed on the spore surface and the fusion protein on the spore surface with thermostability. Specific IgG in sera and intestinal mucus were increased after intraperitoneal and intragastrical immunization. The sIgA level in intestinal mucus, feces and bile of B.s-CotC-CsPmy orally treated mice were also significantly raised. Furthermore, numerous IgA-secreting cells were detected in intestinal mucosa of intragastrically immunized mice. No inflammatory injury was observed in the intestinal tissues and there was no significant difference in levels of enzyme-indicated liver function among the groups. Additionally, the diversity and abundance of gut microbiota were not changed after oral immunization. Intragastric and intraperitoneal immunization of B.s-CotC-CsPmy spores in mice resulted in egg reduction rates of 48.3 and 51.2% after challenge infection, respectively. Liver fibrosis degree in B.s-CotC-CsPmy spores treated groups was also significantly reduced. CsPmy expressed on the spore surface maintained its immunogenicity. Both intragastrical and intraperitoneal immunization with B.s-CotC-CsPmy spores induced systemic and

  5. Hybrid origin of Asian aspermic Fasciola flukes is confirmed by analyzing two single-copy genes, pepck and pold

    PubMed Central

    HAYASHI, Kei; ICHIKAWA-SEKI, Madoka; MOHANTA, Uday Kumar; SHORIKI, Takuya; CHAICHANASAK, Pannigan; ITAGAKI, Tadashi

    2017-01-01

    Nuclear gene markers, phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold), have been developed for precise discrimination of Fasciola flukes instead of internal transcribed spacer 1. In this study, these two genes of 730 Fasciola flukes from eight Asian countries were analyzed. The results were compared with their mitochondrial NADH dehydrogenase subunit 1 (nad1) lineages for obtaining a definitive evidence of the hybrid origin of aspermic Fasciola flukes. All the flukes categorized into the aspermic nad1 lineages possessed both the fragment patterns of F. hepatica and F. gigantica (mixed types) in pepck and/or pold. These findings provide clear evidence for the hybrid origin of aspermic Fasciola lineages and suggest that “aspermic Fasciola flukes” should hereafter be called “hybrid Fasciola flukes”. PMID:29187710

  6. 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

  7. Adherence of carp leucocytes to adults and cercariae of the blood fluke Sanguinicola inermis.

    PubMed

    Richards, D T; Hoole, D; Lewis, J W; Ewens, E; Arme, C

    1996-03-01

    Live adult and cercarial stages of Sanguinicola inermis Plehn, 1905 (Trematoda:Sanguinicolidae) were maintained in vitro in the presence of carp (Cyprinus carpio L.) leucocytes. Cells and parasites were fixed at intervals from 0.25 to 48 h and examined using light microscopy, SEM and TEM. Within 12 h of exposure, leucocytes were found attached to cercariae although, by 24 h, fewer cells were found attached to postcercarial, juvenile adult stages that had shed their tails. Neutrophils and macrophages were found attached to the damaged tegument of cercarie that had not transformed by 48 h. Few cells were attached to the tegument of adult flukes that were alive when fixed. However, there was extensive tegumental damage and numerous cells were attached to adult flukes that had died before fixation. The results are discussed with reference to parasite survival within the vascular system of the host.

  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. Elucidation of the first definitively identified life cycle for a marine turtle blood fluke (Trematoda: Spirorchiidae) enables informed control.

    PubMed

    Cribb, Thomas H; Crespo-Picazo, Jose L; Cutmore, Scott C; Stacy, Brian A; Chapman, Phoebe A; García-Párraga, Daniel

    2017-01-01

    Blood flukes of the family Spirorchiidae are significant pathogens of both free-ranging and captive marine turtles. Despite a significant proportion of marine turtle mortality being attributable to spirorchiid infections, details of their life cycles remain almost entirely unknown. Here we report on the molecular elucidation of the complete life cycle of a marine spirorchiid, identified as Amphiorchis sp., infecting vermetid gastropods and captive hatched neonate Caretta caretta in the Oceanogràfic Aquarium, in Valencia, Spain. Specimens of a vermetid gastropod, Thylaeodus cf. rugulosus (Monterosato, 1878), collected from the aquarium filtration system housing diseased C. caretta, were infected with sporocysts and cercariae consistent with the family Spirorchiidae. We generated rDNA sequence data [internal transcribed spacer 2 (ITS2) and partial 28S rDNA] from infections from the vermetid which were identical to sequences generated from eggs from the serosa of the intestine of neonate C. caretta, and an adult spirorchiid from the liver of a C. caretta from Florida, USA. Given the reliability of these markers in the delineation of trematode species, we consider all three stages to represent the same species and tentatively identify it as a species of Amphiorchis Price, 1934. The source of infection at the Oceanogràfic Foundation Rehabilitation Centre, Valencia, Spain, is inferred to be an adult C. caretta from the western Mediterranean being rehabilitated in the same facility. Phylogenetic analysis suggests that this Amphiorchis sp. is closely related to other spirorchiids of marine turtles (species of Carettacola Manter & Larson, 1950, Hapalotrema Looss, 1899 and Learedius Price, 1934). We discuss implications of the present findings for the control of spirorchiidiasis in captivity, for the better understanding of epidemiology in wild individuals, and the elucidation of further life cycles. Copyright © 2016 Australian Society for Parasitology. Published by

  10. Clonorchis sinensis infection and co-infection with the hepatitis B virus are important factors associated with cholangiocarcinoma and hepatocellular carcinoma.

    PubMed

    Shi, Yunliang; Jiang, Zhihua; Yang, Yichao; Zheng, Peiqiu; Wei, Haiyan; Lin, Yuan; Lv, Guoli; Yang, Qingli

    2017-10-01

    To evaluate the contributions of Clonorchis sinensis and hepatitis B virus to the development of cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC), C. sinensis and hepatitis B virus infections in 20 clinical liver cancer cases from a C. sinensis- and hepatitis B virus-epidemic region were detected. Eight cases of ICC, 11 cases of HCC and one mixed ICC and HCC case were verified by CT, pathological section and (or) observations during surgery. The C. sinensis infection was detected by stool microscopy and ELISA, and the worms and eggs found during surgery and in pathological sections also allowed for diagnoses. Hepatitis B virus infections were detected by ELISA. In the 20 cases, 18 patients were diagnosed with C. sinensis infections. Eight of the 20 patients were infected with the hepatitis B virus, and seven were co-infected with C. sinensis. In the eight ICC patients, seven were diagnosed with C. sinensis infection, and two had mixed infections with the hepatitis B virus. In the 11 HCC patients, 10 were diagnosed with C. sinensis, four had mixed infections with the hepatitis B virus, and only one HCC patient presented a single infection by the hepatitis B virus. These clinical observations revealed that C. sinensis infection and C. sinensis co-infection with the hepatitis B virus are important factors in ICC and HCC.

  11. [Gallbladder Stone Types in Patients with Cholelithiasis and Clonorchis sinensis Infection in the Endemic Area of Clonorchiasis].

    PubMed

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

    2015-06-01

    To investigate the relationship between Clonorchis sinensis infection and the gallbladder stone type in patients with cholelithiasis in the endemic area of clonorchiasis. Gallbladder stones were collected from 598 patients with cholelithiasis through minimally invasive gallbladder-preserving cholelithotomy in the Sixth People's Hospital of Nansha District from May 2009 to October 2012. The stone samples were analyzed for composition by Fourier transform infrared spectroscopy to identify their types. The Clonorchis sinensis eggs were detected in the stones by microscopic examination, and the detection rates of eggs were calculated for different stone types. Then the clinical characteristics and biochemical indicators were compared among patients with different types of stones, as well as between Clonorchis sinensis egg-positive and -negative patients with the calcium-carbonate type of stones. Some calcium-carbonate stones positive for Clonorchis sinensis eggs were randomly selected for further scanning electron microscopy (SEM) examination. Of the stones from 598 patients, 234 (39.1%) were cholesterol type, 133 (22.2%) bile pigment type, 112(18.7%) calcium-carbonate type, 86 (14.4%) mixed types and 33(5.5%) were others. The detection rate of Clonorchis sinensis eggs in these types was 6% (15/234), 44% (59/133), 60% (67/112), 36% (31/ 86) and 30% (10/33), respectively, being highest in calcium-carbonate stones while lowest in cholesterol stones. The Co2-combining power of the plasma was higher in patients with calcium-carbonate and mixed stones than in those with cholesterol stones (P < 0.05), and the CO2-combining power of the bile and biliary pH were both higher in patients with calcium-carbonate types than in those with other types (P < 0.05). In addition, in patients with calcium-carbonate stones, the CO2-combining powers of the plasma and the bile, as well as biliary pH were all higher in the egg-positives than in the egg-negatives. Further, both light

  12. Liver transplant

    MedlinePlus

    ... fully working livers after a successful transplant. The donor liver is transported in a cooled salt-water (saline) ... Liver failure - liver transplant; Cirrhosis - liver transplant Images Donor liver attachment Liver transplant - series References Carrion AF, Martin ...

  13. Three-Dimensional Geometry of the Narwhal (Monodon monoceros) Flukes in Relation to Hydrodynamics

    DTIC Science & Technology

    2011-10-01

    MARINE MAMMAL SCIENCE, 27(4): 889–898 (October 2011) C© 2010 by the Society for Marine Mammalogy DOI: 10.1111/j.1748-7692.2010.00439.x Three...Chester University, West Chester, Pennsylvania 19383, U.S.A. E-mail: ffish@wcupa.edu NATALIA RYBCZYNSKI Canadian Museum of Nature, Ottawa, Ontario K1P...distributed in the ice-packed stretches of waters bordering Greenland and the Canadian High Arctic (Laidre et al. 2003). The flukes of mature male

  14. Cardiovascular flukes (Trematoda: Spirorchiidae) in Caretta caretta Linnaeus, 1758 from the Mediterranean Sea.

    PubMed

    Marchiori, Erica; Negrisolo, Enrico; Cassini, Rudi; Garofalo, Luisa; Poppi, Lisa; Tessarin, Cinzia; Marcer, Federica

    2017-10-10

    The northern Adriatic Sea represents one of the most important neritic foraging grounds for the loggerhead sea turtle Caretta caretta L. in the Mediterranean Sea. Four genera of blood flukes with variable prevalence and pathogenic impact have been reported worldwide in this species. Hapalotrema Looss, 1899 and Amphiorchis Price, 1934 are the only two genera reported in Mediterranean waters; however, updated data describing spirorchiidiasis in the central and eastern Mediterranean and infection prevalence are still lacking. This work aimed to investigate the presence and pathology of spirorchiidiasis in C. caretta in the Mediterranean Sea. One hundred sixty-eight animals stranded along the northwestern Adriatic coast between 2009 and 2015 were submitted to necropsy and subsequent analyses for the detection of adult flukes, detection of eggs in the faeces and spleen and histopathology. Molecular analyses were carried out on hosts (mitochondrial D-loop) and parasites (28S gene and ITS2 spacer) to trace the turtle origins and identify the fluke phylogenetic relationships. Spirorchiidiasis was detected in 16.7% of the animals. Hapalotrema mistroides (Monticelli, 1899) and Neospirorchis sp. were found in twenty-six and ten cases, respectively. Adult flukes were found in six cases, while eggs were detectable through copromicroscopic examination for all infected turtles, and the results for the detection of eggs in the spleen agreed with the copromicroscopic analysis. Only mild lesions were observed. Eggs of types 1 and 3 were grossly visible in the gastrointestinal mucosa, vasculitis was rarely observed in the heart and great vessels, and multifocal granulomas were widespread in the tissues. Molecular identification unambiguously assigned the spirorchiid samples to H. mistroides and Neospirorchis sp. Genetic characterization of loggerhead mtDNA pointed to a Mediterranean origin of the turtle hosts. This survey provides new data on the spread of spirorchiidiasis in the

  15. Increased hepatic Th2 and Treg subsets are associated with biliary fibrosis in different strains of mice caused by Clonorchis sinensis

    PubMed Central

    Fang, Fan; Du, Ying; Ma, Rui; Li, Xiang-Yang; Yu, Qian; Meng, Di; Tang, Ren-Xian; Zheng, Kui-Yang

    2017-01-01

    Previous studies showed that CD4+T cells responses might be involved in the process of biliary fibrosis. However, the underlying mechanism resulting in biliary fibrosis caused by Clonorchis sinensis remains not yet fully elucidated. The objectives of the present study were to investigate the different profiles of hepatic CD4+T cell subsets (Th1, Th2, Th17 and Treg cells) and their possible roles in the biliary fibrosis of different strains of mice (C57BL/6, BALB/c and FVB mice) induced by C. sinensis infection. C57BL/6, BALB/c and FVB mice were orally gavaged with 45 metacercariae. All mice were sacrificed on 28 days post infection in deep anesthesia conditions. The leukocytes in the liver were separated to examine CD4+T cell subsets by flow cytometry and the left lobe of liver was used to observe pathological changes, collagen depositions and the concentrations of hydroxyproline. The most serious cystic and fibrotic changes appeared in FVB infected mice indicated by gross observation, Masson’s trichrome staining and hydroxyproline content detection. In contrast to C57BL/6 infected mice, diffuse nodules and more intensive fibrosis were observed in the BALB/c infected mice. No differences of the hepatic Th1 subset and Th17 subset were found among the three strains, but the hepatic Th2 and Treg cells and their relative cytokines were dramatically increased in the BALB/c and FVB infected groups compared with the C57BL/6 infected group (P<0.01). Importantly, increased Th2 subset and Treg subset all positively correlated with hydroxyproline contents (P<0.01). This result for the first time implied that the increased hepatic Th2 and Treg cell subsets were likely to play potential roles in the formation of biliary fibrosis in C. sinensis-infected mice. PMID:28151995

  16. Eye fluke-induced cataracts in natural fish populations: is there potential for host manipulation?

    PubMed

    Seppälä, O; Karvonen, A; Valtonen, E T

    2011-02-01

    Manipulation of host phenotype (e.g. behaviour, appearance) is suggested to be a common strategy to enhance transmission in trophically transmitted parasites. However, in many systems, evidence of manipulation comes exclusively from laboratory studies and its occurrence in natural host populations is poorly understood. Here, we examined the potential for host manipulation by Diplostomum eye flukes indirectly by quantifying the physiological effects of parasites on fish. Earlier laboratory studies have shown that Diplostomum infection predisposes fish to predation by birds (definitive hosts of the parasites) by reducing fish vision through cataract formation. However, occurrence of cataracts and the subsequent potential for host manipulation in natural fish populations has remained poorly explored. We studied the occurrence of eye fluke-induced cataracts from 7 common fish species (Gymnocephalus cernuus, Rutilus rutilus, Leuciscus leuciscus, Alburnus alburnus, Osmerus eperlanus, Coregonus lavaretus and Gasterosteus aculeatus) from the Bothnian Bay in the Baltic Sea. We found that the parasite-induced cataracts were common in fish and they also reached high levels which are likely to predispose fish to predation. However, we observed such cataracts only in species with the highest parasite abundances, which suggests that only certain hosts may be strongly affected by the infection.

  17. 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

    2015-06-26

    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

  18. The geographical vector in distribution of genetic diversity for Clonorchis sinensis.

    PubMed

    Solodovnik, Daria A; Tatonova, Yulia V; Burkovskaya, Polina V

    2018-01-01

    Clonorchis sinensis, the causative agent of clonorchiasis, is one of the most important parasites that inhabit countries of East and Southeast Asia. In this study, we validated the existence of a geographical vector for C. sinensis using the partial cox1 mtDNA gene, which includes a conserved region. The samples of parasite were divided into groups corresponding to three river basins, and the size of the conserved region had a strong tendency to increase from the northernmost to the southernmost samples. This indicates the availability of the geographical vector in distribution of genetic diversity. A vector is a quantity that is characterized by magnitude and direction. Geographical vector obtained in cox1 gene of C. sinensis has both these features. The reasons for the occurrence of this feature, including the influence of intermediate and definitive hosts on vector formation, and the possibility of its use for clonorchiasis monitoring are discussed. Graphical abstract ᅟ.

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

    PubMed

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

    2016-07-06

    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.

  20. [Detection of Clonorchis sinensis eggs in the ground gallbladder stones by microscopy].

    PubMed

    Ma, Rui-Hong; Qiao, Tie; Luo, Xiao-Bing

    2012-08-30

    Sera, feces, bile and gallbladder stones were collected from 179 patients who accepted gallbladder-preserving cholelithotomy during the period of January to June 2010 at the general surgery department in the Second People's Hospital of Panyu District in Guangzhou. Rapid colloidal gold immunochromatography was used to detect IgG against Clonorchis sinensis. C. sinensis eggs were examined by fecal direct smear, and in bile sediments and ground gallbladder stones. The results showed that the positive rate of rapid colloidal gold immunochromatographic assay for IgG was 51.4%, and the egg positive rate in feces, bile sediments and gallbladder stones was 30.7%, 44.7% and 69.8%, respectively. The detection rate of fecal direct smear was the lowest, while that of the gallbladder stone examination was the highest (P < 0.05). Those patients with egg-positive feces and/or bile sediments were all with egg-positive gallbladder stones.

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

    PubMed

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

    2014-08-01

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

  2. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 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 PRODUCTS...

  3. Consequences of eye fluke infection on anti-predator behaviours in invasive round gobies in Kalmar Sound.

    PubMed

    Flink, Henrik; Behrens, Jane W; Svensson, P Andreas

    2017-06-01

    Larvae of the eye fluke, Diplostomum, emerge from snails and infect fish by penetrating skin or gills, then move to the lens where they may impair the vision of the fish. For the fluke to reproduce, a bird must eat the infected fish, and it has been suggested that they therefore actively manipulate the fish's behaviour to increase the risk of predation. We found that round gobies Neogobius melanostomus, a species that was recently introduced to the Kalmar Sound of the Baltic Sea, had an eye fluke prevalence of 90-100%. We investigated how the infection related to behavioural variation in round gobies. Our results showed that the more intense the parasite-induced cataract, the weaker the host's response was to simulated avian attack. The eye flukes did not impair other potentially important anti-predator behaviours, such as shelter use, boldness and the preference for shade. Our results are in accordance with the suggestion that parasites induce changes in host behaviour that will facilitate transfer to their final host.

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

    PubMed

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

    2014-07-01

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

  5. Molecular and phylogenetic analyses of the liver amphistome Explanatum explanatum (Creplin, 1847) Fukui, 1929 in ruminants from Bangladesh and Nepal based on nuclear ribosomal ITS2 and mitochondrial nad1 sequences.

    PubMed

    Mohanta, U K; Rana, H B; Devkota, B; Itagaki, T

    2017-07-01

    Explanatum explanatum flukes, liver amphistomes of ruminants, cause significant economic loss in the livestock industry by inducing severe liver damage. A total of 66 flukes from 26 buffaloes and 7 cattle in four different geographic areas of Bangladesh and 20 flukes from 10 buffaloes in the Chitwan district of Nepal were subjected for analysis. The sequences (442 bp) of the second internal transcribed spacer (ITS2) of ribosomal DNA and the variable fragments (657 bp) of mitochondrial nicotinamide dehydrogenase subunit 1 (nad1) of E. explanatum flukes from Bangladesh and Nepal were analysed. The aim of this study was molecular characterization of the flukes and to elucidate their origin and biogeography. In the ITS2 region, two genotypes were detected among the flukes from Bangladesh, while flukes from Nepal were of only one genotype. Phylogenetic analyses inferred from the nad1 gene revealed that at least four divergent populations (groups I-IV) are distributed in Bangladesh, whereas two divergent populations were found to be distributed in Nepal. Fst values (pairwise fixation index) suggest that Bangladeshi and Nepalese populations of group I to IV are significantly different from each other; but within groups III and IV, the populations from Bangladesh and Nepal were genetically close. This divergence in the nad1 gene indicates that each lineage of E. explanatum from diverse geography was co-adapted during the multiple domestication events of ruminants. This study, for the first time, provides molecular characterization of E. explanatum in Bangladesh and Nepal, and may provide useful information for elucidating its origin and dispersal route in Asia.

  6. 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.

  7. Advanced enzymology, expression profile and immune response of Clonorchis sinensis hexokinase show its application potential for prevention and control of clonorchiasis.

    PubMed

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

    2015-03-01

    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. 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. 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.

  8. 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

  9. Liver Transplant

    MedlinePlus

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  10. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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. © The Author(s) 2014.

  12. 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

  13. Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

    PubMed

    Machicado, Claudia; Marcos, Luis A

    2016-06-15

    Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. © 2016 UICC.

  14. 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. Copyright 2004 Springer-Verlag

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

    PubMed

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

    2013-07-01

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

  16. 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.

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

    PubMed

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

    2014-10-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed

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

    2014-04-01

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

  20. [Discussion on relationship between hepatobiliary pathological changes under B-ultrasound and Clonorchis sinensis infection].

    PubMed

    Liang, Zhi-cheng; Qiu, Shou-zhong; Luo, Li-xuan

    2015-12-01

    To explore the relationship between the hepatobiliary pathological changes under B-ultrasound examinations and Clonorchis sinensis infection, so as to provide the evidence for further prevention and control. The stool test and ELISA were applied to test the pathogeny and antibody to C. sinensis of the suspicious patients who had the hepatobiliary pathological changes under B-ultrasound examinations in People's Hospital of Wuxuan County from Jan. 2010 to Dec. 2013. Totally 113 suspicious patients of C. sinensis infection were investigated, and the positive rates of egg and serum antibody were 64.60% (73 cases) and 66.37% (75 cases) respectively. The positive rates of the male and those aged ≥ 50 years were significantly higher than those of the female and the cases younger than 50 years respectively (χ² = 3.554, 6.267, both P < 0.05). In the C. sinensis infected patients, the degree of pathological changes of hepatobiliary was positively correlated with the infectiosity of C. sinensis (χ² = 64.952, P < 0.01). The hepatobiliary pathological changes under B-ultrasound examinations may be resulted from the infection of C. sinensis, and the patients with the changes should be further investigated for the pathogen and antibody to C. sinensis.

  1. Concurrent epizootic hyperinfections of sea lice (predominantly Caligus chiastos) and blood flukes (Cardicola forsteri) in ranched Southern Bluefin tuna.

    PubMed

    Hayward, Craig J; Ellis, David; Foote, Danielle; Wilkinson, Ryan J; Crosbie, Phillip B B; Bott, Nathan J; Nowak, Barbara F

    2010-10-11

    Peaks in epizootics of sea lice (mostly Caligus chiastos) and blood flukes (Cardicola forsteri) among Southern Bluefin tuna (Thunnus maccoyii) appear to coincide with the onset of an increased mortality. The mortality event occurs 6-12 weeks after T. maccoyii have been transferred into static ranching pontoons from the wild. However, to date available data on parasite occurrence before commercial harvesting begins, are scant. This research gathered epizootiological data from weeks 4 to 13 post-transfer, for 153 T. maccoyii sampled from two research and four commercial pontoons. Counts of both parasites in the research pontoons reached levels far heavier than previously documented in ranched T. maccoyii. For sea lice, the prevalence in most pontoons was 100%; the highest intensity reached 495 individuals, and mean counts at the peak of the infection exceeded 265 lice per fish. Almost all of the 5407 individual lice counted were identified as adult C. chiastos (89.44% female, 10.14% male); adult females of two other species were also present, C. amblygenitalis (0.13%), in addition to an undescribed species, C. sp. (0.04%). Lice counts were correlated positively with gross eye pathology scores (r(s,151df)=0.3394, p=0.0000), negatively correlated with condition index (r(s,151df)=-0.5396, p=0.0000), and positively correlated with plasma cortisol (r(s,131df)=0.3906, p=0.0000) and glucose (r(s,131df)=0.2240, p=0.0096). For the blood fluke, prevalences were less uniform than those of sea lice, with lower rates of infection at the beginning (ranging from 10% to 40%), reaching 100% mid-study, and declining again (40% in one pontoon). The highest intensity reached 441 individual flukes. Fluke counts were negatively correlated with plasma haemoglobin (r(s,151df)=-0.2436, p=0.0051) and positively with lysozyme (r(s,151df)=0.3013, p=0.0019). Fluke counts were also correlated with sea lice counts (r(s,150df)=0.3143, p=0.0000). Peaks in these epizootics occurred near the onset of

  2. CD44 variant-dependent redox status regulation in liver fluke-associated cholangiocarcinoma: A target for cholangiocarcinoma treatment.

    PubMed

    Thanee, Malinee; Loilome, Watcharin; Techasen, Anchalee; Sugihara, Eiji; Okazaki, Shogo; Abe, Shinya; Ueda, Shiho; Masuko, Takashi; Namwat, Nisana; Khuntikeo, Narong; Titapun, Attapol; Pairojkul, Chawalit; Saya, Hideyuki; Yongvanit, Puangrat

    2016-07-01

    Expression of CD44, especially the variant isoforms (CD44v) of this major cancer stem cell marker, contributes to reactive oxygen species (ROS) defense through stabilizing xCT (a cystine-glutamate transporter) and promoting glutathione synthesis. This enhances cancer development and increases chemotherapy resistance. We investigate the role of CD44v in the regulation of the ROS defense system in cholangiocarcinoma (CCA). Immunohistochemical staining of CD44v and p38(MAPK) (a major ROS target) expression in Opisthorchis viverrini-induced hamster CCA tissues (at 60, 90, 120, and 180 days) reveals a decreased phospho-p38(MAPK) signal, whereas the CD44v signal was increased during bile duct transformation. Patients with CCA showed CD44v overexpression and negative-phospho-p38(MAPK) patients a significantly shorter survival rate than the low CD44v signal and positive-phospho-p38(MAPK) patients (P = 0.030). Knockdown of CD44 showed that xCT and glutathione levels were decreased, leading to a high level of ROS. We examined xCT-targeted CD44v cancer stem cell therapy using sulfasalazine. Glutathione decreased and ROS increased after the treatment, leading to inhibition of cell proliferation and induction of cell death. Thus, the accumulation of CD44v leads to the suppression of p38(MAPK) in transforming bile duct cells. The redox status regulation of CCA cells depends on the expression of CD44v to contribute the xCT function and is a link to the poor prognosis of patients. Thus, an xCT inhibitor could inhibit cell growth and activate cell death. This suggests that an xCT-targeting drug may improve CCA therapy by sensitization to the available drug (e.g. gemcitabine) by blocking the mechanism of the cell's ROS defensive system. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  3. 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.

  4. 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

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

    PubMed

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

    2015-12-01

    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.

  6. Expression of Clonorchis sinensis GIIIsPLA2 protein in baculovirus-infected insect cells and its overexpression facilitating epithelial-mesenchymal transition in Huh7 cells via AKT pathway.

    PubMed

    Shang, Mei; Xie, Zhizhi; Tang, Zeli; He, Lei; Wang, Xiaoyun; Wang, Caiqin; Wu, Yinjuan; Li, Ye; Zhao, Lu; Lv, Zhiyue; Wu, Zhongdao; Huang, Yan; Yu, Xinbing; Li, Xuerong

    2017-04-01

    Although prior studies confirmed that group III secretory phospholipase A 2 of Clonorchis sinensis (CsGIIIsPLA 2 ) had stimulating effect on liver fibrosis by binding to LX-2 cells, large-scale expression of recombinant protein and its function in the progression of hepatoma are worth exploring. Because of high productivity and low lipopolysaccharides (LPS) in the Sf9-baculovirus expression system, we firstly used this system to express the coding region of CsGIIIsPLA 2 . The molecular weight of recombinant CsGIIIsPLA 2 protein was about 34 kDa. Further investigation showed that most of the recombinant protein presented intracellular expression in Sf9 insect cell nucleus and could be detected only into cell debris, which made the protein purification and further functional study difficult. Therefore, to study the role of CsGIIIsPLA 2 in hepatocellular carcinoma (HCC) progression, CsGIIIsPLA 2 overexpression Huh7 cell model was applied. Cell proliferation, migration, and the expression level of epithelial-mesenchymal transition (EMT)-related molecules (E-cadherin, N-cadherin, α-catenin, Vimentin, p300, Snail, and Slug) along with possible mechanism were measured. The results indicated that CsGIIIsPLA 2 overexpression not only inhibited cell proliferation and promoted migration and EMT but also enhanced the phosphorylation of AKT in HCC cells. In conclusion, this study supported that CsGIIIsPLA 2 overexpression suppressed cell proliferation and induced EMT through the AKT pathway.

  7. [Molecular cloning and characterization of a novel Clonorchis sinensis antigenic protein containing tandem repeat sequences].

    PubMed

    Liu, Qian; Xu, Xue-Nian; Zhou, Yan; Cheng, Na; Dong, Yu-Ting; Zheng, Hua-Jun; Zhu, Yong-Qiang; Zhu, Yong-Qiang

    2013-08-01

    To find and clone new antigen genes from the lambda-ZAP cDNA expression library of adult Clonorchis sinensis, and determine the immunological characteristics of the recombinant proteins. The cDNA expression library of adult C. sinensis was screened by pooled sera of clonorchiasis patients. The sequences of the positive phage clones were compared with the sequences in EST database, and the full-length sequence of the gene (Cs22 gene) was obtained by RT-PCR. cDNA fragments containing 2 and 3 times tandem repeat sequences were generated by jumping PCR. The sequence encoding the mature peptide or the tandem repeat sequence was respectively cloned into the prokaryotic expression vector pET28a (+), and then transformed into E. coli Rosetta DE3 cells for expression. The recombinant proteins (rCs22-2r, rCs22-3r, rCs22M-2r, and rCs22M-3r) were purified by His-bind-resin (Ni-NTA) affinity chromatography. The immunogenicity of rCs22-2r and rCs22-3r was identified by ELISA. To evaluate the immunological diagnostic value of rCs22-2r and rCs22-3r, serum samples from 35 clonorchiasis patients, 31 healthy individuals, 15 schistosomiasis patients, 15 paragonimiasis westermani patients and 13 cysticercosis patients were examined by ELISA. To locate antigenic determinants, the pooled sera of clonorchiasis patients and healthy persons were analyzed for specific antibodies by ELISA with recombinant protein rCs22M-2r and rCs22M-3r containing the tandem repeat sequences. The full-length sequence of Cs22 antigen gene of C. sinensis was obtained. It contained 13 times tandem repeat sequences of EQQDGDEEGMGGDGGRGKEKGKVEGEDGAGEQKEQA. Bioinformatics analysis indicated that the protein (Cs22) belonged to GPI-anchored proteins family. The recombinant proteins rCs22-2r and rCs22-3r showed a certain level of immunogenicity. The positive rate by ELISA coated with the purified PrCs22-2r and PrCs22-3r for sera of clonorchiasis patients both were 45.7% (16/35), and 3.2% (1/31) for those of healthy

  8. Prevalence of Clonorchis sinensis Metacercariae in Fish from Water Systems of Seomjin-gang (River)

    PubMed Central

    Sohn, Woon-Mok; Na, Byoung-Kuk; Cho, Shin-Hyeong; Park, Mi-Yeoun; Kim, Cheon-Hyeon; Hwang, Min-Ah; No, Kyeong-Woo; Yoon, Ki-Bok; Lim, Hyun-Cheol

    2017-01-01

    The prevalence of Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fish from the water systems of Seomjin-gang (River), the Republic of Korea. Total 1,604 fish from 7 local sites of Seomjin-gang were examined by artificial digestion methods. The metacercariae of C. sinensis were detected in 102 (39.8%) out of 256 fish (14 species) from the upper reaches of Seomjin-gang, i.e., Osucheon (22.3% in 6 fish species) in Imsil-gun, and Seomjin-gang (63.9% in 9 fish species) in Sunchang-gun, Jeollabuk-do. Their average density was 9.0 per infected fish. They were also found in 132 (48.0%) out of 275 fish (12 spp.) from the middle reaches of Seomjin-gang, i.e., Songdaecheon (58.9% in 4 fish species) in Namwon-si, Jeollabuk-do, and Seomjin-gang (45.2% in 10 fish species) in Gokseong-gun, Jeollanam-do. Their average density was 21.0 per infected fish. CsMc were detected in 77 (56.6%) out of 136 fish (11 species) from the lower reaches of Seomjin-gang, i.e., Seomjin-gang (73.3% in 11 fish species) in Gurye-gun, Jeollanam-do, and Namsancheon (8.6% in 1 fish species) in Hadong-gun, Gyeongsangnam-do. Their average density was 64.9 per infected fish. The metacercariae of Metorchis orientalis were also detected in 6 fish species from 4 sites of Seomjin-gang. Conclusively, it has been confirmed that CsMc are more or less prevalent in fish from some water systems of Seomjin-gang in Korea. PMID:28719955

  9. 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.

  10. 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

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

    PubMed

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

    2014-07-01

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

  12. 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

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

    PubMed

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

    2014-08-29

    The prevalence of Clonorchis sinensis infection in freshwater fishes was surveyed in Heilongjiang Province, northeastern China, between August 2011 and September 2013. Thirteen species of freshwater fish (n=3221) and one species of shrimp (n=93) were collected from Songhua river, Nenjiang river and other lakes or ponds in 37 sites of 15 representative cities in Heilongjiang Province. They were individually examined by digestion technique, and the C. sinensis metacercariae were identified morphologically followed by confirmation using sequences of the second internal transcribed spacer of ribosomal DNA. Ten of the 13 examined species of freshwater fishes were infected with C. sinensis metacercariae, while all shrimps were negative. The overall prevalence of C. sinensis infection in 3221 examined freshwater fishes was 19.96%, with 42.57% (272/639) in Pseudorasbora parva, 22.55% (83/368) in Hemicculter leuciclus, 20.44% (121/592) in Carassius auratus, 17.71% (68/384) in Saurogobio dabryi, 10.85% (23/212) in Rhodeus ocellatus, 10.54% (48/455) in Phoxinus lagowskii, 8.20% (21/256) in Perccottus glehnii, 6.25% (5/80) in Misgurnus anguillicaudatus, 4.55% (1/22) in Xenocypris davidi, and 1.49% (1/67) in Cyprinus carpio. The average infection intensity in P. parva was 103.3 encysted metacercariae per gram of fish meat in Zhaoyuan city. The average prevalence of C. sinensis infection in Songhua river, Nenjiang river and lakes or ponds were 31.96% (503/1574), 11.30% (102/903) and 7.93% (59/744), respectively. The prevalence of C. sinensis infection in Zhaoyuan city (43.68%) was the highest among all sampling locations. These results revealed a high-prevalence of C. sinensis infection in freshwater fishes in Heilongjiang Province, northeastern China, posing significant public health concern. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-06-01

    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.

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

    PubMed

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

    2014-05-01

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

  18. 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.

  19. An Integrated Control Strategy Takes Clonorchis sinensis Under Control in an Endemic Area in South China.

    PubMed

    Huang, Yalan; Huang, Dana; Geng, Yijie; Fang, Shisong; Yang, Fan; Wu, Chunli; Zhang, Hailong; Wang, Miao; Zhang, Ran; Wang, Xin; Wu, Shuang; Cao, Jianping; Zhang, Renli

    2017-12-01

    Clonorchis sinensis is an important foodborne zoonosis worldwide and prevalent in China for more than 2000 years. According to the experience of controlling Schistosoma japonica, China started to establish the integrated control strategy for C. sinensis in endemic areas. Lou village, the largest village in Shenzhen city in South China was taken as a pilot site. This longitudinal study assessed the infection status of C. sinensis among people and intermediate hosts from 2006 to 2014 in Lou village. After a continuous intervention with the integrated control strategy, the prevalence of C. sinensis decreased significantly to 2.01% in 2014. The infection intensity also reduced significantly with eggs per gram varying from 45.6 ± 3.4 in 2010 to 21.7 ± 1.6 in 2012. There is also a statistically significant decrease of the prevalence of C. sinensis metacercariae in fish hosts from 16.51% in 2008 before the intervention to 5.33% in 2014. All the old-styled toilets were replaced by sanitary ones with a harmless processing design in 2014. No viable parasite eggs were detected in stool samples from the reconstructed toilets. Health education played an important role in changing the eating habits among the local residents, with a significant decrease in the prevalence of eating raw fish from 91.99% in 2008 to 59.87% in 2014. The evaluation suggested that the integrated strategy we have performed in Lou village is effective in controlling the C. sinensis infection and maintaining the infection rate at a lower level, which can be promoted in other endemic areas.

  20. Relationship between blood parameters and Clonorchis sinensis infection: A retrospective single center study.

    PubMed

    Chen, Huaping; Chen, Siyuan; Huang, Zhili; Kong, Lingxi; Hu, Zuojian; Qin, Shanzi; Qin, Xue; Li, Shan

    2018-06-01

    Our study aims to retrospectively investigate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and eosinophil-to-lymphocyte ratio (ELR) in patients infected with Clonorchis sinensis. This study analyzes a total of 151 patients with C. sinensis infections and 53 healthy control patients from our hospital. We found close relationships between the three candidate markers and the stages of C. sinensis infection-related biliary obstruction. The NLRs, PLRs and ELRs of patients with C. sinensis infections were significantly higher than those of healthy individuals; of those, ELRs showed the most superior diagnostic accuracy (sensitivity = 62.9%, specificity = 92.5%). Further, we constituted a logistic regression prediction model; applying two variables (age and NLR) with a sensitivity of 88.89% and a specificity of 83.78% in differentiating C. sinensis-related cholelithiasis from C. sinensis-untreated patients. Cancer antigen 19-9 (CA19-9) is a commonly used marker in the diagnosis of cholangiocarcinoma. Significant correlation was observed between NLR and CA19-9 in patients with C. sinensis-related cholangiocarcinoma (r = 0.590, P = 0.000). In the receiver operating characteristic analysis for separating C. sinensis-related cholelithiasis and cholangiocarcinoma, the cutoff value of PLR was 145.14 with a sensitivity of 65.62% and a specificity of 68.89%; the sensitivity of CA19-9 was 75.00% with a specificity of 77.78%. PLR showed acceptable efficiency to separate C. sinensis-related cholelithiasis from cholangiocarcinoma. In conclusion, all of the candidate markers (PLRs, NLRs and ELRs) may act as the valuable supplement in detecting C. sinensis infections and diseases. Copyright © 2018. Published by Elsevier B.V.

  1. 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

  2. Prevalence of Clonorchis sinensis Metacercariae in Fish from Water Systems of Seomjin-gang (River).

    PubMed

    Sohn, Woon-Mok; Na, Byoung-Kuk; Cho, Shin-Hyeong; Park, Mi-Yeoun; Kim, Cheon-Hyeon; Hwang, Min-Ah; No, Kyeong-Woo; Yoon, Ki-Bok; Lim, Hyun-Cheol

    2017-06-01

    The prevalence of Clonorchis sinensis metacercariae ( Cs Mc) was examined in freshwater fish from the water systems of Seomjin-gang (River), the Republic of Korea. Total 1,604 fish from 7 local sites of Seomjin-gang were examined by artificial digestion methods. The metacercariae of C. sinensis were detected in 102 (39.8%) out of 256 fish (14 species) from the upper reaches of Seomjin-gang, i.e., Osucheon (22.3% in 6 fish species) in Imsil-gun, and Seomjin-gang (63.9% in 9 fish species) in Sunchang-gun, Jeollabuk-do. Their average density was 9.0 per infected fish. They were also found in 132 (48.0%) out of 275 fish (12 spp.) from the middle reaches of Seomjin-gang, i.e., Songdaecheon (58.9% in 4 fish species) in Namwon-si, Jeollabuk-do, and Seomjin-gang (45.2% in 10 fish species) in Gokseong-gun, Jeollanam-do. Their average density was 21.0 per infected fish. Cs Mc were detected in 77 (56.6%) out of 136 fish (11 species) from the lower reaches of Seomjin-gang, i.e., Seomjin-gang (73.3% in 11 fish species) in Gurye-gun, Jeollanam-do, and Namsancheon (8.6% in 1 fish species) in Hadong-gun, Gyeongsangnam-do. Their average density was 64.9 per infected fish. The metacercariae of Metorchis orientalis were also detected in 6 fish species from 4 sites of Seomjin-gang. Conclusively, it has been confirmed that Cs Mc are more or less prevalent in fish from some water systems of Seomjin-gang in Korea.

  3. Disability Weight of Clonorchis sinensis Infection: Captured from Community Study and Model Simulation

    PubMed Central

    Qian, Men-Bao; Chen, Ying-Dan; Fang, Yue-Yi; Xu, Long-Qi; Zhu, Ting-Jun; Tan, Tan; Zhou, Chang-Hai; Wang, Guo-Fei; Jia, Tie-Wu; Yang, Guo-Jing; Zhou, Xiao-Nong

    2011-01-01

    Background Clonorchiasis is among the most neglected tropical diseases. It is caused by ingesting raw or undercooked fish or shrimp containing the larval of Clonorchis sinensis and mainly endemic in Southeast Asia including China, Korea and Vietnam. The global estimations for population at risk and infected are 601 million and 35 million, respectively. However, it is still not listed among the Global Burden of Disease (GBD) and no disability weight is available for it. Disability weight reflects the average degree of loss of life value due to certain chronic disease condition and ranges between 0 (complete health) and 1 (death). It is crucial parameter for calculating the morbidity part of any disease burden in terms of disability-adjusted life years (DALYs). Methodology/Principal Findings According to the probability and disability weight of single sequelae caused by C. sinensis infection, the overall disability weight could be captured through Monte Carlo simulation. The probability of single sequelae was gained from one community investigation, while the corresponding disability weight was searched from the literatures in evidence-based approach. The overall disability weights of the male and female were 0.101 and 0.050, respectively. The overall disability weights of the age group of 5–14, 15–29, 30–44, 45–59 and 60+ were 0.022, 0.052, 0.072, 0.094 and 0.118, respectively. There was some evidence showing that the disability weight and geometric mean of eggs per gram of feces (GMEPG) fitted a logarithmic equation. Conclusion/Significance The overall disability weights of C. sinensis infection are differential in different sex and age groups. The disability weight captured here may be referred for estimating the disease burden of C. sinensis infection. PMID:22180791

  4. Prevalence of Clonorchis sinensis Metacercariae in Freshwater Fish from Three Latitudinal Regions of the Korean Peninsula

    PubMed Central

    Cho, Shin-Hyeong; Na, Byoung-Kuk; Kim, Tong-Soo; Kong, Yoon; Eom, Keeseon; Seok, Won-Seok; Lee, Taejoon

    2011-01-01

    A large-scale survey was conducted to investigate the infection status of fresh water fishes with Clonorchis sinensis metacercariae (CsMc) in 3 wide regions, which were tentatively divided by latitudinal levels of the Korean peninsula. A total of 4,071 freshwater fishes were collected from 3 regions, i.e., northern (Gangwon-do: 1,543 fish), middle (Chungcheongbuk-do and Gyeongsangbuk-do: 1,167 fish), and southern areas (Jeollanam-do, Ulsan-si, and Gyeongsangnam-do: 1,361 fish). Each fish was examined by the artificial digestion method from 2003 to 2010. In northern areas, only 11 (0.7%) fish of 2 species, Pungtungia herzi and Squalidus japonicus coreanus from Hantan-gang, Cheolwon-gun, Gangwon-do were infected with av. 2.6 CsMc. In middle areas, 149 (12.8%) fish were infected with av. 164 CsMc. In southern areas, 538 (39.5%) fish were infected with av. 159 CsMc. In the analysis of endemicity in 3 regions with an index fish, P. herzi, 9 (6.2%) of 146 P. herzi from northern areas were infected with av. 2.8 CsMc. In middle areas, 34 (31.8%) of 107 P. herzi were infected with av. 215 CsMc, and in southern areas, 158 (92.9%) of 170 P. herzi were infected with av. 409 CsMc. From these results, it has been confirmed that the infection status of fish with CsMc is obviously different among the 3 latitudinal regions of the Korean peninsula with higher prevalence and burden in southern regions. PMID:22355206

  5. Epidemiological profile of Clonorchis sinensis infection in one community, Guangdong, People's Republic of China.

    PubMed

    Qian, Men-Bao; Chen, Ying-Dan; Fang, Yue-Yi; Tan, Tan; Zhu, Ting-Jun; Zhou, Chang-Hai; Wang, Guo-Fei; Xu, Long-Qi; Zhou, Xiao-Nong

    2013-07-01

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

  6. Identification of Fasciola flukes in Thailand based on their spermatogenesis and nuclear ribosomal DNA, and their intraspecific relationships based on mitochondrial DNA.

    PubMed

    Chaichanasak, Pannigan; Ichikawa, Madoka; Sobhon, Prasert; Itagaki, Tadashi

    2012-12-01

    We analyzed 147 Fasciola flukes obtained from cattle in Thailand based on their spermatogenetic ability, and nuclear ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial nicotiamide adenine dinucleotide dehydrogenase subunit 1 (ND1) genes as molecular markers. One hundred twenty-eight flukes, which had abundant sperm in their seminal vesicles (spermic) and showed the PCR-RFLP pattern of F. gigantica in the ITS1, were accurately identified as F. gigantica. The other 19 flukes that had no sperm in their seminal vesicles were aspermic Fasciola sp. with the RFLP patterns identical to that of F. gigantica. Twenty-nine ND1 haplotypes (Fg-ND1-Thai 2-30) were distinguished in the 128 F. gigantica flukes and were divided into haplotypes unique to Thailand and those common to other countries, suggesting the possibility that ancestral haplotypes were introduced into Thailand. Three haplotypes (Fg-ND1-Thai 7, 9 and 27) appeared to be the major haplotypes found in F. gigantica from Thailand. Only one haplotype (Fg-ND1-Thai 1) was found in the 19 aspermic Fasciola sp. flukes obtained from geographical regions, and the nucleotide sequence of Fg-ND1-Thai 1 was identical to that of the aspermic Fasciola sp. from Japan, Korea, China, Vietnam and Myanmar, suggesting that they were descendants with a common provenance and expanded to these countries in the relatively recent past. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. 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

  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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Identification and characterization of microRNAs in the pancreatic fluke Eurytrema pancreaticum.

    PubMed

    Xu, Min-Jun; Wang, Chun-Ren; Huang, Si-Yang; Fu, Jing-Hua; Zhou, Dong-Hui; Chang, Qiao-Cheng; Zheng, Xu; Zhu, Xing-Quan

    2013-01-25

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

  10. Liver Hemangioma

    MedlinePlus

    Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

  11. 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

  12. Liver disease

    MedlinePlus

    ... Coccidioidomycosis Delta agent (hepatitis D) Drug-induced cholestasis Fatty liver disease Hemochromatosis Hepatitis A Hepatitis B Hepatitis C ... abscess Reye syndrome Sclerosing cholangitis Wilson disease Images Fatty liver, CT scan Liver with disproportional fattening, CT scan ...

  13. 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

  14. 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

  15. 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.

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

    PubMed

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

    2014-01-01

    Fructose-1,6-bisphosphate aldolase (FbA) is a ubiquitous enzyme in glycolysis. In the present study, we screened out three distinct genes encoding FbA isozymes (CsFbAs, CsFbA-1/2/3) from Clonorchis sinensis (C. sinensis) and characterized their sequences and structures profiles as well as biochemical properties. The amino acid sequences of CsFbAs shared homology with those of Class I FbAs from other species. The putative quaternary structures revealed that CsFbA-2 and CsFbA-3 were tetramers, while CsFbA-1 was dimer. Recombinant CsFbA-2 and CsFbA-3 (rCsFbA-2/3) were confirmed to be Class I FbAs for their stable enzymatic activities in the presence of EDTA or metal ions. However, recombinant CsFbA-1 (rCsFbA-1) did not show the catalytic activity, which might be due to the inappropriate fold and interaction between its subunits. Both rCsFbA-2 and rCsFbA-3 showed similar enzymatic properties such as optimal temperatures and broad pH ranges that similar to human FbA isozymes. They showed relatively higher affinities for fructose-1,6-bisphosphate (FBP) than fructose-1-phosphate (F-1-P). Their kcat ratios of FBP to F-1-P were in accordance with those of human FbA-A or C. In addition, CsFbAs were differentially transcribed in the developmental stages of C. sinensis, suggesting their essential roles throughout the life stages. Extensive distribution of CsFbAs in adult worms indicated that ubiquitous activities of CsFbAs took place in these organs. Collectively, these results suggested that long-term parasitic environment might adapt these isozymes similar to host FbAs for metabolic requirement. Our study will provide new insight into CsFbAs in the glycometabolism of C. sinensis and relationship between the host and the parasite. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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

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

    PubMed

    Zhu, Lihui; Zhao, Jiangping; Wang, Jianbin; Hu, Chao; Peng, Jinbiao; Luo, Rong; Zhou, Chunjing; Liu, Juntao; Lin, Jiaojiao; Jin, Youxin; Davis, Richard E; Cheng, Guofeng

    2016-02-01

    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.

  20. Developmental stages of fish blood flukes, Cardicola forsteri and Cardicola opisthorchis (Trematoda: Aporocotylidae), in their polychaete intermediate hosts collected at Pacific bluefin tuna culture sites in Japan.

    PubMed

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

    2017-02-01

    Farming of Pacific bluefin tuna (PBT), Thunnus orientalis, is a rapidly growing industry in Japan. Aporocotylid blood flukes of the genus Cardicola comprising C. orientalis, C. opisthorchis and C. forsteri are parasites of economic importance for PBT farming. Recently, terebellid polychaetes have been identified as the intermediate hosts for all these parasites. We collected infected polychaetes, Terebella sp., the intermediate host of C. opisthorchis, from ropes and floats attached to tuna cages in Tsushima, Nagasaki Prefecture, Japan. Also, Neoamphitrite vigintipes (formerly as Amphitrite sp. sensu Shirakashi et al., 2016), the intermediate host of C. forsteri, were collected from culture cages in Kushimoto, Wakayama Prefecture, Japan. The terebellid intermediate hosts harbored the sporocysts and cercariae in their body cavity. Developmental stages of these blood flukes were molecularly identified using species specific PCR primers. In this paper, we describe the cercaria and sporocyst stages of C. opisthorchis and C. forsteri and compare their morphological characteristics among three Cardicola blood flukes infecting PBT. We also discuss phylogenetic relations of the six genera of the terebellid intermediate hosts (Artacama, Lanassa, Longicarpus, Terebella, Nicolea and Neoamphitrite) of blood flukes infecting marine fishes, based on their morphological characters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Liver Immunology

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2001-01-01

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

  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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Liver Diseases

    MedlinePlus

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

  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. Effect of the Filamentous Fungus Mucor circinelloides On The Development of Eggs of the Rumen Fluke Calicophoron daubneyi (Paramphistomidae).

    PubMed

    Arroyo, Fabián; Hernández, José A; Cazapal-Monteiro, Cristiana F; Pedreira, José; Sanchís, Jaime; Romasanta, Ángel; Sánchez-Andrade, Rita; Paz-Silva, Adolfo; Arias, María S

    2017-06-01

    Ruminants infected by Paramphistomidae flukes shed eggs in the feces, which pass through different stages in the environment until the infective stages (metacercariae) are reached. The activity of the soil fungus Mucor circinelloides on the development of eggs of the rumen fluke Calicophoron daubneyi was presently tested with 3 probes, i.e., in petri plates, feces, and an aqueous environment (tubes). The effect of the fungus was assessed by recording the numbers of undeveloped, nonviable, and embryonated eggs. Nonviable eggs were considered when vacuolization occurred, the inner structures were not clearly observed, the eggshell was broken, or the embryo inside was destroyed. By considering the ability of hyphae of M. circinelloides to develop in the presence of C. daubneyi eggs, attach to their surface, and penetrate and destroy the inner embryo, this ovicidal effect was classified as type 3. After a period of 50 days, the percentage of undeveloped eggs in the feces of infected cattle was 40%; furthermore, 27% of the eggs were nonviable, and 33% were embryonated (1 miracidium inside). The addition of 4 doses of M. circinelloides spores directly onto the feces resulted in 9-31% undeveloped eggs, 38-60% nonviable eggs, and 9-21% embryonated eggs, and no statistical significances were obtained among the different doses. Placing the eggs of C. daubneyi into an aqueous solution containing 10 7 spores of M. circinelloides/ml for 29 days resulted in 43% undeveloped eggs, 40% nonviable eggs, and 17% embryonated eggs, whereas in the controls, the percentages were 48%, 12%, and 40%, respectively. These data demonstrate the usefulness of the spores of the fungus M. circinelloides in limiting the development of the eggs of the trematode C. daubneyi.

  7. Liver enzymes and blood metabolites in a population of free-ranging red deer (Cervus elaphus) naturally infected with Fascioloides magna.

    PubMed

    Severin, K; Mašek, T; Janicki, Z; Konjević, D; Slavica, A; Marinculić, A; Martinković, F; Vengušt, G; Džaja, P

    2012-06-01

    We investigated the effects of Fascioloides magna infection on the serum biochemistry values of the naturally infected red deer population in eastern Croatia. The investigation was performed on 47 red deer with F. magna infection confirmed patho-anatomically in 27 animals (57.4%). Fibrous capsules and migratory lesions were found in 14 deer while only fibrous capsules without migratory lesions were found in 13 deer. In 13 deer both immature and mature flukes were found, in 5 deer only immature flukes were found and in 9 deer only mature flukes were found. Fascioloides magna infected deer with fibrous capsules and migratory lesions had significantly higher values for lactate dehydrogenase (LDH), glutamate dehydrogenase (GLDH) and globulin, and lower values for albumin/globulin ratio and glucose compared to uninfected deer. Fascioloides magna infected deer with fibrous capsules without the presence of migratory lesions had higher values for alanine aminotransferase (ALT) and globulin, and lower values for albumin/globulin ratio and glucose, than the uninfected deer. The number of immature flukes was positively correlated with values of aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), LDH, GLDH, urea and triglycerides. The number of migratory lesions was positively correlated with GGT, GLDH, globulin and urea values. The creatinine value was positively correlated with the number of mature flukes. The trial showed that F. magna infection causes significant changes in serum biochemistry. Moreover, these changes do not completely resemble changes following F. hepatica infection. Further investigation of changes in liver enzymes and other serum metabolites in controlled, experimentally induced fascioloidosis in red deer is needed to better understand the pathogenesis of F. magna.

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

    PubMed Central

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

    2013-01-01

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

  9. Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells.

    PubMed

    Bahk, Young Yil; Pak, Jhang Ho

    2016-10-01

    Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

  10. Cell-free translational screening of an expression sequence tag library of Clonorchis sinensis for novel antigen discovery.

    PubMed

    Kasi, Devi; Catherine, Christy; Lee, Seung-Won; Lee, Kyung-Ho; Kim, Yu Jung; Ro Lee, Myeong; Ju, Jung Won; Kim, Dong-Myung

    2017-05-01

    The rapidly evolving cloning and sequencing technologies have enabled understanding of genomic structure of parasite genomes, opening up new ways of combatting parasite-related diseases. To make the most of the exponentially accumulating genomic data, however, it is crucial to analyze the proteins encoded by these genomic sequences. In this study, we adopted an engineered cell-free protein synthesis system for large-scale expression screening of an expression sequence tag (EST) library of Clonorchis sinensis to identify potential antigens that can be used for diagnosis and treatment of clonorchiasis. To allow high-throughput expression and identification of individual genes comprising the library, a cell-free synthesis reaction was designed such that both the template DNA and the expressed proteins were co-immobilized on the same microbeads, leading to microbead-based linkage of the genotype and phenotype. This reaction configuration allowed streamlined expression, recovery, and analysis of proteins. This approach enabled us to identify 21 antigenic proteins. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:832-837, 2017. © 2017 American Institute of Chemical Engineers.

  11. Inter-individual and intragenomic variations in the ITS region of Clonorchis sinensis (Trematoda: Opisthorchiidae) from Russia and Vietnam.

    PubMed

    Tatonova, Yulia V; Chelomina, Galina N; Nguyen, Hung Manh

    2017-11-01

    Here we examined the intraspecific genetic variability of Clonorchis sinensis from Russia and Vietnam using nuclear DNA sequences (the 5.8S gene and two internal transcribed spacers of the ribosomal cluster). Despite the low level of variability in the ITS1 region, this marker has revealed some features of C. sinensis across multiple geographic regions. The genetic diversity levels for the Russian and Vietnamese populations were similar (0.1 and 0.09%, respectively) but were significantly lower than the C. sinensis from China (0.31%). About half of the sequences of the Chinese (53%) and Korean (47%) populations and about a tenth of the Vietnamese (12%) and Russian (8%) sequences included a 5bp insertion. No sequences with nucleotide substitutions both upstream and downstream of the 5bp insertion were found within the whole data set. The population of northern China had both sequence variants (with substitutions either upstream or downstream of the insertion), while only one of these variants was presented at the other localities. The Vietnamese population had a higher frequency of intragenomic polymorphism than the Russian population (69% vs. 46% and 23% vs. 3% at the 114bp and 339bp positions, respectively). These data are discussed in connection with parasite origin and adaptation, and also its invasive capacity and drug-resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. [Epidemiological investigation of second intermediate hosts of Clonorchis sinensis in Pizhou and Xinyi cities of Jiangsu Province].

    PubMed

    Jin, Xiao-lin; Liu, Jian-feng; Shen, Ming-xue; Dai, Yang; Xu, Xiang-zhen

    2015-12-01

    To understand the endemic situation of Clonorchis sinensis in its second intermediate hosts in Pizhou and Xinyi cities of Jiangsu Province, so as to provide the evidence for the further control and treatment. Pseudorasbora parva and Abbottina rivularis were caught from the natural water body of Pizhou and Xinyi cities, and the tabletting microscopy method was applied to test the metacercaria of C. sinensis. Totally 1 117 fishes were caught and dissected, including 792 P. parva (70.90%) and 325 A. rivularis (29.10%). The metacercaria of C. sinensis infection rates of P. parva and A. rivularis were 29.80% (236/792) and 4.62% (15/325) respectively, and the difference between the two kinds of fishes was significant (χ² = 83.88, P < 0.01). The metacercaria of C. sinensis infection rate of freshwater fishes in Pizhou and Xinyi cities is high, and the local residents are facing the higher risk of clonorchiasis sinensis.

  13. Liver anatomy.

    PubMed

    Abdel-Misih, Sherif R Z; Bloomston, Mark

    2010-08-01

    Understanding the complexities of the liver has been a long-standing challenge to physicians and anatomists. Significant strides in the understanding of hepatic anatomy have facilitated major progress in liver-directed therapies--surgical interventions, such as transplantation, hepatic resection, hepatic artery infusion pumps, and hepatic ablation, and interventional radiologic procedures, such as transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. Without understanding hepatic anatomy, such progressive interventions would not be feasible. This article reviews the history, general anatomy, and the classification schemes of liver anatomy and their relevance to liver-directed therapies. Copyright 2010 Elsevier Inc. All rights reserved.

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

    PubMed

    Truong, Triet Nhat; Bullard, Stephen A

    2013-07-01

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

  15. Role of parasites in cancer.

    PubMed

    Mandong, B M; Ngbea, J A; Raymond, Vhriterhire

    2013-01-01

    In areas of parasitic endemicity, the occurrence of cancer that is not frequent may be linked with parasitic infection. Epidemiological correlates between some parasitic infections and cancer is strong, suggesting a strong aetiological association. The common parasites associated with human cancers are schistosomiasis, malaria, liver flukes (Clonorchis sinenses, Opistorchis viverrini). To review the pathology, literature and methods of diagnosis. Literature review from peer reviewed Journals cited in PubMed and local journals. Parasites may serve as promoters of cancer in endemic areas of infection.

  16. 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 ...

  17. In vitro polarization of carp leucocytes in response to the blood fluke Sanguinicola inermis Plehn, 1905 (Trematoda: Sanguinicolidae).

    PubMed

    Richards, D T; Hoole, D; Lewis, J W; Ewens, E; Arme, C

    1996-05-01

    An in vitro assay was used to determine the effects of Sanguinicola inermis adults and cercariae on the polarization responses of pronephric leucocytes of carp. Leucocytes were isolated and exposed to live adult flukes or cercariae for up to 48 h. Differences in polarization responses were related to the presence of the parasite, the presence or absence of carp serum and the time of incubation. The mean proportions of cells exhibiting polarization in unstimulated controls ranged from 5 to 30% over the experimental period. Within 15 min of exposure to adults or cercariae, significant increases in mean polarization responses were observed of up to 75% and levels remained higher than control values for over 24 h. Overall, the presence of normal carp serum, either untreated or heat inactivated, did not enhance the polarization responses of leucocytes incubated with only cercariae or adults. However, between 0.25 and 3 h, the presence of carp serum with cercariae significantly enhanced polarization responses when compared with cells incubated with cercariae alone.

  18. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Hepatitis C Hepatitis D Hepatitis E Hepatitis G Liver cancer is a disease in which malignant (cancer) cells ... Primary Liver Cancer Treatment Childhood Liver Cancer Treatment Liver cancer is not common in the United States. Liver ...

  19. Benign Liver Tumors

    MedlinePlus

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  20. Liver Function Tests

    MedlinePlus

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  1. Progression of Liver Disease

    MedlinePlus

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  2. Multidrug resistance-associated protein 4 is a bile transporter of Clonorchis sinensis simulated by in silico docking.

    PubMed

    Dai, Fuhong; Yoo, Won Gi; Lee, Ji-Yun; Lu, Yanyan; Pak, Jhang Ho; Sohn, Woon-Mok; Hong, Sung-Jong

    2017-11-21

    Multidrug resistance-associated protein 4 (MRP4) is a member of the C subfamily of the ABC family of ATP-binding cassette (ABC) transporters. MRP4 regulates ATP-dependent efflux of various organic anionic substrates and bile acids out of cells. Since Clonorchis sinensis lives in host's bile duct, accumulation of bile juice can be toxic to the worm's tissues and cells. Therefore, C. sinensis needs bile transporters to reduce accumulation of bile acids within its body. We cloned MRP4 (CsMRP4) from C. sinensis and obtained a cDNA encoding an open reading frame of 1469 amino acids. Phylogenetic analysis revealed that CsMRP4 belonged to the MRP/SUR/CFTR subfamily. A tertiary structure of CsMRP4 was generated by homology modeling based on multiple structures of MRP1 and P-glycoprotein. CsMRP4 had two membrane-spanning domains (MSD1 & 2) and two nucleotide-binding domains (NBD1 & 2) as common structural folds. Docking simulation with nine bile acids showed that CsMRP4 transports bile acids through the inner cavity. Moreover, it was found that CsMRP4 mRNA was more abundant in the metacercariae than in the adults. Mouse immune serum, generated against the CsMRP4-NBD1 (24.9 kDa) fragment, localized CsMRP4 mainly in mesenchymal tissues and oral and ventral suckers of the metacercariae and the adults. Our findings shed new light on MRPs and their homologs and provide a platform for further structural and functional investigations on the bile transporters and parasites' survival.

  3. [Prevalence of Clonorchis sinensis infection and effect of albendazole treatment among residents in two communities of Zhongshan City].

    PubMed

    Ying-Yan, Zheng; Ting-Jun, Xie; Man, Wang; Yue-Yi, Fang; Le, Luo

    2018-02-22

    To understand the prevalence of Clonorchis sinensis infection among residents in two communities of Zhongshan City, and evaluate the effect of albendazole treatment, so as to offer the evidence for formulating the strategy of clonorchiasis prevention and control. The stool specimens were collected from the residents of two comprehensive demonstration areas, and the eggs of C. sinensis were detected by Kato-Katz technique. Those who were tested positive were treated with albendazole (0.4, twice a day for 4 days in adults, and half dosage for children aged 16 years or below). Three weeks after the treatment, the stool specimens were recollected and retested to evaluate the effect. A total of 532 people were investigated and 96 were tested positive, with an infection rate of 18.05%. The infection rate was 28.63% (69/241) in the males and 9.28% (27/291) in the females, and there was a significant difference between them ( χ 2 = 334.99, P < 0.01). The infection rate increased with the increase of the age ( χ 2 = 63.84, P < 0.01). Among the 96 positive residents, 94 received the albendazole treatment, and 86 were retested after the treatment with a negative conversion rate of 91.86% (79/86). Of the 7 residents without the conversion, 5 had irregular medication. No severe adverse reactions were reported during the period of treatment. The infection rate of C. sinensis among residents in the two communities of Zhongshan City is high, especially among the males and aged people. The effect of albendazole is good in the treatment of C. sinensis infection. In the future, the general survey and treatment should be strengthened in order to lower the infection rate.

  4. [Identification of Clonorchis sinensis metacercariae based on PCR targeting ribosomal DNA ITS regions and COX1 gene].

    PubMed

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Yang, Yi-Chao; Li, Hong-Mei; Chen, Ying-Dan; Zhou, Xiao-Nong

    2014-06-01

    To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.

  5. Immune response induced by oral delivery of Bacillus subtilis spores expressing enolase of Clonorchis sinensis in grass carps (Ctenopharyngodon idellus).

    PubMed

    Jiang, Hongye; Chen, Tingjin; Sun, Hengchang; Tang, Zeli; Yu, Jinyun; Lin, Zhipeng; Ren, Pengli; Zhou, Xinyi; Huang, Yan; Li, Xuerong; Yu, Xinbing

    2017-01-01

    Clonorchiasis, caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensisis (C.sinensis), remains a common public health problem. New effective prevention strategies are still urgent to control this food-borne infectious disease. The previous studies suggested Bacillus subtilis (B. subtilis) spores was an ideal vaccines delivery system, and the C.sinensis enolase (CsENO) was a potential vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgM levels by ELISA in sera, intestinal mucus and skin mucus in grass carps (Ctenopharyngodon idella) through oral administration with B. subtilis spores surface expressing CsENO. In addition, immune-related genes expression was also measured by qRT-PCR. Grass carps orally treated with B. subtilis spores or normal forages were used as controls. The results of ELISA manifested that specific IgM levels of grass carps in CsENO group in sera, intestine mucus and skin mucus almost significantly increased from week 4 post the first oral administration when compared to the two control groups. The levels of specific IgM reached its peak in intestine mucus firstly, then in sera, and last in skin mucus. qRT-PCR results showed that 5 immune-related genes expression had different degree of rising trend in CsENO group when compared to the two control groups. Our study demonstrated that orally administrated with B. subtilis spores expressing CsENO induced innate and adaptive immunity, systemic and local mucosal immunity, and humoral and cellular immunity. Our work may pave the way to clarify the exact mechanisms of protective efficacy elicited by B. subtilis spores expressing CsENO and provide new ideas for vaccine development against C. sinensis infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Fatty Liver

    MedlinePlus

    ... Drug Information, Search Drug Names, Generic and Brand Natural Products, ... fat to accumulate in liver cells by causing the body to synthesize more fat or by processing (metabolizing) and excreting fat more slowly. As a ...

  7. Liver biopsy

    MedlinePlus

    ... Primary biliary cirrhosis Primary biliary cholangitis Pyogenic liver abscess Reye syndrome Sclerosing cholangitis Wilson disease Risks Risks may include: Collapsed lung Complications from the sedation Injury to the gallbladder ...

  8. Spatial and Temporal Changes in the Distribution of Blood Fluke Infection in Nicolea gracilibranchis (Polychaeta: Terebellidae), the Intermediate Host for Cardicola orientalis (Digenea: Aporocotylidae), at a Tuna Farming Site in Japan.

    PubMed

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

    2017-10-01

    Fish blood flukes of the genus Cardicola (Digenea: Aporocotylidae) are important pathogens in tuna aquaculture. Recent advances in marine blood fluke research have led to the elucidation of the lifecycles of 3 Cardicola spp. infecting tuna; all 3 flukes utilize terebellid polychaetes as the intermediate host. In our survey, we obtained large numbers of Nicolea gracilibranchis infected by larval Cardicola orientalis at our tuna farming site. To determine the spatial and temporal changes in the distribution of N. gracilibranchis surrounding tuna culture cages and their infection by C. orientalis, we conducted monthly sampling for a period of 1 yr. Terebellids were most abundant on the floats and ropes of culture cages, but a significantly higher proportion of infected N. gracilibranchis was detected on ropes, particularly up to 4 m in depth. Cardicola orientalis infection in N. gracilibranchis was clearly seasonal, with a higher infection rate between April and July. Our findings indicate that the infected terebellids inhabit specific microhabitats, and both abiotic and biotic factors likely influence blood fluke infection in the intermediate terebellid host. This information is important to better understand the general biology of marine aporocotylids and may be useful to develop a control strategy for blood fluke infection in tuna aquaculture.

  9. Blood flukes Cardicola parvus and C. laruei (Trematoda: Aporocotylidae): life cycles and cryptic infection in spotted seatrout, Cynoscion nebulosus (Teleost: Sciaenidae).

    PubMed

    Siegel, Sasha V; Rivero, Andrea V; Oberstaller, Jenna; Colon, Beatrice L; de Buron, Isaure; Kyle, Dennis E

    2018-04-01

    Aporocotylidae comprises a diverse family of fish blood flukes, with adults found in blood or body cavity of marine, brackish, or freshwater fish. Aporocotylids are unique among the Digenea with many developing in polychaetes. The life cycle has been elucidated for only a few species that develop in polychaetes from marine/brackish environments and none for western Atlantic aporocotylids. The basis for this study was observations of blood fluke larvae in annelids from South Carolina, USA in 1982 prior to possible usage of molecular tools to specifically identify parasite larvae. Recent description of aporocotylid species and genotyping tools prompted revisiting original collection sites to examine polychaetes and fish as potential hosts. Polycirrid Enoplobranchus sanguineus and terebellids Amphitrite ornata, and Terebella lapidaria revealed infections with aporocotylid larvae. Adult blood flukes were also collected from fish commonly encountered in the same habitat: spotted seatrout (Cynoscion nebulosus), red drum (Sciaenops ocellatus), black drum (Pogonias cromis), and Atlantic croaker (Micropogonias undulatus). Sporocysts containing cercariae were found in individuals of each annelid species. Adult Cardicola parvus were found in spotted seatrout and Atlantic croaker, C. laruei in spotted seatrout, C. currani in red drum, and C. palmeri in black drum. Genotype analysis of ITS-2 and lsrDNA of all forms confirmed conspecific infections by C. parvus in E. sanguineus and A. ornata and C. laruei in T. lapidaria. This is the first description of complete life cycles of aporocotylids in the Western Atlantic and first evidence of cryptic infections of Cy. nebulosus with C. parvus. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Clonorchis sinensis acetoacetyl-CoA thiolase: identification and characterization of its potential role in surviving in the bile duct.

    PubMed

    Lin, Jinsi; Qu, Hongling; Chen, Guishan; He, Lei; Xu, Yanquan; Xie, Zhizhi; Ren, Mengyu; Sun, Jiufeng; Li, Shan; Chen, Wenjun; Chen, Xueqing; Wang, Xiaoyun; Li, Xuerong; Liang, Chi; Huang, Yan; Yu, Xinbing

    2015-02-25

    Clonorchis sinensis (C. sinensis) inhabits in bile duct of the host. However, the mechanisms involved in why C. sinensis can survive in the bile environment containing lipids have not yet been explored. In this study, C. sinensis acetoacetyl-CoA thiolase (CsACAT), a member of the thiolase family which has a key role in the beta oxidation pathway of fatty acid production, was identified and characterized to understand its potential role in adapting to the bile environment. The encoding sequence, conserved domains and spatial structure of CsACAT were identified and analyzed by bioinformatic tools. Recombinant CsACAT (rCsACAT) was obtained using a procaryotic expression system. The expression pattern of CsACAT was confirmed by quantitative real-time PCR, western blotting, and immunofluorescence. Gradients of lecithin were then set to culture C. sinensis adults in vitro and the survival rate of C. sinensis was analyzed, as well as the expression level and enzymatic activity of CsACAT in different lipid environments. Hypercholesteremia rabbit models were established by feeding with a hyperlipidemic diet and then infected intragastrically with C. sinensis. One and a half months later, the worm burdens and the expression level of CsACAT was detected. CsACAT was confirmed to be a member of the thiolase family and present in the excretory/secretory proteins of C. sinensis. CsACAT was specifically localized at the vitellarium and sub-tegumental muscle layer in adult worms. The mRNA level of CsACAT in eggs was higher than those in adult worms and metacercariae. When adult worms were cultured with higher concentration of lecithin, the expression level and enzyme activity of CsACAT were up-regulated. The survival rate of adult worms was higher than control group. More adult worms were recovered from hypercholesteremia rabbit models. The expression level of CsACAT in these worms was higher than control group. Our results implied that C. sinensis might sense lipid levels and

  11. Identification and Characterization of Paramyosin from Cyst Wall of Metacercariae Implicated Protective Efficacy against Clonorchis sinensis Infection

    PubMed Central

    Lv, Xiaoli; Tian, Yanli; Men, Jingtao; Zhang, Xifeng; Lei, Huali; Zhou, Chenhui; Lu, Fangli; Liang, Chi; Hu, Xuchu; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

    2012-01-01

    Human clonorchiasis has been increasingly prevalent in recent years and results in a threat to the public health in epidemic regions, motivating current strategies of vaccines to combat Clonorchis sinensis (C. sinensis). In this study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins of metacercariae by proteomic approaches and characterized the expressed recombinant pET-26b-CsPmy protein (101 kDa). Bioinformatics analysis indicated that full-length sequences of paramyosin are conserved in helminthes and numerous B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy. Western blot analysis showed that CsPmy was expressed at four life stages of C. sinensis, both cyst wall proteins and soluble tegumental components could be probed by anti-CsPmy serum. Moreover, immunolocalization results revealed that CsPmy was specifically localized at cyst wall and excretory bladder of metacercaria, as well as the tegument, oral sucker and vitellarium of adult worm. Both immunoblot and immunolocalization results demonstrated that CsPmy was highly expressed at the stage of adult worm, metacercariae and cercaria, which could be supported by real-time PCR analysis. Both recombinant protein and nucleic acid of CsPmy showed strong immunogenicity in rats and induced combined Th1/Th2 immune responses, which were reflected by continuous high level of antibody titers and increased level of IgG1/IgG2a subtypes in serum. In vaccine trials, comparing with control groups, both CsPmy protein and DNA vaccine exhibited protective effect with significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05), respectively. In consistence with immune responses in sera, elevated level of cytokines IFN-γ and IL-4 in splenocytes suggested that CsPmy could induce combined cellular immunity and humoral immunity in host. Taken together, CsPmy could be a promising vaccine candidate in the prevention of C. sinensis regarding its high immunogenicity and surface

  12. Detection of Clonorchis sinensis circulating antigen in sera from Chinese patients by immunomagnetic bead ELISA based on IgY.

    PubMed

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

    2014-01-01

    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. 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. Our findings suggest that IgY-IMB-ELISA appears to be a sensitive and specific assay for detection of circulating antigen in human clonorchiasis.

  13. Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma.

    PubMed

    Surapaitoon, Arpa; Suttiprapa, Sutas; Mairiang, Eimorn; Khuntikeo, Narong; Pairojkul, Chawalit; Bethony, Jeffrey; Brindley, Paul J; Sripa, Banchob

    2017-06-01

    Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-1β-511C/T, IL-6-174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α -308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α -308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 -174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

  14. Urinary microRNA-192 and microRNA-21 as potential indicators for liver fluke-associated cholangiocarcinoma risk group.

    PubMed

    Silakit, Runglawan; Loilome, Watcharin; Yongvanit, Puangrat; Thongchot, Suyanee; Sithithaworn, Paiboon; Boonmars, Thidarut; Koonmee, Supinda; Titapun, Attapol; Khuntikeo, Narong; Chamadol, Nittaya; Techasen, Anchalee; Namwat, Nisana

    2017-08-01

    Opisthorchis viverrini infection induces chronic inflammation in the bile ducts, leading to periductal fibrosis (PDF), which possibly associates to cholangiocarcinoma (CCA). Patients with CCA have a poor prognosis, which is linked to asymptomatic disease and late diagnosis. Hence, detecting early stage CCA is essential. Secretory miRNAs have been promoted as biomarkers for pathological changes associated with parasitic infections, fibrosis and/or cancer. We aimed to determine levels of miR-192 and miR-21 in the urine of O. viverrini infected, periductal fibrosis (PDF) and CCA groups using qRT-PCR. We found that miR-192 was significantly higher in O. viverrini infected, PDF and also CCA groups (p<0.05) than in healthy controls. By utilizing the Receiver Operation Characteristics (ROC) analysis, miR-192 differentiated patients with opisthorchiasis (the area under the curve; AUC=0.766), PDF subjects (AUC=0.781) and CCA patients (AUC=0.682) from healthy controls. MiR-21 was significantly higher in PDF and CCA groups (p<0.05) than in healthy controls. MiR-21 discriminated PDF subjects (AUC=0.735) and CCA patients (AUC=0.682) from healthy controls. Combined levels of these two miRNAs revealed an increased AUC of 0.812 for separating opisthorchiasis, AUC of 0.815 in discriminating PDF subjects, and AUC of 0.849 in differentiating CCA from healthy controls. Odds ratios (OR) indicated high levels of miR-192/miR-21 as risk predictors for opisthorchiasis, PDF and CCA. Levels of these miRNAs declined significantly for patients following praziquantel treatment. In conclusion, urinary miR-192/miR-21 have potential as risk indicators for opisthorchiasis and PDF-associated CCA in the endemic region. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma

    PubMed Central

    Surapaitoon, Arpa; Suttiprapa, Sutas; Mairiang, Eimorn; Khuntikeo, Narong; Pairojkul, Chawalit; Bethony, Jeffrey; Brindley, Paul J.; Sripa, Banchob

    2017-01-01

    Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF− and APF+) cases. Polymorphisms in genes encoding IL-1β-511C/T, IL-6-174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α −308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α −308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 −174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA. PMID:28719954

  16. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Hepatic (Liver) Function Panel

    MedlinePlus

    ... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

  18. 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 (C.L.A.S.S.) -- www. ...

  19. Elevated Liver Enzymes

    MedlinePlus

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  20. Sequence analysis and characterization of pyruvate kinase from Clonorchis sinensis, a 53.1-kDa homopentamer, implicated immune protective efficacy against clonorchiasis.

    PubMed

    Chen, Tingjin; Jiang, Hongye; Sun, Hengchang; Xie, Zhizhi; Ren, Pengli; Zhao, Lu; Dong, Huimin; Shi, Mengchen; Lv, Zhiyue; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing; Huang, Yan; Xu, Jin

    2017-11-09

    Clonorchis sinensis, the causative agent of clonorchiasis, is classified as one of the most neglected tropical diseases and affects more than 15 million people globally. This hepatobiliary disease is highly associated with cholangiocarcinoma. As key molecules in the infectivity and subsistence of trematodes, glycolytic enzymes have been targets for drug and vaccine development. Clonorchis sinensis pyruvate kinase (CsPK), a crucial glycolytic enzyme, was characterized in this research. Differences were observed in the sequences and spatial structures of CsPK and PKs from humans, rats, mice and rabbits. CsPK possessed a characteristic active site signature (IKLIAKIENHEGV) and some unique sites but lacked the N-terminal domain. The predicted subunit molecular mass (Mr) of CsPK was 53.1 kDa. Recombinant CsPK (rCsPK) was a homopentamer with a Mr. of approximately 290 kDa by both native PAGE and gel filtration chromatography. Significant differences in the protein and mRNA levels of CsPK were observed among four life stages of C. sinensis (egg, adult worm, excysted metacercaria and metacercaria), suggesting that these developmental stages may be associated with diverse energy demands. CsPK was widely distributed in adult worms. Moreover, an intense Th1-biased immune response was persistently elicited in rats immunized with rCsPK. Also, rat anti-rCsPK sera suppressed C. sinensis adult subsistence both in vivo and in vitro. The sequences and spatial structures, molecular mass, and expression profile of CsPK have been characterized. rCsPK was indicated to be a homopentamer. Rat anti-rCsPK sera suppressed C. sinensis adult subsistence both in vivo and in vitro. CsPK is worthy of further study as a promising target for drug and vaccine development.

  1. Fluke Fairness Act

    THOMAS, 113th Congress

    Rep. Bishop, Timothy H. [D-NY-1

    2014-01-14

    House - 01/16/2014 Referred to the Subcommittee on Fisheries, Wildlife, Oceans, and Insular Affairs. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. 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

  3. Liver transplant for cholestatic liver diseases.

    PubMed

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Pyogenic liver abscess

    MedlinePlus

    Liver abscess; Bacterial liver abscess ... There are many possible 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 ...

  5. Liver function tests

    MedlinePlus

    Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... E, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

  6. 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 ...

  7. Fatty Liver Disease

    MedlinePlus

    ... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

  8. American Liver Foundation

    MedlinePlus

    ... Media Helpful Links Liver Cancer Information Available in Chinese Learn more about liver cancer HERE . Thanks to ... in Northern California, you can speak to a Chinese speaking agent with your liver cancer questions. Call ...

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

    PubMed Central

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

    2013-01-01

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

  10. [Investigation on sanitation of freshwater aquaculture environments and Clonorchis sinensis intermediate host infection in a city of Pearl River Delta region, China].

    PubMed

    Man, Wang; Le, Luo; Xue-Qin, Chen; Lei, Li; Yue-Yi, Fang

    2017-10-19

    To understand the current status of the sanitation of freshwater aquaculture environments, and Clonorchis sinensis infection of freshwater fish in the aquaculture and market in a city of Pearl River Delta region, so as to provide the evidence for formulating the prevention and control strategy of clonorchiasis sinensis. In 2016, based on the distribution of freshwater aquaculture, 36 freshwater fish ponds among 14 towns were selected for sampling and investigation, and 10-20 pieces were collected from each pond. Besides, 3 aquatic product wholesale markets were included, among which 3-6 stalls were selected from each market, and 20-30 pieces were collected from each stall. The metacercaria in the fish was examined by the digestion method. In the 36 fish ponds, there were no toilets with the stool being drained into fish ponds directly, and there was only one pond with duck sheds with the stool being drained into fish ponds directly. Totally 437 pieces of freshwater fish from ponds were detected, with a metacercaria positive rate of 4.35% (19/437). The metacercaria positive fish were distributed in 50% (7/14) of towns and 25% (9/36) ponds. The positive rates of crucian carp, grass carp, dace, aristichthysnobilis, and tilapia were 13.95% (6/43), 4.76% (9/189), 4.44 (2/45), 1.55% (2/129), and 0 (0/31) respectively, with statistically significant difference ( χ 2 = 13.46, P = 0.01). Totally 307 pieces of freshwater fish were collected from the wholesale markets, with a total positive rate of 1.95% (6/307). The positive rate of grass carp and aristichthysnobilis were 3.20% (4/125) and 2.78% (2/72) respectively, and no positive samples were found in crucian carp, dace and tilapia, with no statistically significant difference among the different fish in the infection rate (Fisher exact P = 0.75). The sanitation of freshwater aquaculture environments in a city of Pearl River Delta region is relative good. However, there are different degrees of Clonorchis sinensis

  11. Nonalcoholic Fatty Liver Disease

    MedlinePlus

    ... fatty liver, alcoholic steatohepatitis, ascites, choline deficiency, cirrhosis, drug-induced fatty liver, edema, encephalopathy, glycogen storage disorder, gynecomastia, hepatic steatosis, hepatomegaly, hereditary fructose intolerance, homocystinuria, hyperlipidemia, ...

  12. Alcoholic Liver Disease and Liver Transplantation.

    PubMed

    Gallegos-Orozco, Juan F; Charlton, Michael R

    2016-08-01

    Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Role of liver progenitors in liver regeneration

    PubMed Central

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

    2015-01-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs. PMID:25713804

  14. Role of liver progenitors in liver regeneration.

    PubMed

    Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

    2015-02-01

    During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

  15. Infection rates of Enterobius vermicularis and Clonorchis sinensis of primary school children in Hamyang-gun, Gyeongsangnam-do (Province), Korea

    PubMed Central

    Kim, Bong Jin; Yeon, Je Wook

    2001-01-01

    The egg positive rate of Enterobius vermicularis and Clonorchis sinensis of school children in the rural area was studied in Hamyang-gun. Gyeongsangnam-do in Korea. Cellotape anal swab and formalin ether concentration methods were performed one time to 720 primary school children. The total egg positive rate of E. vermicularis was 12.6% in two schools (Baekjeon and Wiseong). In the Baekjeon and Wiseong primary school, the egg positive rate of E. vermicularis was 4.6% and 13.4%, respectively. Pinworm egg positive rate was 17.6% in the lower grades (1st. 2nd and 3rd), and 7.7% in higher grades (4th, 5th and 6th). The total egg positive rate of male and female was 12.6% and 12.7%, respectively. The egg positive rate of C. sinensis of Baekjeon and Wiseong primary school was 1.5% and 0.46%, respectively. The total egg positive rate of C. sinensis was 0.56%. This survey showed that continuous education and chemotherapy is necessary to treat and prevent reinfection of E. vermicularis. In the case of C. sinensis, health education for school children is recommended to prevent potential infection of adolescents. PMID:11775334

  16. Venom allergen-like protein 28 in Clonorchis sinensis: four epitopes on its surface and the potential role of Cys124 for its conformational stability.

    PubMed

    Lee, Myoung-Ro; Yoo, Won Gi; Kim, Yu Jung; Chung, Eun Ju; Cho, Shin-Hyeong; Ju, Jung-Won

    2018-06-06

    Venom allergen-like (VAL) proteins are important to host-parasite interactions. We previously demonstrated that a Clonorchis sinensis VAL (CsVAL) protein-derived synthetic peptide suppresses allergic and inflammatory responses. However, little is known regarding the physicochemical and antigenic properties of CsVAL proteins. Here, we identified a novel 194 amino acid VAL protein, named C. sinensis VAL 28 (CsVAL28), and characterized its functional motifs and structural details as a new member of the CAP superfamily. Unlike members of the Schistosoma mansoni VAL (SmVAL) family, CsVAL28 has a single CAP1 motif and six highly conserved disulfide bond-forming cysteines. Tertiary models of wild-type CsVAL28 and mutants were built using SmVAL4 as template via homology modeling. Normal mode analysis predicted that disulfide bond breaking by mutation of cysteine 124 to serine would greatly affect protein mobility. Four major immunoreactive linear epitopes were identified in the surface-exposed region or its vicinity via epitope mapping, using sera from clonorchiasis patients and healthy controls. Our findings provide in-depth knowledge on the structure-function properties of VAL proteins and may help determine highly antigenic regions for developing new diagnostic approaches.

  17. Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis.

    PubMed

    Song, Tianzhang; Gan, Wenjia; Chen, Jintao; Huang, Lilin; Yin, Hongling; He, Tailong; Huang, Huaiqiu; Hu, Xuchu

    2016-04-01

    Lactate dehydrogenase (LDH) is a terminal enzyme in anaerobic glycolytic pathway. It widely exists in various organisms and is in charge of converting the glycolysis product pyruvic acid to lactic acid. Most parasites, including Clonorchis sinensis, predominantly depend on glycolysis to provide energy. Bioinformatic analysis predicts that the LDHs from many species have more than one transmembrane region, suggesting that it may be a membrane protein. C. sinensis LDH (CsLDH) has been confirmed as a transmembrane protein mainly located in the tegument. The antibodies against CsLDH can inhibit the worm's energy metabolism, kill the worm, and may have the same effects on human cancer cells. In this study, we cloned and characterized human LDHA (HsLDHA), HsLDHB, and CsLDH. Semi-quantitative real-time RCP showed that HsLDHB only existed in hepatocarcinoma cell SMMC-7721. Confocal microscopy and Western blot experiments revealed that HsLDHB was localized in the plasma membrane of SMMC-7721 cells, and the antibodies against CsLDH could cross-react with it. This cross-reaction could inhibit the enzymatic activity of HsLDHB. The cancer cells co-cultured with anti-CsLDH sera showed a significant decrease in cell proliferation rate and increases in caspase 9 and reactive oxygen species (ROS) levels. Therefore, anti-CsLDH antibodies can induce the apoptosis of cancer cells SMMC-7721 and may serve as a new tool to inhibit tumor.

  18. 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.

  19. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-07

    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.

  20. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Alcoholic liver disease.

    PubMed

    Penny, Steven M

    2013-01-01

    In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

  2. Biomarkers for liver fibrosis

    DOEpatents

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

    2017-05-16

    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.

  3. Biomarkers for liver fibrosis

    DOEpatents

    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.

  4. 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.

  5. Liver transplantation for metastatic liver malignancies.

    PubMed

    Foss, Aksel; Lerut, Jan P

    2014-06-01

    Liver transplantation is a validated treatment of primary hepatobiliary tumours. Over the last decade, a renewed interest for liver transplantation as a curative treatment of colorectal liver metastasis (CR-LM) and neuro-endocrine metastasis (NET-LM) has developed. The ELTR and UNOS analyses showed that liver transplantation may offer excellent disease-free survival (ranging from 30 to 77%) in case of NET-LM, on the condition that stringent selection criteria are implemented. The interest for liver transplantation in the treatment of CR-LM has been fostered by the Norwegian SECA study. Five-year A 5-year survival rate of 60% could be reached. Despite the high recurrence rate (90%), one-third of patients were disease free following pulmonary surgery for metastases. Liver transplantation will take a more prominent place in the therapeutic algorithm of CR-LM and NET-LM. Larger experiences are necessary to improve knowledge about tumour biology and to refine selection criteria. A multimodal approach adding neo and adjuvant medical treatment to the transplant procedure will be key to bring this oncologic transplant project into the clinical arena. The preserved liver function in these patients will allow a more deliberate access to split liver and living donation for these indications.

  6. Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples

    PubMed Central

    Rahman, S. M. Mazidur; Song, Hyun Beom; Jin, Yan; Oh, Jin-Kyoung; Lim, Min Kyung; Hong, Sung-Tae

    2017-01-01

    Background Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited. Methodology/Principle findings The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1–99.2) of sensitivity and 100% (95% CI, 92.9–100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%. Conclusions To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis. PMID:28991924

  7. Prevalence and Intensity of Clonorchis sinensis Metacercariae in Freshwater Fish from Wicheon Stream in Gunwi-gun, Gyeongsangbuk-do, Korea

    PubMed Central

    Sohn, Woon-Mok; Na, Byoung-Kuk; Cho, Shin-Hyeong; Ju, Jung-Won; Son, Dong-Chul

    2018-01-01

    The infection status of Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fish from a highly prevalent site, Wicheon (a branch of Nakdong-gang), which is located in Gunwi-gun, Gyeongsangbuk-do, the Republic of Korea. Total 1,162 fish in 32 species were examined by the artificial digestion method through 6 years. CsMc were detected in 720 (67.5%) out of 1,067 fish (26 spp.) and their density was 610 per fish infected. In the susceptible gobioninid fish group, i.e., Pungtungia herzi, Squalidus gracilis majimae, Squalidus japonicus coreanus, Sarcocheilichthys variegatus wakiyae and Pseudorasbora parva, all of 323 fish were infected with an average of 1,310 CsMc. Total 23 (95.8%) gobioninid fish, i.e., Pseudogobio esocinus, Abbottina springeri, Hemibarbus longirostris, Microphysogobio koreensis, and Microphysogobio jeoni, were infected with 127 CsMc in average. In the acheilognathinid fish (bitterlings) group, the prevalence was 77.0%, and the density was 50 CsMc per fish infected. In the rasborinid fish (chubs) group, i.e., Zacco platypus, Zacco temminckii, Zacco koreanus, and Opsariichthys uncirostris amurensis, 147 (36.5%) out of 403 fish examined were infected with 15 CsMc in average. The susceptibility indices of CsMc were 412 in the overall positive fish group, 1,310 in the gobioninid group-1, 122 in the gobioninid group-2, 38.5 in the acheilognathinid group, and 5.5 in the rasborinid fish group. Conclusively, it was confirmed that CsMc are highly prevalent in fish from Wicheon, and their infection tendency varied according to the subfamily groups in Cyprinidae fish hosts. PMID:29529849

  8. Comparative analysis of immune effects in mice model: Clonorchis sinensis cysteine protease generated from recombinant Escherichia coli and Bacillus subtilis spores.

    PubMed

    Wu, Zhanshuai; Tang, Zeli; Shang, Mei; Zhao, Lu; Zhou, Lina; Kong, Xiangzhan; Lin, Zhipeng; Sun, Hengchang; Chen, Tingjin; Xu, Jin; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2017-07-01

    Clonorchiasis remains a nonnegligible public health problem in endemic areas. Cysteine protease of Clonorchis sinensis (CsCP) plays indispensable roles in the parasitic physiology and pathology, and has been exploited as a promising drug and vaccine candidate. In recent years, development of spore-based vaccines against multiple pathogens has attracted many investigators' interest. In previous studies, the recombinant Escherichia coli (BL21) and Bacillus subtilis spores expressing CsCP have been successfully constructed, respectively. In this study, the immune effects of CsCP protein purified from recombinant BL21 (rCsCP) and B. subtilis spores presenting CsCP (B.s-CsCP) in Balb/c mice model were conducted with comparative analysis. Levels of specific IgG, IgG1 and IgG2a were significantly increased in sera from both rCsCP and B.s-CsCP intraperitoneally immunized mice. Additionally, recombinant spores expressing abundant fusion CsCP (0.03125 pg/spore) could strongly enhance the immunogenicity of CsCP with significantly higher levels of IgG and isotypes. Compared with rCsCP alone, intraperitoneal administration of mice with spores expressing CsCP achieved a better effect of fighting against C. sinensis infection by slowing down the process of fibrosis. Our results demonstrated that a combination of Th1/Th2 immune responses could be elicited by rCsCP, while spores displaying CsCP prominently induced Th1-biased specific immune responses, and the complex cytokine network maybe mediates protective immune responses against C. sinensis. This work further confirmed that the usage of B. subtilis spores displaying CsCP is an effective way to against C. sinensis.

  9. 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

  10. Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples.

    PubMed

    Rahman, S M Mazidur; Song, Hyun Beom; Jin, Yan; Oh, Jin-Kyoung; Lim, Min Kyung; Hong, Sung-Tae; Choi, Min-Ho

    2017-10-01

    Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited. The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1-99.2) of sensitivity and 100% (95% CI, 92.9-100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%. To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.

  11. Amebic liver abscess

    MedlinePlus

    ... abscess URL of this page: //medlineplus.gov/ency/article/000211.htm Amebic liver abscess To use the sharing features on this page, please enable JavaScript. Amebic liver abscess is a collection of pus ...

  12. 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

  13. Liver Transplant: Nutrition

    MedlinePlus

    ... transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver disease do ... to lose weight sensibly and slowly, without causing malnutrition (especially protein malnutrition). Losing excess weight decreases the ...

  14. Microbiota and the liver.

    PubMed

    Shen, Ting-Chin David; Pyrsopoulos, Nikolaos; Rustgi, Vinod K

    2018-04-01

    The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

  15. Stages of Childhood Liver Cancer

    MedlinePlus

    ... Liver Cancer Prevention Liver Cancer Screening Research Childhood Liver Cancer Treatment (PDQ®)–Patient Version Treatment Option Overview Go ... different types of treatment for patients with childhood liver cancer. Different types of treatments are available for children ...

  16. 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.

  17. 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

  18. Clonorchis sinensis omega-class glutathione transferases play major roles in the protection of the reproductive system during maturation and the response to oxidative stress.

    PubMed

    Kim, Jeong-Geun; Ahn, Chun-Seob; Kim, Seon-Hee; Bae, Young-An; Kwon, Na-Young; Kang, Insug; Yang, Hyun-Jong; Sohn, Woon-Mok; Kong, Yoon

    2016-06-13

    Clonorchis sinensis causes a major food-borne helminthic infection. This species locates in mammalian hepatobiliary ducts, where oxidative stressors and hydrophobic substances are profuse. To adapt to the hostile micromilieu and to ensure its long-term survival, the parasite continuously produces a diverse repertoire of antioxidant enzymes including several species of glutathione transferases (GSTs). Helminth GSTs play pertinent roles during sequestration of harmful xenobiotics since most helminths lack the cytochrome P-450 detoxifying enzyme. We isolated and analyzed the biochemical properties of two omega-class GSTs of C. sinensis (CsGSTo1 and CsGSTo2). We observed spatiotemporal expression patterns in accordance with the maturation of the worm's reproductive system. Possible biological protective roles of CsGSTos in these organs under oxidative stress were investigated. The full-length cDNAs of CsGSTo1 and 2 constituted 965 bp and 1,061 bp with open reading frames of 737 bp (246 amino acids) and 669 bp (223 amino acids). They harbored characteristic N-terminal thioredoxin-like and C-terminal α-helical domains. A cysteine residue, which constituted omega-class specific active site, and the glutathione-binding amino acids, were recognized in appropriate positions. They shared 44 % sequence identity with each other and 14.8-44.8 % with orthologues/homologues from other organisms. Bacterially expressed recombinant proteins (rCsGSTo1 and 2) exhibited dehydroascorbate reductase (DHAR) and thioltransferase activities. DHAR activity was higher than thioltransferase activity. They showed weak canonical GST activity toward 1-chloro-2,4-dinitrobenzene. S-hexylglutathione potently and competitively inhibited the active-site at nanomolar concentrations (0.63 and 0.58 nM for rCsGSTo1 and 2). Interestingly, rCsGSTos exhibited high enzyme activity toward mu- and theta-class GST specific substrate, 4-nitrobenzyl chloride. Expression of CsGSTo transcripts and proteins

  19. 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

  20. [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.

  1. Orchestrating liver development.

    PubMed

    Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

    2015-06-15

    The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

  2. 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.

  3. 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

  4. Autoimune liver disease panel

    MedlinePlus

    ... liver cirrhosis or chronic active hepatitis. Risks Slight risks from having blood drawn include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection ( ...

  5. Adipokines in Liver Cirrhosis.

    PubMed

    Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

    2017-06-29

    Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

  6. Adipokines in Liver Cirrhosis

    PubMed Central

    Haberl, Elisabeth M.; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

    2017-01-01

    Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively. PMID:28661458

  7. [Nosoareas of clonorchiasis in the Primorye Territory].

    PubMed

    Besprozvannykh, V V; Ermolenko, A V; Rumiantseva, E E; Maslov, D V; Voroniuk, V M; Tatonova, Iu V

    2012-01-01

    The mammalian liver parasite (Clonorchis sinensis flukes) has spread in the Primorye Territory. The areas of the first intermediate hosts for the parasite mollusks of the genus Parafossarulus have been found to recently become wider south-western predominantly due to lotus acclimatization, resulting in the expansion of a parasite habitation area. The intensity of newly formed foci of clonorchiasis is an order of magnitude greater than that of natural ones and they are a higher hazard since they have formed in the recreation areas used by the population for rest and fishing. The carp is the second intermediate host of trematodes. Patients' medical history data show that European and crucian carps (less frequently skygazer, rudd, gudgeon, minnow) have served as the main sources of human infection with trematodes.

  8. Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna naturally infected with blood flukes from genus Cardicola (Trematoda: Aporocotylidae).

    PubMed

    Pennacchi, Ylenia; Shirakashi, Sho; Nowak, Barbara F; Bridle, Andrew R

    2016-11-01

    Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on the market is an economically valuable fish species. Infections by blood flukes from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The accumulation of numerous Cardicola eggs in the fish gills causes severe pathology that has been linked to mortality in PBT juveniles up to one year old. The only effective treatment used to mitigate the infection is the oral administration of the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with the need to minimise therapeutic drug use in aquaculture it is hoped that immunoprophylaxis can provide a future alternative to protect the PBT juveniles against Cardicola infection. Currently, little is known of the host immune response to these parasites and of their infection dynamics. In this study, using real-time qPCR we aimed to quantitatively detect C. orientalis and C. opisthorchis DNA within the gills and heart of cultured PBT juveniles and to investigate the host immune response at the transcriptional level in the gills. The research focused mainly during early stages of infection soon after young PBT were transferred to culture cages (from 14 to 77 days post-transfer). An increase (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-β and IL-1β was observed in the PBT gills infected with Cardicola spp. (28-77 days post-transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase) transcription was strongly up-regulated in gill samples of PBT infected with C. orientalis relative to uninfected fish but not in fish infected with C. opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post-transfer (DPT) to sea-cages which was 55 days earlier than the first detection of parasite eggs and adults by microscopy. Oral administration of PZQ did not have an immediate effect

  9. Echinococcosis of the Liver

    DTIC Science & Technology

    2007-03-01

    and 1b. The lack of internal enhancement confirms the cystic nature of these lesions. Discussion Echinococcosis , also known as Hydatid disease... Echinococcosis of the Liver Radiology Corner Echinococcosis of the Liver Guarantor...abbreviated answer in the March 2007 issue. 1 Echinococcosis is a parasitic infection that poses a potential health threat to military members and

  10. Cod Liver Oil

    MedlinePlus

    Cod liver oil contains certain "fatty acids" that prevent the blood from clotting easily. These fatty acids also reduce pain and swelling. ... Morue, Huile de Poisson, Liver Oil, N-3 Fatty Acids, Omega 3, Oméga 3, Omega 3 Fatty Acids, ...

  11. Living Donor Liver Transplantation

    MedlinePlus

    ... What are Some Benefits of a Living-donor Liver Transplant? In the U.S., more than 17,500 patients ... 1,700 patients die each year while waiting. Liver transplants are given to patients on the basis of ...

  12. Polyploidization of liver cells.

    PubMed

    Celton-Morizur, Séverine; Desdouets, Chantal

    2010-01-01

    Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

  13. Fatty liver in children

    PubMed Central

    Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

    2009-01-01

    Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 ± 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 ± 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). Conclusion: The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children. PMID:19536316

  14. 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.

  15. 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

  16. Fluke Fairness Act of 2013

    THOMAS, 113th Congress

    Sen. Schumer, Charles E. [D-NY

    2013-11-21

    Senate - 11/21/2013 Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  17. Liver transplantation in Japan.

    PubMed

    Soyama, Akihiko; Eguchi, Susumu; Egawa, Hiroto

    2016-10-01

    As of December 31, 2014, 7937 liver transplants (7673 living donor transplants and 264 deceased donor liver transplantations [DDLTs; 261 from heart-beating donors and 3 from non-heart-beating donors]) have been performed in 67 institutions in Japan. The revised Organ Transplant Law in Japan came into effect in July 2010, which allows organ procurement from brain-dead individuals, including children, with family consent if the patient had not previously refused organ donation. However, the number of deceased donor organ donations has not increased as anticipated. The rate of deceased organ donations per million population (pmp) has remained at less than 1. To maximize the viability of the limited numbers of donated organs, a system has been adopted that includes the partnership of well-trained transplant consultant doctors and local doctors. For compensating for the decreased opportunity of on-site training, an educational system regarding quality organ procurement for transplant surgeons has also been established. Furthermore, experts in the field of liver transplantation are currently discussing adoption of the Model for End-Stage Liver Disease score for allocation, promoting split-liver transplantation, arranging in-house coordinators, and improving the frequency of proposing the option to donate organs to the families. To overcome the shortage of donors during efforts to promote organ donation, living donor liver transplantation (LDLT) has been developed in Japan. Continuous efforts to increase DDLT in addition to the successful experience of LDLT will increase the benefits of liver transplantation for more patients. Liver Transplantation 22 1401-1407 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  18. TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis.

    PubMed

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Shi, Yun-Liang; Wan, Xiao-Ling; Yang, Yi-Chao

    2017-08-07

    Although the responses of inducible nitric oxide synthase (iNOS) and associated cytokine after Clonorchis sinensis infection have been studied recently, their mechanisms remain incompletely understood. In this study, we investigated the effects of toll-like receptor 2 (TLR2) signals on iNOS/nitric oxide (NO) responses after C. sinensis infection. We also evaluated the correlations between iNOS responses and worm development, which are possibly regulated by TLR2 signal. TLR2 wild-type and mutant C57BL/6 J mice were infected with 60 C. sinensis metacercariae, and the samples were collected at 30, 60, 90 and 120 days post-infection (dpi). The total serum NO levels were detected using Griess reagent after nitrate was reduced to nitrite. Hepatic tissue samples from the infected mice were sliced and stained with hematoxylin and eosin (HE) to observe worm development in the intrahepatic bile ducts. The iNOS mRNA transcripts in the splenocytes were examined by real time reverse transcriptase polymerase chain reaction (qRT-PCR), and iNOS expression was detected by immunohistochemistry. Developing C. sinensis juvenile worms were more abundant in the intrahepatic bile ducts of TLR2 mutant mice than those of TLR2 wild-type mice. However, no eggs were found in the faeces of both mice samples. The serum levels of total NO significantly increased in TLR2 mutant mice infected with C. sinensis at 30 (t (5)  = 2.595, P = 0.049), 60 (t (5)  = 7.838, P = 0.001) and 90 dpi (t (5)  = 3.032, P = 0.029). Meanwhile, no changes occurred in TLR2 wild-type mice compared with uninfected controls during the experiment. The iNOS expression in splenocytes showed unexpected higher background levels in TLR2 mutant mice than those in TLR2 wild-type mice. Furthermore, the iNOS mRNA transcripts in splenocytes were significantly increased in the TLR2 wild-type mice infected with C. sinensis at 30 (t (5)  = 5.139, P = 0.004), 60 (t (5)  = 6.138, P = 0.002) and 90 dpi (t (5)  = 6

  19. Alcoholic liver disease

    MedlinePlus

    ... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:59-60. Carithers RL, McClain C. Alcoholic ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 86. Haines EJ, Oyama LC. ...

  20. 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

  1. Pregnancy Complications: Liver Disorders

    MedlinePlus

    ... resulting from the liver disorder and decreased bile flow. A pregnant woman should call her health care provider if she has these symptoms. How common is ICP? In the United States, ICP affects less than 1 percent of women ( ...

  2. Diet - liver disease

    MedlinePlus

    ... of toxic waste products. Increasing your intake of carbohydrates to be in proportion with the amount of ... severe liver disease include: Eat large amounts of carbohydrate foods. Carbohydrates should be the major source of ...

  3. Genererating a core cluster of Fasciola hepatica virulence and immunomodulation-related genes using a comparative in silico approach.

    PubMed

    Haçarız, Orçun; Sayers, Gearóid P

    2018-04-01

    A total of 71 virulence and immunomodulation-related transcripts (VIRs) of Fasciola hepatica have been previously proposed (Haçarız et al., 2015). In an attempt to further refine this cohort, an in silico meta analysis approach was carried out using publicly available sequence data of related liver flukes, Clonorchis sinensis and Opisthorchis viverrini. Data of both liver flukes were investigated in terms of sequential homology with data of non-parasitic organisms, pathogens and VIRs of F. hepatica, directional selection (Ka/Ks), and cytokine signaling relation (protein motif based). Some VIRs of F. hepatica [showing homology with immune receptors (for toll/interleukin-1, TGF-β or TNF-α), TGF-β, TNF-α, CD147, or relation with suppressors of cytokine signaling/IKBKE 1 or stimulation of TGF-β (through thrombospondin similarity)] were found to be orthologous with those of both C. sinensis and O. viverrini. The in silico analysis indicates that on the basis of genetic commonality, a total of 30 VIRs of F. hepatica are highlighted as of foremost importance in the parasite evasion strategy, through controlling of host immune system. Findings in this study could be important to further enhance our understanding of the parasitic mechanisms and develop effective control strategies against F. hepatica and other related parasites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Autoimmune liver disease 2007.

    PubMed

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  5. Fortuitously discovered liver lesions.

    PubMed

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

    2013-06-07

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

  6. Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

    PubMed

    Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

    2018-01-01

    An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

  7. Computational Modeling in Liver Surgery

    PubMed Central

    Christ, Bruno; Dahmen, Uta; Herrmann, Karl-Heinz; König, Matthias; Reichenbach, Jürgen R.; Ricken, Tim; Schleicher, Jana; Ole Schwen, Lars; Vlaic, Sebastian; Waschinsky, Navina

    2017-01-01

    The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery. PMID:29249974

  8. 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. © 2016 American

  9. 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

  10. Encephalopathy and liver transplantation.

    PubMed

    Chavarria, Laia; Cordoba, Juan

    2013-06-01

    Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

  11. Transjugular Liver Biopsy

    PubMed Central

    Behrens, George; Ferral, Hector

    2012-01-01

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

  12. [Deceased donor liver transplantation].

    PubMed

    Seehofer, D; Schöning, W; Neuhaus, P

    2013-05-01

    Deceased donor liver transplantation is nowadays a routine procedure for the treatment of terminal liver failure and often represents the only chance of a cure. Under given optimal conditions excellent long-term results can be obtained with 15-year survival rates of well above 60 %.In Germany the outcome after liver transplantation has deteriorated since the introduction of an allocation policy, which is based on the medical urgency. At present 25 % of liver graft recipients die within the first year after transplantation. In contrast 1-year survival in most other countries, e.g. in the USA or the United Kingdom is around 90 % and therefore significantly better. Reasons for the inferior results in Germany are on the one hand an increasing number of critically ill recipients and on the other hand an unfavorable situation for organ donation. In comparison with other countries the organ donation rate is low and moreover the risk profile of these donors is above average. This combination of organ shortage and organ allocation represents a big challenge for the future orientation of liver transplantation and creates the potential for conflict. These cannot be solved on a medical basis but require a social consensus.Because of the present inferior results and because of the high expenses of the present system we suggest a discussion on future allocation policies as well as on future centre structures in Germany. In addition to the medical urgency the maximum benefit should also be considered for organ allocation.

  13. Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

    PubMed Central

    Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

    2011-01-01

    Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

  14. Liver biopsy under hypnosis.

    PubMed

    Adams, P C; Stenn, P G

    1992-09-01

    Two patients underwent outpatient percutaneous liver biopsy under hypnosis without complications. One patient had severe anxiety about the procedure because of a previous adverse experience with liver biopsy and the other had a history of severe allergy to local anesthesia. Both patients had undergone a session of hypnosis at least once prior to the biopsy. One received no local anesthetic and the other received 1% lidocaine as a local anesthetic. Both patients were completely cooperative during the procedure with the required respiratory maneuvers. Both patients stated that they were aware of the procedure under hypnosis but described no pain and would be most willing to have the procedure done under hypnosis in the future. Hypnosis can be a useful method of preparing carefully selected patients for percutaneous liver biopsy.

  15. Liver natural killer cells: subsets and roles in liver immunity

    PubMed Central

    Peng, Hui; Wisse, Eddie; Tian, Zhigang

    2016-01-01

    The liver represents a frontline immune organ that is constantly exposed to a variety of gut-derived antigens as a result of its unique location and blood supply. With a predominant role in innate immunity, the liver is enriched with various innate immune cells, among which natural killer (NK) cells play important roles in host defense and in maintaining immune balance. Hepatic NK cells were first described as ‘pit cells' in the rat liver in the 1970s. Recent studies of NK cells in mouse and human livers have shown that two distinct NK cell subsets, liver-resident NK cells and conventional NK (cNK) cells, are present in this organ. Here, we review liver NK cell subsets in different species, revisiting rat hepatic pit cells and highlighting recent progress related to resident NK cells in mouse and human livers, and also discuss the dual roles of NK cells in liver immunity. PMID:26639736

  16. Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease.

    PubMed

    Dou, Lei; Ono, Yoshihiro; Chen, Yi-Fa; Thomson, Angus W; Chen, Xiao-Ping

    2018-05-01

    The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Liver and chorion cytochemistry.

    PubMed

    Roels, F; De Prest, B; De Pestel, G

    1995-01-01

    Microscopic visualization of peroxisomes in chorionic villus cytotrophoblast and in biopsy and autopsy samples of liver and kidney, the presence of enlarged liver macrophages containing lipid droplets insoluble in acetone and n-hexane as well as polarizing inclusions formed by stacks of trilamellar sheets are of diagnostic value in peroxisomal disorders. Methods are presented for evaluating these structures by light microscopy; trilamellar inclusions are only detected by electron microscopy. Macrophage features are preserved in archival paraffin blocks. In adrenal cortex, insoluble lipid, polarizing inclusions and trilamellar structures should be looked for. The stains are easily reproducible, and all reagents are commercially available.

  18. 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...

  19. [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. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  20. Plants Consumption and Liver Health

    PubMed Central

    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

  1. Liver Disease and Pulmonary Hypertension

    MedlinePlus

    ... Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that ... diagnosed? A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), ...

  2. Takotsubo cardiomyopathy post liver transplantation.

    PubMed

    Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

    2016-10-23

    A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

  3. About the Operation: Liver Transplant

    MedlinePlus

    ... liver is one of the largest and most complex organs in the body. It weighs about three pounds in adults and is made up ... for life. The liver helps process carbohydrates, fats and proteins, and stores vitamins. It processes ...

  4. Coffee and liver health.

    PubMed

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

    2014-01-01

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

  5. Polyploidization in liver tissue.

    PubMed

    Gentric, Géraldine; Desdouets, Chantal

    2014-02-01

    Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Liver Disease and IBD

    MedlinePlus

    ... loss, and itching. PSC may not improve with medical treatment for IBD and may ultimately require liver transplantation. The cause is not known and there is no effective medication for PSC. To correct severe narrowing of the bile ducts, a balloon-tipped tube may be inserted into the duct ...

  7. 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 (...

  8. Calcium signaling in liver.

    PubMed

    Gaspers, Lawrence D; Thomas, Andrew P

    2005-01-01

    In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP3) evoke transient increases or spikes in cytosolic free calcium ([Ca2+]i), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP3-dependent [Ca2+]i spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+]i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca2+]i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ.

  9. 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

  10. [Robot-assisted liver resection].

    PubMed

    Aselmann, H; Möller, T; Kersebaum, J-N; Egberts, J H; Croner, R; Brunner, M; Grützmann, R; Becker, T

    2017-06-01

    Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

  11. 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

  12. Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

    PubMed

    Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

    2017-01-01

    Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  13. Nutrition and Liver Health.

    PubMed

    Jackson, Alan A

    2017-01-01

    Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools

  14. Colorectal liver metastases.

    PubMed

    Tzeng, Ching-Wei D; Aloia, Thomas A

    2013-01-01

    With modern multimodality therapy, patients with resected colorectal cancer (CRC) liver metastases (CLM) can experience up to 50-60 % 5-year survival. These improved outcomes have become more commonplace via achievements in multidisciplinary care, improved definition of resectability, and advances in technical skill. Even patients with synchronous and/or extensive bilateral disease have benefited from novel surgical strategies. Treatment sequencing of synchronous CRC with CLM can be simplified into the following three paradigms: (classic colorectal-first), simultaneous (combined), or reverse approach (liver-first). The decision of whether to treat the CLM or CRC first depends on which site dominates oncologically and symptomatically. Oxaliplatin with 5-fluorouracil/leucovorin (FOLFOX) and irinotecan with 5-fluorouracil/leucovorin (FOLFIRI) are the foundations of modern chemotherapy. Although each regimen has positively impacted survivals, both have the potential for negative effects on the non-tumor liver. Oxaliplatin is associated with vascular injury (sinusoidal ballooning, microvascular injury, nodular regenerative hyperplasia, and long-term fibrosis) but not steatosis. Irinotecan has been associated with steatohepatitis, especially in patients with obesity and diabetes. Steatohepatitis from irinotecan is the only chemotherapy-associated liver injury (CALI) associated with increased mortality from postoperative hepatic insufficiency. Extended duration of preoperative chemotherapy is also associated with CALI. To determine resectability and to prevent overtreatment with systemic therapy, all patients should receive high-quality cross-sectional imaging and be evaluated by a hepatobiliary surgeon before starting chemotherapy. Even as chemotherapy improves, liver surgeons will continue to play a central role in treatment planning by offering the best chance for prolonged survival-safe R0 resection with curative intent.

  15. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  16. Helminths and Cancers From the Evolutionary Perspective.

    PubMed

    Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

    2018-01-01

    Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

  17. Autoimmune paediatric liver disease

    PubMed Central

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  18. Autoimmune paediatric liver disease.

    PubMed

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-06-07

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  19. Probiotics in Pediatric Liver Disease.

    PubMed

    Miloh, Tamir

    2015-01-01

    The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

  20. The liver sieve and atherosclerosis.

    PubMed

    Fraser, Robin; Cogger, Victoria C; Dobbs, Bruce; Jamieson, Hamish; Warren, Alessandra; Hilmer, Sarah N; Le Couteur, David G

    2012-04-01

    The 'liver sieve' is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins. The liver sieve is a very efficient exchange system, however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus and old age, there is defenestration of the liver sieve. Such defenestration has been shown to influence the hepatic uptake of various substrates including lipoproteins. In the future, pharmacological manipulation of the liver sieve may play a number of therapeutic roles including the management of dyslipidaemia; increasing the efficiency of liver-targeted gene therapy; and improving regeneration of old livers. (C) 2012 Royal College of Pathologists of Australasia.

  1. Liver Disease in Mitochondrial Disorders

    PubMed Central

    Lee, Way S.; Sokol, Ronald J.

    2013-01-01

    Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

  2. Drug-induced Liver Injury

    PubMed Central

    David, Stefan; Hamilton, James P

    2011-01-01

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

  3. A bioartificial liver to treat severe acute liver failure.

    PubMed Central

    Rozga, J; Podesta, L; LePage, E; Morsiani, E; Moscioni, A D; Hoffman, A; Sher, L; Villamil, F; Woolf, G; McGrath, M

    1994-01-01

    OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients. Images Figure 2. Figure 3. PMID:8185403

  4. Pediatric pyogenic liver abscess.

    PubMed

    Israeli, Rafi; Jule, Jose Ernesto; Hom, Jeffrey

    2009-02-01

    Pyogenic liver abscess (PLA) is a rare pediatric disease. Typically, PLA is found in adults with biliary disease. There are no typical physical findings or symptoms. Often, pathogenic organisms are not recovered for identification. This case illustrates a teenager presenting with prolonged episodes of fever and vomiting. With percutaneous drainage and month-long antibiotic therapy, the PLA resolved. This case illustrates that a high index of suspicion is needed for diagnosis.

  5. Distribution of Foxp3+ T cells in the liver and hepatic lymph nodes of goats and sheep experimentally infected with Fasciola hepatica.

    PubMed

    Escamilla, A; Zafra, R; Pérez, J; McNeilly, T N; Pacheco, I L; Buffoni, L; Martínez-Moreno, F J; Molina-Hernández, V; Martínez-Moreno, A

    2016-10-30

    Foxp3 regulatory T cells (Tregs) are now considered to play a key role in modulation of immune responses during parasitic helminth infections. Immunomodulation is a key factor in Fasciola hepatica infection; however, the distribution and role of Foxp3 + Tregs cells have not been investigated in F. hepatica infected ruminants. The aim of this study was to evaluate the presence of Foxp3 + Tregs in the liver and hepatic lymph nodes from experimentally infected sheep and goats during acute and chronic stages of infection. Three groups of goats (n=6) and three groups of sheep (n=6) were used in this study. Goats in groups 1-2 and sheep in groups 4-5 were orally infected with metacercarie of ovine origin. Groups 1 and 4 were killed during the acute stage of the infection, at nine days post infection (dpi); groups 2 and 5 were killed during the chronic stage, at 15 and19 weeks post infection respectively (wpi). Groups 3 (goats) and 6 (sheep) were left as uninfected controls. Fluke burdens and liver damage were assessed and the avidin-biotin-complex method was used for the immunohistochemical study. At nine dpi in acute hepatic lesions, the number of both Foxp3 + and CD3 + T lymphocytes increased significantly in goats and sheep. In the chronic stages of infection (15-19wpi), the number of Foxp3 + and CD3 + T lymphocytes were also significantly increased with respect to control livers, particularly in portal spaces with severely enlarged bile ducts (response to adult flukes) while the increase was lower in granulomas, chronic tracts and smaller portal spaces (response to tissue damage). Foxp3 + Tregs were increased in the cortex of hepatic lymph nodes of sheep (chronic infection) and goats (acute and chronic infection). The estimated proportion of T cells which were Foxp3+ was significantly increased in the large bile ducts and hepatic lymph node cortex of chronically infected goats but not sheep. This first report of the expansion of Foxp3 + Tregs in acute and chronic

  6. Liver Disease in Sri Lanka.

    PubMed

    Wijewantha, Hasitha S

    2017-01-01

    Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic and amebic liver abscesses and dengue infection are the other causes of liver disease. Some of the commonly used plants as traditional herbal medicine in Sri Lanka have been shown to have deleterious effects on the liver in animal studies. Considering the high popularity of traditional herbal medicine in the country, it is likely that herbal medicine is an etiological factor for liver disease in Sri Lanka, but no published data are available. Address reprint requests to: Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol 2017;7(1):78-81.

  7. Liver transplantation in the treatment of severe iatrogenic liver injuries

    PubMed Central

    Lauterio, Andrea; De Carlis, Riccardo; Di Sandro, Stefano; Ferla, Fabio; Buscemi, Vincenzo; De Carlis, Luciano

    2017-01-01

    The place of liver transplantation in the treatment of severe iatrogenic liver injuries has not yet been widely discussed in the literature. Bile duct injuries during cholecystectomy represent the leading cause of liver transplantation in this setting, while other indications after abdominal surgery are less common. Urgent liver transplantation for the treatment of severe iatrogenic liver injury may-represent a surgical challenge requiring technically difficult and time consuming procedures. A debate is ongoing on the need for centralization of complex surgery in tertiary referral centers. The early referral of patients with severe iatrogenic liver injuries to a tertiary center with experienced hepato-pancreato-biliary and transplant surgery has emerged as the best treatment of care. Despite widespread interest in the use of liver transplantation as a treatment option for severe iatrogenic injuries, reported experiences indicate few liver transplants are performed. This review analyzes the literature on liver transplantation after hepatic injury and discusses our own experience along with surgical advances and future prospects in this uncommon transplant setting. PMID:28932348

  8. 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. Copyright © 2016. Published by Elsevier Ltd.

  9. 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

  10. Experimental models of liver fibrosis.

    PubMed

    Yanguas, Sara Crespo; Cogliati, Bruno; 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

    2016-05-01

    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.

  11. The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2 Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis sinensis Excretory/Secretory Products.

    PubMed

    Hua, Hui; Du, Ying; Ma, Rui; Zhang, Bei-Bei; Yu, Qian; Li, Bo; Xu, Jiang-Tao; Li, Xiang-Yang; Tang, Ren-Xian; Yan, Chao; Zheng, Kui-Yang

    2018-02-01

    The roles of TLR4 in mediation of innate immune response and in regulation of adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were collected, and the concentrations of type 1 and type 2 relative cytokines were determined by ELISA. The maturation of BMDCs indicated by surface markers of CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that the levels of IFN-γ, IL-6, TNF-α, and IL-10 in the splenocytes from C. sinensis-infected TLR4 mut mice were significantly lower than those from TLR4 wild mice when they were further exposed to ESP. For BMDCs, the productions of the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation mice were predominantly decreased compared with those from TLR4 wild mice when the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis showed that ESP could significantly decrease the high levels of CD80, CD86, and MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4 may play a regulatory role in type 1 immune responses during C. sinensis infection.

  12. Protothecosis after liver transplantation.

    PubMed

    Narita, Masashi; Muder, Robert R; Cacciarelli, Thomas V; Singh, Nina

    2008-08-01

    Prototheca species are unicellular algae of low virulence that are rarely associated with human infections. We report a liver transplant recipient with disseminated protothecosis and review the literature on this unusual opportunistic infection in transplant recipients. Of 9 cases, including ours, 5 had a localized infection, and 4 had disseminated protothecosis. Seven cases were due to Prototheca wickerhamii, and 2 were due to Prototheca zopfii. Overall mortality in transplant recipients with Prototheca infections was 88% (7/8). All 4 cases of disseminated protothecosis died despite therapy with amphotericin B. Posttransplant protothecosis is a rare but significant infection that is associated with a grave prognosis.

  13. Liver transplantation around the world.

    PubMed

    Trotter, James F

    2017-04-01

    In the past few years, there have been important changes in the development of liver transplantation around the world. In particular, several emerging countries have rapidly developed transplant programs. There have also been important changes in liver allocation, utilization of donors by cardiac death, and living donors. A review of the practices in different countries around the world will help provide the reader with a better appreciation of their own program as well as the recognition of potential areas of improvement based on the experience of their colleagues. A recent series of articles has been published in the journal Liver Transplantation summarizing the practice of liver transplantation from representative countries around the world. The volume of liver transplant varies widely by country and there has been an important growth in volume in emerging countries. Most liver transplant candidates are prioritized for surgery by the Model for Endstage Liver Disease score and with the exception of Germany and the USA most patients are transplanted at Model for Endstage Liver Disease score from 18 to 20. Hepatitis C is the most common indication for liver transplant with the notable exception of several European countries. Innovative strategies to incentivize donation have been developed in several countries.

  14. Liver immunology and herbal treatment

    PubMed Central

    Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

    2017-01-01

    Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

  15. Gut microbiome and liver diseases.

    PubMed

    Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

    2016-12-01

    The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Iron homeostasis in the liver

    PubMed Central

    Anderson, Erik R; Shah, Yatrik M

    2014-01-01

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

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

    PubMed

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

    1999-04-01

    The recent case-control studies in Thailand indicate that a high incidence of liver cancer in Thailand has not been associated with common risk factors such as hepatitis B infection, aflatoxin intake and alcohol consumption. While the infestation by the liver fluke Opisthorchis viverrini (OV) accounted for the high risk in north-east Thailand, there was no such exposure in the other regions of the country where the incidence of liver cancer is also high. Case-control studies suggest that exposure to exogenous and possibly endogenous nitrosamines in food or tobacco in betel nut and cigarettes may play a role in the development of hepatocellular carcinoma (HCC), while OV infestation and chemical interaction of nitrosamines may also be aetiological factors in the development of cholangiocarcinoma (CCA). Over 1800 samples of fresh and preserved food were systematically collected and tested between 1988 and 1996. All the food items identified by anthropological studies to be consumed frequently in four major regions of Thailand were analysed for volatile nitrosamines using gas chromatography combined with a thermal energy analyser. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were detected in fermented fish ("Plasalid"). NDMA was also detected at levels ranging from trace amounts to 66.5 microg/kg in several salted and dried fish ("Larb-pla" and "Pla-siu"). NDMA and NPYR were frequently detected in several vegetables, particularly fermented beans ("Tau-chiau") at levels ranging between 1 and 95.1 microg/kg and 0-146 microg/kg, respectively. The possible role of nitrosamines in Thai food in the aetiology of liver cancer (HCC, CCA) is discussed.

  18. Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

    PubMed

    Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

    2015-01-01

    The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

  19. Polycystic Liver Disease

    SciT

    Linda, Nguyen, E-mail: nguyenli@einstein.edu

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations.more » The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.« less

  20. Quantitative PET of liver functions.

    PubMed

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

  1. Quantitative PET of liver functions

    PubMed Central

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

  2. 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…

  3. Management of paediatric liver trauma.

    PubMed

    van As, A B; Millar, Alastair J W

    2017-04-01

    Of all the intra-abdominal solid organs, the liver is the most vulnerable to blunt abdominal trauma. The majority of liver ruptures present in combination with other abdominal or extra-abdominal injuries. Over the last three decades, the management of blunt liver trauma has evolved from obligatory operative to non-operative management in over 90% of cases. Penetrating liver injuries more often require operative intervention and are managed according to adult protocols. The greatest clinical challenge remains the timely identification of the severely damaged liver with immediate and aggressive resuscitation and expedition to laparotomy. The operative management can be taxing and should ideally be performed in a dedicated paediatric surgical centre with experience in dealing with such trauma. Complications can occur early or late and include haemobilia, intrahepatic duct rupture with persistent biliary fistula, bilaemia, intrahepatic haematoma, post-traumatic cysts, vascular outflow obstruction, and gallstones. The prognosis is generally excellent.

  4. [Primary cancer of the liver].

    PubMed

    Orozco, H; Mercado, M A

    1997-01-01

    The epidemiologic and pathogenic aspects of primary hepatic malignancies are discussed. The role of viruses in the etiology of the disease is stressed. Imageology methods have a preponderant role for diagnosis and treatment options. Liver resection has a one years survival between 60 and 80% and a five years survival of 20 to 40%. A good surgical results is expected for tumors with no more than 5 cm in diameter, encapsulated and without vascular invasion non-cirrhotic livers, large tumors can also be removed. Surgical resection margin should be of 1 cm. For cirrhotic livers, a good liver function is needed (Child A-B) and no safe major resection can be done. History of bleeding portal hypertension has a negative role in the outcome. Liver transplantation should be limited to selected case, in which the tumors are small and asymptomatic (incidental). For larger tumors, long term results are not good with invariable recurrency of the tumor.

  5. [Surgical techniques in liver transplantation].

    PubMed

    Chan, Carlos; Plata-Muñoz, Juan José; Franssen, Bernardo

    2005-01-01

    Liver transplantation (LT) is probably the biggest surgical aggression that a patient can endure. It was considered only as a last option in the era of experimental LT, yet it evolved into the definitive treatment for some types of acute and chronic end stage liver disease. In terms of technique LT is the most complex of all types of transplantations. The surgical procedure in itself is well established and has changed little through time. Liver transplantation owes its improvement to better and more systematic anesthetic procedures and to perioperative care more than being due to improvement of the surgical technique. The first surgical procedure was described by Thomas Starzl in 1969. His initial work has been strengthened with the development of venous bypass, the refinement in vascular and biliary reconstruction technique and the development of the split liver. Up to date technical aspects of orthotopic liver transplantation are described in the present article.

  6. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

    PubMed

    Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

    2018-02-09

    Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

  7. 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).

  8. Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

    PubMed Central

    Carrion, Andres F.; Czul, Frank; Arosemena, Leopoldo R.; Selvaggi, Gennaro; Garcia, Monica T.; Tekin, Akin; Tzakis, Andreas G.; Martin, Paul; Ghanta, Ravi K.

    2010-01-01

    Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death. PMID:21234410

  9. 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

  10. 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. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  11. Nutritional status and liver transplantation.

    PubMed

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2011-12-01

    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 review

  12. Liver Transplantation: East versus West

    PubMed Central

    Shukla, Akash; Vadeyar, Hemant; Rela, Mohamed; Shah, Samir

    2013-01-01

    Liver transplantation (LT) has evolved rapidly since the first successful liver transplant performed in1967. Despite a humble beginning, this procedure gained widespread acceptance in the western world as a suitable option for patients with end stage liver disease (ESLD) by the beginning of the 1980s. At present, approximately 25,000 liver transplants are being performed worldwide every year with approximately 90% one year survival. The techniques of living donor liver transplantation (LDLT) developed in East Asia in the 1990s to overcome the shortage of suitable grafts for children and scarcity of deceased donors. While deceased donor liver transplantation (DDLT) constitutes more than 90% of LT in the western world, in India and other Asian countries, most transplants are LDLT. Despite the initial disparity, outcomes following LDLT in eastern countries have been quite satisfactory when compared to the western programs. The etiologies of liver failure requiring LT vary in different parts of the world. The commonest etiology for acute liver failure (ALF) leading to LT is drugs in the west and acute viral hepatitis in Asia. The most common indication for LT due to ESLD in west is alcoholic cirrhosis and hepatitis C virus (HCV), while hepatitis B virus (HBV) predominates in the east. There is a variation in prognostic models for assessing candidature and prioritizing organ allocation across the world. Model for end–stage liver disease (MELD) is followed in United States and some European centers. Other European countries rely on the Child–Turcotte–Pugh (CTP) score. Some parts of Asia still follow chronological order of listing. The debate regarding the best model for organ allocation is far from over. PMID:25755506

  13. Acute liver failure with thyrotoxicosis treated with liver transplantation.

    PubMed

    Cascino, Matthew D; McNabb, Brian; Gardner, David G; Woeber, Kenneth A; Fox, Alyson N; Wang, Bruce; Fix, Oren K

    2013-01-01

    We describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF). We present a case report and review the relevant literature. An extensive evaluation excluded possible causes of ALF other than thyrotoxicosis. The management of thyrotoxicosis posed several unique challenges in the setting of ALF, particularly because we did not want to use potentially hepatotoxic thionamides. The patient was treated with prednisone and propranolol and was started on potassium iodide when she was listed for liver transplantation. She underwent an uncomplicated liver transplant and subsequent thyroidectomy and is doing well. This well-characterized case describes thyrotoxicosis as a possible cause of ALF after thoroughly excluding other possible causes and illustrates the challenges of simultaneously managing both disorders. To our knowledge, this is the first report of ALF possibly resulting from untreated thyrotoxicosis that was successfully treated with liver transplantation.

  14. [Jaundice and pathological liver values].

    PubMed

    Schwarzenbach, Hans-Rudolf

    2013-06-05

    Jaundice corresponds to elevated bilirubin- levels, whereat one has to distinguish between direct and indirect serum-bilirubin. In the present Mini Review causes and differential diagnosis of jaundice are outlined. Ultrasound-diagnostic plays a major role in identifying intrahepatic or extrahepatic jaundice. Attention is given to the differential diagnosis of elevated liver enzymes in presence of jaundice, pointing out the distinction between hepatocellular and cholestatic parameters as well as the differentiation in acute or chronic increase. Moreover, the consequences of liver enzyme elevations including further diagnostic procedures, are highlighted. Finally, possibilities and limitations of modern diagnostic tests for liver fibrosis are briefly overviewed.

  15. Abacavir-induced liver toxicity.

    PubMed

    Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

    2016-01-01

    Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  16. Dr. Liver: A preoperative planning system of liver graft volumetry for living donor liver transplantation.

    PubMed

    Yang, Xiaopeng; Yang, Jae Do; Yu, Hee Chul; Choi, Younggeun; Yang, Kwangho; Lee, Tae Beom; Hwang, Hong Pil; Ahn, Sungwoo; You, Heecheon

    2018-05-01

    Manual tracing of the right and left liver lobes from computed tomography (CT) images for graft volumetry in preoperative surgery planning of living donor liver transplantation (LDLT) is common at most medical centers. This study aims to develop an automatic system with advanced image processing algorithms and user-friendly interfaces for liver graft volumetry and evaluate its accuracy and efficiency in comparison with a manual tracing method. The proposed system provides a sequential procedure consisting of (1) liver segmentation, (2) blood vessel segmentation, and (3) virtual liver resection for liver graft volumetry. Automatic segmentation algorithms using histogram analysis, hybrid level-set methods, and a customized region growing method were developed. User-friendly interfaces such as sequential and hierarchical user menus, context-sensitive on-screen hotkey menus, and real-time sound and visual feedback were implemented. Blood vessels were excluded from the liver for accurate liver graft volumetry. A large sphere-based interactive method was developed for dividing the liver into left and right lobes with a customized cutting plane. The proposed system was evaluated using 50 CT datasets in terms of graft weight estimation accuracy and task completion time through comparison to the manual tracing method. The accuracy of liver graft weight estimation was assessed by absolute difference (AD) and percentage of AD (%AD) between preoperatively estimated graft weight and intraoperatively measured graft weight. Intra- and inter-observer agreements of liver graft weight estimation were assessed by intraclass correlation coefficients (ICCs) using ten cases randomly selected. The proposed system showed significantly higher accuracy and efficiency in liver graft weight estimation (AD = 21.0 ± 18.4 g; %AD = 3.1% ± 2.8%; percentage of %AD > 10% = none; task completion time = 7.3 ± 1.4 min) than the manual tracing method (AD = 70

  17. Association of nonalcoholic fatty liver disease and liver cancer

    PubMed Central

    Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

    2015-01-01

    AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

  18. 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)

  19. Maximum residue level validation of triclabendazole marker residues in bovine liver, muscle and milk matrices by ultra high pressure liquid chromatography tandem mass spectrometry.

    PubMed

    Whelan, Michelle; O'Mahony, John; Moloney, Mary; Cooper, Kevin M; Furey, Ambrose; Kennedy, D Glenn; Danaher, Martin

    2013-02-01

    Triclabendazole is the only anthelmintic drug, which is active against immature, mature and adult stages of fluke. The objective of this work was to develop an analytical method to quantify and confirm the presence of triclabendazole residues around the MRL. In this work, a new analytical method was developed, which extended dynamic range to 1-100 and 5-1000 μg kg(-1) for milk and tissue, respectively. This was achieved using a mobile phase containing trifluoroacetic acid (pK(a) of 0.3), which resulted in the formation of the protonated pseudomolecular ions, [M+H](+), of triclabendazole metabolites. Insufficient ionisation of common mobile phase additives due to low pK(a) values (<2) was identified as the cause of poor linearity. The new mobile phase conditions allowed the analysis of triclabendazole residues in liver, muscle and milk encompassing their EU maximum residue levels (MRL) (250, 225 and 10 μg kg(-1) respectively). Triclabendazole residues were extracted using a modified QuEChERS method and analysed by positive electrospray ionisation mass spectrometry with all analytes eluted by 2.23 min. The method was validated at the MRL according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCα) of the method was in the range of 250.8-287.2, 2554.9-290.8 and 10.9-12.1 μg kg(-1) for liver, muscle and milk, respectively. The performance of the method was successfully verified for triclabendazole in muscle by participating in a proficiency study, the method was also applied to incurred liver, muscle and milk samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Probabilistic liver atlas construction.

    PubMed

    Dura, Esther; Domingo, Juan; Ayala, Guillermo; Marti-Bonmati, Luis; Goceri, E

    2017-01-13

    Anatomical atlases are 3D volumes or shapes representing an organ or structure of the human body. They contain either the prototypical shape of the object of interest together with other shapes representing its statistical variations (statistical atlas) or a probability map of belonging to the object (probabilistic atlas). Probabilistic atlases are mostly built with simple estimations only involving the data at each spatial location. A new method for probabilistic atlas construction that uses a generalized linear model is proposed. This method aims to improve the estimation of the probability to be covered by the liver. Furthermore, all methods to build an atlas involve previous coregistration of the sample of shapes available. The influence of the geometrical transformation adopted for registration in the quality of the final atlas has not been sufficiently investigated. The ability of an atlas to adapt to a new case is one of the most important quality criteria that should be taken into account. The presented experiments show that some methods for atlas construction are severely affected by the previous coregistration step. We show the good performance of the new approach. Furthermore, results suggest that extremely flexible registration methods are not always beneficial, since they can reduce the variability of the atlas and hence its ability to give sensible values of probability when used as an aid in segmentation of new cases.

  1. 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.

  2. Infections After Orthotopic Liver Transplantation

    PubMed Central

    Pedersen, Mark; Seetharam, Anil

    2014-01-01

    Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

  3. Kava Linked to Liver Damage

    MedlinePlus

    ... of these countries to remove kava from the market. Although liver damage appears to be rare, the ... are marketed to men, women, children, and the elderly. Advice to Consumers Safety is a concern for ...

  4. Liver Cancer and Hepatitis B

    MedlinePlus

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  5. 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

  6. Tuberculous pseudotumor of the liver

    SciT

    Dhekne, R.D.; Moore, W.H.; Long, S.E.

    1987-10-01

    Tuberculosis of the liver in association with generalized miliary tuberculosis is not an uncommon clinical entity. A solitary tuberculous liver abscess, however, is rare. Two such cases, in which there was no clinical evidence of extrahepatic tuberculosis, are reported. The similarities between this condition and other causes of hepatic lesions are discussed, with particular emphasis placed on the imaging patterns of various diagnostic imaging procedures.

  7. Peripheral neuropathy in liver cirrhosis.

    PubMed

    Kharbanda, Parampreet S; Prabhakar, Sudesh; Chawla, Yogesh K; Das, Chandi P; Syal, Puneet

    2003-08-01

    Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied. Patients having an identifiable cause of peripheral neuropathy, except alcohol, were excluded from the study. Patients with evidence of vitamin B12 deficiency or diabetes were also excluded from the study. In this study, 33 patients with liver cirrhosis were evaluated clinically and electrophysiologically to detect any evidence of peripheral neuropathy. Nerve conduction studies were performed in the upper and lower limbs using surface electrodes. These patients also underwent a detailed clinical examination. Clinical signs of peripheral neuropathy were found in seven (21%) patients. Nerve conduction studies were abnormal in 24 (73%) patients. The pattern of involvement was predominantly of an axonal sensory motor polyneuropathy. Neuropathy was found both in patients with alcohol-related and non-alcohol-related cirrhosis. The presence of encephalopathy did not have a significant bearing on the incidence and severity of neuropathy. The neuropathy was also not significantly related to the severity of liver disease. The present study reveals that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis, and is subclinical in a majority of these patients. The cause of neuropathy was probably the liver disease itself, as the incidence and severity of neuropathy in the alcohol-related cirrhosis, although higher, was not significantly different from the neuropathy in patients

  8. Metabonomics Research Progress on Liver Diseases.

    PubMed

    Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

    2017-01-01

    Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

  9. Pediatric Liver Transplantation: Our Experiences.

    PubMed

    Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

    2016-10-01

    The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months-17 years). The 4 most common reasons for liver transplantation were: Wilson's disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature.

  10. Molecular mechanisms of liver preconditioning

    PubMed Central

    Alchera, Elisa; Dal Ponte, Caterina; Imarisio, Chiara; Albano, Emanuele; Carini, Rita

    2010-01-01

    Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery. PMID:21182220

  11. Sexual dysfunction after liver transplantation.

    PubMed

    Burra, Patrizia

    2009-11-01

    1. The goal of liver transplantation is not only to ensure the survival of patients but also to offer patients the opportunity to achieve a good balance between the functional efficacy of the graft and their psychological and physical integrity. The quality of life after transplantation may be affected by unsatisfactory sexual activity and reproductive performance. 2. Sexual dysfunction and sex hormone disturbances are widely reported in men and women with chronic liver disease before liver transplantation. 3. Successful liver transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, therefore improving reproductive performance, but immunosuppressive drugs may interfere with hormone metabolism. 4. Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy, but fetal and maternal outcomes should be regularly assessed. 5. More detailed and comprehensive data are needed in the field of sexual function after transplantation, and new strategies are needed to support and inform patients on the waiting list and after liver transplantation. (c) 2009 AASLD.

  12. Validation of graft and standard liver size predictions in right liver living donor liver transplantation.

    PubMed

    Chan, See Ching; Lo, Chung Mau; Chok, Kenneth S H; Sharr, William W; Cheung, Tan To; Tsang, Simon H Y; Chan, Albert C Y; Fan, Sheung Tat

    2011-12-01

    To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, ( R 2  = 0.476) ( p  = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively ( R 2  = 0.781) ( p  = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. SLV and graft weight estimations were accurate using the formula and conversion factor.

  13. 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.

  14. Impact of Estimated Liver Volume and Liver Weight on Gender Disparity in Liver Transplantation

    PubMed Central

    Mindikoglu, Ayse L.; Emre, Sukru H.; Magder, Laurence S.

    2012-01-01

    OBJECTIVES While lower Model for End-Stage Liver Disease (MELD) scores due to lower levels of serum creatinine in women might account for some gender disparity in liver transplant (LT) rates, even within MELD scores, women are transplanted at lower rates than men. It is unclear what causes this disparity, but transplant candidate-donor liver size mismatch may be a factor. METHODS We analyzed Organ Procurement and Transplantation Network data for patients with end-stage liver disease on the waiting list. Pooled conditional logistic regression analysis was used to assess the association between gender and LT and determine the degree to which this association was explained by lower MELD scores or liver size. RESULTS A total of 28,866 patients and 424,001 person-months were included in the analysis. Median estimated liver volume (eLV) and liver weight (eLW) were significantly lower in women than in men on the LT waiting list (P<0.0001). Controlling for region and blood type, women were 25% less likely to receive LT in a given month compared to men (P<0.0001). When MELD was included in the model, the odds ratio (OR) for gender increased to 0.84 suggesting that 9 percentage points of the 25% gender disparity was due to MELD score. When eLV was added to the model, there was an additional 3% increase in OR of gender suggesting that transplant candidate-donor liver size mismatch is an underlying factor for lower LT rates in women compared to men (OR=0.87, P<0.0001). CONCLUSIONS Lower LT rates among women on the waiting list can be explained in part by lower MELD scores, eLV and eLW than those of men. However; at least half of the gender disparity still remains unexplained. PMID:23008117

  15. Impact of liver volume and liver function on posthepatectomy liver failure after portal vein embolization- A multivariable cohort analysis.

    PubMed

    Alizai, Patrick H; Haelsig, Annabel; Bruners, Philipp; Ulmer, Florian; Klink, Christian D; Dejong, Cornelis H C; Neumann, Ulf P; Schmeding, Maximilian

    2018-01-01

    Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 μg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

  16. In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import

    PubMed Central

    2013-01-01

    Background Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. Methods A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. Results We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous

  17. In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import.

    PubMed

    Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun; Yoshino, Timothy P

    2013-07-09

    Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly

  18. 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

  19. [Kidney function and liver transplantation].

    PubMed

    Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

    2013-06-30

    In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

  20. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    PubMed

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

  1. Clinical uses of liver stem cells.

    PubMed

    Dan, Yock Young

    2012-01-01

    Liver transplantation offers a definitive cure for many liver and metabolic diseases. However, the complex invasive procedure and paucity of donor liver graft organs limit its clinical applicability. Liver stem cells provide a potentially limitless source of cells that would be useful for a variety of clinical applications. These stem cells or hepatocytes generated from them can be used in cellular transplantation, bioartificial liver devices and drug testing in the development of new drugs. In this chapter, we review the technical aspects of clinical applications of liver stem cells and the progress made to date in the clinical setting. The difficulties and challenges of realizing the potential of these cells are discussed.

  2. 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. Copyright © 2016. Published by Elsevier B.V.

  3. Pediatric Liver Transplantation: Our Experiences

    PubMed Central

    Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

    2016-01-01

    Objective: The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Materials and Methods: Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. Results: In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months–17 years). The 4 most common reasons for liver transplantation were: Wilson’s disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. Conclusion: The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature. PMID:28149148

  4. Energy metabolism in the liver.

    PubMed

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. 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/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and 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 key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  5. Octogenarian Donors in Liver Transplantation.

    PubMed

    Gastaca, M; Guerra, M; Alvarez Martinez, L; Ruiz, P; Ventoso, A; Palomares, I; Prieto, M; Matarranz, A; Valdivieso, A; Ortiz de Urbina, J

    2016-11-01

    Due to the disparity between the number of patients on the list for liver transplantation and the availability of organs, the use of older donors has become necessary. The aim of this study was to investigate the outcomes of liver transplantation using octogenarian donors. From December 2003 to February 2016, 777 liver transplantations were performed at our institution, 33 of them (4.2%) with donors 80 years old and above. Our policy for the acceptance of these donors is based on preoperative liver function tests, donor hemodynamic stability, and intraoperative normal gross aspect. Octogenarian grafts were deliberately not assigned to retransplantations or to recipients with multiple previous surgical procedures or extensive portal thrombosis. Mean donor age was 82.7 ± 2.1 years, with a range between 80 and 88. Only 12.1% suffered hemodynamic instability during the intensive care unit stay. Three donors (9.1%) had a history of diabetes mellitus. The mean Model for End-Stage Liver Disease score among recipients was 14.7 ± 5.6. Mean cold ischemia time was 302 ± 61 minutes. After a median follow-up of 18.5 months (range 7.5 to 47.5), no graft developed primary nonfunction. We observed hepatic artery thrombosis in 1 patient (3%) and biliary complications in 4 patients (12.5%). There was 1 case of ischemic-type biliary lesion, although it was related to hepatic artery thrombosis. Patient survival at 1 and 3 years was 90.3%, whereas graft survival was 92.6% and 86.4%, respectively. Excellent mid-term results can be obtained after liver transplantation with octogenarian donors with strict donor selection and adequate graft allocation. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Operative risks of domino liver transplantation for the FAP liver donor and the FAP liver recipient.

    PubMed

    Azoulay, Daniel; Salloum, Chady; Samuel, Didier; Planté-Bordeneuve, Violaine

    2012-06-01

    This study aimed at evaluating the operative risks of domino liver transplantation (LT). Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy (FAP) liver donors [61 patients] versus FAP nondonors [39 patients] and FAP liver recipients [61 patients] versus cadaveric liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). Both groups had similar vascular and biliary complication rates. Both groups had similar 1- and 5-year patient and graft survival rates (83.4 % versus 87.2%, and 79.8 % versus 71.8%, p = 0.7) and (83.3% versus 87.2%, and 79.1% versus 71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients versus 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% versus 13.1%, p = 0.45) and (0.18 versus 0.15, p = 0.65). Domino procedure doesn't add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied cadaveric LT.

  7. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  8. Ablative therapy for liver tumours

    PubMed Central

    Dick, E A; Taylor-Robinson, S D; Thomas, H C; Gedroyc, W M W

    2002-01-01

    Established ablative therapies for the treatment of primary and secondary liver tumours, including percutaneous ethanol injection, cryotherapy, and radiofrequency ablation, are discussed. Newer techniques such as magnetic resonance imaging guided laser interstitial thermal therapy of liver tumours has produced a median survival rate of 40.8 months after treatment. The merits of this newly emerging technique are discussed, together with future developments, such as focused ultrasound therapy, which holds the promise of non-invasive thermoablation treatment on an outpatient basis. PMID:11950826

  9. Imaging of the transplant liver.

    PubMed

    Babyn, Paul Sheppard

    2010-04-01

    As the number of patients with liver transplants continues to increase, radiologists need to be aware of the normal post-operative appearance of the different liver transplants currently performed along with the wide variety of complications encountered. The complications commonly affect the biliar and vascular systems and can include anastomotic bile leakage and biliary stenosis along with stenosis or obstruction of the hepatic artery, portal or hepatic veins and IVC. Other complications include parenchymal abnormalities such as hepatic infarction, organ rejection, localized collections and post transplant lymphoproliferative disorder. This article reviews and illustrates the role of imaging for pediatric transplantation including the role of interventional radiology.

  10. Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells

    PubMed Central

    Navarro-Tableros, Victor; Herrera Sanchez, Maria Beatriz; Figliolini, Federico; Romagnoli, Renato; Tetta, Ciro

    2015-01-01

    In the present study, rat liver acellular scaffolds were used as biological support to guide the differentiation of human liver stem-like cells (HLSC) to hepatocytes. Once recellularized, the scaffolds were maintained for 21 days in different culture conditions to evaluate hepatocyte differentiation. HLSC lost the embryonic markers (alpha-fetoprotein, nestin, nanog, sox2, Musashi1, Oct 3/4, and pax2), increased the expression of albumin, and acquired the expression of lactate dehydrogenase and three subtypes of cytochrome P450. The presence of urea nitrogen in the culture medium confirmed their metabolic activity. In addition, cells attached to tubular remnant matrix structures expressed cytokeratin 19, CD31, and vimentin. The rat extracellular matrix (ECM) provides not only a favorable environment for differentiation of HLSC in functional hepatocytes (hepatocyte like) but also promoted the generation of some epithelial-like and endothelial-like cells. When fibroblast growth factor–epidermal growth factor or HLSC-derived conditioned medium was added to the perfusate, an improvement of survival rate was observed. The conditioned medium from HLSC potentiated also the metabolic activity of hepatocyte-like cells repopulating the acellular liver. In conclusion, HLSC have the potential, in association with the natural ECM, to generate in vitro a functional “humanized liver-like tissue.” PMID:25794768

  11. Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

    PubMed Central

    French, Samuel W.

    2013-01-01

    Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

  12. Pinworm infection masquerading as colorectal liver metastasis.

    PubMed

    Roberts, K J; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-09-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E. vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur.

  13. Pinworm infection masquerading as colorectal liver metastasis

    PubMed Central

    Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-01-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

  14. Treatment Option Overview (Adult Primary Liver Cancer)

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  15. Treatment Options for Adult Primary Liver Cancer

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  16. Stages of Adult Primary Liver Cancer

    MedlinePlus

    ... adult primary liver cancer may include the following: Total hepatectomy and liver transplant . Partial hepatectomy . Ablation Transarterial chemoembolization and targeted therapy with sorafenib , as palliative therapy to relieve symptoms and improve quality of life . A clinical trial of a new ...

  17. General Information about Liver (Hepatocellular) Cancer

    MedlinePlus

    ... condition or to keep cancer from starting. General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer ... PDQ Screening and Prevention Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. Nonacetaminophen Drug-Induced Acute Liver Failure.

    PubMed

    Thomas, Arul M; Lewis, James H

    2018-05-01

    Acute liver failure of all causes is diagnosed in between 2000 and 2500 patients annually in the United States. Drug-induced acute liver failure is the leading cause of acute liver failure, accounting for more than 50% of cases. Nonacetaminophen drug injury represents 11% of all cases in the latest registry from the US Acute Liver Failure Study Group. Although rare, acute liver failure is clinically dramatic when it occurs, and requires a multidisciplinary approach to management. In contrast with acetaminophen-induced acute liver failure, non-acetaminophen-induced acute liver failure has a more ominous prognosis with a lower liver transplant-free survival. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Urea Biosynthesis Using Liver Slices

    ERIC Educational Resources Information Center

    Teal, A. R.

    1976-01-01

    Presented is a practical scheme to enable introductory biology students to investigate the mechanism by which urea is synthesized in the liver. The tissue-slice technique is discussed, and methods for the quantitative analysis of metabolites are presented. (Author/SL)

  20. Liver transplantation for Wilson disease.

    PubMed

    Catana, Andreea M; Medici, Valentina

    2012-01-27

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

  1. Liver transplantation for Wilson disease

    PubMed Central

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  2. Imaging biomarkers in liver fibrosis.

    PubMed

    Berzigotti, A; França, M; Martí-Aguado, D; Martí-Bonmatí, L

    There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Isolating Lysosomes from Rat Liver.

    PubMed

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays. © 2016 Cold Spring Harbor Laboratory Press.

  4. Liver Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  5. Hepatitis C and liver transplantation.

    PubMed

    Martini, Silvia

    2018-06-01

    Hepatitis C virus (HCV)-related liver disease represents the leading indication for liver transplantation (LT) in the USA and Europe and HCV recurrence is universal in recipients who are viremic at LT. Until a few years ago, pegylated-interferon in association with ribavirin was the only therapeutic strategy, usable only in compensated cirrhotic patients, in order to prevent post-LT viral recurrence. The recent advent of direct-acting antiviral agents (DAAs) has dramatically increased the chances of curative treatment for the transplant population and the debate about which should be the best time for treating the infection is still open: whether to pursue HCV eradication 1) before LT, in order to improve liver function, delist some patients and prevent graft infection; or 2) as early as possible after LT, rather than 3) waiting for hepatitis C recurrence before starting treatment. In addition, in the DAA era, the use of HCV-positive donors may represent a potential approach to safely expanding the donor pool. As more HCV patients achieve cure with DAA regimens, the LT trend for HCV in the future would be expected to mimic the trend observed for hepatitis B virus in the past decade and in the United States, during the DAA-period 2014-2015, the rate of LT wait-listing for HCV complicated by decompensated cirrhosis has already decreased by 32%. This review summarizes the published data and emphasizes DAA treatment applicability to patients with decompensated cirrhosis and to liver transplant recipients.

  6. Management in Acute Liver Failure

    PubMed Central

    Shalimar; Acharya, Subrat K.

    2015-01-01

    Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. PMID:26041950

  7. Kupffer Cells in the Liver

    PubMed Central

    Dixon, Laura J.; Barnes, Mark; Tang, Hui; Pritchard, Michele T.; Nagy, Laura E.

    2016-01-01

    Kupffer cells are a critical component of the mononuclear phagocytic system and are central to both the hepatic and systemic response to pathogens. Kupffer cells are reemerging as critical mediators of both liver injury and repair. Kupffer cells exhibit a tremendous plasticity; depending on the local metabolic and immune environment, then can express a range of polarized phenotypes, from the proinflammatory M1 phenotype to the alternative/M2 phenotype. Multiple M2 phenotypes can be distinguished, each involved in the resolution of inflammation and wound healing. Here, we have provided an update on recent research that has contributed to the developing delineation of the contribution of Kupffer cells to different types of liver injury, with an emphasis on alcoholic and nonalcoholic liver diseases. These recent advances in our understanding of Kupffer cell function and regulation will likely provide new insights into the potential for therapeutic manipulation of Kupffer cells to promote the resolution of inflammation and enhance wound healing in liver disease. PMID:23720329

  8. Predictive Models of Liver Cancer

    EPA Science Inventory

    Predictive models of chemical-induced liver cancer face the challenge of bridging causative molecular mechanisms to adverse clinical outcomes. The latent sequence of intervening events from chemical insult to toxicity are poorly understood because they span multiple levels of bio...

  9. Current approach to liver traumas.

    PubMed

    Kaptanoglu, Levent; Kurt, Necmi; Sikar, Hasan Ediz

    2017-03-01

    Liver injuries remain major obstacle for successful treatment, due to size and location of the liver. Requirement for surgery should be determined by clinical factors, most notably hemodynamical state. In this present study we tried to declare our approach to liver traumas. We also tried to emphasize the importance of conservative treatment, since surgeries for liver traumas carry high mortality rates. Patients admitted to the Department of Emergency Surgery at Kartal Research and Education Hospital, due to liver trauma were retrospectively analyzed between 2003 and 2013. Patient demographics, hepatic panel, APTT (activated partial thromboplastin time), PT (prothrombin time), INR (international normalized ratio), fibrinogen, biochemistry panel were recorded. Hemodynamic instability was the most prominent factor for surgery decision, in the lead of current Advanced Trauma Life Support (ATLS) protocols. Operation records and imaging modalities revealed liver injuries according to the Organ Injury Scale of the American Association for the Surgery of Trauma. 300 patients admitted to emergency department were included in our study (187 males and 113 females). Mean age was 47 years (range, 12-87). The overall mortality rate was 13% (40 out of 300). Major factor responsible for mortality rates and outcome was stability of cases on admission. 188 (% 63) patients were counted as stable, whereas 112 (% 37) cases were found unstable (blood pressure ≤ 90, after massive resuscitation). 192 patients were observed conservatively, whereas 108 cases received abdominal surgery. High levels of AST, ALT, LDH, INR, creatinine and low levels of fibrinogen and low platelet counts on admission were found to be associated with mortality and these cases also had Grade 4 and 5 injuries. Hemodynamic instability on admission and the type and grade of injury played major role in mortality rates). Packing was performed in 35 patients, with Grade 4 and 5 injuries. Mortality rate was %13 (40

  10. Transcriptional Ontogeny of the Developing Liver

    EPA Science Inventory

    During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hemato...

  11. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Campylobacter prevalence in retail chicken liver

    Foodborne campylobacteriosis has been linked to undercooked chicken liver. It is unknown how commonly chicken livers are contaminated with Campylobacter. The objective of this study was to determine the prevalence of Campylobacter on chicken livers available at retail. For each of five weeks, t...

  13. Liver Transplantation for Budd-Chiari Syndrome

    PubMed Central

    Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.

    2011-01-01

    Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334

  14. Chronic hepatitis C and liver fibrosis

    PubMed Central

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy. PMID:25170193

  15. Autoimmune liver disease in children.

    PubMed

    Mieli-Vergani, G; Vergani, D

    2003-03-01

    Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

  16. Oncologic results of laparoscopic liver resection for malignant liver tumors.

    PubMed

    Akyuz, Muhammet; Yazici, Pinar; Yigitbas, Hakan; Dural, Cem; Okoh, Alexis; Aliyev, Shamil; Aucejo, Federico; Quintini, Cristiano; Fung, John; Berber, Eren

    2016-02-01

    There are scant data regarding oncologic outcomes of laparoscopic liver resection (LLR). The aim of this study is to analyze the oncologic outcomes of LLR for malignant liver tumors (MLT). This was a prospective IRB-approved study of 123 patients with MLT undergoing LLR. Kaplan-Meier disease-free (DFS) and overall survival (OS) was calculated. Tumor type was colorectal in 61%, hepatocellular cancer in 21%, neuroendocrine in 5% and others in 13%. Mean tumor size was 3.2 ± 1.9 cm and number of tumors 1.6 ± 1.2. A wedge resection or segmentectomy was performed in 63.4%, bisegmentectomy in 24.4%, and hemihepatectomy in 12.2%. Procedures were totally laparoscopic in 67% and hand-assisted in 33%. Operative time was 235.2 ± 94.3 min, and conversion rate 7.3%. An R0 resection was achieved in 90% of patients and 94% of tumors. Median hospital stay was 3 days. Morbidity was 22% and mortality 0.8%. For patients with colorectal liver metastasis, DFS and OS at 2 years was 47% and 88%, respectively. This study shows that LLR is a safe and efficacious treatment for selected patients with MLT. Complete resection and margin recurrence rate are comparable to open series in the literature. © 2015 Wiley Periodicals, Inc.

  17. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports

  18. Segmentation of liver region with tumorous tissues

    NASA Astrophysics Data System (ADS)

    Zhang, Xuejun; Lee, Gobert; Tajima, Tetsuji; Kitagawa, Teruhiko; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kondo, Hiroshi; Hoshi, Hiroaki; Nawano, Shigeru; Shinozaki, Kenji

    2007-03-01

    Segmentation of an abnormal liver region based on CT or MR images is a crucial step in surgical planning. However, precisely carrying out this step remains a challenge due to either connectivities of the liver to other organs or the shape, internal texture, and homogeneity of liver that maybe extensively affected in case of liver diseases. Here, we propose a non-density based method for extracting the liver region containing tumor tissues by edge detection processing. False extracted regions are eliminated by a shape analysis method and thresholding processing. If the multi-phased images are available then the overall outcome of segmentation can be improved by subtracting two phase images, and the connectivities can be further eliminated by referring to the intensity on another phase image. Within an edge liver map, tumor candidates are identified by their different gray values relative to the liver. After elimination of the small and nonspherical over-extracted regions, the final liver region integrates the tumor region with the liver tissue. In our experiment, 40 cases of MDCT images were used and the result showed that our fully automatic method for the segmentation of liver region is effective and robust despite the presence of hepatic tumors within the liver.

  19. Quantification of liver fat: A comprehensive review.

    PubMed

    Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

    2016-04-01

    Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Surgical anatomy of segmental liver transplantation.

    PubMed

    Deshpande, R R; Heaton, N D; Rela, M

    2002-09-01

    The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

  1. [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. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  2. The history of liver transplantation in Turkey.

    PubMed

    Moray, Gökhan; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    Liver transplantation is the definitive treatment for end-stage liver diseases. The first successful liver transplant was performed in the United States by Thomas Starzl in 1967. The first successful solid organ transplant in Turkey was a living-related kidney transplant performed by Dr. Haberal in 1975. After much effort by Dr. Haberal, the Turkish parliament enacted a law about organ transplantation in 1979. After clinical and experimental studies, the first liver transplant in Turkey was performed by Dr. Haberal in 1988. The first successful partial living-donor liver transplant in children in Turkey was performed by the same team on March 15, 1990. On April 24, 1990, the first living-donor liver transplant was performed on a child in Turkey using a left lateral segment by Dr. Haberal and coworkers. On May 16, 1992, Dr. Haberal performed a simultaneous living-donor liver and kidney transplantation to an adult from the same donor. There currently are 30 liver transplantation centers in Turkey. According to data from the Ministry of Health, there presently are 2065 patients in Turkey who are waiting for a liver transplantation. From January 2002 to June 2013, there were 6091 liver transplants performed in Turkey (4020 living-donor [66% ] and 2071 deceased donor liver transplants [34% ]). From January 2011 to June 2013, there were 2514 patients who had liver transplants in Turkey, and 437 patients (17%) died. The number of liver transplants per year in Turkey reached 1000 transplants in 2012 and more than 1150 transplants in 2013 (15.1/million/y). Therefore, Turkey has one of the highest volumes of liver transplantation per population worldwide, with 90% survival within 1 year after transplantation.

  3. Split liver transplantation in adults.

    PubMed

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-09-07

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

  4. Evolving therapies for liver fibrosis

    PubMed Central

    Schuppan, Detlef; Kim, Yong Ook

    2013-01-01

    Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for liver that address specific cell types and functional units that orchestrate fibrotic wound healing responses and have a sound preclinical database or antifibrotic activity in early clinical trials. We also touch upon relevant clinical study endpoints, optimal study design, and developments in fibrosis imaging and biomarkers. PMID:23635787

  5. Lipid flopping in the liver.

    PubMed

    Linton, Kenneth J

    2015-10-01

    Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment. © 2015 Authors; published by Portland Press Limited.

  6. Gastrointestinal dysfunction in liver cirrhosis

    PubMed Central

    Kalaitzakis, Evangelos

    2014-01-01

    Patients with liver cirrhosis exhibit several features of gut dysfunction which may contribute to the development of cirrhosis complications as well as have an impact on nutritional status and health-related quality of life. Gastrointestinal symptoms are common in cirrhosis and their pathophysiology probably involves factors related to liver disease severity, psychological distress, and gut dysfunction (e.g., increased gastric sensitivity to distension and delayed gut transit). They may lead to reduced food intake and, thus, may contribute to the nutritional status deterioration in cirrhotic patients. Although tense ascites appears to have a negative impact on meal-induced accommodation of the stomach, published data on gastric accommodation in cirrhotics without significant ascites are not unanimous. Gastric emptying and small bowel transit have generally been shown to be prolonged. This may be related to disturbances in postprandial glucose, insulin, and ghrelin levels, which, in turn, appear to be associated to insulin resistance, a common finding in cirrhosis. Furthermore, small bowel manometry disturbances and delayed gut transit may be associated with the development of small bowel bacterial overgrowth. Finally, several studies have reported intestinal barrier dysfunction in patients with cirrhosis (especially those with portal hypertension), which is related to bacterial translocation and permeation of intestinal bacterial products, e.g., endotoxin and bacterial DNA, thus potentially being involved in the pathogenesis of complications of liver cirrhosis. PMID:25356031

  7. Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation

    PubMed Central

    Mazza, Giuseppe; Rombouts, Krista; Rennie Hall, Andrew; Urbani, Luca; Vinh Luong, Tu; Al-Akkad, Walid; Longato, Lisa; Brown, David; Maghsoudlou, Panagiotis; Dhillon, Amar P.; Fuller, Barry; Davidson, Brian; Moore, Kevin; Dhar, Dipok; De Coppi, Paolo; Malago, Massimo; Pinzani, Massimo

    2015-01-01

    Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development. PMID:26248878

  8. [Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

    PubMed

    Restellini, Sophie; Spahr, Laurent

    2012-06-27

    Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

  9. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  10. Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration.

    PubMed

    Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W; Davis, James G; Agarwal, Beamon; Baur, Joseph A

    2017-02-01

    The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630). © 2016 by the American Association for the Study of Liver Diseases.

  11. Alcoholic Liver Disease: Pathogenesis and Current Management

    PubMed Central

    Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

    2017-01-01

    Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

  12. Assessment of liver size by ultrasonography.

    PubMed

    Patzak, Monika; Porzner, Marc; Oeztuerk, Suemeyra; Mason, Richard Andrew; Wilhelm, Manfred; Graeter, Tilmann; Kratzer, Wolfgang; Haenle, Mark Martin; Akinli, Atilla Serif

    2014-09-01

    To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size. A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire. The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence. Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span. © 2014 Wiley Periodicals, Inc.

  13. Liver cancer mortality rate model in Thailand

    NASA Astrophysics Data System (ADS)

    Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

    2013-09-01

    Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cance