Sample records for liver fluke clonorchis

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

    Microsoft Academic Search

    Won Gi Yoo; Dae-Won Kim; Jung-Won Ju; Pyo Yun Cho; Tae Im Kim; Shin-Hyeong Cho; Sang-Haeng Choi; Hong-Seog Park; Tong-Soo Kim; Sung-Jong Hong

    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

  2. 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 physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens. PMID:21738807

  3. 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

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

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2014-10-01

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

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

    PubMed

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

    2015-06-01

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

  7. The complete mitochondrial genomes of the liver flukes Opisthorchis felineus and Clonorchis sinensis (Trematoda).

    PubMed

    Shekhovtsov, Sergei V; Katokhin, Alexei V; Kolchanov, Nikolai A; Mordvinov, Viatcheslav A

    2010-03-01

    The complete mitochondrial genomes of the parasitic trematodes Opisthorchis felineus and Clonorchis sinensis (family Opisthorchiidae) were fully sequenced in order to develop markers for DNA diagnostics of the liver flukes infection, molecular ecology, population and phylogenetic studies. The complete sequences of mitochondrial genomes of these species comprise 14,277 and 13,875bp, respectively, and are thus the shortest trematode mitochondrial genomes sequenced to date. The gene content and arrangement are identical to that of Fasciola hepatica. ATG and GTG are used as the start-codons and TAG and TAA are used as the stop-codons. The stop-codon TAG of the C. sinensis nad1 gene overlap by 1nt with the downstream tRNA-Asn gene. Alternative structures for the Ser(UCN) tRNAs were found for both species. The noncoding control regions are separated into two parts by the tRNA-Gly gene and contain neither tandem repeats, which are characteristic for trematode control regions, nor secondary structures. In conclusion, the complete mitochondrial DNA sequences of O. felineus and C. sinensis will serve as a resource for comparative mitochondrial genomics and systematic studies of parasitic trematodes. PMID:19906359

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

    PubMed

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

    2013-12-01

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

  9. Genome-wide identification of antimicrobial peptides in the liver fluke, Clonorchis sinensis

    PubMed Central

    Yoo, Won Gi; Lee, Sanghyun; Lee, Myoung-Ro; Yun, Mi-Ran; Kwon, Taesoo; Kim, Dae-Won

    2015-01-01

    The increase in prevalence of antimicrobial resistance makes the search for new antibiotic agents imperative. Antimicrobial peptides (AMPs) from natural resources have been recognized as suitable tools to combat antibiotic-resistant bacteria. The liver fluke Clonorchis sinensis living in germ-filled environments could be a good source of antimicrobials. Here, we report the use of a rational protocol that combines AMP predictions based on their physicochemical properties and their in vivo stability to discover AMP candidates from the entire genome of C. sinensis. To screen AMP candidates, in silico analyses based on the physicochemical properties of known AMPs, such as length, charge, isoelectric point, and in vitro and in vivo aggregation values were performed. To enhance their in vivo stability, proteins having proteolytic cleavage sites were excluded. As a consequence, four high-activity, highstability peptides were identified. These peptides could be potential starting materials for the development of new AMPs via structural modification and optimization. Thus, this study proposes a refined computational method to develop new AMPs and identifies four AMP candidates, which could serve as templates for further development of peptide antibiotics. PMID:25780275

  10. Molecular identification of Clonorchis sinensis and discrimination with other opisthorchid liver fluke species using multiple Ligation-depended Probe Amplification (MLPA)

    PubMed Central

    2011-01-01

    Background Infections with the opisthorchid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and O. felineus cause severe health problems globally, particularly in Southeast Asia. Early identification of the infection is essential to provide timely and appropriate chemotherapy to patients. Results In this study we evaluate a PCR-based molecular identification method, Multiplex Ligation-dependent Probe Amplification (MLPA), which allows rapid and specific detection of single nucleotide acid differences between Clonorchis sinensis, Opisthorchis viverrini and O. felineus. Three probe pairs were derived from the Internally Transcribed Spacer 1 (ITS1) of three opisthorchid liver flukes using a systematic phylogenetic analysis. Specific loci were detected in all three species, yielding three amplicons with 198,172 and 152 bp, respectively, while no cross reactions were observed. A panel of 66 C. sinensis isolates was screened using MLPA. All species were positively identified, and no inhibition was observed. The detection limit was 103 copies of the ITS gene for the three liver flukes, or about 60 pg genomic DNA for Clonorchis sinensis. Amplification products can be detected by electrophoresis on agarose gel or in a capillary sequencer. In addition, genomic DNA of Clonorchis sinensis in fecal samples of infected rats was positively amplified by MLPA. Conclusion The flexibility and specificity make MLPA a potential tool for specific identification of infections by opisthorchid liver flukes in endemic areas. PMID:21649899

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2013-10-01

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

  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?

  14. Liver flukes: the malady neglected.

    PubMed

    Lim, Jae Hoon

    2011-01-01

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected. PMID:21603286

  15. Liver Flukes: the Malady Neglected

    PubMed Central

    2011-01-01

    Liver fluke disease is a chronic parasitic inflammatory disease of the bile ducts. Infection occurs through ingestion of fluke-infested, fresh-water raw fish. The most well-known species that cause human infection are Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. Adult flukes settle in the small intrahepatic bile ducts and then they live there for 20-30 years. The long-lived flukes cause long-lasting chronic inflammation of the bile ducts and this produces epithelial hyperplasia, periductal fibrosis and bile duct dilatation. The vast majority of patients are asymptomatic, but the patients with heavy infection suffer from lassitude and nonspecific abdominal complaints. The complications are stone formation, recurrent pyogenic cholangitis and cholangiocarcinoma. Approximately 35 million people are infected with liver flukes throughout the world and the exceptionally high incidence of cholangiocarcinoma in some endemic areas is closely related with a high prevalence of liver fluke infection. Considering the impact of this food-borne malady on public health and the severe possible clinical consequences, liver fluke infection should not be forgotten or neglected. PMID:21603286

  16. Trematode infections: liver and lung flukes.

    PubMed

    Fürst, Thomas; Duthaler, Urs; Sripa, Banchop; Utzinger, Jürg; Keiser, Jennifer

    2012-06-01

    Food-borne trematodiases are an emerging public health problem in Southeast Asia and Latin America and of growing importance for travel clinics in Europe and North America. The disease is caused by chronic infections with liver, lung, and intestinal flukes. This article focuses on the most important liver and lung flukes that parasitize man, namely Clonorchis sinensis, Fasciola gigantica, Fasciola hepatica, Opisthorchis felineus, Opisthorchis viverrini, and Paragonimus spp. The article describes the epidemiology of major liver and lung fluke infections, including current distribution, burden, life cycle, clinical signs and symptoms, diagnostic approaches, and current tools for prevention, treatment, and control. PMID:22632646

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

    Microsoft Academic Search

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

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

  18. 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 ?-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

  19. Taxonomy and biology of liver flukes.

    PubMed

    Kaewkes, Sasithorn

    2003-11-01

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

  20. [Research progress on the relationship between three kinds of liver fluke infections and cholangiocarcinoma].

    PubMed

    Liu, Guo-xing; Wu, Xiu-ping; Wang, Zi-jian; Bai, Xue; Liu, Ming-yuan

    2010-08-01

    Liver fluke disease caused by Clonorchis sinensis, Opisthorchis viverrini and O. felineus is a food-borne zoonotic parasitic disease and widely prevalent in Asia. The definitive hosts including human beings get the infection by ingestion of raw or undercooked fish or shrimp infested with metacercariae. Long-term or severe infection of the flukes can lead to dysfunction of the liver, such as cholelithiasis, cholecystitis, and so on. Researches indicated that there is an etiology relation between the fluke infection and cholangiocarcinoma. This paper reviews the relationship and possible mechanisms of the liver fluke-associated cholangiocarcinoma PMID:21137319

  1. Roles of liver fluke infection as risk factor for cholangiocarcinoma.

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    PubMed Central

    Laha, Thewarach; Pinlaor, Porntip; Mulvenna, Jason; Sripa, Banchob; Sripa, Manop; Smout, Michael J; Gasser, Robin B; Brindley, Paul J; Loukas, Alex

    2007-01-01

    Background Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes. PMID:17587442

  4. 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. PMID:23411375

  5. Is Opisthorchis viverrini an avian liver fluke?

    PubMed

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

    2015-03-01

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

  6. Opisthorchis viverrini: The carcinogenic human liver fluke

    PubMed Central

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

    2008-01-01

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

  7. Liver Flukes: the Common Fluke (Distomum hepaticum). A New Species (Distomum texanicum). 

    E-print Network

    Francis, M. (Mark)

    1891-01-01

    TEXAS AGRICULTURAL EXPERIMENT STATION. BULLETIN NO. 18. OCTOBER. 1891. LIVER FLUKES: THE cOMMO~' FLUKE (DISTOMUM HEPATICUJf> A NEW SPECIES (DISTOMUM TEXANICUM). AGRICULTURAL ARD MECHAR'ICAL COJALEGE OF TEXAS. All : lqq h Bulletins... they pro- i lace, is arranged in two parts. Part I gives an account of the com- inon fluke (Distomum, hepaticz~m), and part I1 gives a partial ac- count of a species, new to Science, that is found, sometimes alone, I)nt usually associated...

  8. Human Infections with Liver and Minute Intestinal Flukes in Guangxi, China: Analysis by DNA Sequencing, Ultrasonography, and Immunoaffinity Chromatography

    PubMed Central

    Jeon, Hyeong-Kyu; Lee, Dongmin; Park, Hansol; Min, Duk-Young; Rim, Han-Jong; Zhang, Hongman; Yang, Yichao; Li, Xueming

    2012-01-01

    The prevalence of liver and intestinal fluke infections was determined by surveying inhabitants of Hengxuan, Fusui, and Shanglin villages which were known to be endemic for liver flukes in Guangxi, China in May 2010. A total of 718 people were examined for helminth eggs by the Kato-Katz thick smear technique, ultrasonography, immunoaffinity chromatography, and DNA sequencing. The overall egg positive rate was found to be 59.6% (28.0-70.6%) that included mixed infections with liver and intestinal flukes. Cases showing higher than 20,000 eggs per gram of feces (EPG) were detected between 1.3% and 16.2%. Ultrasonographic findings exhibited overall 28.2% (72 of 255 cases) dilatation rate of the intrahepatic bile duct. Clonorchis sinensis infection was detected serologically in 88.3% (38 of 43 cases) among C. sinensis egg positive subjects by the immunoaffinity chromatography using a specific antigen for C. sinensis. For differential diagnosis of the liver and intestinal flukes, more precise PCR and nucleotide sequencing for copro-DNA were performed for 46 egg positive cases. Mixed infections with C. sinensis and Metagonimus yokogawai were detected in 8 of 46 egg positive cases, whereas 29 specimens were positive for Haplorchis taichui. Ultrasonographic findings and immunoaffinity chromatography results showed usefulness, even in a limited way, in figuring out of the liver fluke endemicity. PMID:23230343

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  11. Infection with the carcinogenic human liver fluke, Opisthorchis viverrini

    PubMed Central

    Smout, Michael J.; Sripa, Banchob; Laha, Thewarach; Mulvenna, Jason; Gasser, Robin B.; Young, Neil D.; Bethony, Jeffrey M.; Brindley, Paul J.; Loukas, Alex

    2013-01-01

    Summary Throughout Southeast Asia there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium), particularly in people from rural settings in Laos and Northeast Thailand who are infected with the liver fluke, Opisthorchis viverrini, one of only three carcinogenic eukaryotic pathogens. More ubiquitous carcinogenic microbes, such as Helicobacter pylori, induce cancer in less than 1% of infected people, while as many as one-sixth of people with opisthorchiasis will develop CCA. The mechanisms by which O. viverrini causes cancer are multi-factorial, involving mechanical irritation from the activities and movements of the flukes, immunopathology, dietary nitrosamines and the secretion of parasite proteins that promote a tumourigenic environment. Genomic and proteomic studies of the liver fluke secretome have accelerated the discovery of parasite proteins with known/potential roles in pathogenesis and tumourigenesis, establishing a framework towards understanding, and ultimately preventing, the morbidity and mortality attributed to this highly carcinogenic parasite. PMID:21311794

  12. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    Microsoft Academic Search

    Thewarach Laha; Porntip Pinlaor; Jason Mulvenna; Banchob Sripa; Manop Sripa; Michael J Smout; Robin B Gasser; Paul J Brindley; Alex Loukas

    2007-01-01

    BACKGROUND: Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. RESULTS: Approximately 5,000 randomly selected cDNAs from the adult stage of O.

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

    PubMed Central

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

    2009-01-01

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

  14. [Liver fluke infection and sarcoptic mange in red foxes in Berlin].

    PubMed

    Schuster, R; Wanjek, C; Bartnik, C; Wittstatt, U; Baumann, M; Schein, E

    2001-01-01

    396 red foxes originating from the city of Berlin were examined for opisthorchiid liver flukes and clinical sarcoptic mange between January 1997 and March 1998. Out of 232 (= 58.6%) foxes positive for opisthorchiid flukes 221 animals harboured Metorchis bilis and 70 were infected with Opisthorchis felineus. Pseudamphistomum truncatum was found only in 8 foxes. M. bilis occurred as mono-infection in 154 animals. M. bilis in combination with O. felineus was found in 61 cases. Pure Opisthorchis infection as well as other fluke combinations were found in a small number of animals only. 85 (= 21.5%) foxes showed clinical sarcoptic mange. Liver fluke positive foxes showed a higher mange prevalence than uninfected animals. However, significant associations between flukes and manage were only found when comparing uninfected foxes with those having the highest worm burden. The association of liver flukes and mange could be established for adult female foxes by a significant Odds Ratio of 4.3. PMID:11413713

  15. Cross-antigenicity Between Ruminal and Hepatic Paramphistomes and Liver Flukes of Buffalo Origin

    Microsoft Academic Search

    B. P. Maji; P. Dwivedi; J. R. Rao; S. C. Yadav

    1999-01-01

    Maji, B.P., Dwivedi, P., Rao, J.R. and Yadav, S.C. 1999. Cross-antigenicity between ruminal and hepatic paramphistomes and liver flukes of buffalo origin. J. Appl. Anim. Res., 16: 53–57.The crossantigencity among paramphistomes, Paramphistomum epiclitum, Gastrothylax crumenifer, Gigantocotyle explanatum and the common liver fluke Fasciola gigantica of buffalo was studied by Ouchterlony double immunodiffusion (DID) test. When soluble whole worm antigens of

  16. The Sigma Class Glutathione Transferase from the Liver Fluke Fasciola hepatica

    Microsoft Academic Search

    E. James LaCourse; Samirah Perally; Russell M. Morphew; Joseph V. Moxon; Mark Prescott; David J. Dowling; Sandra M. ONeill; Anja Kipar; Udo Hetzel; Elizabeth Hoey; Rafael Zafra; Leandro Buffoni; José Pérez Arévalo; Peter M. Brophy

    2012-01-01

    BackgroundLiver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone

  17. Potential targeted therapy for liver fluke associated cholangiocarcinoma.

    PubMed

    Vaeteewoottacharn, Kulthida; Seubwai, Wunchana; Bhudhisawasdi, Vajarabhongsa; Okada, Seiji; Wongkham, Sopit

    2014-06-01

    Biliary tree cancer or cholangiocarcinoma (CCA) is an unusual subtype of liver cancer with exceptionally poor prognosis. Lack of specific symptoms and availability of early diagnostic markers account for late diagnosis of CCA. Surgical treatment is a gold standard choice but few patients are candidates and local recurrence after surgery is high. Benefit of systemic chemotherapy is limited; hence, better treatment options are required. The differences in etiology, anatomical positions and pathology make it difficult to generalize all CCA subtypes for a single treatment regimen. Herein, we review the uniqueness of molecular profiling identified by multiple approaches, for example, serial analysis of gene expression, exome sequencing, transcriptomics/proteomics profiles, protein kinase profile, etc., that provide the opportunity for treatment of liver fluke-associated CCA. Anti-inflammatory, immunomodulator/immunosuppressor, epidermal growth factor receptor or platelet-derived growth factor receptor inhibitors, multi-targeted tyrosine kinase inhibitor, IL6 antagonist, nuclear factor-?B inhibitor, histone modulator, proteasome inhibitor as well as specific inhibitors suggested from various study approaches, such as MetAP2 inhibitor, 1,25(OH)2 D3 and cyclosporine A are suggested in this review for the treatments of this specific CCA subtype. This might provide an alternative treatment option for CCA patients; however, clinical trials in this specific CCA group are required. PMID:24408866

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

    PubMed Central

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

    2014-01-01

    Infections by the fish-borne liver flukes Opisthorchis viverrini and Clonorchis sinensis can lead to bile duct cancer. These neglected tropical disease pathogens occur in East Asia, with O. viverrini primarily in Thailand and Laos and C. sinensis in Cambodia, Vietnam, and China. Genomic information about these pathogens holds the potential to improve disease treatment and control. Transcriptome analysis indicates that mobile genetic elements are active in O. viverrini, including a novel non-Long Terminal Repeat (LTR) retrotransposon. A consensus sequence of this element, termed OV-RTE-1, was assembled from expressed sequence tags and PCR amplified genomic DNA. OV-RTE-1 was 3,330 bp in length, encoded 1,101 amino acid residues and exhibited hallmark structures and sequences of non-LTR retrotransposons including a single open reading frame encoding apurinic-apyrimidinic endonuclease (EN) and reverse transcriptase (RT). Phylogenetic analyses confirmed that OV-RTE-1 was member of the RTE clade of non-LTR retrotransposons. OV-RTE-1 is the first non-LTR retrotransposon characterized from the trematode family Opisthorchiidae. Sequences of OV-RTE-1 were targeted to develop a diagnostic tool for detection of infection by O. viverrini. PCR specific primers for detection of O. viverrini DNA showed 100% specificity and sensitivity for detection of as little as five femtograms of O. viverrini DNA whereas the PCR based approach showed 62% sensitivity and 100% specificity with clinical stool samples. The OV-RTE-1 specific PCR could be developed as a molecular diagnostic for Opisthorchis infection targeting parasite eggs in stool samples, especially in regions of mixed infection of O. viverrini and/or C. sinensis and minute intestinal flukes. PMID:24394447

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

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

    Microsoft Academic Search

    Takahiro Fujino; Yoichi Ishii; Dong Wik Choi

    1979-01-01

    The tegumental ultrastructure of the cercaria of the liver fluke,Clonorchis sinensis (Cobbold, 1875), was studied by scanning and transmission electron microscopy. The body surface is almost encircled by many rows of regularly arranged spines. The tegumental syncytium of the body contains many rod-shaped dense granules and central electron-lucent bodies, neither of which are present in the tail tegument. There are

  2. Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype

    E-print Network

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

    2015-05-17

    , and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype Sujittra Chaiyadet1,2,*, Javier... ://jid.oxfordjournals.org/ D ow nloaded from A c c e p t e d M a n u s c r ip t 3 Introduction The liver fluke, Opisthorchis viverrini, is classified as a group 1 carcinogen by the International Agency for Research on Cancer, and is a major public health problem in many...

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

    Microsoft Academic Search

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

    2010-01-01

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

  4. Cathepsin L proteinases as vaccines against infection with Fasciola hepatica (liver fluke) in ruminants

    Microsoft Academic Search

    G. MULCAHY; J. P. DALTON

    2001-01-01

    Fasciolosis, caused by trematodes of the genus Fasciola, is one of the most important diseases of farmed ruminants in temperate and tropical zones. The appearance of Fasciola hepatica populations that are resistant to common flukicidal drugs means that new methods of treatment will soon be required. The future prospect for the development of anti-liver fluke vaccines is optimistic and given

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

    PubMed Central

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

    2015-01-01

    Objective To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes. Methods Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0. Result A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical heterogeneity was significant, no significant difference was observed in the sensitivity analysis, and no publication bias was found. Conclusion The meta-analysis found that liver fluke infection was significantly associated with cholangitis, cholecystitis, cholelithiasis, hepatocellular carcinoma and cholangiocarcinoma and that more severe infection was associated with higher incidence. However, the association between liver fluke infection and cirrhosis was not significant. PMID:26186510

  6. Liver flukes in dogs and treatment with praziquantel.

    PubMed

    Schuster, R K; Heidrich, J; Pauly, A; Nöckler, K

    2007-12-25

    Opisthorchiid eggs were found in 6 out of 27 (22%) huskies while an ELISA detected antibodies against Opisthorchis felineus and Metorchis bilis in 24 (89%) and 25 (93%) sera taken from these dogs, respectively. All dogs showed an increased activity of glutamate dehydrogenase while aspartate aminotransferase was normal in all samples. Ten weeks after treatment with praziquantel no fluke eggs were found in the faeces from any animal and antibody titres dropped in all animals. PMID:17981396

  7. The effect of liver flukes on nutrient utilization in beef cattle 

    E-print Network

    Crain, Richard Arnold

    1978-01-01

    . duodenum with the common bile duct from the liver, partial blockage of one or both may have occurred. Reduced pancreatic secretion decreases the rate of flow and concentration of bicarbonate and the amount of digestive enzymes such as trypsin entering... December 1978 Major Subject: Animal Nutrition THE EFFECT OF LIVER FLUKES ON NUTRIFNT UTILIZATION IN BEEF CATTLE A Thesis by RICHARD ARNOLD CRAIN Approued as to style and content by: p Chairman of Committee a CC~ laced of o /t. ti Member :", ;6...

  8. Molecular identification and phylogenetic analysis of nuclear rDNA sequences among three opisthorchid liver fluke species (Opisthorchiidae: Trematoda).

    PubMed

    Kang, Seokha; Sultana, Tahera; Loktev, Valery B; Wongratanacheewin, Surasakdi; Sohn, Woon-Mok; Eom, Keeseon S; Park, Joong-Ki

    2008-06-01

    In this study, we describe the development of a fast and accurate molecular identification system for human-associated liver fluke species (Opisthorchis viverrini, Opisthorchis felineus, and Clonorchis sinensis) using the PCR-RFLP analysis of the 18S-ITS1-5.8S nuclear ribosomal DNA region. Based on sequence variation in the target rDNA region, we selected three species-specific restriction enzymes within the ITS1 regions, generating different restriction profiles among the species: MunI for O. viverrini, NheI for O. felineus, and XhoI for C. sinensis, respectively. Each restriction enzyme generated different-sized fragments specific to the species examined, but no intraspecific polymorphism or cross-reaction between the species was detected in their restriction pattern. These results indicate that PCR-linked restriction analysis of the ITS1 region allows for the rapid and reliable molecular identification among these opisthorchid taxa. In addition, phylogenetic analysis of rDNA sequences using different methods (MP, ML, NJ, and Bayesian inference) displayed O. viverrini and O. felineus as a sister group, but this relationship was not strongly supported. The failure of recovering a robust phylogeny may be due to the relatively small number of synapomorphic characters shared among the species, yielding weak phylogenetic signal. Alternatively, rapid speciation within a very short period time could be another explanation for the relatively poorly resolved relationships among these species. Our data are insufficient for discriminating between sudden cladogenesis and other potential causes of poor resolution. Further information from independent loci might help resolve this phylogeny. PMID:18276183

  9. Comparative fluke burden and pathology in condemned and non-condemned cattle livers from selected abattoirs in Zambia.

    PubMed

    Phiri, A M; Phiri, I K; Sikasunge, C S; Chembensofu, M; Monrad, J

    2006-12-01

    After dissecting 70 condemned and 32 non-condemned cattle livers collected from Lusaka, Chisamba, Mongu and Senanga abattoirs and Turnpike slaughter slab, significantly higher numbers of liver flukes (Fasciola gigantica) (P < 0.001) were found in the condemned livers (mean +/- SD = 100.6 +/- 16.7) than in the non-condemned livers (mean +/- SD = 0.7 +/- 0.5). Liver flukes found in 9.4% of the non-condemned livers suggest that abattoir records of liver inspection may underestimate F. gigantica infections. Average faecal fluke egg counts from animals with condemned livers (5 eggs per gram [EPG]) were significantly higher (P < 0.001) than in animals with non-condemned livers (0.8 EPG). No correlation was found between egg counts and number of flukes. Fibrosis and calcification were common in condemned livers, being severest in the vicinity of the bile ducts. Only two (6.3%) of the non-condemned livers showed pathological changes on the liver edges. The severe liver damage and high worm burden may explain low production levels experienced in cattle in Zambia maintained under traditional systems of management where worm control and good management programmes are rarely practiced. PMID:17283728

  10. Molecular Characterization of a Tetraspanin from the Human Liver Fluke, Opisthorchis viverrini

    PubMed Central

    Piratae, Supawadee; Tesana, Smarn; Jones, Malcolm K.; Brindley, Paul J.; Loukas, Alex; Lovas, Erica; Eursitthichai, Veerachai; Sripa, Banchob; Thanasuwan, Sirikanda; Laha, Thewarach

    2012-01-01

    Background The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, and are major targets for a schistosomiasis vaccine. We propose that similar molecules in the surface membranes of O. viverrini are integral to tegument biogenesis and will be efficacious vaccine antigens. Methodology/Principal Findings The cDNA sequence encoding O. viverrini tetraspanin-1 (Ov-TSP-1) was identified and cloned. The Ov-tsp-1gene was isolated from a cDNA library. Ov-tsp-1 mRNA was expressed most highly in metacercariae and eggs, and to a lesser extent in juvenile and adult worms. Immunolocalization with adult flukes confirmed that Ov-TSP-1 was expressed in the tegument and eggs in utero. Western blot analysis of rOv-TSP-1 probed with sera from O. viverrini-infected humans and hamsters indicated that both hosts raise antibody responses against the native TSP. Using RNA interference we silenced the expression level of Ov-tsp-1 mRNA in adult flukes by up to 72% by 10 days after delivery of dsRNA. Ultrastructural morphology of adult worms treated with Ov-tsp-1 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Conclusions/Significance This is the first report of a tetraspanin from the tegument of a liver fluke. Our data imply that tetraspanins play important structural roles in the development of the tegument in the adult fluke. Potential uses of O. viverrini tetraspanins as novel interventions are discussed. PMID:23236532

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    Microsoft Academic Search

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

    Eggs of most species digenean flukes hatch in the external environment to liberate larvae that seek and penetrate a snail\\u000a intermediate host. Those of the human liver flukes, Opisthorchis viverrini, hatch within the gastrointestinal canal of their snail hosts. While adult parasites are primarily responsible for the pathology\\u000a in cases of human opisthorchiasis, their eggs also contribute by inducing granulomata

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Gundamaraju, Rohit; Vemuri, Ravi Chandra

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

  17. The effect of liver flukes on nutrient utilization in beef cattle

    E-print Network

    Crain, Richard Arnold

    1978-01-01

    and increased red blood cell destruction. The adult flukes, because of their large size, may also block the bile duct. The bile flow obstruc- tion that results may lead to jaundice and may predispose the formation of gall stones (Lapage, 1962), Research from.... In the United States, there has been little research concerning the ii er ii ke, Fas ioi ~hatt; y t it i kn n th t ~F. h ti and Fascioloides maxima are responsible for condemnation of 1. 5 to 1. 7 million bovine livers annually (USDA, 1977). The intermediate...

  18. Clonorchis sinensis and clonorchiasis, an update.

    PubMed

    Hong, Sung-Tae; Fang, Yueyi

    2012-03-01

    Clonorchis sinensis is the most common human liver fluke in East Asia. Several studies proved its carcinogenesis in humans and it was reclassified as a group 1 biological carcinogen in 2009. It is still actively transmitted in endemic areas of Korea, China, Russia, and Vietnam. Currently it is estimated that more than 200 million people are at risk of infection, 15-20 million people are infected and 1.5-2 million show symptoms or complications. Several molecules and genes of the fluke have been identified and characterized. Studies on its oncogenesis and omics-based findings have been especially encouraging. Diagnosis of its infection depends mainly on detection of eggs in feces but other methods have been developed. ELISA using crude extract antigen is now popular for its diagnosis. Diagnosis by detecting DNAs from eggs in feces has been developed using PCR, real-time PCR, and LAMP, which have been found sensitive and specific. Imaging diagnosis has been studied in depth and is widely used. Any evidence of clonorchiasis, such as eggs, DNAs, or images, may lead to recommendations of chemotherapy in endemic areas. Praziquantel is the major chemotherapeutic agent for clonorchiasis and recently tribendimidine was found effective and is now under investigation as a promising chemotherapeutic alternative. Sustainable control programs which include mass chemotherapy with praziquantel and education for prevention of re-infection may reduce its morbidity and eliminate its infections in endemic areas. PMID:21741496

  19. Risk biomarkers for assessment and chemoprevention of liver fluke-associated cholangiocarcinoma.

    PubMed

    Yongvanit, Puangrat; Pinlaor, Somchai; Loilome, Watcharin

    2014-05-01

    Human liver fluke, Opisthorchis viverrini (Ov), is the major risk factor of cholangiocarcinoma (CCA) in northeastern Thailand. Our approach focuses on genetic progression and molecular changes in the carcinogenic pathway of liver fluke-associated CCA aimed at assessing patients at risk of CCA and using chemoprevention as the secondary cancer prevention to reduce the incidence of CCA. This review summarizes altered gene expressions, biomolecules and their modification, i.e. DNA adducts, oxidized proteins, oxysterols and fibrotic markers in hamster- and human-CCA. Potential risk biomarker(s) and chemopreventive agent(s) criteria and selection were based on results from experimental and epidemiological studies identifying hepatobiliary disease, including CCA. Laboratory results reveal that oxidative stress induced by Ov infection leads to bimolecular damage, tissue remodeling especially periductal fibrosis and alteration of gene expressions, which could be involved in all steps of CCA carcinogenesis. Some of these molecules are reported to change their levels in opisthorchiasis, periductal fibrosis diagnosed by ultrasonography and CCA. Chemoprevention in experimental CCA tumorigenesis is discussed. These multiple risk biomarkers could now be explored for screening including chemopreventive intervention of subjects living in endemic areas where the prevalence of opisthorchiasis remains high. PMID:24408859

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2011-09-27

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

  2. Dynamics of host–parasite interactions: the example of population biology of the liver fluke ( Fasciola hepatica )

    Microsoft Academic Search

    Sylvie Hurtrez-Boussčs; Cécile Meunier; Patrick Durand; François Renaud

    2001-01-01

    Knowledge of the population dynamics of parasites and their hosts is essential to build veterinary and health programs. The example chosen is that of Fasciola hepatica, a food-borne trematode responsible for severe human and animal infections on the five continents. In this paper, we review the relationships between the liver fluke and its intermediate (mollusc) and definitive (vertebrate) hosts.

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

    Microsoft Academic Search

    P. J. Skuce; I. Fairweather

    1990-01-01

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

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

    PubMed

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

    2015-01-01

    There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms were collected and the presence of species of Helicobacter determined by PCR-based approaches. In addition, O. viverrini worms were cultured in vitro with and without ABx for four weeks, after which the presence of Helicobacter spp. was determined. In situ localization of H. pylori and Helicobacter-like species was performed using a combination of histochemistry and immunohistochemistry. The prevalence of H. pylori infection in O. viverrini-infected hamsters was significantly higher than that of O. viverrini-uninfected hamsters (p?0.001). Interestingly, O. viverrini-infected hamsters treated with ABx and PZQ (to remove the flukes) had a significantly lower frequency of H. pylori than either O. viverrini- infected hamsters treated only with ABx or O. viverrini-infected hamsters, respectively (p?0.001). Quantitative RT-PCR strongly confirmed the correlation between intensity H. pylori infection and the presence of liver fluke infection. In vitro, H. pylori could be detected in the O. viverrini worms cultured with ABx over four weeks. In situ localization revealed H. pylori and other Helicobacter-like bacteria in worm gut. The findings indicate that the liver fluke O. viverrini in the biliary tree of the hamsters harbors H. pylori and Helicobacter-like bacteria. Accordingly, the association between O. viverrini and H. pylori may be an obligatory mutualism. PMID:25773821

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

    Microsoft Academic Search

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

    2003-01-01

    The functions of the cathepsin B-like proteases in liver flukes are unknown and analysis has been hindered by a lack of protein for study, since the protein is produced in small amounts by juvenile flukes. To circumvent this, we isolated and characterized a cDNA encoding the major secreted cathepsin B from Fasciola hepatica. The predicted preproprotein is 339 amino acids

  6. 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 and CCA, as well as providing a scaffold for sequencing the genome of this fluke. PMID:20049860

  7. Obstruction of common bile duct caused by liver fluke--Fasciola hepatica.

    PubMed

    Kiladze, M; Chipashvili, L; Abuladze, D; Jatchvliani, D

    2000-01-01

    Three cases of obstruction of the common bile duct by Fasciola hepatica with two of the patients presenting jaundice are reported. The authors have reviewed several publications concerning common bile duct obstruction by liver fluke, a quite rare complication of fascioliasis. Only nineteen cases of common bile duct obstruction caused by Fasciola hepatica have been reported in a review of medical publications during last ten years. Clinical presentation, diagnostic methods and considerations, types of surgery are fairly uniform in all of the reported cases. Almost all of patients reviewed, had the history, symptoms and signs characteristic for cholelithiasis including recurrent colic pain in right hypochondriac area, fever or subfebrile temperature, fluctuating or stabile jaundice, and palpable painful gallbladder. The laboratory findings in all cases reviewed had shown leucocytosis, eosinophilia, high or slight elevated serum bilirubin. Echographically commonly revealed dilated intra- and extrahepatic bile ducts containing one or more hyperechogenic elements with or without casting an acoustic shadow. All patients underwent open surgery, comprised with choledochotomy and if possible extraction of the fluke. Only two postoperative cases were of necessity followed by ERCP. In all of our cases the primary pre-operative diagnosis was choledocholithiasis, with diagnose of fascioliasis established at the operation. According to the literature this uncertainty in diagnosis is common because of difficulties in differentiation of fascioliasis versus choledocholithiasis. Considerations for making the differential diagnosis--a history of origin or visiting in endemic area of infection, history of eating of aquatic vegetables, laboratory findings including eosinophilia, fasciola eggs in stool, sonography and radiological imaging results and enzyme-linked immunosorbent essay (ELISA) which has been shown to be rapid, sensitive and quantitative. In all three cases we have observed intraoperative significant signs for liver fascioliasis to include surface scarring of the left lobe on the liver--tracks caused by subcapsular migration and location of the hepatic lesions (these findings were also seen by two authors in literature) with resemblance to Japanese letters. The most effective drug for treatment of fascioliasis according to our experience and literature reviewed is bithionol. PMID:11220154

  8. Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia.

    PubMed

    Mordvinov, Viatcheslav A; Yurlova, Natalia I; Ogorodova, Ludmila M; Katokhin, Aleksey V

    2012-03-01

    Liver fluke infections are gradually transforming from a local problem of individual geographic regions to a widespread problem. The observed expansion is likely to be connected with the ever-increasing intensity of traffic flow and migration of the infected carriers between cities, regions, and countries. Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a well known causative agent of the infection called opisthorchiasis. Metorchis bilis, also a member of the family Opisthorchiidae, causes metorchiasis, a disease very close to opisthorchiasis in symptomatology. Genetic markers can be used to develop methods for differential diagnostics of these diseases. However, the questions connected with epidemiology of these trematode infections, their clinical characteristics, prognosis and therapy remain open. This review briefs the general biological characteristics of O. felineus and M. bilis persisting in various countries of Eurasia, their geographical range, epidemiology and molecular diagnostics of these liver flukes. PMID:21840415

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

    Microsoft Academic Search

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

    2009-01-01

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

  10. Discovery of Opisthorchis lobatus (Trematoda: Opisthorchiidae): a new record of small liver flukes in the Greater Mekong Sub-region.

    PubMed

    Thaenkham, Urusa; Nuamtanong, Supaporn; Vonghachack, Youthanavanh; Yoonuan, Tippayarat; Sanguankiat, Surapol; Dekumyoy, Paron; Prommasack, Bounlay; Kobayashi, Jun; Waikagul, Jitra

    2011-12-01

    Metacercariae, morphologically similar to those of small liver flukes, were found to parasitize red-tailed snakehead fish, Channa limbata, collected from the city of Vientiane, Lao People's Democratic Republic. Adult worms that were recovered from experimentally-infected hamsters showed characteristics distinctly different from Opisthorchis viverrini, but closely similar to Opisthorchis lobatus, which was first reported in poultry (Anas sp.) from Pakistan. The present study aimed to redescribe O. lobatus based on the adult worms recovered from experimentally-infected hamsters. Additionally, it aimed to document the genetic relationships among O. lobatus and other opisthorchiid liver flukes using the mitochondrial cytochrome c oxidase subunit 1 (COI) gene and the internal transcribed spacer 2 (ITS2) region. DNA alignment of the O. lobatus and O. viverrini COI partial sequences (330 bp) showed 3.03% fixed differences (2.72% of amino acids changed) while the ITS2 region (350 bp) indicated a 0.86% difference for nucleotides. Species boundaries between the 2 parasites were determined by neighbor-joining analysis using the molecular sequence data. The phenogram confirmed that O. lobatus was distinctly different from O. viverrini, representing the first reported instance of O. lobatus in the Greater Mekong Sub-region (GMS) and the first record of C. limbata as the second intermediate host of a small liver fluke. Questions regarding human infection and the extent of the geographic distribution of these species should be investigated further. PMID:21682557

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

    PubMed Central

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

    2013-01-01

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

  12. Ultrastructure of spermatozoa in the seminal receptacle of the liver fluke Opisthorchis felineus (Rivolta, 1884).

    PubMed

    Zhukova, Mariya V; Mordvinov, Viatcheslav A; Kiseleva, Elena

    2014-03-01

    The spermatozoon ultrastructure in the seminal receptacle of the liver fluke Opisthorchis felineus (Digenea, Opisthorchiidae), the agent of human opisthorchiasis endemic to Russia and Eastern Europe, was examined. The bean-shaped seminal receptacle of O. felineus has a wall consisting of epithelial and muscle layers. Mature spermatozoa are located in the interior of the seminal receptacle, whereas vacuoles containing degenerating spermatozoa are detectable at the periphery. The mature spermatozoon of O. felineus has two axonemes of a 9 + "1" pattern, a nucleus, two mitochondria, a lamellar body, two bundles of parallel cortical microtubules and an external ornamentation of the plasma membrane in the anterior area of the sperm. The lamellar body is likely to be the third mitochondrion of a small size. The cytoplasm of the spermatozoon is filled with numerous electron-dense granules of storage polysaccharides. Additionally, the ultrastructural characteristics of the seminal receptacle and spermatozoa of O. felineus were compared to available published data on other trematode species. The functional roles of the observed structures of this spermatozoon are discussed. PMID:24452915

  13. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma.

    PubMed

    Saltykova, Irina V; Ogorodova, Ludmila M; Bragina, Elena Yu; Puzyrev, Valery P; Freidin, Maxim B

    2014-11-01

    According to epidemiological observations, Opisthorchis felineus liver fluke invasion is negatively associated with the development and severity of allergic diseases in endemic regions of Russia. We hypothesized that the invasion is an important factor in gene-environmental interactions (GEI) underlying allergy. To prove this, we tested 10 single nucleotide polymorphisms of immune response modifying genes in 428 individuals stratified by atopic bronchial asthma presence and O. felineus invasion. Using regression models, a statistically significant interaction between the rs6737848 polymorphism of SOCS5 gene and O. felineus invasion was observed (pint=0.001, OR=5.66, 95% CI 1.96-16.31 for dominant model; pint=0.003; OR=4.38, 95% CI 1.68-11.45 for additive model). The interaction is based on the statistically significant association between the SOCS5 gene and atopic bronchial asthma in patients without O. felineus infection, while no such association is seen in patients infected by the helminth. These data confirm for the first time the importance of the helminth invasion as an environmental factor influencing the association between genetic factors and atopic bronchial asthma. In particular, O. felineus diminishes the risk of atopic bronchial asthma associated with the SOCS5 gene polymorphism. PMID:25017311

  14. Liver enzyme activity and histological changes in the liver of silver foxes (Vulpes vulpes fulva) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis.

    PubMed

    Schuster, R; Dell, K; Nöckler, K; Vöster, J; Schwartz-Porsche, D; Haider, W

    2003-03-01

    Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose, species of flukes and individual peculiarities. The highest individual deviation of infected from control animals was registered in the case of GLDH, reaching increases of up to 200-fold. In contrast, AST showed the lowest deviation from control values (less than 10-fold). By the end of the study period, enzyme activities had declined. The prepatent periods for M. bilis and O. felineus in foxes were 2 weeks and 4 weeks, respectively. High egg per gram values were established at the beginning of the patent period. At necropsy, chronic inflammatory reactions were found in the bile ducts and in the wall of the gall bladder. The number of flukes at the end of the study was low. PMID:12632157

  15. Time-course and accumulation of triclabendazole and its metabolites in bile, liver tissues and flukes collected from treated sheep.

    PubMed

    Moreno, Laura; Ceballos, Laura; Fairweather, Ian; Lanusse, Carlos; Alvarez, Luis

    2014-01-01

    The flukicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of its sulphoxide (TCBZ.SO) and sulphone (TCBZ.SO2) metabolites, usually recovered from the bile of treated animals. The aim of the current work was to evaluate the time-course and pattern of in vivo accumulation of TCBZ/metabolites into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of the TCBZ-susceptible Cullomptom isolate of F. hepatica. Sixteen weeks after infection, animals were intraruminally treated with TCBZ (10mg/kg). At 3, 24, 48 and 60h post-treatment (pt), animals were sacrificed (n=3/time period) and samples of blood, bile, liver tissue and adult F. hepatica specimens were collected. The concentrations of TCBZ/metabolites were measured by HPLC. TCBZ.SO and TCBZ.SO2 were the only molecules recovered in the bloodstream, with peak plasma concentrations of 10.8?g/mL (TCBZ.SO) and 12.6?g/mL (TCBZ.SO2). The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35?g/g (TCBZ.SO) and 13.9?g/g (TCBZ.SO2) at 24h pt, which was coincident with the time when the maximum plasma concentration was attained. Low levels of TCBZ parent drug (0.14?g/g at 24h pt) were measured within collected flukes. TCBZ parent drug and its sulpho- and hydroxy-derivatives were recovered in bile collected from treated sheep between 3 and 60h pt. Although relatively high concentrations of hydroxy-TCBZ (ranging from 0.86 to 10.1?g/mL) were measured in bile, this metabolite was not recovered within the flukes at any time pt. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60h pt period. The time-course and drug concentration patterns within the adult liver fluke after TCBZ treatment followed a similar trend to those observed in plasma. Overall, the data reported here confirm that oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites. However, the presence of TCBZ within the adult fluke (despite being absent in the systemic circulation) may be related to some degree of trans-tegumental diffusion from bile or by a direct oral ingestion from portal blood. PMID:24211244

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

    PubMed

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

    2012-04-01

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

  17. 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. PMID:22925823

  18. Comparative histopathology of Opisthorchis felineus and Opisthorchis viverrini in a hamster model: an implication of high pathogenicity of the European liver fluke.

    PubMed

    Lvova, Maria N; Tangkawattana, Sirikachorn; Balthaisong, Suwit; Katokhin, Alexey V; Mordvinov, Viatcheslav A; Sripa, Banchob

    2012-03-01

    European liver fluke (Opisthorchis felineus) and Asian liver fluke (Opisthorchis viverrini) are similar in morphology but comparative pathology of the infections has not been described. We therefore did comparative histopathology of both parasites in an experimental animal model. The study was conducted in 3 groups of 105 Syrian golden hamsters; the first and second groups fed with 50 metacercariae of O. felineus (OF) or O. viverrini (OV) and the last group was uninfected controls. Five hamsters in each group were euthanized on weeks 1, 2, 4, 8, 12 and 24 post-infection. The liver tissue was fixed and processed for routine histopathology and immunohistochemistry for proliferation markers (BrdU or PCNA). Overall, the liver histopathology of O. felineus and O. viverrini infection was generally similar. However, various histopathogical features including intense inflammation, fibrosis, biliary and goblet cell hyperplasia and dysplasia occurred earlier in the OF group. In addition, the existence of precancerous lesions such as cholangiofibrosis in a long-term infection was observed only in this group. O. felineus is larger in size than O. viverrini which, together with its excreted and secreted antigens, likely is crucial in the induction of liver fluke induced disease. The differences in nature and timing of the histopathological profile indicate that opisthorchiasis caused by the European liver fluke O. felineus is more pathogenic than its Asian relative O. viverrini. PMID:21854870

  19. 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 (P<0.05) in the use of triclabendazole and albendazole between positive and negative farms, with triclabendazole use being more common in positive farms. This study highlighted differences in dairy management practices between Irish farms with dairy herds exposed or not exposed to liver fluke and stressed the need of fine-scale mapping of the disease patterns even at farm level to increase the accuracy of risk models. Also, comprehensive advice and professional support services to farmers on appropriate farm management practices are very important for an effective anthelmintic control strategy. PMID:25591405

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2015-09-01

    Fascioliasis has recently been included in the WHO list of Neglected Zoonotic Diseases. Besides being a major veterinary health problem, fascioliasis has large underdeveloping effects on the human communities affected. Though scarcely considered in fascioliasis epidemiology, it is well recognized that both native and introduced wildlife species may play a significant role as reservoirs of the disease. The objectives are to study the morphological characteristics of Fasciola hepatica adults and eggs in a population of Lepus europaeus, to assess liver fluke prevalence, and to analyze the potential reservoir role of the European brown hare in northern Patagonia, Argentina, where fascioliasis is endemic. Measures of F. hepatica found in L. europaeus from northern Patagonia demonstrate that the liver fluke is able to fully develop in wild hares and to shed normal eggs through their faeces. Egg shedding to the environment is close to the lower limit obtained for pigs, a domestic animal whose epidemiological importance in endemic areas has already been highlighted. The former, combined with the high prevalence found (14.28%), suggest an even more important role in the transmission cycle than previously considered. The results obtained do not only remark the extraordinary plasticity and adaptability of this trematode species to different host species, but also highlight the role of the European brown hare, and other NIS, as reservoirs capable for parasite spillback to domestic and native cycle, representing a potentially important, but hitherto neglected, cause of disease emergence. PMID:26204194

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

    PubMed

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

    2015-07-01

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

  3. 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

  4. The first report in new zealand of Lymnaea columella say (Mollusca: gastropoda) an intermediate host of the liver fluke Fasciola hepatica L

    Microsoft Academic Search

    N. B. Pullan

    1969-01-01

    ExtractSir—In New Zealand, the common liver fluke Fasciola hepatica L. has within the last ten years, spread progressively to parts where it was previously not considered to be a problem (R. M. Salisbury, pers. comm.; B. Fraser, pers. comm.; and Moxham et al., 1969). This has prompted an interest in the Lymnaeid snail intermediate hosts.

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

    PubMed Central

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

    2015-01-01

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

  6. Performance characteristics of an enzyme-linked immunosorbent assay for the detection of liver fluke ( Fasciola hepatica) infection in sheep and cattle

    Microsoft Academic Search

    M. P Reichel

    2002-01-01

    Aim: To validate an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against liver fluke (Fasciola hepatica) in sheep and cattle sera.Methods: Gold-standard sera from sheep and cattle of known infection status, i.e. sera from non-infected animals and from animals known to be infected with F. hepatica were assayed with a commercially available ELISA and results analysed by ROC

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

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

    2015-01-01

    The Leloir pathway enzyme UDP-galactose 4’-epimerase from the common liver fluke Fasciola hepatica (FhGALE) was identified and characterised. The enzyme can be expressed in, and purified from, Escherichia coli. The recombinant enzyme is active: the Km (470 µM) is higher than the corresponding human enzyme (HsGALE), whereas the kcat (2.3 s?1) is substantially lower. FhGALE binds NAD+ and was shown to be dimeric by analytical gel filtration. Like the human and yeast GALEs, FhGALE is stabilised by the substrate UDP-galactose. Molecular modelling predicted that FhGALE adopts a similar overall fold to HsGALE and that tyrosine 155 is likely to be the catalytically critical residue in the active site. In silico screening of the NCI DTP library identified 40 potential inhibitors of FhGALE which were tested in vitro. Of these, six showed concentration-dependent inhibition of FhGALE, some with nanomolar IC50 values. Two inhibitors (5-fluoroorotate and N-[(benzyloxy)carbonyl]leucyltryptophan) demonstrated selectivity for FhGALE over HsGALE. These compounds also thermally destabilised FhGALE in a concentration-dependent manner. Interestingly the selectivity of 5-fluoroorotate was not shown by orotic acid, which differs in structure by one fluorine atom. These results demonstrate that, despite the structural and biochemical similarities of FhGALE and HsGALE, it is possible to discover compounds which preferentially inhibit FhGALE. PMID:25124392

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

    PubMed

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

    2015-04-01

    Parasites that primarily infect white-tailed deer (Odocoileus virginianus), such as liver flukes (Fascioloides magna) and meningeal worm (Parelaphostrongylus tenuis), can cause morbidity and mortality when incidentally infecting moose (Alces alces). Ecological factors are expected to influence spatial variation in infection risk by affecting the survival of free-living life stages outside the host and the abundance of intermediate gastropod hosts. Here, we investigate how ecology influenced the fine-scale distribution of these parasites in deer in Voyageurs National Park, Minnesota. Deer pellet groups (N = 295) were sampled for the presence of P. tenuis larvae and F. magna eggs. We found that deer were significantly more likely to be infected with P. tenuis in habitats with less upland deciduous forest and more upland mixed conifer forest and shrub, a pattern that mirrored microhabitat differences in gastropod abundances. Deer were also more likely to be infected with F. magna in areas with more marshland, specifically rooted-floating aquatic marshes (RFAMs). The environment played a larger role than deer density in determining spatial patterns of infection for both parasites, highlighting the importance of considering ecological factors on all stages of a parasite's life cycle in order to understand its occurrence within the definitive host. PMID:25498206

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2014-12-01

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

  12. Somatic Antigens of Tropical Liver Flukes Ameliorate Collagen-Induced Arthritis in Wistar Rats

    PubMed Central

    Khan, Yasir Akhtar; Umar, Sadiq; Abidi, Syed M. A.

    2015-01-01

    Parasitic helminths polarize immune response of their vertebrate hosts towards anti-inflammatory Th2 type and therefore it is hypothesized that they may suppress the inflammatory conditions in autoimmune disorders. The present study was undertaken to investigate in vivo immunomodulatory and therapeutic potential of somatic antigens (Ag) of liver infecting digenetic trematodes [Fasciola gigantica (Fg) and Gigantocotyle explanatum (Ge)] in collagen-induced arthritic (CIA) Wistar rats. The CIA rats were administered subcutaneously with different doses (50 ?g, 100 ?g and 150 ?g) of somatic antigens of Fg and Ge, daily for 21 days, the time period required to establish infection in natural host (Bubalus bubalis). Thereafter, the control, diseased and treated rats were compared for different parameters viz. hind paw thickness; serum interleukins, IL-4 and IL-10, tumor necrosis factor-? (TNF-?) and interferon-? (IFN-?); expression level of matrix metalloproteinases (MMPs) -2, -9, -13 and nitric oxide (NO) in knee joints and patellar morphology. The CIA rats treated with different antigens, Fg-Ag and Ge-Ag, show significant amelioration of the disease by down regulation of serum TNF-? and IFN-? (p< 0.05) and upregulation of IL-4 and IL-10 cytokines (p< 0.05); inhibition (p< 0.05) of MMPs (-2,-9,-13) and NO in knee joints and improved patellar morphology with decreased synovial hypertrophy and reduced infiltration of ploymorphonuclear cells. The activity of pro as well as active MMPs (-2 and -9) and active MMP-13 in knee joints of CIA rats was very high compared to the control and treatment groups, suggesting the extent of collagen degradation in CIA rats. Interestingly, the highest dose (150 ?g) of Ge-Ag almost wiped out MMP-13 expression. The overall findings suggest that the somatic proteins of Ge-Ag appeared to be therapeutically more effective than Fg-Ag, reflecting interspecific molecular differences which could contribute to the ability of these worms to successfully ameliorate the pathology of CIA. PMID:25992888

  13. Somatic antigens of tropical liver flukes ameliorate collagen-induced arthritis in wistar rats.

    PubMed

    Khan, Yasir Akhtar; Umar, Sadiq; Abidi, Syed M A

    2015-01-01

    Parasitic helminths polarize immune response of their vertebrate hosts towards anti-inflammatory Th2 type and therefore it is hypothesized that they may suppress the inflammatory conditions in autoimmune disorders. The present study was undertaken to investigate in vivo immunomodulatory and therapeutic potential of somatic antigens (Ag) of liver infecting digenetic trematodes [Fasciola gigantica (Fg) and Gigantocotyle explanatum (Ge)] in collagen-induced arthritic (CIA) Wistar rats. The CIA rats were administered subcutaneously with different doses (50 ?g, 100 ?g and 150 ?g) of somatic antigens of Fg and Ge, daily for 21 days, the time period required to establish infection in natural host (Bubalus bubalis). Thereafter, the control, diseased and treated rats were compared for different parameters viz. hind paw thickness; serum interleukins, IL-4 and IL-10, tumor necrosis factor-? (TNF-?) and interferon-? (IFN-?); expression level of matrix metalloproteinases (MMPs) -2, -9, -13 and nitric oxide (NO) in knee joints and patellar morphology. The CIA rats treated with different antigens, Fg-Ag and Ge-Ag, show significant amelioration of the disease by down regulation of serum TNF-? and IFN-? (p< 0.05) and upregulation of IL-4 and IL-10 cytokines (p< 0.05); inhibition (p< 0.05) of MMPs (-2,-9,-13) and NO in knee joints and improved patellar morphology with decreased synovial hypertrophy and reduced infiltration of ploymorphonuclear cells. The activity of pro as well as active MMPs (-2 and -9) and active MMP-13 in knee joints of CIA rats was very high compared to the control and treatment groups, suggesting the extent of collagen degradation in CIA rats. Interestingly, the highest dose (150 ?g) of Ge-Ag almost wiped out MMP-13 expression. The overall findings suggest that the somatic proteins of Ge-Ag appeared to be therapeutically more effective than Fg-Ag, reflecting interspecific molecular differences which could contribute to the ability of these worms to successfully ameliorate the pathology of CIA. PMID:25992888

  14. 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.

  15. Comparative Proteomics of Excretory Secretory Proteins Released by the Liver Fluke Fasciola hepatica in Sheep Host Bile and

    Microsoft Academic Search

    Russell M. Morphew; Hazel A. Wright; E. James LaCourse; Debra J. Woods; Peter M. Brophy

    Livestock infection by the parasitic fluke Fasciola hepat- ica causes major economic losses worldwide. The excre- tory-secretory (ES) products produced by F. hepatica are key players in understanding the host-parasite interaction and offer targets for chemo- and immunotherapy. For the first time, subproteomics has been used to compare ES products produced by adult F. hepatica in vivo, within ovine host

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

    PubMed

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

    2015-03-28

    Flukicides are commonly administered at housing to cattle that have grazed fluke-infected pastures or that have been purchased from endemic areas. The choice of product is determined by numerous factors, one of which is the stages of Fasciola hepatica that are killed. Flukicides can be categorised into three main groups: (A) those that kill all juvenile stages and adults; (B) those that kill juveniles from six to eight weeks of age and adults and (C) those that kill adults only. This study was conducted on a commercial beef farm in Scotland and was designed to compare the efficacy of flukicides from each of these three classes in terms of their effects on faecal egg output, coproantigen and liveweight gain. The majority of animals in the untreated control group were positive for coproantigen, fluke eggs or both throughout the study duration of 16?weeks. Egg reappearance interval following housing treatment was eight weeks for clorsulon and 13?weeks for nitroxynil, though patent infections in both groups developed in only a small minority of animals; no fluke eggs were recovered from cattle treated with triclabendazole. Coproantigen was detected four weeks before the reappearance of fluke eggs in the dung. Animals treated with flukicides had significantly fewer faecal samples positive for eggs (P<0.006) and coproantigen (P<0.05) following treatment compared with the controls. Despite differences in the efficacy profiles among the flukicide-treated groups, there were no significant differences (P>0.05) in growth rates among any of the four treatment groups. There was, however, a significant negative association (P<0.001) between fluke positivity at housing and subsequent growth performance, irrespective of treatment group. PMID:25549916

  17. Cytokine/chemokine secretion and proteomic identification of upregulated annexin A1 from peripheral blood mononuclear cells cocultured with the liver fluke Opisthorchis viverrini.

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    2012-04-01

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

  19. Cloning and expression of the major secreted cathepsin B-like protein from juvenile Fasciola hepatica and analysis of immunogenicity following liver fluke infection.

    PubMed

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

    2003-12-01

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    PubMed Central

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

    2010-01-01

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

  3. Liver enzyme activity and histological changes in the liver of silver foxes ( Vulpes vulpes fulva ) experimentally infected with opisthorchiid liver flukes. A contribution to the pathogenesis of opisthorchiidosis

    Microsoft Academic Search

    Rolf Schuster; Kerstin Dell; Karsten Nöckler; Jens Vöster; Dorothea Schwartz-Porsche; Wolfram Haider

    2003-01-01

    Blood samples from silver foxes experimentally infected with Opisthorchis felineus and Metorchis bilis, respectively, were examined for the activity of liver enzymes. The average activities of aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), alkaline phosphatase and alanine aminotransferase in uninfected control animals were 20, 1.8, 57 and 44 units\\/l, respectively. The liver enzymes in infected foxes reacted differently, depending on dose,

  4. Evaluation of the immune responses induced by four targeted DNA vaccines encoding the juvenile liver fluke antigen, cathepsin B in a mouse model

    PubMed Central

    2012-01-01

    Background Liver fluke can infect cattle and sheep, and is also emerging as a human pathogen in developing countries. Cathepsin B (Cat B2) is a major cysteine protease secreted by the juvenile flukes. To enhance the immune responses of Cat B2, the cDNA sequence was fused with four different DNA vaccine vectors. The induced cellular and antibody responses were compared in vaccinated mice. Methods The following recombinant DNA vaccine constructs were constructed: empty vector VR1012 as negative control, cytoplasmic construct pVR1012 Cat B2, secretory construct pVR1020 Cat B2, chemokine-fused construct pMCP3 Cat B2 and lymph node targeting construct pCTLA-4 Cat B2. Plasmids were constructed using standard procedures, and positive constructs screened and selected using restriction digestion analysis followed by sequence analysis. The constructs were then tested in Cos-7 cells for in vitro expression, which was analysed using immunoblotting. Subsequently, female BALB/c mice were immunised with DNA constructs as vaccines. Elicited antibody responses were measured using ELISA. The ratio between IgG1 and IgG2a antibody responses was estimated among different vaccine groups. IgG antibody avidity assay was performed and the relative avidity index was calculated. The induced cytokine production from splenocytes of vaccinated animals was estimated using ELISPOT. Results DNA vaccine constructs carrying Cat B2 were expressed in Cos-7 cell lines and encoded protein was recognised using western blotting using rat anti- cathepsin B antibody. DNA vaccines elicited high Cat B2- specific IgG, IgG1, IgE and also modest IgG2a antibody responses. Cat B2 specific IL-4?T cell responses were also observed in Cat B2 vaccinated mice. The comparison of immunogenic potential in each of these constructs was demonstrated as enhanced antibody responses on the lymph-node targeting vector pCTLA-4 Cat B2, the high antibody avidity of chemo-attractant pMCP3 Cat B2 and stronger T cellular responses of non-secretory DNA vaccine pVR1012 Cat B2 in vaccinated animals. Conclusion This study showed that the targeting DNA vaccine strategies enhanced specific immune responses to juvenile fluke Cat B2. The results of our current study have demonstrated that a gene-based vaccine as an immunotherapeutic approach to combat Fasciola infection may be feasible. PMID:22938392

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

    PubMed Central

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

    2014-01-01

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

  6. 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. PMID:21729765

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

    PubMed

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

    2013-01-01

    Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases. PMID:23320421

  8. A novel GlcNAcalpha1-HPO3-6Gal(1-1)ceramide antigen and alkylated inositol-phosphoglycerolipids expressed by the liver fluke Fasciola hepatica.

    PubMed

    Wuhrer, Manfred; Grimm, Christiane; Zahringer, Ulrich; Dennis, Roger D; Berkefeld, Clemens M; Idris, Mohamed A; Geyer, Rudolf

    2003-02-01

    The acidic (glyco)lipids of the parasitic liver fluke Fasciola hepatica exhibited two different phosphate-containing species, designated AL-I and AL-II, which were analyzed by MALDI-TOF MS, ESI MS, NMR, methylation analysis, and combined GC-MS in conjunction with HF treatment. AL-I was structurally determined as 1-O-hexadecyl-sn-glycerol-3-phosphoinositol, an ether bond variant of lysophosphatidylinositol. The structure of AL-II was shown to be GlcNAcalpha1-HPO3-6Gal(1-1)ceramide. Ceramide analysis revealed as major components 2-hydroxyoctadecanoic acid [18:0(2-OH)] together with C18- and C20-phytosphingosines. AL-II was apparently highly antigenic and strongly recognized by both animal- and human-F. hepatica infection sera. Furthermore, inhibition ELISAs revealed that the unusual antigenic determinant GlcNAcalpha1-HPO3- phosphate might have a potential in the serodiagnosis of F. hepatica infections. PMID:12626405

  9. Genetic variation among Clonorchis sinensis isolates from different geographic regions in China revealed by sequence analyses of four mitochondrial genes.

    PubMed

    Liu, G H; Li, B; Li, J Y; Song, H Q; Lin, R Q; Cai, X Q; Zou, F C; Yan, H K; Yuan, Z G; Zhou, D H; Zhu, X Q

    2012-12-01

    The present study examined sequence variation in four mitochondrial (mt) genes, namely cytochrome c oxidase subunits 1 (cox1) and 2 (cox2), and NADH dehydrogenase subunits 1 and 2 (nad1 and nad2) among Clonorchis sinensis isolates from different endemic regions in China, and their phylogenetic relationships with other zoonotic trematodes were reconstructed. A portion of the cox1 and cox2 genes (pcox1 and pcox2), and nad1 and nad2 genes (pnad1 and pnad2) were amplified separately from individual liver flukes by polymerase chain reaction (PCR) and the amplicons were subjected to sequencing from both directions. The intra-specific sequence variations within C. sinensis were 0-1.6% for pcox1, 0-1.4% for pcox2, 0-0.9% for pnad1 and 0-1.0% for pnad2. Phylogenetic analyses based on the combined sequences of pcox1, pcox2, pnad1 and pnad2 revealed that all the C. sinensis isolates grouped together and were closely related to Opisthorchis felineus. These findings revealed the existence of intra-specific variation in mitochondrial DNA (mtDNA) sequences among C. sinensis isolates from different geographic regions, and demonstrated that mtDNA sequences provide reliable genetic markers for phylogenetic studies of zoonotic trematodes. PMID:22152452

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

    PubMed Central

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

    2013-01-01

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

  11. Combination chemotherapy against Clonorchis sinensis: experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in a rat model.

    PubMed

    Keiser, Jennifer; Xiao, Shu-Hua; Smith, Thomas A; Utzinger, Jürg

    2009-09-01

    Caused by the Chinese liver fluke Clonorchis sinensis, clonorchiasis is of growing public health importance. Treatment and control of the disease rely on a single drug, praziquantel, and little information regarding combination chemotherapy is available. Here, we evaluated the in vivo efficacy of praziquantel combined with artemether, artesunate, OZ78, and tribendimidine, as well as an artesunate-tribendimidine combination against C. sinensis, in a rat model. Data from previous experiments were included, and negative binomial regression analyses were carried out to determine dose-response relationships and to study the effect of drug combination. All drugs given in monotherapy were efficacious in killing the worms; doses of 16 and 70 mg/kg of body weight of artesunate, for example, reduced worm burden by 50% and 95%, respectively. Artemether and OZ78 (12.5 to 50 mg/kg) showed dose-dependent killing of worms but no significant drug interactions when given with 150 mg/kg praziquantel, suggesting independent additive effects. In contrast, artesunate and tribendimidine (12.5 to 50 mg/kg) showed synergistic interactions with 150 mg/kg praziquantel. When low doses of 3.1 and 6.25 mg/kg OZ78 and artemether, respectively, were combined with praziquantel (150 mg/kg) an increased worm survival, above the level observed with praziquantel monotherapy, was noted. A similar antagonism was seen when praziquantel (75 mg/kg) was combined with several of the companion drugs at various doses. In conclusion, in vivo efficacy of praziquantel, the artemisinins, OZ78, and tribendimidine against C. sinensis is confirmed, and combination chemotherapy with praziquantel produces synergistic and antagonistic effects depending on the doses administered. Further preclinical investigations are warranted. PMID:19581454

  12. Combination Chemotherapy against Clonorchis sinensis: Experiments with Artemether, Artesunate, OZ78, Praziquantel, and Tribendimidine in a Rat Model?

    PubMed Central

    Keiser, Jennifer; Xiao, Shu-Hua; Smith, Thomas A.; Utzinger, Jürg

    2009-01-01

    Caused by the Chinese liver fluke Clonorchis sinensis, clonorchiasis is of growing public health importance. Treatment and control of the disease rely on a single drug, praziquantel, and little information regarding combination chemotherapy is available. Here, we evaluated the in vivo efficacy of praziquantel combined with artemether, artesunate, OZ78, and tribendimidine, as well as an artesunate-tribendimidine combination against C. sinensis, in a rat model. Data from previous experiments were included, and negative binomial regression analyses were carried out to determine dose-response relationships and to study the effect of drug combination. All drugs given in monotherapy were efficacious in killing the worms; doses of 16 and 70 mg/kg of body weight of artesunate, for example, reduced worm burden by 50% and 95%, respectively. Artemether and OZ78 (12.5 to 50 mg/kg) showed dose-dependent killing of worms but no significant drug interactions when given with 150 mg/kg praziquantel, suggesting independent additive effects. In contrast, artesunate and tribendimidine (12.5 to 50 mg/kg) showed synergistic interactions with 150 mg/kg praziquantel. When low doses of 3.1 and 6.25 mg/kg OZ78 and artemether, respectively, were combined with praziquantel (150 mg/kg) an increased worm survival, above the level observed with praziquantel monotherapy, was noted. A similar antagonism was seen when praziquantel (75 mg/kg) was combined with several of the companion drugs at various doses. In conclusion, in vivo efficacy of praziquantel, the artemisinins, OZ78, and tribendimidine against C. sinensis is confirmed, and combination chemotherapy with praziquantel produces synergistic and antagonistic effects depending on the doses administered. Further preclinical investigations are warranted. PMID:19581454

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2014-10-15

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

  15. Production and Deformation of Clonorchis sinensis Eggs during In Vitro Maintenance

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    2011-04-22

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed

    Keiser, Jennifer; Vargas, Mireille

    2010-09-01

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

  19. Clonorchis sinensis infestation: a case report.

    PubMed

    McSherry, J A

    1981-05-01

    A young female refugee from Indochina suffered recurring episodes of upper abdominal pain for several months before developing acute cholangitis and pancreatitis, associated with the presence of ova of Clonorchis sinensis in her stool. Microscopy of her stools was negative for this parasite on several previous occasions. The attention of all family physicians caring for 'boat people' is drawn to the possibility of disease developing after arrival in Canada, despite screening on arrival. PMID:21289739

  20. Clonorchis Sinensis Infestation: A Case Report

    PubMed Central

    McSherry, J. A.

    1981-01-01

    A young female refugee from Indochina suffered recurring episodes of upper abdominal pain for several months before developing acute cholangitis and pancreatitis, associated with the presence of ova of Clonorchis sinensis in her stool. Microscopy of her stools was negative for this parasite on several previous occasions. The attention of all family physicians caring for ‘boat people’ is drawn to the possibility of disease developing after arrival in Canada, despite screening on arrival. PMID:21289739

  1. The Use Of Hetol On The Infection Of Clonorchis Sinensis.

    PubMed

    Cho, Moo Joon; Cho, Kee Mok; Soh, Chin Thak

    1966-08-01

    The 16 cases of Clonorchis sinensis infection were divided into 6 groups, according to the method of administration of 1, 4-Bis-trichlormethyl-benzol. The number of egg-out and clinical manifestation of pre.and post drug administration were observed. 1. In all groups, the number of ova transiently increased at the early stage of treatment and followed rather abrupt decrease reaching to E.P.G. zero by Stoll's method on 4 weeks after the medication, except group 6 which showed a few ova by M.G.L. method. 2. Subjective symptoms: fatigability, disappetite and other general complaints by the drug administration were markedly improved in all cases. 3. Blood counts and bleeding time were within normal value before and after the treatment. 4. Liver function test was normal during pre-and post-treatment except case No. 9. Serum alkaline phosphatase of No.9 was high level lbefore treatment, but recovered to noraml level 3 weeks later of the drug administrations. 5. SGOT and SGPT in 10 cases examined showed normal value. 6. The level of serum protein was not changed during observation period. 7. Urine albumin was noted in 2 cases before medication, but they also converted to negative within 3 weeks. Serum creatinine were all normal limits. 8. Bradycardia were noted in 2 cases during observed no significant abnormalities of EKG. Serum electrophoresis were also normal limits. PMID:12913574

  2. Investigation on the epidemiological factors of Clonorchis sinensis infection in an area of south China.

    PubMed

    Lin, Rui; Li, Xueming; Lan, Chungeng; Yu, Senhai; Kawanaka, Masanori

    2005-09-01

    To detect the epidemiological factors of Clonorchis sinensis infection in Hengxian County, one of counties in Guangxi Zhuang Autonomous Region where Schistosoma japonicum was endemic but eliminated in the late 1980s, a questionnaire was designed with 37 questions covering socioeconomic conditions and human behavior, contamination of the environment and fish ponds, inadequate farming/fishery practices; and the formalin-ether sedimentation technique was used to examine the feces of cats, dogs and pigs for the eggs of C. sinensis. Fresh fish was sliced and digested to detect the metacercariae of C. sinensis under a stereomicroscope. Of 1,521 people interviewed, 64% of the interviewees did not know about fluke disease or its transmission route, 46% of those who knew about the fluke believed that the infection caused no harm or only slight harm to their health. More than half of the interviewees (51%) ate raw fish at least 1-2 times per month, more among the middle-aged males. Eight percent of them used the same utensils for both raw fish and cooked food. When advice was given not to eat raw fish, 73% of the interviewees thought it was not feasible. In relation to pisciculture, 25% and 9% of the owners of fish ponds fed their fish with feces of domestic animals and human feces, respectively. The prevalences of C. sinensis infection in cats, dogs and pigs were 70, 50 and 27%, respectively, and the infection rate in fish was 40%. These results indicate the poor knowledge, and beliefs, and unhealthy behaviors in the human population. They also show poor environmental hygiene and inappropriate farming/fishery practices are important in the increase of C. sinensis prevalence in humans. Combined interventions, including health education, environmental modification, reform of traditional farming/fishery practices, mass screening and chemotherapy for humans, and the management of domestic animals are needed in developing control strategies to decrease C. sinensis infection in the human population. PMID:16438134

  3. 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

  4. Cytochrome P450 in fluke Opisthorchis felineus: identification and characterization.

    PubMed

    Pakharukova, Maria Y; Ershov, Nikita I; Vorontsova, Elena V; Katokhin, Alexei V; Merkulova, Tatiana I; Mordvinov, Viatcheslav A

    2012-02-01

    Infection with the human liver fluke Opisthorchis felineus is a serious public health problem in Russia and other Eastern Europe countries. The aim of this work was to identify and sequence cytochrome P450 mRNA from O. felineus and to analyze its expression at different developmental stages. We found only one cytochrome P450 in O. felineus. It contains a conserved Pfam00067 domain which was typical of the CYP450 II eukaryotic microsomal type, and a putative transmembrane domain. Additionally, we identified a high degree of homology between a 3D model of O. felineus CYP450 and mammalian CYP2 structures. The level of O. felineus CYP mRNA expression in maritae (adult stage in definitive mammal host) is significantly higher than in metacercaria. This fact indicates an important role of this biotransformation enzyme in the biochemistry of the parasite at the maritae stage. PMID:22115821

  5. An attempt to vaccinate sheep against Fasciola hepatica using a juvenile fluke antigen sheep antibody complex.

    PubMed

    Sandeman, R M; Howell, M J; Campbell, N J

    1980-09-01

    Sheep were injected intramuscularly with a mixture of Freund's complete adjuvant and a precipitated fluke antigen-antibody complex isolated from in vitro cultures of excysted metacercariae of Fasciola hepatica in serum from infected sheep. Control groups of sheep were given Freund's complete adjuvant or were untreated. All sheep were then challenged with 200 metacercariae of F hepatica. Assays of antibody and liver enzymes in serum collected during the experiment indicated that although vaccination with the complex resulted in a pronounced antibody response to its antigenic component(s), there was no apparent effect on the migratory activity of the juvenile flukes in these animals. Failure to confer protection on vaccinated sheep was confirmed at autopsy when no significant difference was found between the worm burden of these animals and the controls. PMID:6110229

  6. 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 detection of further human cases, are required. PMID:19885337

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

    PubMed

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

    2013-07-01

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

  8. Comparative effect of mebendazole, albendazole, tribendimidine, and praziquantel in treatment of rats infected with Clonorchis sinensis.

    PubMed

    Xiao, Shu-hua; Xue, Jian; Xu, Li-li; Zhang, Yong-nian; Qiang, Hui-qin

    2011-03-01

    The aim of the study is to understand the anti-Clonorchis sinensis properties of mebendazole and albendazole, and compare to praziquantel and tribendimidine. Two hundred and thirty rats were divided into five batches for experimental treatment. In four batches, each rat was infected orally with 50 or 100 C. sinensis metacercariae. Twenty-eight to 46 days post-infection, groups of rats were treated orally with single doses of mebendazole, albendazole, praziquantel, tribendimidine, or multiple daily doses of albendazole. While in the remaining batch, mebendazole or praziquantel was administered to groups of rats infected each with 50 metacercariae for 7 or 14 days. In each batch of test, untreated but infected rats served as control. All rats were euthanized 2-4 weeks post-drug administration for assessment of efficacy. In the first batch of test, rats treated with mebendazole or tribendimidine at single doses of 150, 75, and 37.5 mg/kg resulted in worm burden reductions of 99.0%, 94.0%, and 73.1%, or 98.0%, 80.6%, and 60.4%, respectively. When rats were treated with albendazole at the same dose levels, no or poor effect was seen. In the second batch of test, promising effect against adult C. sinensis in rats treated with mebendazole or tribendimidine at single doses of 100 and 50 mg/kg were also observed, but under the single dose of 25 mg/kg, only tribendimidine still remained the effect. In the third batch of test, the aforementioned three single dose levels of mebendazole, albendazole and praziquantel were applied. Again, mebendazole exhibited higher effect and albendazole exhibited no or poor effect. While praziquantel, administered at a higher dose of 300 mg/kg, also showed promising effect. In the fourth batch of test, oral administration of albendazole at a daily dose of 150 or 100 mg/kg for 2 or 3 days resulted in moderate or higher efficacy with worm burden reductions of 79.2% and 91.9%, respectively. In the fifth batch of test, single mebendazole doses of 150 or 75 mg/kg exhibited promising effect against 14-day-old C. sinensis in rats with worm burden reductions of 95.3% and 86.4%, respectively, but mebendazole was short of the effect against 7-day-old worms. Under the same dose level, praziquantel possessed an effect against both 7- and 14-day-old juvenile C. sinensis. The results confirm that in infected rats, mebendazole administered orally at a single dose of 150 mg/kg exhibits potential effect against juvenile (14-day-old) and adult C. sinensis. No or less effect is obtained from albendazole under the same dose levels, but extension of treatment course may enhance the effect of albendazole against this species of fluke. The single effective dose ranges of mebendazole and tribendimidine against C. sinensis in rats are similar with a broad window, while the window for praziquantel is narrow. PMID:21136080

  9. Prevalence of the intestinal flukes Haplorchis taichui and H. yokogawai in a mountainous area of Phongsaly Province, Lao PDR.

    PubMed

    Chai, Jong-Yil; Yong, Tai-Soon; Eom, Keeseon S; Min, Duk-Young; Shin, Eun-Hee; Banouvong, Virasack; Insisiengmay, Bounnaloth; Insisiengmay, Sithat; Phommasack, Bounlay; Rim, Han-Jong

    2010-12-01

    Phongsaly Province, located in the northernmost area of Lao PDR, was previously suggested to be endemic for the liver fluke Opisthorchis viverrini infection. To confirm, or rule out, this suggestion, the Phonxay village in the Khoua District, Phongsaly Province, was selected for a survey. Ten volunteers (8 men and 2 women aged 31-57 years) who consumed raw freshwater fish and had gastrointestinal troubles were treated with a single dose of praziquantel (40 mg/kg) and pyrantel pamoate (10 mg/kg) and purged with magnesium sulfate to recover any worm parasites. Eight of the 10 volunteers expelled 1 or more species of trematodes, nematodes, or cestodes (worm positive rate; 80%). The worms were morphologically identified as H. taichui (861 worms from 8 people), H. yokogawai (59 from 6 people), Phaneropsolus bonnei (1 from 1 person), Trichostrongylus sp. (2 from 2 people), Ascaris lumbricoides (2 from 1 person), Enterobius vermicularis (11 from 3 people), and Taenia saginata (1 strobila with scolex from 1 person). The results indicate that the mountainous area of Phongsaly Province, Lao PDR, is not endemic for the liver fluke but endemic for intestinal flukes, in particular, Haplorchis taichui and H. yokogawai. PMID:21234239

  10. [Scanning electron microscopic observations on Clonorchis sinensis cercariae].

    PubMed

    Li, B Z; Deng, L J; Pang, X L; Yu, X H; Liu, R D; Su, R P; Li, J B

    1991-01-01

    The surface structure of Clonorchis sinensis cercariae was observed under scanning electron microscope. The cercaria was of the parapleuro-lophocercous type. The measurements of the cercariae were as follows: body 137-240 x 62-90 microns, tail 320-470 x 21-34 microns, oral sucker 27-46 x 23-33 microns. The ventral sucker was incompletely developed and much smaller than the oral one. The whole body surface was covered with backward pointing spines. Four horizontal rows of oral spines were found around the mouth opening of the oral sucker. These spines diminished in size with the distance of the rows from the opening and their numbers were 12, 18, 19 and 18 respectively. Transverse and longitudinal plicae formed from tegument were found on the surface of the tail, being in connection with dorsal and ventral fins along posterior half of the tail. Many sensory structures or papillae were observed on the body. They were of three different types: 1) papillae with long or short cilia distributed widely on the body surface and around the mouth opening, the number of papillae with cilia on the body surface being greater than that described by Komiya et al (1940); 2) a few sensory fossa on the tail, measuring 1.0 x 0.6 microns; 3) a few ring-type papillae with knob on the body surface with pore of 0.5 micron in diameter. PMID:1959177

  11. Human consumption of rumen flukes of cattle in India.

    PubMed

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

    2014-01-01

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

  12. In Vitro Maintenance of Clonorchis sinensis Adult Worms

    PubMed Central

    Uddin, Md. Hafiz; Li, Shunyu; Bae, Young Mee; Choi, Min-Ho

    2012-01-01

    Clonorchis sinensis is a biological carcinogen inducing human cholangiocarcinoma, and clonorchiasis is one of the important endemic infectious diseases in East Asia. The present study investigated survival longevity of C. sinensis adult worms in various in vitro conditions to find the best way of keeping the worms longer. The worms were maintained in 0.85% NaCl, 1×PBS, 1×Locke's solution, RPMI-1640, DMEM, and IMDM media, and in 1×Locke's solution with different supplements. All of the worms died within 3 and 7 days in 0.85% NaCl and 1×PBS, respectively, but survived up to 57 days in 1×Locke's solution. The worms lived for 106 days in DMEM, and 114 days in both RPMI-1640 and IMDM media. The survival rate in RPMI-1640 medium was the highest (50%) compared to that in DMEM (20±10%) and in IMDM (33.3±25.2%) after 3 months. The 1×Locke's solution with 0.005% bovine bile supplement showed increased duration of maximum survival from 42 days to 70 days. Higher concentration of bile supplements than 0.005% or addition of glucose were disadvantageous for the worm survival. The worms died rapidly in solutions containing L-aspartic acid, L-glutamic acid, and adenine compared to L-arginine, L-serine, and L-tryptophan. In conclusion, the 1×Locke's solution best supports the worms alive among inorganic solutions for 57 days, and the RPMI-1640 medium maintains living C. sinensis adults better and longer up to 114 days in vitro than other media. PMID:23230328

  13. Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2008-04-01

    We comparatively assessed the in vivo efficacy of artemether, artesunate, praziquantel and tribendimidine against different stages of Clonorchis sinensis. Rats were infected with 40-50 C. sinensis metacercariae, and drugs were administered singly by the oral route at different dosages. Rats were dissected 2-4 weeks post-treatment and C. sinensis trematodes were removed from the liver and bile ducts and counted. We used a negative binomial regression model to test the effect of drug and dosage in terms of worm burden reduction. Single 150 mg/kg oral doses of artesunate, artemether, tribendimidine and praziquantel, administered to rats infected with adult C. sinensis, resulted in mean worm burden reductions of 100, 100, 89.5 and 80.7%, respectively (all P<0.001). Halving the dose to 75 mg/kg still resulted in highly significant worm burden reductions for artesunate, artemether and tribendimidine (71.4-100%), but not for praziquantel (20.7%). In the juvenile infection model, a single 150 mg/kg oral dose of tribendimidine and praziquantel resulted in mean worm burden reductions of 99.1 and 90.0%, respectively, whereas considerably lower reductions were observed for artemether (59.2%) and artesunate (57.6%) when used at the same single dose. The in vivo results presented here with the artemisinins and tribendimidine provide further data for clinical investigations to assess the safety and efficacy of these drugs in clonorchiasis patients. PMID:18308285

  15. In vitro fasciolicide activity of some plant extracts against newly excysted flukes.

    PubMed

    Vera-Montenegro, Yolanda; Ibarra-Velarde, Froylán; Ramírez-Avila, Guillermo; Munguía-Xochihua, Javier

    2008-12-01

    The aim of the present study was to evaluate, under in vitro conditions, the activity of 20 plant extracts against newly excysted Fasciola hepatica metacercariae. The plants were selected on the basis of anthelmintic activity, traditional use, availability, solubility, and permanence in the liver. For the in vitro evaluation, 24-well Nunc-immunoplates containing RPMI-1640 culture medium bovine sera plus antibiotics were used. Extract concentrations of 500 and 50 mg/mL were placed in triplicate. Approximately 10 newly excysted flukes were placed in each well, and the plates were incubated in a CO(2) incubator at 5% atmosphere for 3 days. In each plate four control wells containing nontreated flukes were included. All procedures were undertaken under an air-flow cabinet. Efficacy was measured on days 1 and 3 by considering the motility of the live or dead trematodes evaluated with the aid of an inverted microscope. Results indicated that, from all extracts evaluated, Tilia mexicana showed an average efficacy for concentrations of 500 and 50 mg/mL, respectively, of 100 and 100%; Eriobotrya japonica, 100 and 95%; Coffea arabica, 100 and 100%; Crataegus mexicana, 95 and 90%; and Ternstroemia pringlei 100 and 100%. From this preliminary evaluation, we conclude that further and more detailed evaluations at lower concentrations should be undertaken to understand the real efficacy of these plant extracts. PMID:19120205

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2014-01-01

    The liver fluke, Opisthorchis felineus of the Opisthorchiidae family, is a well-known causative agent of opisthorchiasis in Russia and Europe. The aim of this work was to identify genes encoding thyroid hormone receptors in O. felineus, and to analyze the expression of possible target genes in response to treatment with exogenous thyroid hormones. We identified two genes encoding thyroid hormone receptors in the O. felineus genome, THRA and THRB. The genes were differentially expressed through the life cycle. The maximal level of mRNA expression of THRA1 and THRB was observed in adult worms. Treatment of the worms with triiodothyronine and thyroxine resulted in an increase in glucose 6-phosphatase mRNA expression and a decrease in malate dehydrogenase mRNA expression, potential gene targets of thyroid hormones. These data indicate that thyroid hormone receptors may perform essential roles in physiological processes in adult O. felineus. PMID:24798031

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

    Microsoft Academic Search

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

    2005-01-01

    The cDNA library of Clonorchis sinensis was screened for genes encoding antigenic proteins by using sera from clonorchiasis patients. A gene of 888 bp encoding a 28-kDa protein (Cs28) was cloned and found to contain a high percentage of glycine (20%), tyrosine (11%), and lysine (11%). The amino acid sequence of Cs28 showed 60% homology with the vitelline B precursor protein

  19. Coproantigen capture ELISA for detection of Clonorchis sinensis infection in experimentally infected rats

    Microsoft Academic Search

    S. M. Mazidur Rahman; Min-Ho Choi; Young Mee Bae; Sung-Tae Hong

    The present study investigated the diagnostic value of an ELISA for the detection of Clonorchis sinensis antigen in the feces of experimentally infected rats. A mouse polyclonal IgG antibody against adult C. sinensis crude antigen (CsAg) was used to capture the C. sinensis coproantigen. The detection limit for pure CsAg was 20ng\\/ml in sample buffer and 40ng\\/ml in uninfected fecal

  20. [Strengthening the research on clonorchiasis in China].

    PubMed

    Qian, Men-Bao; Zhou, Xiao-Nong; Fang, Yue-Yi; Liang, Song; Chen, Ying-Dan

    2011-06-01

    Liver flukes mainly include Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus. The international congress of liver flukes was held in Khon Kaen, Thailand, during 7-8th March, 2011. The congress assembled a wide array of studies and reflected the current status of research, control and prevention of liver flukes in the world. This paper summarizes basic information from the meeting. Meanwhile, based on the research status and needs for control and prevention, priorities of research on clonorchiasis in China are discussed. PMID:21970113

  1. Genomic linkage map of the human blood fluke Schistosoma mansoni

    Microsoft Academic Search

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

    2009-01-01

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

  2. Proteomic Analysis of Skin Invasion by Blood Fluke Larvae

    Microsoft Academic Search

    Elizabeth Hansell; Simon Braschi; Katalin F. Medzihradszky; Mohammed Sajid; Moumita Debnath; Jessica Ingram; K. C. Lim; James H. McKerrow

    2008-01-01

    BackgroundDuring invasion of human skin by schistosome blood fluke larvae (cercariae), a multicellular organism breaches the epidermis, basement membrane, and dermal barriers of skin. To better understand the pathobiology of this initial event in schistosome infection, a proteome analysis of human skin was carried out following invasion by cercariae of Schistosoma mansoni.Methodology and ResultsHuman skin samples were exposed to cercariae

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

    PubMed Central

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

    2007-01-01

    We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica. PMID:17194822

  4. Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini.

    PubMed

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

    2007-03-01

    We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica. PMID:17194822

  5. Phylogeny and paraphyly among tetrapod blood flukes (Digenea: Schistosomatidae and Spirorchiidae)

    Microsoft Academic Search

    Scott D. Snyder

    2004-01-01

    The blood flukes of turtles (Digenea: Spirorchiidae) and the blood flukes of crocodilians, birds and mammals (Digenea: Schistosomatidae) have long been considered as closely related, but distinct evolutionary lineages. Recent morphological and molecular studies have considered these families as sister taxa within the Schistosomatoidea. Representatives of both families have similar furcocercous cercariae and similar two-host life cycles, but have different

  6. [Experimental study progress on tribendimidine, artemether and artesunate against Clonorchis sinensis and other trematodes].

    PubMed

    Xiao, Shu-hua; Xue, Jian; Wu, Zhong-xin

    2009-02-28

    Currently praziquantel is one of the major drugs used in treatment of schistosomiasis and other trematode infections. Recent experimental studies indicate that a new anthelmintic, tribendimidine, is used in the treatment of intestinal nematodes, also possesses effect against several species of trematodes including Clonorchis sinensis, Opisthorchis viverrini and Echinostoma caproni. Tribendimidine is even more effective against C. sinensis in rats that a single 300 mg/kg oral dose cures almost all of the animals treated, a lower cure dose than praziquantel (375-500 mg/kg). The anti-malarial drugs artemether and artesunate are not only effective in the prevention of schistosomiasis, but also effective against several species of trematodes, especially C. sinensis. The single oral dose of both drugs to cure or achieve high efficacy in infected rats is 75 mg/kg. This review summarized research progress on tribendimidine, artesunate, and artemether in experimental animals infected with C. sinensis and other species of trematodes. PMID:19459505

  7. Molecular cloning and analysis of stage and tissue-specific expression of Cathepsin L-like protease from Clonorchis sinensis

    Microsoft Academic Search

    Yanwen Li; Xuchu Hu; Xiaoquan Liu; Jing Xu; Fengyu Hu; Changling Ma; Xinbing Yu

    2009-01-01

    Cathepsin L of parasite plays multiple roles in growth, food uptake, and invasion into host and pathogenesis, which makes\\u000a it a valuable target for diagnosis, vaccine, and drug. In this study, we identified a cDNA encoding cathepsin L homolog (CsCPL)\\u000a from the library of Clonorchis sinensis adult by bioinformatics analysis. Sequence encoding proenzyme of CsCPL (removal of signal peptide, CsproCPL)

  8. 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

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

    E-print Network

    Craik, Charles S.

    : Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN) view clusters Sm

  10. Host specificity of a parasitic fluke: is Posthodiplostomum minimum a centrarchid-infecting generalist or specialist?

    PubMed

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

    2015-02-01

    Parasite host specificity has important implications for species diversity estimates, food web dynamics, and host shifts. "White grub" is the metacercaria stage of a fluke ( Posthodiplostomum minimum ) that occurs in many fish species, but no attempt has been made to quantify variation in host use by this worm. Here we used 2 approaches to evaluate host specificity within the strain that infects centrarchids ( P. minimum centrarchi). First, we measured parasite loads in 2 centrarchid hosts, bluegill ( Lepomis macrochirus ) and white crappie ( Pomoxis annularis ), from Spring Lake in McDonough County, Illinois. We found that infection levels differed significantly between these hosts. Prevalence in bluegill was 100% and the median intensity was 940 metacercariae, but only 57% of white crappie were infected (median intensity = 4). Site specificity of white grub also differed significantly between the 2 hosts. In bluegills, kidneys were most heavily infected, whereas in white crappies, livers harbored the most worms. We also performed a literature survey of P. minimum prevalence estimates from 14 centrarchid species from other localities. We calculated the mean white grub prevalence for each host species and used this to calculate STD*, a quantitative index of host specificity. STD* was 1.33, significantly closer to the value for a specialist (STD* = 1.00) than a generalist (STD* = 2.00). This reflects the fact that P. minimum prevalence is higher in Lepomis species than it is in centrarchids outside this genus. These data show that P. minimum centrarchi specializes on Lepomis species, but the causes of this specialization are unknown. This worm may be a single species that differs in host use due to ecological or physiological host differences, or it may be a complex of species that vary in host use for similar reasons. Genetic data are required to evaluate these possibilities. PMID:25260116

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

    PubMed

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

    2015-01-15

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

  12. 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. PMID:24458653

  13. 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. PMID:23609597

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

    PubMed

    Hong, S J; Lee, J Y; Lee, D H; Sohn, W M; Cho, S Y

    2001-06-01

    In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high degree of sequence identity and folding topology similar to the mu-class GSTs. The estimated molecular mass of the protein, 26 kDa, was consistent with an expression by pcsGSTM1 cDNA. The bacterially expressed recombinant csGSTM1 protein possessed an enzymatic GST activity and conjugated GSH to reactive carbonyls of lipid peroxidation. The recombinant csGSTM1 protein did not share antigenic epitope(s) with GSTs of Fasciola hepatica, Paragonimus westermani and Schistosoma japonicum. The csGSTM1 was identified to a mu-class GST in C. sinensis. PMID:11377741

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

    PubMed

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

    2005-02-01

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

  16. Coproantigen capture ELISA for detection of Clonorchis sinensis infection in experimentally infected rats.

    PubMed

    Mazidur Rahman, S M; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2012-03-01

    The present study investigated the diagnostic value of an ELISA for the detection of Clonorchis sinensis antigen in the feces of experimentally infected rats. A mouse polyclonal IgG antibody against adult C. sinensis crude antigen (CsAg) was used to capture the C. sinensis coproantigen. The detection limit for pure CsAg was 20 ng/ml in sample buffer and 40 ng/ml in uninfected fecal extract. The test was evaluated using a follow-up of five groups of rats experimentally infected with 100, 50, 10, 5 and 1 metacercariae of C. sinensis and an uninfected control group. Coproantigen was detected in all infected groups of rats from 2 weeks of infection, whereas fecal eggs were not observed until 3 weeks of infection. As the infection period progressed, the fecal CsAg concentration increased in all groups of infected rats, even those infected with a single metacercaria. The fecal CsAg concentration was correlated positively with fecal egg counts and worm burden. This coproantigen capture ELISA is highly sensitive for the detection of CsAg in rat feces, and with further development, should be useful for mass screening of human subjects in clonorchiasis-endemic areas. PMID:21864712

  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. PMID:25138068

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

    PubMed

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

    2005-04-01

    The NAD-dependent cytosolic malate dehydrogenase (cMDH, EC 1.1.1.37) plays a pivotal role in the malate-aspartate shuttle pathway that operates in a metabolic coordination between cytosol and mitochondria, and thus is crucial for the survival and pathogenicity of the parasite. In the high throughput sequencing of the cDNA library constructed from the adult stage of Clonorchis sinensis, a cDNA clone containing 1152bp insert was identified to encode a putative peptide of 329 amino acids possessing more than 50% amino acid sequence identities with the cMDHs from other organisms such as fish, plant, and mammal. But low sequence similarities have been found between this cMDH and mitochondrial malate dehydrogenase as well as glyoxysomal malate dehydrogenase from other organisms. Northern blot analysis showed the size of the C. sinensis cMDH mRNA was 1.2 kb. The cMDH was expressed in Escherichia coli M15 as a His-tag fusion protein and purified by BD TALON metal affinity column. The recombinant cMDH showed high MDH activity of 241 U mg(-1), without lactate dehydrogenase and NADP(H) selectivity. It provides a model for the structure, function analysis, and drug screening on cMDH. PMID:15755419

  19. Determination of the minmum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in rats.

    PubMed

    Fan, Ping-Chin; Wu, Chin-Cheng; Huang, Ping; Yen, Chih-Wei

    2005-10-01

    In order to determine the minimum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats, each rat was infected with 30 metacercariae and treated with one of three drugs. The rats were killed and examined 25 days after praziquantel treatment or 11 days after albendazole or mebendazole treatment. The minimum effective dosages were a single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150 mg/kg. Trials are required to determine whether these dosages are useful in the treatment of human clonorchiasis. PMID:16302447

  20. Mouflon ( Ovis musimon) dicrocoeliosis: Effects of parasitosis on the activities of biotransformation enzymes and albendazole metabolism in liver

    Microsoft Academic Search

    L. Skálová; V. K?ížová; V. Cvilink; B. Szotáková; L. Štorkánová; J. Velík; J. Lamka

    2007-01-01

    Parasitic infections can modify the host's ability to metabolize drugs and other xenobiotics by altering the biotransformation enzymes; these changes may have various pharmacological, toxicological or physiological consequences. In our study, several activities of liver biotransformation enzymes and in vitro metabolism of albendazole (ABZ) were tested and compared in non-infected mouflons (Ovis musimon) and in mouflons infected by lancet fluke

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

    PubMed Central

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

    2014-01-01

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

  2. Genomic linkage map of the human blood fluke Schistosoma mansoni

    PubMed Central

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

    2009-01-01

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

  3. 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

  4. 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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2013-04-01

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

  7. Detection of Clonorchis sinensis in stool samples using real-time PCR.

    PubMed

    Kim, E-M; Verweij, J J; Jalili, A; van Lieshout, L; Choi, M-H; Bae, Y M; Lim, M K; Hong, S-T

    2009-09-01

    Human clonorchiasis, caused by infection with the trematode Clonorchis sinensis, is a common health problem in East Asia. In an attempt to develop a new, sensitive method for the diagnosis of the disease, the use of a real-time PCR (targeting the internal-transcribed-spacer-2 sequence of the parasite) to detect C. sinensis-specific DNA in faecal samples has recently been evaluated. The PCR-based assay, which included an internal control to detect any inhibition of the amplification by faecal constituents in the sample, was performed on stool samples and on DNA controls representing a wide range of intestinal microorganisms. The assay appeared very specific, only showing positivity with C. sinensis and Opisthorchis felineus. The sensitivity of the assay was explored by testing 170 preselected samples of human faeces, from an endemic area of South Korea, which had known (microscopically-determined) densities of C. sinensis eggs. The sensitivity of the assay was 100% for the 74 samples that each had > 100 eggs/g and 91.4% for the other 70 samples found egg-positive by microcopy (i.e. those that had

  8. 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 present study improves our understanding of the global epidemiology and evolution of C. sinensis. PMID:23825605

  9. 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. PMID:24831344

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

    Microsoft Academic Search

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

    2004-01-01

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

  11. Immune responses directed at egg proteins during experimental infection with the liver fluke Fasciola hepatica.

    PubMed

    Moxon, J V; Flynn, R J; Golden, O; Hamilton, J V; Mulcahy, G; Brophy, P M

    2010-02-01

    Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. Unlike the well characterized schistosomes, only the adult and juvenile stages of F. hepatica are implicated in disease, whereas the freely voided egg is not thought to contribute to host-parasite interactions. We investigated specific immune responses to soluble F. hepatica egg proteins (SFHEP), during a 14-week experimental infection, demonstrating significant increases in anti-SFHEP IgG1 (P = 0.001), transforming growth factor beta-1 (P = 0.008) and IL-10 (P < 0.001) titres at the onset of egg production. Western blot analysis of soluble SFHEP demonstrates that protein bands migrating at 61.6, 54.8 and 44 kDa become sero-reactive before the appearance of eggs within host faeces. Therefore, expression of some egg-associated proteins indicates progression to chronic disease. Antigenic bands were investigated through mass spectrometry, identifying a protein disulphide isomerase (PDI) (61.6 kDa), an enolase and ferritin-related proteins (54.8 kDa), and a cocktail of dehydrogenases (44 kDa). Biochemical analysis of egg secretions reveals proteolytic activity, which increases over time, indicating that proteases may be continually secreted during the course of egg maturation. The implications of egg-specific immune responses and proteolytic secretions are further discussed. PMID:20070825

  12. Incidence of liver fluke infections ( Fasciola gigantica and Dicrocoelium hospes ) in ruminants in northern Nigeria

    Microsoft Academic Search

    T. W. Schillhorn van Veen; D. O. B. Folaranmi; S. Usman; T. Ishaya

    1980-01-01

    One thousand and twenty-four cattle, 550 sheep and 1,748 goats slaughtered in a rural slaughter slab during 1973 to 1975 were examined for evidence of liverfluke infections. The prevalence rate ofFasciola gigantica andDicrocoelium hospes infections was respectively 65.4% and 56.0% in cattle, 40.8 and 13.1% in sheep and 17.6 and 5.2% in goats. Other trematodes detected wereSchistosoma bovis and paramphistomes.

  13. Incidence of liver fluke infections (Fasciola gigantica and Dicrocoelium hospes) in ruminants in northern Nigeria.

    PubMed

    Schillhorn van Veen, T W; Folaranmi, D O; Usman, S; Ishaya, T

    1980-05-01

    One thousand and twenty-four cattle, 550 sheep and 1,748 goats slaughtered in a rural slaughter slab during 1973 to 1975 were examined for evidence of liverfluke infections. The prevalence rate of Fasciola gigantica and Dicrocoelium hospes infections was respectively 65.4% and 56.0% in cattle, 40.8 and 13.1% in sheep and 17.6 and 5.2% in goats. Other trematodes detected were Schistosoma bovis and paramphistomes. The seasonal incidence of F. gigantica as well as of D. hospes was highest during and directly after the rainy season. The lower prevalence rate of F. gigantica, especially in the younger animals, during 1973-1974 was thought to be related to the 1973 drought. This was supported by the low prevalence rate in the long-range trade cattle which originated from drier areas. The results are discussed in relation to the climatic conditions during the survey period, as well as to the difference in epidemiology of F. gigantica and D. hospes infections in northern Nigeria. PMID:7414705

  14. Biochemical characterisation of the recombinant peroxiredoxin (FhePrx) of the liver fluke, Fasciola hepatica

    Microsoft Academic Search

    Mary Sekiya; Grace Mulcahy; Jane A. Irwin; Colin M. Stack; Sheila M. Donnelly; Weibo Xu; Peter Collins; John P. Dalton

    2006-01-01

    The parasitic helminth Fasciola hepatica secretes a 2-Cys peroxiredoxin (Prx) that may play important functions in host–parasite interaction. Recombinant peroxiredoxin (FhePrx) prevented metal-catalyzed oxidative nicking of plasmid DNA and detoxified hydrogen peroxide when coupled with Escherichia coli thioredoxin and thioredoxin reductase (kcat\\/Km=5.2×105M?1s?1). Enzyme kinetic analysis revealed that the catalytic efficiency of FhePrx is similar to other 2-Cys peroxiredoxins; the enzyme

  15. Black, wide and notched fluke Right whales return to the First Coast

    E-print Network

    they face. RECOGNIZING THE NORTH ATLANTIC RIGHT WHALE V-shaped spray Because the whales favor shallow threats are ship collisions and entanglements in fishing gear. WHY THEY ARE ENDANGERED Fluke Reaching only right whales in the Bay of Biscay. The Basques used watchtowers on shore to look for the whale

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

    PubMed Central

    2014-01-01

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

  17. PCR diagnosis of infections with different species of Opisthorchiidae using a rapid clean-up procedure for stool samples and specific primers.

    PubMed

    Müller, Boris; Schmidt, Jürgen; Mehlhorn, Heinz

    2007-03-01

    Infections with the opisthorchiid liver flukes Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus cause serious health problems in endemic areas of Southeast Asia and countries of the former Soviet Union. Chronic infections--even with low worm burdens--may lead to the development of fatal cholangiocarcinoma and related symptoms. A more sensitive diagnosis is needed since the tiny eggs of the worms are often not seen in microscopic examinations of stool samples, especially in patients with low infections. This communication reports a rapid cleanup procedure for human stool samples, which enables reliable identification of DNA by polymerase chain reaction from few eggs of opisthorchiid flukes in fecal samples. PMID:17061114

  18. Humoral response (IgG) of goats experimentally infected with Fasciola hepatica against cysteine proteinases of adult fluke

    Microsoft Academic Search

    José Manuel; Pedro Nolasco; Álvaro MARTÍNEZ-MORENOb

    The use of cysteine proteinases from Fasciola hepatica adult flukes for the serodiagnosis of caprine fasciolosis by means of an indirect ELISA test was studied. Two proteolytic fractions from adult fluke homogenates, with apparent molecular weights of 28 and 34 kDa (P28 and P34 respectively), were characterised as cysteine proteinases using azocasein assays and gelatin gel analysis. Both P28 and

  19. Occurrence of a Diploid Type and a New First Intermediate Host of a Human Lung Fluke, Paragonimus westermani, in Korea

    Microsoft Academic Search

    Gab Man Park; K. J. Lee; K. I. Im; T. S. Yong

    2001-01-01

    Park, G. M., Lee, K. J., Im, K. I., Park, H., and Yong, T. S. 2001. Occurrence of a diploid type and a new first intermediate host of a human lung fluke Paragonimus westermani, in Korea. Experimental Parasitology99, 206–212. The biology, chromosome number, and karyotype of a lung fluke, Paragonimus westermani (Kerbert, 1878) collected in Haenam, Haenam-gun Chollanam-do, Korea were

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

    PubMed

    Hanna, Robert

    2015-01-01

    This review summarises the findings of a series of studies in which the histological changes, induced in the reproductive system of Fasciola hepatica following treatment of the ovine host with the anthelmintic triclabendazole (TCBZ), were examined. A detailed description of the normal macroscopic arrangement and histological features of the testes, ovary, vitelline tissue, Mehlis' gland and uterus is provided to aid recognition of the drug-induced lesions, and to provide a basic model to inform similar toxicological studies on F. hepatica in the future. The production of spermatozoa and egg components represents the main energy consuming activity of the adult fluke. Thus the reproductive organs, with their high turnover of cells and secretory products, are uniquely sensitive to metabolic inhibition and sub-cellular disorganisation induced by extraneous toxic compounds. The flukes chosen for study were derived from TCBZ-sensitive (TCBZ-S) and TCBZ-resistant (TCBZ-R) isolates, the status of which had previously been proven in controlled clinical trials. For comparison, flukes collected from flocks where TCBZ resistance had been diagnosed by coprological methods, and from a dairy farm with no history of TCBZ use, were also examined. The macroscopic arrangement of the reproductive system in flukes was studied using catechol/carmine stained whole mounts, and the histology of the main organs was examined using conventional haematoxylin-eosin stained sections. Validation of apoptosis in the fluke sections was carried out using an in situ hybridisation method designed to label endonuclease-induced DNA strand breaks. In TCBZ-S flukes exposed to TCBZ metabolites for 24-96 h in vivo, but not in TCBZ-R flukes, those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), were found to display progressive loss of cell content. This was due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. In the treated TCBZ-S flukes, strong positive labelling indicating apoptosis was associated with the morphologically abnormal cells undergoing mitosis or meiosis in the testis, ovary and vitelline follicles. In treated flukes from field outbreaks of suspected TCBZ-R fasciolosis, no significant histological changes were observed, nor was there any positive labelling for apotosis. On the other hand, sections of TCBZ treated flukes derived from a field case of fasciolosis where TCBZ resistance was not suspected displayed severe histological lesions, and heavy positive labelling for apoptosis. The triggering of apoptosis is considered to be related to failure of spindle formation at cell division, supporting the contention that TCBZ inhibits microtubule formation. In treated TCBZ-S flukes, protein synthesis and transport was apparently inhibited in the Mehlis' secretory cells, perhaps due to energy uncoupling or to microtubule defects. In the uterus, successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland. Histological evidence indicating failure of ovigenesis in TCBZ-S flukes was evident from as early as 24 h post-treatment onwards. Light labelling for apoptosis was associated with the testis of untreated Cullompton (TCBZ-S) and Sligo type 2 (TCBZ-R) flukes, which exhibit abnormal spermatogenesis and spermiogenesis, respectively. This was attributed to apoptosis and to heterophagy of effete germ line cells by the sustentacular tissue. The studies summarised in this review illustrate the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance. Histology can also be used to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. The ac

  1. The in vitro and in vivo effect of tribendimidine and its metabolites against Clonorchis sinensis.

    PubMed

    Xiao, Shu-hua; Xue, Jian; Xu, Li-li; Zheng, Qi; Qiang, Hui-qin; Zhang, Yong-nian

    2009-11-01

    The purpose of the study was to understand the in vitro and in vivo effect of tribendimidine (TBD) and its metabolites of p-(1-dimethylamino ethylimino)aniline (aminoamidine, deacylated amidantel, BAY d 9216, dADT), acetylated dADT (AdADT), terephthalaldehyde (TPAL), and terephthalic acid (TPAC) against adult Clonorchis sinensis. In in vitro test, the adults of C. sinensis were placed to each of the 24 wells of a Falcon plate and maintained in Hanks' balanced salt solution-20% calf serum. Besides observation on the direct in vitro effect of TBD and its metabolites, the worms exposed to TBD and its metabolites for 1-24 h were transferred to the medium without drug and incubated continually for another 72 h. The reversible effect of TBD and its metabolites was assessed by the recovery of worm motor activity and parasite survival. In in vivo test, 235 rats were divided into five batches for oral infection of each rat with 50 C. sinensis metacercariae. Five to 6 weeks post-infection, groups of rats were treated orally or intramuscularly with a single dose of TBD or its metabolites, while untreated but infected rats served as control. All treated rats were killed 2 weeks post-treatment for assessment of efficacy. When adult C. sinensis were exposed to TBD or dADT 0.5 microg/mL, they were paralyzed rapidly accompanied by dilatation of the gut. The in vitro effect of AdADT decreased significantly, which was at least lower than 20- to 40-fold compared with TBD and dADT. TPAL and TPAC at a high concentration of 100 microg/mL exhibited no effect against adult C. sinensis. In the worms exposed to TBD or dADT 1 microg/mL for 1 h, well recovery of the worm motor activity from paralysis was seen in the medium without drug. If exposure time extended to 4-24 h before transferred to the medium without drug, few worms were dead and most worms showed very poor recovery of their activity. When the worms exposed to TBD or dADT 10 microg/mL for 1, 4, and 24 h were transferred to the drug-free medium, recovery of poor motor activity of worms or worm death was seen. In the worms exposed to AdADT 20 and 40 microg/mL for 1-24 h, more worms recovered poor motor activity in the medium without drug. In rats infected with C. sinensis and treated orally with TBD or dADT, the ED(50) and ED(95) were 20.318 and 195.358 mg/kg or 18.969 and 268.882 mg/kg. Under the equal dosages used in the treatment of rats infected with C sinensis, the effects between TBD and dADT or TBD and AdADT were similar. Intramuscular TBD or dADT at a single dose of 12.5-75 mg/kg showed effect against adult C. sinensis harbored in rats. TPAL and TPAC exhibit no effect against C sinensis harbored in rats treated orally with a higher dose of 1 g/kg. The results indicate that TBD and dADT exhibit a strong in vitro effect to paralyze the adult C. sinensis, but less in vitro effect was seen in AdADT. TBD, dADT, and AdADT exhibit similar therapeutic effect in oral treatment of rats infected with C. sinensis, and intramuscular TBD and dADT also show promising effect against C. sinensis in rats. TPAL and TPAC are ineffective metabolites of TBD. PMID:19655171

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

    Microsoft Academic Search

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

    2009-01-01

    BackgroundBlood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins.Methodology\\/Principal FindingsWe identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence

  3. Liver Wellness

    MedlinePLUS

    ... virus (HAV). HAV can cause the liver to swell and not work well. Prevention: Hepatitis A vaccination ... virus (HBV). HBV can cause the liver to swell and can lead to cirrhosis and liver cancer. ...

  4. Liver Regeneration

    PubMed Central

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

    2014-01-01

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

  5. Effect of single-dose oral artemether and tribendimidine on the tegument of adult Clonorchis sinensis in rats.

    PubMed

    Xiao, Shu-Hua; Keiser, Jennifer; Xue, Jian; Tanner, Marcel; Morson, Gianni; Utzinger, Jürg

    2009-02-01

    The tegument of trematodes plays a key role in nutrient absorption, exerts secretory functions, protects the parasite against the immune system of the host, and is a target for anti-trematocidal drugs. We performed a temporal examination of tegumental changes following artemether and tribendimidine administration on adult Clonorchis sinensis in rats using scanning electron microscopy. Rats infected with C. sinensis for 6 weeks were treated orally with a single dose of artemether (150 mg/kg) or tribendimidine (300 mg/kg). Worms were collected between 8 h and 7 days (artemether) and between 4 h and 2 days post-treatment (tribendimidine). Worms recovered from untreated rats served as controls. Eight hours after artemether administration, the tegument of C. sinensis was extensively disrupted, including severe swelling, fusion and vacuolization, and the suckers were damaged. Four hours after administration of tribendimidine, C. sinensis worms showed extensive tegumental alterations, characterized by massive sloughing, and the suckers were damaged. Interestingly, the severity of tegumental changes did not progress further with time. Our results show that both artemether and tribendimidine rapidly disrupt the tegument and damage the suckers of adult C. sinensis. The subtle differences in tegumental changes induced by artemether and tribendimidine might indicate different mechanisms of action of these drugs against C. sinensis. PMID:18975004

  6. Fatty Liver

    Microsoft Academic Search

    Jaideep Behari

    \\u000a The liver plays a central role in maintaining energy balance in the body. After a meal, dietary lipids are transported to\\u000a the liver in the form of chylomicrons by the lymphatic system. The liver then releases the dietary lipids by the action of\\u000a lipoprotein lipase and incorporates them into very-low-density lipoproteins (VLDL), which are then secreted from the liver\\u000a and

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    Microsoft Academic Search

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

    1989-01-01

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

  10. Liver transplantation?

    PubMed Central

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

    2007-01-01

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

  11. Global status of fish-borne zoonotic trematodiasis in humans.

    PubMed

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

    2013-09-01

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

  12. The serodiagnosis of chronic fascioliasis (Fasciola gigantica) using a fluorescent-antibody technique with single and multiple whole-fluke antigens.

    PubMed

    Schillhorn van Veen, T W; Buys, J

    1979-06-01

    Sera from cattle with single or mixed infections of Fasciola gigantica. Dicrocoelium hospes, Schistosoma bovis and paramphistomes were examined for fluorescent antibodies. Cross-reacting antibodies of the heterologous flukes were easily detected by using cryostat sections with whole-fluke-antigen of all three flukes. The presence of F. gigantica antibodies in a cattle herd was tested at two monthly intervals in order to establish the occurrence of chronic fascioliasis. The lack of significant differences in antibody levels of infected, treated and uninfected cattle however showed that herd antibody levels are not very useful to detect chronic Fasciola infections. PMID:384628

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

    PubMed

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

    2014-08-01

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

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

    PubMed

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

    2015-04-30

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

  15. The majority of parasitic worms belong to either the Platyhelminthes (flatworms/flukes and tape-worms) or Nematoda (roundworms/nematodes).

    E-print Network

    Jawitz, James W.

    The majority of parasitic worms belong to either the Platyhelminthes (flatworms/flukes and tape- worms) or Nematoda (roundworms/nematodes). Unlike earthworms, nematodes are un becomes capable of reproducing (eggs produced after male worm inseminates female). In some instances

  16. 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

  17. THE LIVER FLUKE METORCHIS BILIS - A NEW THREAT FOR THE WHITE-TAILED SEA EAGLE (HALIAEETUS ALBICILLA) IN MIDDLE EUROPE?

    Microsoft Academic Search

    O. KRONE; R. SCHUSTER

    Extendet abstract: The white-tailed sea eagle (Haliaeetus albicilla) an endangered species in Germany suffers a lot of threats in the highly civilised landscape. Amongst the main causes of death such as traumata due to interference with human structures, i.e. collisions with trains, wire, electrocution, and poisoning, parasites do also play an important role in the health status of these birds

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

    PubMed

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

    2013-12-01

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

  19. A sero-epidemiological survey on the occurrence of opisthorchiid liver flukes in red foxes ( Vulpes vulpes) in Berlin, Germany.

    PubMed

    Schuster, Rolf; Gregor, Bettina; Heidrich, Jana; Nöckler, Karsten; Kyule, Moses; Wittstatt, Ulrich

    2003-08-01

    Serum samples collected from red foxes in the city of Berlin between 1996 and 1999 were analysed for the presence of antibodies against Opisthorchis felineus and Metorchis bilis using an indirect ELISA. Out of 1,000 specimens, 30.6% and 46.5% reacted positively with specific O. felineus and M. bilis antigens, respectively. Seroprevalence in adult foxes was always higher than in juveniles. While no significant differences were observed in adult foxes throughout the period, in juvenile specimens seroprevalence declined from 1996 to 1997, then stayed at a comparable level in 1998 and increased in 1999. A varying availability of fresh cyprinid fish in different years seems to be the reason for changes in seroprevalence. By grouping the samples from juvenile foxes by season, antibodies against both Metorchis and Opisthorchis antigens started to appear between April and June, increased between July and September()and reached a level comparable to adult foxes in the October to December quarter. The lowest seroprevalence was found in Pankow, which is the district with the lowest share of the surface water. PMID:12743797

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

    PubMed Central

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

    2013-01-01

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

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

    Microsoft Academic Search

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

    2003-01-01

    Fasciola hepatica secretes cathepsin L proteases that facilitate the penetration of the parasite through the tissues of its host, and also participate in functions such as feeding and immune evasion. The major proteases, cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) are members of a lineage that gave rise to the human cathepsin Ls, Ks and Ss, but while they exhibit

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

    PubMed

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

    2014-05-27

    Experimental infections of three Egyptian Pseudosuccinea columella populations with sympatric miracidia of Fasciola sp., coming from cattle- or sheep-collected eggs, were carried out to determine the capacity of this lymnaeid to support larval development of the parasite. Using microsatellite markers, the isolates of Egyptian miracidia were identified as Fasciola hepatica. Apart from being independent of snail origin, prevalences ranging from 60.4 to 75.5% in snails infected with five miracidia of F. hepatica were significantly higher than values of 30.4 to 42.2% in snails with bi-miracidial infections. The number of metacercariae ranged from 243 to 472 per cercarial-shedding snail and was independent of snail origin, parasite origin and miracidial dose used for infection. If P. columella was subjected to two successive bi-miracidial infections with F. hepatica, prevalence of infection was 63.3%, with a mean of 311 metacercariae per snail. These values were clearly greater than those already reported for Radix natalensis infected with the same parasite and the same protocol. Successful experimental infection of P. columella with F. hepatica suggests that this lymnaeid snail is an important intermediate host for the transmission of fascioliasis in Egypt. PMID:24865184

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

    PubMed

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

    2015-07-01

    Opisthorchiasis secondary to Opisthorchis viverrini infection leads to cholangiocellular carcinoma through chronic inflammation of the bile ducts and possibly inducing autoimmunity. It was hypothesized that plasma autoantibodies directed against self-proteins are biomarkers for opisthorchiasis. Plasma from patients with opisthorchiasis was tested using proteins derived from immortalized cholangiocyte cell lines, and spots reacting with plasma were excised and subjected to LC-MS/MS. Seven protein spots were recognized by IgG autoantibodies, and the highest matching scored protein was actin-related protein 3 (ARP3). The antibody against ARP3 was tested in plasma from 55 O. viverrini-infected patients, 24 patients with others endemic parasitic infections and 17 healthy controls using Western blot and ELISA. Immunoreactivity against recombinant ARP3 was significantly more prevalent in opisthorchiasis compared to healthy controls at Western blotting and ELISA (P < 0·05). Plasma ARP3 autoantibody titres were also higher in opisthorchiasis compared to healthy individuals (P < 0·01) and other parasitic infections including Strongyloides stercoralis (P < 0·001), echinostome (P < 0·05), hookworms (P < 0·001) and Taenia spp. (P < 0·05). It was further characterized in that the ARP3 autoantibody titre had a sensitivity of 78·18% and specificity of 100% for opisthorchiasis. In conclusion, it may be suggested that plasma anti-ARP3 might represent a new diagnostic antibody for opisthorchiasis. PMID:25809205

  4. Liver Biopsy

    MedlinePLUS

    ... for a liver biopsy by talking with a health care provider having blood tests arranging for a ride home fasting before the ... for a liver biopsy by talking with a health care provider having blood tests arranging for a ride home fasting before the ...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-08-01

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

  7. Biogenic monoamines in the freshwater snail, Biomphalaria glabrata: Influence of infection by the human blood fluke, Schistosoma mansoni

    Microsoft Academic Search

    Philip Manger; Jianyong Li; Bruce M Christensen; Timothy P Yoshino

    1996-01-01

    The biogenic monoamines, serotonin (5-HT), dopamine (DA) and l-dopa were measured using high performance liquid chromatography with electrochemical detection (HPLC-ED) in the extracts of the central nervous system (CNS) and plasma of uninfected freshwater snails, Biomphalaria glabrata, and in snails at 7, 14, 21 and 28 days postexposure (PE) to the miracidia of the human blood fluke, Schistosoma mansoni. Relative

  8. High annealing temperature-random amplified polymorphic DNA (HAT-RAPD) analysis of three paramphistome flukes from Thailand

    Microsoft Academic Search

    Pralongyut Sripalwit; Chalobol Wongsawad; Pheravut Wongsawad; Somboon Anuntalabhochai

    2007-01-01

    The rumen flukes of 37 cows (Bos indicus) from Chiang Mai and Lamphun provinces were investigated, and the overall prevalence of infection was 78.38% (29\\/37). Three species were found: Paramphistomum epiclitum, Orthocoelium streptocoelium, and Fischoederius elongatus with prevalences of infection of 75.68%, 48.65%, and 40.54%, respectively. Genomic DNA was amplified by polymerase chain reaction based on the high annealing temperature-random

  9. Liver bioengineering

    PubMed Central

    Caralt, Mireia; Velasco, Enrique; Lanas, Angel; Baptista, Pedro M

    2014-01-01

    Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications. PMID:25102189

  10. Fasciola hepatica: development of monoclonal antibodies and their use to characterize a glycocalyx antigen in migrating flukes.

    PubMed

    Hanna, R E; Trudgett, A G

    1983-07-01

    Using mice harbouring early Fasciola hepatica infections, six monoclonal antibodies were prepared against a tegumental antigen present in T1 granules and glycocalyx of flukes. Blocking tests indicated that all monoclonals bound the same T1 epitope (or epitopes in close proximity on the antigen molecule), but this was not the determinant recognized by sheep and cattle. Localization of antibody binding at light and electron microscope levels showed that T1-type antigen also occurred in metacercarial tegument and in glycocalyx of gut cells and excretory ducts in juvenile and adult flukes. This indicates that the natural host-antibody response to F. hepatica may be to one antigen early in the infection. Protein A-gold labelling of monoclonal treated fluke sections revealed that the epitope was probably a polypeptide, unmodified by glycosylation in Golgi bodies. When isolated by immunoadsorption and separated electrophoretically under reducing conditions T1-type antigen was found to consist of a polypeptide mol. wt. 50 000, possibly linked to smaller entities mol. wt. 25-40 000. Tissue-specific variations in the antigen molecule might be conferred by linkage of different polypeptides or carbohydrate side-chains to an antigenic core polypeptide. A component of T1-type antigen was found to have mol. wt. of 25 000, possibly resembling a polypeptide of mol. wt. 24 000 from Schistosoma mansoni tegument. PMID:6194499

  11. Liver tumors.

    PubMed

    Stringer, M D

    2000-11-01

    Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and/or MR), supplemented by liver biopsy and measurement of tumor markers. The most common benign tumors are hemangiomas, but mesenchymal hamartoma, focal nodular hyperplasia, and adenoma also are found. In Western countries, hepatoblastoma is the most common primary malignant liver tumor; disease-free survival is now possible in more than 80% of affected patients because of advances in combination chemotherapy, improved techniques of surgical resection, and the selective use of liver transplantation. In contrast, there has been less progress in the management of hepatocellular cancer, which still poses many therapeutic challenges. PMID:11112837

  12. Liver tumors

    Microsoft Academic Search

    Mark D. Stringer

    2000-01-01

    Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and\\/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and\\/or MR), supplemented by liver biopsy and measurement of tumor

  13. 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.

  14. Rapid and simple identification of human pathogenic heterophyid intestinal fluke metacercariae by PCR-RFLP.

    PubMed

    Thaenkham, Urusa; Phuphisut, Orawan; Pakdee, Wallop; Homsuwan, Nirundorn; Sa-nguankiat, Surapol; Waikagul, Jitra; Nawa, Yukifumi; Dung, Do Trung

    2011-12-01

    Six species of heterophyid intestinal flukes (HIFs) constitute the major endemic zoonotic fish-borne pathogens in Asia: Haplorchis taichui, H. pumilio, H. yokogawai, Procerovum varium, Stellantchasmus falcatus, and Centrocestus formosanus. Several different species of these parasites are often found co-infecting the same second intermediate fish host. Because of their morphological similarities, differentiating between species of HIF metacercariae is difficult, time-consuming, and frequently results in misidentification. In this study, we aimed to develop an efficient and accurate method of identifying metacercariae of these 6 HIFs. Metacercariae were roughly grouped together, based on morphological characteristics seen under a stereomicroscope. Then, PCR-restriction fragment length polymorphism (PCR-RFLP) was used to identify the exact species of each metacercaria, using the 28S ribosomal RNA gene as the genetic marker and MboII as the restriction enzyme. Using a combination of morphological and molecular methods eliminates the need for DNA sequencing and infecting animal subjects to obtain adult worms, increases accuracy, and decreases the need for laborious morphological identification. Because the method is simple, rapid, and relatively cheap compared with PCR-sequencing, it may be an effective tool for epidemiological studies of HIFs in endemic areas. PMID:21946336

  15. The Digenea parasite Opisthorchis felineus: a target for the discovery and development of novel drugs.

    PubMed

    Mordvinov, Viatcheslav A; Furman, Dagmara P

    2010-10-01

    Opisthorchosis is a helminthiasis affecting mainly the hepatobiliary system and pancreas; its most dramatic complication is malignization of the organs infected by the parasites. The causative agents of opisthorchosis are two species of liver flukes, the trematodes belonging to the family Opisthorchiidae--Opisthorchis felineus and O. viverrini. The Chinese liver fluke, Clonorchis sinensis, also member of the family Opisthorchiidae, causes clonorchosis, a disease very close in symptomatology. According to different estimations, up to 40 million people are currently infected with these liver flukes and up to 600-750 million people in Eurasian countries constitute the risk group. These parasites colonize ever-increasing new areas in Eurasia where this disease has never been previously reported. Opisthorchiases are gradually transforming from a local problem of individual geographic regions to a widespead problem; in particular, O. viverrini is now referred to as "an underestimated parasite." As we see it, O. felineus has all the reasons to share this status. First and foremost, the observed expansion is likely to be connected with the ever-increasing intensity of traffic flows and migration of the infection carriers between cities, regions, and countries. This review briefs the characteristics of O. felineus and the other liver flukes persisting in various countries of Eurasia, clinical manifestations of opisthorchosis, the drugs for chemotherapy of trematodiasis, and the strategy for discovery of new antihelminthic drugs. PMID:20701571

  16. 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. PMID:22575172

  17. Liver disease - resources

    MedlinePLUS

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

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

    PubMed Central

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

    2009-01-01

    Background Blood flukes of the genus Schistosoma are platyhelminth parasites that infect 200 million people worldwide. Digestion of nutrients from the host bloodstream is essential for parasite development and reproduction. A network of proteolytic enzymes (proteases) facilitates hydrolysis of host hemoglobin and serum proteins. Methodology/Principal Findings We identified a new cathepsin L termed SmCL3 using PCR strategies based on S. mansoni EST sequence data. An ortholog is present in Schistosoma japonicum. SmCL3 was heterologously expressed as an active enzyme in the yeast, Pichia pastoris. Recombinant SmCL3 has a broad pH activity range against peptidyl substrates and is inhibited by Clan CA protease inhibitors. Consistent with a function in degrading host proteins, SmCL3 hydrolyzes serum albumin and hemoglobin, is localized to the adult gastrodermis, and is expressed mainly in those life stages infecting the mammalian host. The predominant form of SmCL3 in the parasite exists as a zymogen, which is unusual for proteases. This zymogen includes an unusually long prodomain with alpha helical secondary structure motifs. The striking specificity of SmCL3 for amino acids with large aromatic side chains (Trp and Tyr) at the P2 substrate position, as determined with positional scanning-synthetic combinatorial library, is consistent with a molecular model that shows a large and deep S2 pocket. A sequence similarity network (SSN) view clusters SmCL3 and other cathepsins L in accordance with previous large-scale phylogenetic analyses that identify six super kingdoms. Conclusions/Significance SmCL3 is a gut-associated cathepsin L that may contribute to the network of proteases involved in degrading host blood proteins as nutrients. Furthermore, this enzyme exhibits some unusual sequence and biophysical features that may result in additional functions. The visualization of network inter-relationships among cathepsins L suggests that these enzymes are suitable ‘marker sequences’ for inclusion in future phylogenetic analyses. PMID:19488406

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

    PubMed Central

    Fajtová, Pavla; Štefani?, Saša; Hradilek, Martin; Dvo?ák, Jan; Vondrášek, Ji?í; 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

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

    PubMed

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

    2009-12-01

    Opisthorchis felineus, O. viverrini, and Clonorchis sinensis, the trematodes of the family Opisthorchiidae, are important human parasites. Two previous studies (Kang et al. Parasitol Int 57:191-197, 2008; Katokhin et al. Dokl Biochem Biophys 421:214-217, 2008) have provided evidence using ribosomal and mitochondrial sequences that O. viverrini, O. felineus, and C. sinensis are closely related. We developed a novel nuclear marker, Pm-int9, which included the ninth intron of the paramyosin gene and flanking exon sequences. Samples of O. felineus from four localities of West Siberia, C. sinensis from the Russian Far East, and O. viverrini from Thailand were genotyped by Pm-int9. Little variation was detected in exon sequences, however, intron sequences turned out to be more variable than ribosomal internal transcribed spacers. We can conclude that Pm-int9 is valuable for interspecific variation studies. Phylogenetic analysis based on Pm-int9 revealed that O. viverrini and C. sinensis were closer to each other than either of them to O. felineus, supporting the opinion that C. sinensis should be considered the sister species of Opisthorchis spp. PMID:19777262

  1. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Extracorporeal liver support.

    PubMed

    Leckie, Pamela; Davenport, Andrew; Jalan, Rajiv

    2012-01-01

    Mortality of patients with liver failure remains unacceptably high. As the liver has an enormous potential to regenerate, extracorporeal liver support devices may allow patients with liver failure to be bridged to recovery. Alternatively, liver assist may allow patients with advanced liver disease to be managed until a suitable organ for transplant is available. Current approaches to liver support include the use of biological devices that contain hepatocytes and those that function as detoxification devices, and artificial liver support systems. This review describes the current state of the art and existing data on the use of these devices to treat patients with liver failure. PMID:23095415

  4. Cloning and expression of 21.1-kDa tegumental protein of Clonorchis sinensis and human antibody response to it as a trematode–nematode pan-specific serodiagnosis antigen

    Microsoft Academic Search

    Jiajia Chen; Hongxu Xu; Zhaoping Zhang; Suxiang Zeng; Wenjia Gan; Xinbing Yu; Xuchu Hu

    2011-01-01

    A complete cDNA encoding a 21.1-kDa tegumental protein (CsTP21.1) was recognized from Clonorchis sinensis adult full-length cDNA plasmid library by bioinformatics analysis. Recombinant CsTP21.1 was highly expressed in Escherichia coli, purified by affinity chromatography, and identified by Western blotting. Immunohistochemistry demonstrated that CsTP21.1\\u000a is localized in the tegument of the adult worm. The rCsTP21.1-specific IgG1, IgG2, and IgG4 subclasses could

  5. Liver Cell Death

    Microsoft Academic Search

    Harmeet Malhi; Gregory J. Gores

    \\u000a Hepatocyte cell death is an indispensible and cardinal element that precipitates and perpetuates liver injury [1]. Accordingly,\\u000a liver injury can result in acute or chronic liver disease. This distinction between acute and chronic liver disease is arbitrary;\\u000a a reflection of the etiology and time course of liver injury. Hepatocytes are the predominant parenchymal cell type in the\\u000a liver. Commonly encountered

  6. 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

  7. Fasciola hepatica: characterization of somatic and excretory-secretory antigens of adult flukes recognized by infected sheep.

    PubMed

    Ruiz-Navarrete, M A; Arriaga, C; Bautista, C R; Morilla, A

    1993-01-01

    The immune response of sheep to somatic components and excretory/secretory products of adult Fasciola hepatica, was studied during an experimental infection. Antibodies against adult fluke somatic and excretory/secretory antigens were detected by thin layer immunoassay from the second week post infection. Similarly, the results of Western blot analysis showed specific recognition of several components as early as two weeks after infection. However, an increase in the number and intensity of bands with time of infection was observed in the patterns of antigenic recognition. Most notorious was the strong reactivity of all infected sheep sera towards components of 20-23 kDa in the somatic preparation and components of 23-27 kDa in the excretory/secretory products of adult F. hepatica, specially noticeable after the sixth week post-infection. Since these polypeptides were recognized by all infected animals, they could play an important role in the diagnosis of sheep fascioliasis. PMID:8047733

  8. 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. PMID:24291605

  9. Liver disease in menopause.

    PubMed

    Brady, Carla W

    2015-07-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure. PMID:26167064

  10. Liver disease in menopause

    PubMed Central

    Brady, Carla W

    2015-01-01

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

  11. Reverse transcriptase activity and untranslated region sharing of a new RTE-like, non-long terminal repeat retrotransposon from the human blood fluke, Schistosoma japonicum

    Microsoft Academic Search

    Thewarach Laha; Paul J. Brindley; Michael J. Smout; Christiana K. Verity; Donald P. McManus; Alex Loukas

    2002-01-01

    A new RTE-like, non-long terminal repeat retrotransposon, termed SjR2, from the human blood fluke, Schistosomajaponicum, is described. SjR2 is ?3.9 kb in length and is constituted of a single open reading frame encoding a polyprotein with apurinic\\/apyrimidinic endonuclease and reverse transcriptase domains. The open reading frame is bounded by 5?- and 3?-terminal untranslated regions and, at its 3?-terminus, SjR2 bears

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

    Microsoft Academic Search

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

    2005-01-01

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

  13. Fasciola hepatica : Tegumental surface changes in adult and juvenile flukes following treatment in vitro with the sulphoxide metabolite of triclabendazole (Fasinex)

    Microsoft Academic Search

    A. W. Stitt; I. Fairweather

    1993-01-01

    The effects of the novel benzimidazole, triclabendazole (Fasinex, Ciba-Geigy), in its active sulphoxide metabolite form (TCBZ-SX), on the tegumental surface ofFasciola hepatica has been examined in vitro. The tegument of adult flukes incubated in TCBZ-SX (50 µg\\/ml) appeared swollen and blebbed after only 6 h. In addition, progressive spine loss at the oral cone was evident following 12 h treatment.

  14. 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 of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

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

    PubMed

    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 of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

  16. Fishborne Zoonotic Intestinal Trematodes, Vietnam

    PubMed Central

    Dung, Do Trung; Van De, Nguyen; Waikagul, Jitra; Dalsgaard, Anders; Chai, Jong-Yil; Sohn, Woon-Mok

    2007-01-01

    Although fishborne zoonotic trematodes that infect the liver are well documented in Vietnam, intestinal fishborne zoonotic trematodes are unreported. Recent discoveries of the metacercarial stage of these flukes in wild and farmed fish prompted an assessment of their risk to a community that eats raw fish. A fecal survey of 615 persons showed a trematode egg prevalence of 64.9%. Infected persons were treated to expel liver and intestinal parasites for specific identification. The liver trematode Clonorchis sinensis was recovered from 51.5%, but >1 of 4 intestinal species of the family Heterophyidae was recovered from 100%. The most numerous were Haplorchis spp. (90.4% of all worms recovered). These results demonstrate that fishborne intestinal parasites are an unrecognized food safety risk in a country whose people have a strong tradition of eating raw fish. PMID:18258031

  17. Opisthorchiidosis--a review.

    PubMed

    Schuster, Rolf K

    2010-10-01

    The discovery history of opisthorchiid flukes dates back more than 200 years. The life cycle of these liver flukes includes prosobranch snails as the first and a big variety of freshwater fish as the second intermediate hosts. Opisthorchis felineus, O. viverrini and Clonorchis sinensis are species of major medical importance, while sporadic cases of human infection with other representatives of this family are also documented in the literature. There are estimations that 17 million people are infected and more than 350 million people are at risk, mainly in Asian countries. Although opisthorchiid flukes live in the bile ducts of the liver and in the gall bladder, they can affect surrounding liver tissue and even other organs. They are also known to induce the production of autoantibodies as well as allergic reactions. However, the main medical significance is their role in the formation of malignant tumors. Since the clinical symptoms are not specific, a diagnosis must be confirmed by parasitological examination or the detection of antibodies. Apart from coproscopical methods, there are more recent and highly specific assays available, like the detection of coproantigen or the detection of DNA. Praziquantel is the drug of choice for the treatment of opisthorchiidosis. In order to prevent infection, consumption of raw flesh of freshwater fish must be avoided. PMID:20701569

  18. Diet and Your Liver

    MedlinePLUS

    ... have a lot of fiber such as fresh fruits and vegetables, whole grain breads, rice and cereals Are there diet changes for those with liver disease? It is important for people with liver disease ...

  19. Cell Therapies for Liver Diseases

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    1995-06-01

    An enzyme-linked immunosorbent assay (ELISA) is described utilizing the surface glycocalyx crude antigen of adult blood trematodes Learedius learedi, Hapalotrema dorsopora, and Carettacola hawaiiensis, for the detection of circulating antibodies (Ab) in Hawaiian green turtles (Chelonia mydas) naturally infected with the parasites and with or without green turtle fibropapillomatosis (GTFP). A concentration of 10.0 micrograms/ml of antigen was optimal in terms of test specificity and sensitivity. A direct ELISA with anti-reptilian/amphibian phosphatase-labeled IgG identified C. mydas Ab at a dilution of 1/12,800. Utilizing indirect ELISA, it was possible to detect Ab to blood flukes at a dilution of 1/3,200. The gross lesions and histopathology were typical for cardiovascular spirorchidiasis in C. mydas. No significant relationship was found between the size of turtles and the degree of GTFP severity. Forty-seven of 59 (80%) samples, from 5 sites, gave a positive ELISA reaction; 6 of the 47 (13%) specimens gave significantly (P < 0.001) higher absorbance values, with 5 from the same location. All 12 (20%) ELISA-negative turtles originated from 1 site, and the absorbance values of the 41 animals from this location were significantly lower (P < 0.015) when compared with the other 4 sites. The proposed assay is fast, has the feature of visual scoring, and can be used for determination of exposure of C. mydas to the spirorchid trematodes. PMID:7776127

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

    PubMed Central

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

    2012-01-01

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

  2. Proteomic Analysis of Human Skin Treated with Larval Schistosome Peptidases Reveals Distinct Invasion Strategies among Species of Blood Flukes

    PubMed Central

    Ingram, Jessica; Knudsen, Giselle; Lim, K. C.; Hansell, Elizabeth; Sakanari, Judy; McKerrow, James

    2011-01-01

    Background Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts. Methods Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays. Conclusions This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts. PMID:21980548

  3. Managing liver failure

    Microsoft Academic Search

    D A Kelly

    2002-01-01

    Liver disease is rare in childhood, but important new developments have altered the natural history and outcome. It is important that clinicians are aware of these diseases and their management. Acute liver failure is most often due to viral hepatitis, paracetamol overdose, or inherited metabolic liver disease. The clinical presentation includes jaundice, coagulopathy, and encephalopathy. Early diagnosis is necessary to

  4. Laparoscopic Liver Resection for Malignant Liver Tumors

    PubMed Central

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

    2002-01-01

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

  5. Elucidation of genetic variability among different isolates of Fasciola gigantica (giant liver fluke) using random-amplified polymorphic DNA polymerase chain reaction

    Microsoft Academic Search

    K. R. Gunasekar; A. K. Tewari; C. Sreekumar; S. C. Gupta; J. R. Rao

    2008-01-01

    The present communication focuses on molecular characterization of Fasciola gigantica isolates derived from cattle, buffalo, and goat using random-amplified polymorphic DNA (RAPD)–polymerase chain reaction (PCR)\\u000a analysis to elucidate genetic variability between the three isolates. Seventeen random oligonucleotide primers of 10–11 bases\\u000a with GC content varying from 50–81.8% were used in the study. Depending upon the F. gigantica isolate–primer combination, one

  6. Tolerance Induction in Liver

    PubMed Central

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

    2015-01-01

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

  7. Robotic liver surgery.

    PubMed

    Leung, Universe; Fong, Yuman

    2014-10-01

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

  8. Cryotherapy for liver metastases

    Microsoft Academic Search

    Joachim K. Seifert; Tobias Achenbach; Achim Heintz; Thomas C. Böttger; Theodor Junginger

    2000-01-01

    Cryotherapy is undergoing a renaissance in the treatment of nonresectable liver tumors. In a prospective case control study\\u000a we assessed the morbidity, mortality, and efficacy of hepatic cryotherapy for liver metastases. Between January 1996 and September\\u000a 1999 a total of 54 cryosurgical procedures were performed on 49 patients (median age 66 years, 21 women) with liver metastases.\\u000a Patient, tumor, and

  9. Laser repair of liver

    NASA Astrophysics Data System (ADS)

    Prahl, Scott A.; Denison, Tim; LaJoie, Elaine

    2001-05-01

    Laser repair of liver using albumin is a promising method for treating liver trauma. Concentrated human serum albumin is applied to a liver laceration and then denatured using a laser. These repairs were pulled with a material tester to measure the ultimate strength of the laser repair. We show that the ultimate strength of the liver repairs tends to increase with delivered laser energy, that the mode of delivery (pulsed versus continuous) does not matter, that the repair strength correlates with the area of denatured albumin, and that strong welds cause about 1.5 mm of thermal damage.

  10. Liver transplantation for adult polycystic liver disease.

    PubMed

    Swenson, K; Seu, P; Kinkhabwala, M; Maggard, M; Martin, P; Goss, J; Busuttil, R

    1998-08-01

    Polycystic liver disease, commonly associated with polycystic kidney disease, can result in massive hepatomegaly and debilitating symptoms. Surgical intervention for symptomatic polycystic liver disease has been associated with significant morbidity and inconsistent long-term palliation; it is more appropriate in patients with a single dominant cyst or cysts which is/are confined to one lobe. At our institution, nine patients have undergone orthotopic liver transplantation for symptomatic hepatic cysts with excellent long-term results and minimal morbidity and mortality. Surgical candidates were selected based on severe limitations in daily activities and on sequelae of hepatic cystic involvement. Other factors considered were the extent and pattern of hepatic cystic disease, the degree of hepatic and renal dysfunction, and prior surgical intervention. Three patients (33%) required combined liver and kidney transplantation because of renal cystic involvement with renal insufficiency. The one-year survival rate was 89% with excellent symptomatic relief and improved quality of life in all the surviving patients. One death occurred in a significantly malnourished 62-year-old female. Complications included one case each of hepatic artery thrombosis requiring retransplantation, biliary leak necessitating biliary reconstruction, and postoperative bleeding requiring re-exploration. The mean hospital stay was 23 days and the mean intraoperative blood transfusion requirement was 18 units. Our experience demonstrates that appropriately selected patients with extensive hepatic involvement with adult polycystic liver disease can have an excellent outcome with transplantation, with morbidity comparable with other surgical options. PMID:9696005

  11. Hypoxia and fatty liver

    PubMed Central

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

    2014-01-01

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

  12. General Information about Adult Primary Liver Cancer

    MedlinePLUS

    ... General Information About Adult Primary Liver Cancer Key Points Adult primary liver cancer is a disease in ... liver. Stages of Adult Primary Liver Cancer Key Points After adult primary liver cancer has been diagnosed, ...

  13. Stages of Adult Primary Liver Cancer

    MedlinePLUS

    ... General Information About Adult Primary Liver Cancer Key Points Adult primary liver cancer is a disease in ... liver. Stages of Adult Primary Liver Cancer Key Points After adult primary liver cancer has been diagnosed, ...

  14. 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

  15. Food-borne trematodiases.

    PubMed

    Keiser, Jennifer; Utzinger, Jürg

    2009-07-01

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

  16. Imaging of liver cancer

    PubMed Central

    Ariff, Ben; Lloyd, Claire R; Khan, Sameer; Shariff, Mohamed; Thillainayagam, Andrew V; Bansi, Devinder S; Khan, Shahid A; Taylor-Robinson, Simon D; Lim, Adrian KP

    2009-01-01

    Improvements in imaging technology allow exploitation of the dual blood supply of the liver to aid in the identification and characterisation of both malignant and benign liver lesions. Imaging techniques available include contrast enhanced ultrasound, computed tomography and magnetic resonance imaging. This review discusses the application of several imaging techniques in the diagnosis and staging of both hepatocellular carcinoma and cholangiocarcinoma and outlines certain characteristics of benign liver lesions. The advantages of each imaging technique are highlighted, while underscoring the potential pitfalls and limitations of each imaging modality. PMID:19294758

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

    PubMed Central

    Biswal, Devendra K.; Chatterjee, Anupam

    2014-01-01

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

  18. Emerging Therapies for Liver Fibrosis

    Microsoft Academic Search

    Andrew J. Fowell; John P. Iredale

    2006-01-01

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

  19. Liver function tests

    MedlinePLUS

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

  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. Diet - liver disease

    MedlinePLUS

    Liver disease can affect the absorption of food and the production of proteins and vitamins. Therefore, your diet may influence your weight, appetite, and the amounts of vitamins in your body. Do not limit ...

  2. [Diabetes in liver cirrhosis].

    PubMed

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

    2013-01-01

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

  3. Optical diagnostics of liver pathology

    NASA Astrophysics Data System (ADS)

    Randeberg, Lise L.; Haugen, Olav A.; Svaasand, Lars O.

    2003-10-01

    The applicability of reflectance spectroscopy to detect pathological changes in human liver tissue was investigated. Post mortem reflectance spectra were collected from liver tissue originating from 13 individuals. A point counting method was applied to determine relative areas of connective tissue, liver cells with or without fat vacuoles, and vascular spaces in the liver. Preliminary results show that the amount of fat and connective tissue in liver can be estimated from reflectance spectra.

  4. Fortuitously discovered liver lesions

    PubMed Central

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

    2013-01-01

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

  5. Neuropilins and liver

    PubMed Central

    Elpek, Gülsüm Özlem

    2015-01-01

    Neuropilins (NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1 (NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor ?1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized. PMID:26109793

  6. Mice with human livers.

    PubMed

    Grompe, Markus; Strom, Stephen

    2013-12-01

    Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals. The advent of transgenic immune-deficient mice has made it possible to generate chimeric animals harboring human tissues and cells, including hepatocytes. The liver plays a central role in many human-specific biological processes and mice with humanized livers can be used to model human metabolism, liver injury, gene regulation, drug toxicity, and hepatotropic infections. PMID:24042096

  7. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure. PMID:26049068

  8. Neoplasms of the liver

    SciTech Connect

    Okuda, K.; Ishak, K.G.

    1987-01-01

    Primary Liver Cancer is perhaps the most prevalent malignancy in the world, particularly in South East Asia and Africa. After the discovery of hepatitis B virus as a cause of chronic liver disease often terminating cirrhosis and hepatocellular carcinoma, and, more recently, the integration of viral DNA into host chromosomal DNA, the progress made in this field has been remarkable. This book contains 35 chapters and covers all topical aspects, such as oncogenes, epidemiology, carcinogenic role of hepatitis viruses, histopathology, new imaging techniques and new treatment modalities that include ultrasound-guided intratumor injections of ethanol and targeting chemotherapy.

  9. Polycystic liver disease treated by fenestration and segmental liver resection.

    PubMed

    Haron, A; Hisham, A N; Samad, S A

    1994-03-01

    A case of symptomatic polycystic liver disease treated by fenestration and segmental liver resection is reported. The intraoperative use of ultrasound to define the plane of liver resection is emphasised. No significant post-operative complication was encountered. The clinical presentation, management and treatment are discussed. PMID:8057997

  10. What's New in Liver Cancer Research?

    MedlinePLUS

    ... can I learn more about liver cancer? What`s new in liver cancer research? There is always research ... liver cancer worldwide. Finding liver cancer early Some new blood tests are being studied to see if ...

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

    Microsoft Academic Search

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

    2003-01-01

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

  12. Arteriovenous shunts involving the liver.

    PubMed

    Adler, J; Goodgold, M; Mitty, H; Gordon, D; Kinkhabwala, M

    1978-11-01

    Arteriovenous shunting in the liver is a rare angiographic finding. Review of the literature shows that most cases are related to trauma or neoplasm. The authors discuss several entities which should also be included in the differential diagnosis, among them congenital arteriovenous malformations or hemangiomas of the liver and pancreas, cirrhosis with rearterialization of the liver, hepatic abscess, hypervascular liver metastases, and primary tumors with invasion of the portal and hepatic veins by arterial neovasculature. PMID:704843

  13. Glycosylation and liver cancer.

    PubMed

    Mehta, Anand; Herrera, Harmin; Block, Timothy

    2015-01-01

    Liver cancer is the fifth most common cancer, but the second leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus or hepatitis C virus infection. While chronic viral infection remains the main cause of liver disease and risk of hepatocellular carcinoma (HCC), rates of nonviral-associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2-7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation, and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development. PMID:25727150

  14. 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 (...

  15. 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. PMID:25291138

  16. Liver transplantation for hepatoblastoma.

    PubMed

    Faraj, Walid; Dar, Faisal; Marangoni, Gabriele; Bartlett, Adam; Melendez, Hector Vilca; Hadzic, Dino; Dhawan, Anil; Mieli-Vergani, Georgina; Rela, Mohamed; Heaton, Nigel

    2008-11-01

    From October 1993 to February 2007, 25 liver transplantations were performed for hepatoblastoma. Of these 25, 18 children received cadaveric grafts, and 7 received left lateral segments from living donors. Fifteen patients were at level IV in the pretreatment extent of disease staging system for hepatoblastoma (PRETEXT IV; 11 received cadaveric grafts and 4 underwent living related liver transplantation [LRLT]) and 10 were level III (PRETEXT III; 7 received cadaveric grafts and 3 underwent LRLT). Preoperative chemotherapy was given according to the risk stratification system for children with hepatoblastoma protocols of the International Childhood Liver Tumour Strategy Group of the International Society of Paediatric Oncology (SIOPEL): SIOPEL I in the first 3 patients, SIOPEL II in 6, SIOPEL III in 10, and SIOPEL IV in 3 patients. Patient and graft survival after cadaveric transplantation was 91%, 77.6%, and 77.6%, at 1, 5, and 10 years, respectively, with no retransplantations. Patient and graft survival for children undergoing LRLT was 100%, 83.3%, and 83.3%, at 1, 5, and 10 years, respectively. All surviving children but 1 remain disease-free, with a median follow up of 6.8 years (range, 0.9-14.9). There were 5 deaths at a median of 13 months post-transplantation, secondary to tumor recurrence (4) and respiratory failure (1). Liver transplantation is an established treatment for unresectable hepatoblastoma confined to the liver following chemotherapy. LRLT is a therapeutic option given that the outcome is similar to that of resection and cadaveric transplantation. PMID:18975296

  17. Differences in susceptibility and immune responses of three-spined sticklebacks (Gasterosteus aculeatus) from lake and river ecotypes to sequential infections with the eye fluke Diplostomum pseudospathaceum

    PubMed Central

    2014-01-01

    Background The eye fluke Diplostomum pseudospathaceum is a frequent parasite of many fresh-water fish species, among those three-spined sticklebacks, particularly in lakes with lymnaeid snails, its first intermediate hosts. Cercariae released from host-snails, penetrate the skin of their fish hosts and within 24 h migrate to the immunologically inert eye lenses. Thus, individual D. pseudospathaceum are exposed to the fish immune system only for a short time, suggesting that only innate immunity can be active against the parasite. However, in nature sticklebacks are exposed to D. pseudospathaceum repeatedly since snails are shedding cercariae from late spring to autumn. Therefore, acquired immunity after initial infection would be advantageous against subsequent parasite encounters. Methods We investigated if sticklebacks originating from a lake with high and from a river with low prevalence of D. pseudospathaceum differ in susceptibility to repeated exposure to the parasite. We compared infection success and immune functions in laboratory-bred sticklebacks from both habitats in naďve fish with fish that had been pre-exposed to eye flukes. Head kidney leukocytes (HKL) from experimental sticklebacks were investigated for respiratory burst activity and the proliferation of lymphocytes and monocytes 1.5, 5 and 15 days after infection. Results Lake sticklebacks were less susceptible than river sticklebacks, however, in both populations pre-exposure led to a similar relative reduction in infection success. The respiratory burst activity was higher with HKL from lake sticklebacks and was up-regulated in pre-exposed fish but dropped 1.5d after an additional exposure, suggesting that activation of phagocytic cells is crucial for the defense against D. pseudospathaceum. Changes in lymphocyte proliferation were only detectable 1.5d after the last exposure in lake sticklebacks, but not 5 and 15d post exposure, indicating that a lymphocyte mediated acquired immune response was not induced. Proliferation of monocytes was significantly increased 1.5d after the last exposure with HKL from both stickleback populations. Conclusions Increased resistance to D. pseudospathaceum in sticklebacks from both populations upon pre-exposure cannot be explained by a prominent adaptive immune response. Monocytic leukocytes were more responsive, suggesting that rather cells of the innate than the adaptive immune system are active in the defense of D. pseudospathaceum. PMID:24656136

  18. Hedgehog Signaling in the Liver

    PubMed Central

    Omenetti, Alessia; Choi, Steve; Michelotti, Gregory; Diehl, Anna Mae

    2010-01-01

    Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include expansion of liver progenitor populations to promote liver regeneration, but also hepatic accumulation of inflammatory cells, liver fibrogenesis, and vascular remodeling. All of these latter responses are known to be involved in the pathogenesis of cirrhosis. In addition, Hh signaling may play a role in primary liver cancers, such as cholangiocarcinoma and hepatocellular carcinoma. Study of Hedgehog signaling in liver cells is in its infancy. Additional research in this area is justified given growing experimental and clinical data supporting a role for the pathway in regulating outcomes of liver injury. PMID:21093090

  19. Liver transplantation for hepatocellular carcinoma

    PubMed Central

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

    2009-01-01

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

  20. 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

  1. [Antioxidants in liver protection].

    PubMed

    Hagymási, Krisztina; Blázovics, Anna

    2004-07-01

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

  2. Fatty liver in childhood

    PubMed Central

    Ozturk, Yesim; Soylu, Ozlem Bekem

    2014-01-01

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

  3. Liver transplantation in children.

    PubMed

    Muiesan, Paolo; Vergani, Diego; Mieli-Vergani, Giorgina

    2007-02-01

    Liver transplantation (LT) is now a standard treatment for children with end-stage liver disease with excellent 1- and 5-year survival. This has been achieved through improvement of surgical techniques and anti-rejection treatment and management. The donor pool for children has been extended by the use of cut-down, split, living-related and, recently, non-heart-beating donor and isolated hepatocyte transplantation. Though the majority of transplanted children enjoy an excellent quality of life, there remain a high number of possible complications, including short-term primary non-function, vascular and biliary problems, bowel perforation, severe rejection, infection, hypertension and long-term renal impairment, chronic rejection, de novo autoimmunity, lymphoproliferative disease and cancer, most of which are related to anti-rejection drug toxicity. Hence, the focus of research for paediatric LT should be induction of tolerance, avoiding long-term immunosuppression and its toxicity. PMID:17161491

  4. LIVER PARENCHYMAL CELL INJURY

    PubMed Central

    Reynolds, Edward S.

    1965-01-01

    Accumulation of calcium in the mitochondria of rat liver parenchymal cells at 16 and 24 hours after poisoning with carbon tetrachloride is associated with an increase in amount of liver inorganic phosphate, the persistence of mitochondrial adenosine triphosphatase activity, and the formation of electron-opaque intramitochondrial masses in cells with increased calcium contents. These masses, which form within the mitochondrial matrix adjacent to internal mitochondrial membranes, resemble those observed in isolated mitochondria which accumulate calcium and inorganic phosphate; are present in a locus similar to that of electron opacities which result from electron-histochemical determination of mitochondrial ATPase activity; and differ in both appearance and position from matrix granules of normal mitochondria. After poisoning, normal matrix granules disappear from mitochondria prior to their accumulation of calcium. As calcium-associated electron-opaque intramitochondrial masses increase in size, mitochondria degenerate in appearance. At the same time, cytoplasmic membrane systems of mid-zonal and centrilobular cells are disrupted by degranulation of the rough endoplasmic reticulum and the formation of labyrinthine tubular aggregates. The increase in amount of inorganic phosphate in rat liver following poisoning is balanced by a decreased amount of phosphoprotein. These chemical events do not appear to be related, however, as the inorganic phosphate accumulated is derived from serum inorganic phosphate. PMID:4284648

  5. Voriconazole and the liver

    PubMed Central

    Mih?il?, Romeo-Gabriel

    2015-01-01

    Voriconazole is an azole useful for the prophylaxis and the treatment of aspergillosis and other fungal infections in immunosuppressed subjects, as those found in aplasia after aggressive polychemotherapy treatments, after hematopoietic stem cell, liver or lung transplantation. Its administration in therapeutic doses lead to extremely varied serum levels from patient to patient and even to the same patient. The explanations are varied: nonlinear pharmacokinetics, certain patient-related factors, including genetic polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function, simultaneous administration with other drugs metabolised by the same cytochrome. It is recommended to maintain the serum concentrations of voriconazole between 1.5 and 4 ?g/mL. At lower values its efficacy decreases and at higher values the risk of neurological toxicity increases. Even at these concentrations it is not excluded the possible appearance of a variety of toxic effects, including on the liver, manifested by cholestasis, hepatocytolisis, or their combination. It is recommended to monitor the clinical and laboratory evolution of all patients treated with voriconazole, and of the serum levels of the drug of those who belong to risk groups, even if there is still no consensus on this issue, given the lack of correlation between the serum level and the occurrence of adverse effects in many patients.

  6. Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni

    PubMed Central

    Yoshino, Timothy P.; Dinguirard, Nathalie; Kunert, John; Hokke, Cornelius H.

    2008-01-01

    In the present study, a tandem-repeat type galectin was characterized from an embryonic cell line (Bge) and circulating hemocytes of the snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni. The predicted B. glabrata galectin (BgGal) protein of 32 kDa possessed 2 carbohydrate recognition domains, each displaying 6 of 8 conserved amino acids involved in galactoside-binding activity. A recombinant BgGal (rBgGal) demonstrated hemagglutinating activity against rabbit erythrocytes, which was specifically inhibited by galactose-containing sugars (lacNAc/lac > galNAc/gal). Although native galectin was immunolocalized in the cytoplasm of Bge cells and the plasma membrane of a subset of snail hemocytes (60%), it was not detected in cell-free plasma by Western blot analysis. The findings that rBgGal selectively recognizes the schistosome-related sugar, lacNAc, and strongly binds to hemocytes and the tegument of S. mansoni sporocysts in a sugar-inhibitable fashion suggest that hemocyte-bound galectin may be serving as pattern recognition receptor for this, or other pathogens possessing appropriate sugar ligands. Based on molecular and functional features, BgGal represents an authentic galectin, the first to be fully characterized in the medically-important molluscan Class Gastropoda. PMID:18280060

  7. Current techniques of liver transection

    PubMed Central

    2007-01-01

    The operative mortality rate of liver resection has decreased from 10% to 20% before the 1980s to <5% in most specialized hepatobiliary centers nowadays. The most important factor for better outcome is reduced blood loss due to improvement in surgical techniques. Liver transection is the most challenging part of liver resection, associated with a risk of massive hemorrhage. Understanding the segmental anatomy of the liver and delineation of the proper transection plane using intraoperative ultrasound are prerequisites to safe liver transection. Clamp crushing and ultrasonic dissection are the two most widely used transection techniques. In recent years, new instruments using different types of energy for coagulation or sealing of vessels have been developed for liver transection. These include radiofrequency devices, Harmonic Scalpel, Ligasure and TissueLink dissecting sealer. Whether these new instruments, used alone or in combination with clamp crushing or ultrasonic dissection, improve the safety of liver transection has not been clearly demonstrated. The use of the vascular stapler for transection of major intrahepatic vascular trunks is also gaining popularity. These new instruments are particularly useful in liver transection during laparoscopic liver resection. Adjunctive measures such as intermittent Pringle maneuver and low central venous pressure anesthesia are also useful measures to reduce the risk of hemorrhage. This article reviews the safety and efficacy of different techniques of liver transection, with particular attention to evidence from randomized controlled trials available in the literature. PMID:18333217

  8. Genetic diversity of nuclear ITS1-5.8S-ITS2 rDNA sequence in Clonorchis sinensis Cobbold, 1875 (Trematoda: Opisthorchidae) from the Russian Far East.

    PubMed

    Tatonova, Yulia V; Chelomina, Galina N; Besprosvannykh, Vladimir V

    2012-12-01

    The present study examined the molecular organisation and sequence variation in the nuclear ribosomal DNA (rDNA) region, including the two internal transcribed spacers (ITS1 and ITS2) and the 5.8S gene of the Clonorchis sinensis from the Russian Far East. The relevant sequences from other parts of this species' area were downloaded from GenBank. The results showed 100% identity for all investigated 5.8S-ITS2 rDNA sequences. In contrast, two levels of intraspecific variations were revealed in the complete ITS1 sequences. The intra-genomic variation resulted from a C/T polymorphism in a single position. The inter-individual differences between the ITS1 sequences were both due to nucleotide and size polymorphisms resulting from a varying number of five-nucleotide repeats and followed by two ITS1 length variants. These variant frequencies correlate with the clonorchiasis level in some geographical localities. ITS1 differences, both in the mutation profile and mutation localisation, were revealed between northern and southern geographical samples. The presence of GC boxes that are identical to known regulatory motifs in eukaryotes was detected within the ITS1 sub-repeats. The predicted secondary structures for ITS1 consist of two large branches, one of which was invariable, while another depended on ITS1 length. The predicted secondary structure for ITS2 includes four helices around the core. The main differences between C. sinensis and other opisthorchids were localised on the tops of helices 2, 3, and 4. A phylogenetic MST reconstruction subdivided all ITS1 sequences into two well differentiated clusters, each with the major widespread ribotype, and showed that ribotype diversity in both Russia and Korea is much lower than in China. The results obtained demonstrate the feasibility of complete ITS1 sequences in C. sinensis population genetics and can be considered as a basis for further studies of the parasite infection because they may help to elucidate the molecular mechanisms of pathogen evolution and adaptation. PMID:22824337

  9. Radiation-Associated Liver Injury

    SciTech Connect

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

    2010-03-01

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

  10. Chronic liver inflammation: Clinical implications beyond alcoholic liver disease

    PubMed Central

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

    2014-01-01

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

  11. Chronic liver inflammation: clinical implications beyond alcoholic liver disease.

    PubMed

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

    2014-03-01

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

  12. Results of liver transplantation in children with unresectable liver tumors

    Microsoft Academic Search

    Riccardo Superina; Ron Bilik

    1996-01-01

    Liver cancer is an uncommon indication for liver transplantation in children. Between 1986 and 1995, five children with hepatocellular cancer (HCC), three with hepatoblastoma (HEP), and one with sarcoma were referred to the transplant service. All nine tumors were considered unresectable. Four of the five children with HCC had underlying predisposing conditions (2 hepatitis B, 1 biliary atresia, 1 tyrosinemia).

  13. Antifibrinolytics in liver surgery

    PubMed Central

    Makwana, Jalpa; Paranjape, Saloni; Goswami, Jyotsna

    2010-01-01

    Hyperfibrinolysis, a known complication of liver surgery and orthotopic liver transplantation (OLT), plays a significant role in blood loss. This fact justifies the use of antifibrinolytic drugs during these procedures. Two groups of drug namely lysine analogues [epsilon aminocaproic acid (EACA) and tranexamic acid (TA)] and serine-protease-inhibitors (aprotinin) are frequently used for this purpose. But uniform data or guidelines on the type of antifibrinolytic drugs to be used, their indications and correct dose, is still insufficient. Antifibrinolytics behave like a double-edged sword. On one hand, there are benefits of less transfusion requirements but on the other hand there is potential complication like thromboembolism, which has been reported in several studies. We performed a systematic search in PubMed and Cochrane Library, and we included studies wherein antifibrinolytic drugs (EACA, TA, or aprotinin) were compared with each other or with controls/placebo. We analysed factors like intraoperative red blood cell and fresh frozen plasma requirements, the perioperative incidence of hepatic artery thrombosis, venous thromboembolic events and mortality. Among the three drugs, EACA is least studied. Use of extensively studied drug like aprotinin has been restricted because of its side effects. Haemostatic effect of aprotinin and tranexamic acid has been comparable. However, proper patient selection and individualized treatment for each of them is required. Purpose of this review is to study various clinical trials on antifibrinolytic drugs and address the related issues like benefits claimed and associated potential complications. PMID:21224964

  14. Experience of laparoscopic liver resection for various liver diseases

    PubMed Central

    Park, Juhong; Kim, Seokhwan; Song, Insang

    2014-01-01

    Backgrounds/Aims We present our experience of laparoscopic liver resection for various liver diseases. Methods From April 2008 to August 2012 in Chungnam National University, 68 of 253 liver resections were performed laparoscopically. During the first year, laparoscopy-assisted liver resection was mainly performed and subsequently totally laparoscopic liver resection was the main operative type. Surgery type for treatment purposes was decided preoperatively. Clinical data were collected retrospectively and analyzed. Results Preoperatively, 43 patients (63.2%) were diagnosed with benign disease, 19 patients (27.9%) were malignant liver tumors and 6 patients (8.8%) were indeterminate liver tumor but favorable towards malignancy. Anatomical major liver resection was performed in 58 cases (85.3%) and 10 cases (14.7%) were non-anatomical resection. Left hemihepatectomy was performed in 38 cases (55.8%) followed by left lateral sectionectomy in 18 cases (26.5%), and segment IV and IVa segmentectomy, were each in 1 case. Mean operation time was 235.0 minutes (range, 60-470) and 14 patients (18.6%) had intraoperative transfusion. Mean postoperative hospital stay was 10.2 days (range, 4-32). Mean operation time of laparoscopy-assisted left lobectomy was 317 minutes and totally laparoscopic left lobectomy was 281 minutes, but there was no significant statistical difference between these two operation types. There were 11 episodes of postoperative complications in 8 patients. There was no mortality after laparoscopic liver resection. Conclusions We concluded that laparoscopic liver resection is a feasible operation, but needs to be carefully conducted in malignant tumors.

  15. Chronic Liver Disease and Hispanic Americans

    MedlinePLUS

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While the ...

  16. Methotrexate-Induced Liver Cirrhosis

    Microsoft Academic Search

    H. Zachariae; H. Sřgaard

    1987-01-01

    Studies on serial liver biopsies from 25 patients with methotrexate-induced liver cirrhosis, taken from 1 to 13 years after cirrhosis was established, confirm that this type is not of aggressive nature. When evaluated blind no progression was found in most of the later biopsies. Alcohol and previous use of hepatotoxic drugs such as the combination of arsenics and vitamin A

  17. Fatty liver in dairy cows.

    PubMed

    Herdt, T H

    1988-07-01

    An increase in liver fat concentration during the peripartum period is extremely common in dairy cows and, to some degree, is probably normal. When severe, it is associated with clinical problems including increased morbidity and mortality and reduced breeding efficiency. Fatty liver develops when serum NEFA concentrations rise and hepatic uptake of NEFA exceeds the liver's ability to synthesize and secrete lipoproteins. In most cases, hepatic lipid accumulation appears to commence prepartum, in association with rising serum NEFA concentrations and declining serum lipoprotein concentrations. Commonly used clinicopathologic tests of liver function do not yield clearly abnormal results except in animals with extremely high concentrations of liver fat. Clinically useful estimates of hepatic lipid concentration can be obtained in the field by determining the buoyancy of needle biopsy samples in liquids of various specific gravities. Clinically ill animals with liver fat concentrations of greater than 35 per cent by weight have a poor prognosis, and those that do survive will have a protracted convalescence. Treatment of dairy cows with clinical fatty liver should be aimed at reducing further adipose lipid mobilization and promoting hepatic lipoprotein synthesis; however, protocols for therapy have not as yet been evaluated critically. Prevention of fatty liver is more rewarding than treatment. Dry cows should be maintained in a moderately fat condition and fed high-quality, palatable feeds in amounts necessary to met or slightly exceed their energy requirements. Free-choice feeding of high-energy feeds should be avoided in late lactation and during the nonlactating period. PMID:3061611

  18. How Is Liver Cancer Found?

    MedlinePLUS

    ... They can also be used to look at blood vessels in and around the liver and can help show if liver cancer has spread to other parts of the body. MRI scans use radio waves and strong magnets instead of x-rays to take pictures. A computer makes the pattern of radio waves into a detailed picture of ...

  19. Detoxification pathways in the liver

    Microsoft Academic Search

    D. M. Grant

    1991-01-01

    Summary The liver plays an important rôle in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water-soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is

  20. Transfusion Predictors in Liver Transplant

    Microsoft Academic Search

    Luc Massicotte; Marie-Pascale Sassine; Serge Lenis

    2004-01-01

    In this study we sought to determine the factors influ- encing red blood cell (RBC) transfusions and to study the transfusion practice of anesthesiologists during liver transplants. A retrospective study of 206 succes- sive liver transplants was undertaken during a period of 52 mo. Transfused blood products were identified. Twenty variables were analyzed in a univariate fash- ion. For the

  1. 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…

  2. SCANNING OF LIVER CELL ADENOMA

    Microsoft Academic Search

    JOSEPH F. SACKETT; WILLIAM T. MOSENTHAL; REGINALD K. HOUSE; ROBERT F. JEFFERY

    This examination showed a large mass in the right lobe of the liver, with marked displacement of the gall- bladder and duodenum to the left. Barium enema examination, intravenous pyelography, and retroperitoneal air study were intrinsically normal, but confirmed the presence of a liver mass. Exploratory laparotomy was done and the large mass was biopsied. Microscopically, the tissue contained normal

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

    PubMed Central

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

    2013-01-01

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

  4. Artificial and Bioartificial Liver Support

    PubMed Central

    2007-01-01

    The fact that liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation, lead to the development of various artificial and bioartificial liver support devices. While artificial systems are based on the principles of adsorption and filtration, the more complex concept of bioartificial devices includes the provision of liver cells. Instead of solely focussing on detoxification, these concepts also support the failing organ concerning synthetic and regulative functions. The systems were evaluated in a variety of clinical studies, demonstrating their safety and investigating the impact on the patient's clinical condition. This review gives an overview over the most common artificial and bioartificial liver support devices and summarizes the results of the clinical studies. PMID:19279696

  5. Liver Antigen-Presenting Cells

    PubMed Central

    Crispe, Ian Nicholas

    2010-01-01

    The liver is an organ is which several major pathogens evade immune clearance, and achieve chronicity. How do they do it? Recent research has documented multiple mechanisms by which immune responses in the liver are biased towards tolerance. In this review, the induction of local, intrahepatic tolerance is explored from the perspective of antigen presentation. Experiments support the role of liver Dendritic Cell subsets, but also of diverse subsets of unconventional antigen-presenting cells, in inducing immune suppression. The literature on this topic is controversial and sometimes contradictory, making it difficult to formulate a unified model of antigen handling and T cell priming in liver. Here I offer a critical review of the state of the art in understanding antigen presentation in the liver. PMID:21084131

  6. Liver transplantation after paracetamol overdose.

    PubMed Central

    O'Grady, J G; Wendon, J; Tan, K C; Potter, D; Cottam, S; Cohen, A T; Gimson, A E; Williams, R

    1991-01-01

    OBJECTIVE--To evaluate the role of liver transplantation after paracetamol overdose. DESIGN--Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING--Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES--Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS--30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION--Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol. PMID:1884059

  7. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2014-03-20

    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)

  8. Liver-brain inflammation axis.

    PubMed

    D'Mello, Charlotte; Swain, Mark G

    2011-11-01

    It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including chronic inflammatory liver diseases, are associated with changes in central neural transmission that result in alterations in behavior. These behavioral changes include sickness behaviors, such as fatigue, cognitive dysfunction, mood disorders, and sleep disturbances. While such behaviors have a significant impact on quality of life, the changes within the brain and the communication pathways between the liver and the brain that give rise to changes in central neural activity are not fully understood. Traditionally, neural and humoral communication pathways have been described, with the three cytokines TNF?, IL-1?, and IL-6 receiving the most attention in mediating communication between the periphery and the brain, in the setting of peripheral inflammation. However, more recently, we described an immune-mediated communication pathway in experimentally induced liver inflammation whereby, in response to activation of resident immune cells in the brain (i.e., the microglia), peripheral circulating monocytes transmigrate into the brain, leading to development of sickness behaviors. These signaling pathways drive changes in behavior by altering central neurotransmitter systems. Specifically, changes in serotonergic and corticotropin-releasing hormone neurotransmission have been demonstrated and implicated in liver inflammation-associated sickness behaviors. Understanding how the liver communicates with the brain in the setting of chronic inflammatory liver diseases will help delineate novel therapeutic targets that can reduce the burden of symptoms in patients with liver disease. PMID:21868631

  9. Liver disease in cystic fibrosis

    PubMed Central

    Klincewicz, Beata; Cichy, Wojciech

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated “gold standard” in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

  10. Pediatric nonalcoholic fatty liver disease.

    PubMed

    Bozic, Molly A; Subbarao, Girish; Molleston, Jean P

    2013-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population. Increased recognition of this form of liver disease parallels the dramatic rise in childhood and adolescent obesity over the past 2 decades. Like adults, most children with NAFLD are obese, and comorbidities include insulin resistance, hypertension, and dyslipidemia. Unfortunately, pediatric NAFLD is not always a benign condition, with some children progressing to hepatic fibrosis and even cirrhosis in severe cases. The etiology of nonalcoholic steatohepatitis is not yet fully understood; however, hepatic steatosis in the context of insulin resistance and increased oxidative stress may lead to progressive disease. Although physical examination, laboratory evaluation, and radiographic findings provide clues to the potential presence of fatty liver disease, liver biopsy remains the gold standard for diagnosis. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease. Antioxidant pharmacologic therapy such as use of vitamin E has shown some benefit in patients with biopsy-proven steatohepatitis. Nutrition plays an essential role not only in the development of fatty liver disease but also potentially in the treatment and prevention of progression to more severe disease. PMID:23917437

  11. Telocytes in human liver fibrosis

    PubMed Central

    Fu, Siyi; Wang, Fei; Cao, Yan; Huang, Qi; Xiao, Junjie; Yang, Changqing; Popescu, Laurentiu M

    2015-01-01

    Liver fibrosis is a wound-healing response which engages a variety of cell types to encapsulate injury. Telocyte (TC), a novel type of interstitial cell, has been identified in a variety of tissues and organs including liver. TCs have been reported to be reduced in fibrotic areas after myocardial infarction, human interstitial wall's fibrotic remodelling caused either by ulcerative colitis or Crohn's disease, and skin of systemic sclerosis. However, the role of TCs in human liver fibrosis remains unclear. Liver samples from human liver biopsy were collected. All samples were stained with Masson's trichrome to determine fibrosis. TCs were identified by several immunofluorescence stainings including double labelling for CD34 and c-kit/CD117, or vimentin, or PDGF Receptor-?, or ?. We found that hepatic TCs were significantly decreased by 27%–60% in human liver fibrosis, suggesting that loss of TCs might lead to the altered organization of extracellular matrix and loss the control of fibroblast/myofibroblast activity and favour the genesis of fibrosis. Adding TCs might help to develop effective and targeted antifibrotic therapies for human liver fibrosis. PMID:25661250

  12. Liver disease in cystic fibrosis.

    PubMed

    Kobelska-Dubiel, Natalia; Klincewicz, Beata; Cichy, Wojciech

    2014-01-01

    Cystic fibrosis-associated liver disease (CFLD) affects ca. 30% of patients. The CFLD is now considered the third cause of death, after lung disease and transplantation complications, in CF patients. Diagnostics, clinical assessment and treatment of CFLD have become a real challenge since a striking increase of life expectancy in CF patients has recently been observed. There is no elaborated "gold standard" in the diagnostic process of CFLD; clinical evaluation, laboratory tests, ultrasonography and liver biopsy are used. Clinical forms of CFLD are elevation of serum liver enzymes, hepatic steatosis, focal biliary cirrhosis, multilobular biliary cirrhosis, neonatal cholestasis, cholelithiasis, cholecystitis and micro-gallbladder. In children, CFLD symptoms mostly occur in puberty. Clinical symptoms appear late, when damage of the hepatobiliary system is already advanced. The CFLD is more common in patients with severe mutations of CFTR gene, in whom a complete loss of CFTR protein function is observed. CFLD, together with exocrine pancreatic insufficiency and meconium ileus, is considered a component of the severe CF phenotype. Treatment of CFLD should be complex and conducted by a multispecialist team (gastroenterologist, hepatologist, dietician, radiologist, surgeon). The main aim of the treatment is to prevent liver damage and complications associated with portal hypertension and liver cirrhosis. Ursodeoxycholic acid is used in the treatment of CFLD. There is no treatment of proven long-term efficacy in CFLD. Liver transplantation is a treatment of choice in end-stage liver disease. PMID:25097709

  13. Cellular Therapy for Liver Disease

    PubMed Central

    Huebert, Robert C.; Rakela, Jorge

    2014-01-01

    Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease. PMID:24582199

  14. 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

  15. Oral contraceptives and liver function

    PubMed Central

    Hargreaves, Tom

    1969-01-01

    Oral contraceptives can cause liver damage and jaundice but this is very rare in women in the United Kingdom. The drugs are contraindicated where there is a history of recurrent intrahepatic cholestasis of pregnancy and acute or chronic disturbance of liver function which can be congenital or acquired. It is not yet known whether the oestrogenic or progestogenic components of oral contraceptives cause the hepatic abnormalities. The available data suggest that neither oestrogens nor progestogens in low doses impair hepatic excretory processes. The full implications of the continued administration of oestrogens and progestogens for many years on liver proteins are not yet known.

  16. “Vanishing liver metastases”—A real challenge for liver surgeons

    PubMed Central

    Zendel, Alex; Lahat, Eylon; Dreznik, Yael; Zakai, Barak Bar; Eshkenazy, Rony

    2014-01-01

    Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested. PMID:25392841

  17. Liver diseases in pregnancy: Liver transplantation in pregnancy

    PubMed Central

    Hammoud, Ghassan M; Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat; Ibdah, Jamal A

    2013-01-01

    Pregnancy in patients with advanced liver disease is uncommon as most women with decompensated cirrhosis are infertile and have high rate of anovulation. However, if gestation ensued; it is very challenging and carries high risks for both the mother and the baby such as higher rates of spontaneous abortion, prematurity, pulmonary hypertension, splenic artery aneurysm rupture, postpartum hemorrhage, and a potential for life-threatening variceal hemorrhage and hepatic decompensation. In contrary, with orthotopic liver transplantation, menstruation resumes and most women of childbearing age are able to conceive, give birth and lead a better quality of life. Women with orthotopic liver transplantation seeking pregnancy should be managed carefully by a team consultation with transplant hepatologist, maternal-fetal medicine specialist and other specialists. Pregnant liver transplant recipients need to stay on immunosuppression medication to prevent allograft rejection. Furthermore, these medications need to be monitored carefully and continued throughout pregnancy to avoid potential adverse effects to mother and baby. Thus delaying pregnancy 1 to 2 years after transplantation minimizes fetal exposure to high doses of immunosuppressants. Pregnant female liver transplant patients have a high rate of cesarean delivery likely due to the high rate of prematurity in this population. Recent reports suggest that with close monitoring and multidisciplinary team approach, most female liver transplant recipient of childbearing age will lead a successful pregnancy. PMID:24282354

  18. Platelet-Derived Serotonin Mediates Liver Regeneration

    Microsoft Academic Search

    Mickael Lesurtel; Rolf Graf; Boris Aleil; Diego J. Walther; Yinghua Tian; Wolfram Jochum; Christian Gachet; Michael Bader; Pierre-Alain Clavien

    2006-01-01

    The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors

  19. Calcium Signaling in the Liver

    PubMed Central

    Amaya, Maria Jimena; Nathanson, Michael H.

    2014-01-01

    Intracellular free Ca2+ ([Ca2+]i) is a highly versatile second messenger that regulates a wide range of functions in every type of cell and tissue. To achieve this versatility, the Ca2+ signaling system operates in a variety of ways to regulate cellular processes that function over a wide dynamic range. This is particularly well exemplified for Ca2+ signals in the liver, which modulate diverse and specialized functions such as bile secretion, glucose metabolism, cell proliferation, and apoptosis. These Ca2+ signals are organized to control distinct cellular processes through tight spatial and temporal coordination of [Ca2+]i signals, both within and between cells. This article will review the machinery responsible for the formation of Ca2+ signals in the liver, the types of subcellular, cellular, and intercellular signals that occur, the physiological role of Ca2+ signaling in the liver, and the role of Ca2+ signaling in liver disease. PMID:23720295

  20. MRI of Focal Liver Lesions.

    PubMed

    Albiin, Nils

    2012-05-01

    Magnetic resonance imaging, MRI has more advantages than ultrasound, computed tomography, CT, positron emission tomography, PET, or any other imaging modality in diagnosing focal hepatic masses. With a combination of basic T1 and T2 weighted sequences, diffusion weighted imaging, DWI, and hepatobiliary gadolinium contrast agents, that is gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB), most liver lesions can be adequately diagnosed. Benign lesions, as cyst, hemangioma, focal nodular hyperplasia, FNH or adenoma, can be distinguished from malignant lesions. In a non-cirrhotic liver, the most common malignant lesions are metastases which may be hypovascular or hypervascular. In the cirrhotic liver hepatocellular carcinoma, HCC, is of considerable importance. Besides, intrahepatic cholangiocarcinoma and other less common malignancies has to be assessed. In this review, the techniques and typical MRI features are presented as well as the new algorithm issued by American Association for the Study of the Liver Diseases (AASLD). PMID:23049491

  1. MRI of Focal Liver Lesions

    PubMed Central

    Albiin, Nils

    2012-01-01

    Magnetic resonance imaging, MRI has more advantages than ultrasound, computed tomography, CT, positron emission tomography, PET, or any other imaging modality in diagnosing focal hepatic masses. With a combination of basic T1 and T2 weighted sequences, diffusion weighted imaging, DWI, and hepatobiliary gadolinium contrast agents, that is gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB), most liver lesions can be adequately diagnosed. Benign lesions, as cyst, hemangioma, focal nodular hyperplasia, FNH or adenoma, can be distinguished from malignant lesions. In a non-cirrhotic liver, the most common malignant lesions are metastases which may be hypovascular or hypervascular. In the cirrhotic liver hepatocellular carcinoma, HCC, is of considerable importance. Besides, intrahepatic cholangiocarcinoma and other less common malignancies has to be assessed. In this review, the techniques and typical MRI features are presented as well as the new algorithm issued by American Association for the Study of the Liver Diseases (AASLD). PMID:23049491

  2. 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.

  3. Hydrogen sulfide and the liver.

    PubMed

    Mani, Sarathi; Cao, Wei; Wu, Lingyun; Wang, Rui

    2014-09-15

    Hydrogen sulfide (H2S) is a gasotransmitter that regulates numerous physiological and pathophysiological processes in our body. Enzymatic production of H2S is catalyzed by cystathionine ?-lyase (CSE), cystathionine ?-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST). All these three enzymes present in the liver and via H2S production regulate liver functions. The liver is the hub for metabolism of glucose and lipids, and maintains the level of circulatory lipids through lipoprotein metabolism. Hepatic H2S metabolism affects glucose metabolism, insulin sensitivity, lipoprotein synthesis, mitochondrial biogenetics and biogenesis. Malfunction of hepatic H2S metabolism may be involved in many liver diseases, such as hepatic fibrosis and hepatic cirrhosis. PMID:24582857

  4. Adenomatous hyperplasia of the liver.

    PubMed

    Gindhart, T D; Cimis, R J; Mosenthal, W T; Longnecker, D S

    1979-01-01

    An unusual case of adenomatous hyperplasia of the liver arose spontaneously in an 82-year-old woman. Massive fatal ascites developed during an eight-week period in the absence of cirrhosis. No drug, chemical, or hormone could be identified as the causative agent. Estrogens may play a role as possible promoters in the growth of hepatic tumors. Identifying liver tumors in women that are not associated with oral contraceptive use is valuable. PMID:215102

  5. Liver transplantation for hepatocellular carcinoma

    Microsoft Academic Search

    Rick Selby; Zakiyah Kadry; Brian Cari; Andreas Tzakis; Juan R. Madariaga; Shunzaburo Iwatsuki

    1995-01-01

    Total hepatectomy plus liver transplantation was performed on 105 patients considered unsuitable for liver resection. Postoperative 5-year actuarial survivals correlated with the pathologic stage of the tumor: stage I 75%, stage II 68%, stage III 52,1%, and stage IVA 11%. The overall 5-year survival for all patients was 36%. Nodal disease, bilobar tumor, and macroscopic venous invasion were significant poor-prognosis

  6. Liver involvement in cystic fibrosis

    Microsoft Academic Search

    Catherine Brigman; Andrew Feranchak

    2006-01-01

    Opinion statement  The hepatobiliary manifestations of cystic fibrosis (CF) encompass a broad clinical spectrum, from mild steatosis, associated\\u000a with poor nutrition, to multilobular cirrhosis and the complications of portal hypertension. The factor(s) responsible for\\u000a the development and progression of liver disease in a subset of patients with CF are unknown. Liver disease can be silent\\u000a and progressive, manifesting only with complications

  7. Drug-Induced Liver Injury.

    PubMed

    Fisher, Kurt; Vuppalanchi, Raj; Saxena, Romil

    2015-07-01

    Context .- Drug-induced liver injury (DILI) represents a diverse set of responses following exposure to any manufactured or naturally occurring chemical compound. Drug-induced liver injury is of major concern owing to the ever increasing number of compounds introduced into the market for treatment of various diseases as well as the increasing popularity of herbals, which lend themselves to self-medication but are not rigorously regulated. Objective .- To provide an overview of the prevalence, classification, and diagnosis of DILI with emphasis on pathogenesis and the role of a liver biopsy. To focus on the most common, emerging, and herbal agents that cause DILI with emphasis on the histologic pattern of injury observed. Data Sources .- A review of the literature was drawn from the PubMed (US National Library of Medicine) repository, textbooks, and online databases. All figures were taken from cases seen at our tertiary referral center, which is 1 of 12 participating sites in the National Institutes of Health-funded Drug-Induced Liver Injury Network. Conclusions .- Drug-induced liver injury due to prescription, over-the-counter, and herbal products is a major cause of liver disease in the United States and around the world. Diagnosis of DILI is challenging because there is no single clinical, laboratory, or histologic feature specific to DILI. Accurate diagnosis requires establishing a causal relationship with the suspected agent and excluding competing causes of liver injury. The liver biopsy is an essential component in the management of DILI by offering clues to the underlying pathogenesis, providing prognostic information, and guiding therapy. PMID:26125428

  8. Liver transplantation for neuroendocrine tumors

    Microsoft Academic Search

    Sander Florman; Ben Toure; Leona Kim; Gabriel Gondolesi; Sasan Roayaie; Nancy Krieger; Thomas Fishbein; Sukru Emre; Charles Miller; Myron Schwartz

    2004-01-01

    Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible,\\u000a it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying\\u000a results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen\\u000a symptomatic patients with unresectable NET liver

  9. SYBR, TaqMan, or both: highly sensitive, non-invasive detection of Cardicola blood fluke species in Southern Bluefin Tuna (Thunnus maccoyii).

    PubMed

    Polinski, Mark; Hamilton, Dylan Belworthy; Nowak, Barbara; Bridle, Andrew

    2013-09-01

    Three species of blood fluke from the genus Cardicola are known to parasitize and cause disease in Bluefin Tunas--C. forsteri, C. orientalis, and C. opisthorchis. Although initially believed to be separated by geography and host specificity, recent identification of at least two Cardicola spp. concurrently present within all three Bluefin species has raised questions concerning pathogenicity, relative abundance, and distribution of these parasites within Bluefin populations. Here, we present sensitive and differential real-time qPCR nucleic acid detection of these Cardicola spp. by targeting the ITS2 region of the parasite rDNA for PCR amplification. A limit of sensitivity of 1-5 genome copy equivelents was achieved for each of the three Cardicola species tested without cross-species or host genomic amplification. Similar sensitivity was further achieved in the presence of up to 20 ng/?L non-target host gDNA using SYBR Green chemistry alone, or in the presence of up to 160 ng/?L host gDNA through the utilization of a TaqMan probe common-reporter detection system. These methods were subsequently used to positively identify both C. forsteri and C. orientalis DNA in preserved samples of serum, gill, and heart from ranched Southern Bluefin Tuna Thunnus maccoyii. Both methods were more sensitive for positively and differentially identifying the presence of Cardicola spp. than either histological or heart-flush microscopy techniques previously employed, and also possess the ability to be applied in non-lethal blood sampling of these highly valued fish. This is the first report for rapid and differential molecular quantitative detection of Cardicola, and opens the potential for effective monitoring of infection in cultured bluefin populations. Further, it is anticipated that the use of SYBR Green for melt-curve analyses in conjunction with a common-reporter TaqMan assay will present a flexible, accurate, and cost-effective approach for differential detection of a variety of other pathogens in future. PMID:23896120

  10. Enisoprost in liver transplantation.

    PubMed

    Ismail, T; Ayres, R; Kiff, P; McMaster, P; Neuberger, J

    1995-05-15

    Previous human studies in renal transplant recipients have shown a lower incidence of acute rejection and cyclosporine-associated acute nephrotoxicity when prostaglandins are administered in conjunction with standard immunosuppressants. This study evaluates the effects of enisoprost (EP), a synthetic PGE methyl ester analog, in a single-center, prospective, randomized, double-blind, placebo-controlled, parallel group trial in 81 consecutive adult patients undergoing orthotopic liver transplantation (OLT). The subjects received EP 100 mg p.o. t.i.d. (n = 40) or placebo (n = 41) for the first 12 weeks after OLT. Immunosuppression was based on cyclosporine, azathioprine, and corticosteroids. Effective renal plasma flow and glomerular filtration rate were determined at 4 and 12 weeks after OLT. Eighty-one patients entered the study; sixty-six patients completed the 16-week study period. There were no statistically significant differences between EP- and placebo-treated groups at 12 weeks for creatinine clearance, glomerular filtration rate, and effective renal plasma flow. At least 1 episode of cyclosporine nephrotoxicity occurred in 7/40 patients (17.5%) in the EP group compared with 9/41 patients (20.0%) in the placebo group (P = 0.781). There was no significant difference in the incidence of graft rejection episodes in the 2 groups. Enisoprost, as used in this study, does not have any beneficial effect on renal function or incidence of rejection in OLT recipients. PMID:7762065

  11. Correlation of specific antibody titre and avidity with protection in cattle immunized against Fasciola hepatica

    Microsoft Academic Search

    Grace Mulcahy; Fiona O'Connor; Sharon McGonigle; Andrew Dowd; Dianne G Clery; Stuart J Andrews; John P Dalton

    1998-01-01

    Cattle produce specific serum antibody mainly of the IgG1 isotype in response to infection with the liver fluke, Fasciola hepatica. In these animals a positive correlation between fluke-specific serum IgG1 levels and fluke-burden in non-immunized infected animals was observed. In contrast, immunization of cattle with a combination of the fluke-derived antigens cathepsin L2 (CL2) and fluke haemoglobin (FHb) in Freund's

  12. Intrahepatic cholangiocarcinoma masquerading as liver abscess.

    PubMed

    Shah, Vinit; Arora, Anil; Tyagi, Pankaj; Sharma, Praveen; Bansal, Naresh; Singla, Vikas; Bansal, Rinkesh K; Gupta, Varun; Kumar, Ashish

    2015-03-01

    Malignancy masquerading as liver abscess, and presenting with fever, is mainly described in patients with colorectal cancers with liver metastasis. Primary liver tumors such as hepatocellular carcinoma or intrahepatic cholangiocarcinoma presenting as non-resolving liver abscess is extremely uncommon and carries a dismal prognosis. We present a rare case of non-resolving liver abscess as a presenting manifestation of intrahepatic cholangiocarcinoma. PMID:25941437

  13. Antigen Processing and Presentation in the Liver

    Microsoft Academic Search

    Masanori Abe; Angus W. Thomson

    The liver is an important site of infectious, parasitic, autoimmune, and malignant diseases. Immune responses and their modulation\\u000a within the liver are critical to the outcome of these conditions and also in liver transplantation. Immune responses in, or\\u000a elicited by, the liver can result in tolerance rather than immunity. Hepatic tolerance was demonstrated initially by the acceptance\\u000a of liver allografts

  14. Ultrasonography and amoebic liver abscesses.

    PubMed Central

    Abul-Khair, M H; Kenawi, M M; Korashy, E E; Arafa, N M

    1981-01-01

    Twenty-four patients were admitted to Kasr-El-Aini Hospital with suspected diagnoses of amoebic liver abscesses. The patients underwent clinical examinations, stool specimen analyses for cysts and trophozoites of Entamoeba histolytica, radiologic examinations, and routine liver function tests. In one patient, a liver scintiscan was obtained. Ultrasonographic examination was performed on all patients using the gray scale imaging technique. In 20 patients, the diagnoses of amoebic liver abscesses were demonstrated by ultrasonographic examination. In 19 patients, amoebic liver abscesses were verified by aspiration biopsies (95%), and one patient had a false-positive result. This false-positive result was due to a degenerated hepatoma, demonstrated by aspiration biopsy. Of the 19 patients, 12 patients (63.12%) had right lobe abscesses and seven (36.89%) had left lobe abscesses. The site, size and nature of the pus contained in the abscess could be determined by ultrasonographic examination and, therefore, helped in the management and technique of the aspiration biopsy. In addition, follow-up data could be more detailed using ultrasonographic examinations. Ultrasonographic examination is a noninvasive, safe, accurate, and rapid method of diagnosis, and is highly recommended as a routing procedure in all cases of suspected amoebic liver abscesses in the pre- and posttreatment stages of the disease. It is also recommended as an indicator of complete cure at follow-up examination. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:7469556

  15. Neurologic complications after liver transplantation

    PubMed Central

    Živkovi?, Saša A

    2013-01-01

    Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

  16. 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.

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

    E-print Network

    Paris-Sud XI, Université de

    Virtual Reality Liver Biopsy Simulator Virtual Reality, Ultrasound-guided Liver Biopsy Simulator: Development and Performance Discrimination1 Running head: Virtual Reality Liver Biopsy Simulator Word count (exc. Figures / tables): 4210 Key Words: Interventional Radiology, Simulation, Virtual Reality

  18. Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

    PubMed Central

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-01-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  19. Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation.

    PubMed

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-05-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  20. Resistance of Fasciola hepatica against triclabendazole in cattle and sheep in The Netherlands

    Microsoft Academic Search

    Lammert Moll; Cor P. H Gaasenbeek; Piet Vellema; Fred H. M Borgsteede

    2000-01-01

    In the winter of 1998\\/1999, sheep on a farm in the province of North Holland, The Netherlands, died from subacute and chronic liver fluke disease despite four previous treatments with triclabendazole (TCBZ). Faecal examinations of sheep and cattle on the farm showed high number of liver fluke eggs. In a randomised clinical trial, the fluke egg output was monitored weekly

  1. Hydroxycut-induced Liver Toxicity

    PubMed Central

    Kaswala, DH; Shah, S; Patel, N; Raisoni, S; Swaminathan, S

    2014-01-01

    In the recent era, use of various nutritional supplements is highly encouraged amongst the people of United States. Weight loss supplements are major part of the nutritional supplements and their usage is unregulated in the US. Obesity is a major health concern in the US and Americans spend around $30 billion a year for weight loss supplements. At times, these supplements can be responsible for documented or undocumented adverse drug effects. The health consequences related to these supplements are often overlooked by the general public, even though FDA issues advisories regarding them. One common supplement used for weight loss was Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada). Hydroxycut was recalled from the market after a FDA warning in May 2009 because of 23 reports of serious health problems ranging from jaundice and elevated liver enzymes to liver damage. 1 This case report adds evidence for Hydroxycut - induced hepatotoxicity. A 27 year old man with right upper quadrant pain and jaundice was found to have elevated liver enzymes and was taking Hydroxycut along with other supplements. Liver biopsy showed drug induced hepatotoxicity. Discontinuation of Hydroxycut dramatically improved liver functions and related symptoms. PMID:24669349

  2. [Living Donor Liver Transplantation - Past and Present.

    PubMed

    Rauchfuss, F; Bauschke, A; Bärthel, E; Scheuerlein, H; Schüle, S; Malessa, C; Settmacher, U

    2013-07-01

    Since the first living donor liver transplantations at the end of the 1980s, this transplantation technique has developed as an established tool within the modern transplantation medicine. Especially in Asia, the majority of liver transplantation is performed through living donation, mainly for religious reasons. Liver grafts for adult recipients are mainly the right liver lobe of the donor, for paediatric recipients mainly the left lateral lobe. In some cases, the living donor liver transplantation is realised from two different donors for one recipient, the so-called "dual graft" transplantation. This article summarises the history of living donor liver transplantation up to the current status of this transplantation procedure worldwide. PMID:23824621

  3. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  4. Evaluation of liver transplant recipients.

    PubMed

    Thuluvath, Paul J

    2011-12-01

    The outcome of liver transplantation (LT) is dependent on many factors including graft quality, surgical techniques, postoperative care, immunosuppressive regimens and most importantly, careful pre-transplant recipient evaluation and selection. Currently, the expected 1-year and 5-year survival rates after LT are 85-95% and 75-85%, respectively. The improvement in outcomes and better awareness has resulted in an increasing demand for LT around the world including India. Transplant physicians have responded to this increased demand by developing several strategies including the use of older donors, grafts from hepatitis C positive donors or those with previous hepatitis B infection (positive hepatitis B virus [HBV] core immunoglobulin G [IgG] antibody), graft from nonheart beating donors, domino transplantation (liver from patients with familial amyloid polyneuropathy transplanted into older recipients), split-liver grafts, and live donor liver transplant (LDLT). Currently, the only treatment that prolongs survival in those with end-stage acute or chronic liver failure is transplantation of either partial or full liver donor graft. Because of the enormous disparity in supply and demand for donor organs, costs, and potential morbidity and mortality of live donors in LDLT, it has become incumbent on the transplant community to ration the available organs in a way that provides the best outcomes and in the process, serves the best interest of the population as a whole. When evaluating a potential candidate for LT, it is imperative to determine whether the recipient is going to benefit from the procedure immediately and in the long-term. In this review, we will discuss the process of selection and optimal evaluation of potential LT recipients. PMID:25755386

  5. Autophagy and Liver Ischemia-Reperfusion Injury

    PubMed Central

    2015-01-01

    Liver ischemia-reperfusion (I-R) injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS), leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R. PMID:25861623

  6. Nodular regenerative hyperplasia of the liver: diagnosis by liver biopsy.

    PubMed Central

    Qizilbash, A. H.; Castelli, M.

    1980-01-01

    Specimens of liver obtained by needle biopsy from two patients with rheumatoid arthritis showed features of nodular regenerative hyperplasia. In one patient the nodularity was apparent on gross examination of the specimen. Portal hypertension was present in the other patient. The cause and pathogenesis of the disorder are poorly understood. Images FIG. 1 FIG. 2 FIG. 3 PMID:7388707

  7. Liver transplantation in alcoholic liver disease current status and controversies

    PubMed Central

    Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

    2013-01-01

    Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

  8. Multiscale tissue engineering for liver reconstruction

    PubMed Central

    Sudo, Ryo

    2014-01-01

    The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies. PMID:24500493

  9. Humanized mice with ectopic artificial liver tissues

    E-print Network

    Thomas, David K.

    “Humanized” mice offer a window into aspects of human physiology that are otherwise inaccessible. The best available methods for liver humanization rely on cell transplantation into immunodeficient mice with liver injury ...

  10. Potential Liver Recipients May Have New Option

    MedlinePLUS

    ... nih.gov/medlineplus/news/fullstory_152932.html Potential Liver Recipients May Have New Option Organs harvested after ... 5, 2015 FRIDAY, June 5, 2015 (HealthDay News) -- Livers from donors who suffered cardiac death can be ...

  11. Platelet-Derived Serotonin Mediates Liver Regeneration

    NASA Astrophysics Data System (ADS)

    Lesurtel, Mickael; Graf, Rolf; Aleil, Boris; Walther, Diego J.; Tian, Yinghua; Jochum, Wolfram; Gachet, Christian; Bader, Michael; Clavien, Pierre-Alain

    2006-04-01

    The liver can regenerate its volume after major tissue loss. In a mouse model of liver regeneration, thrombocytopenia, or impaired platelet activity resulted in the failure to initiate cellular proliferation in the liver. Platelets are major carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype serotonin receptors in the liver increased after hepatectomy. Antagonists of 5-HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting enzyme for the synthesis of peripheral serotonin. This failure of regeneration was rescued by reloading serotonin-free platelets with a serotonin precursor molecule. These results suggest that platelet-derived serotonin is involved in the initiation of liver regeneration.

  12. General Information about Liver (Hepatocellular) Cancer

    MedlinePLUS

    ... cirrhosis ). This may lead to liver cancer. Blood banks test all donated blood for hepatitis B, which ... cirrhosis). This may lead to liver cancer. Blood banks test all donated blood for hepatitis C, which ...

  13. Role of liver stem cells in hepatocarcinogenesis

    PubMed Central

    Xu, Lei-Bo; Liu, Chao

    2014-01-01

    Liver cancer is an aggressive disease with a high mortality rate. Management of liver cancer is strongly dependent on the tumor stage and underlying liver disease. Unfortunately, most cases are discovered when the cancer is already advanced, missing the opportunity for surgical resection. Thus, an improved understanding of the mechanisms responsible for liver cancer initiation and progression will facilitate the detection of more reliable tumor markers and the development of new small molecules for targeted therapy of liver cancer. Recently, there is increasing evidence for the “cancer stem cell hypothesis”, which postulates that liver cancer originates from the malignant transformation of liver stem/progenitor cells (liver cancer stem cells). This cancer stem cell model has important significance for understanding the basic biology of liver cancer and has profound importance for the development of new strategies for cancer prevention and treatment. In this review, we highlight recent advances in the role of liver stem cells in hepatocarcinogenesis. Our review of the literature shows that identification of the cellular origin and the signaling pathways involved is challenging issues in liver cancer with pivotal implications in therapeutic perspectives. Although the dedifferentiation of mature hepatocytes/cholangiocytes in hepatocarcinogenesis cannot be excluded, neoplastic transformation of a stem cell subpopulation more easily explains hepatocarcinogenesis. Elimination of liver cancer stem cells in liver cancer could result in the degeneration of downstream cells, which makes them potential targets for liver cancer therapies. Therefore, liver stem cells could represent a new target for therapeutic approaches to liver cancer in the near future. PMID:25426254

  14. Pediatric liver tumors – a pictorial review

    Microsoft Academic Search

    Priyanka Jha; Soni C. Chawla; Sidhartha Tavri; Chirag Patel; Charles Gooding; Heike Daldrup-Link

    2009-01-01

    Hepatic masses constitute about 5–6% of all intra-abdominal masses in children. The majority of liver tumors in children are\\u000a malignant; these malignant liver tumors constitute the third most common intra-abdominal malignancy in the pediatric age group\\u000a after Wilms’ tumor and neuroblastoma. Only about one third of the liver tumors are benign. A differential diagnosis of liver\\u000a tumors in children can

  15. Nonalcoholic Fatty Liver Disease: Predictors of Nonalcoholic Steatohepatitis and Liver Fibrosis in the Severely Obese

    Microsoft Academic Search

    John B. Dixon; Prithi S. Bhathal; Paul E. O'Brien

    2001-01-01

    Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is common in severely obese subjects and can progress to cirrhosis and liver failure. Predicting advanced or progressive disease may help in selecting patients for liver biopsy and assist the development of therapeutic options. Methods: Liver biopsies were taken at laparoscopic obesity surgery in 105 consecutive patients. The clinical and biochemical variables

  16. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease

    Microsoft Academic Search

    Mirella Fraquelli; Cristina Rigamonti; Giovanni Casazza; Dario Conte; Maria Francesca Donato; Guido Ronchi; Massimo Colombo; Regina Elena; Via F Sforza

    2010-01-01

    Objective: Transient elastography (TE) is gaining popularity as a non-invasive method for predicting liver fibrosis, but intraobserver and interobserver agreement and factors influencing TE reproducibility have not been adequately assessed. This study investigated these aspects. Setting: Tertiary referral liver unit. Patients: Over a 4-month period, 200 patients with chronic liver disease (CLD) with varying aetiology consecutively underwent TE and liver

  17. HCV-associated liver cancer without cirrhosis

    Microsoft Academic Search

    M. S. De Mitri; E. Pisi; K. Poussin; P. Paterlini; C. Bréchot; P. Baccarini; A. D'Errico; W. Grigiani; A. Alberti; P. Pontisso; N. Simon; M. Beaugrand

    1995-01-01

    Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for

  18. Update on Nonalcoholic Fatty Liver Disease

    Microsoft Academic Search

    Arthur J. McCullough

    2002-01-01

    Nonalcoholic fatty liver disease is now recognized as the most common liver disease in the United States, with a prevalence of approximately 5% in the general population and up to 25% to 75% in patients with obesity and type II diabetes mellitus. Nonalcoholic fatty liver disease is a clinicopathologic syndrome with a wide spectrum of histologic abnormalities and clinical outcomes.

  19. Fatty Infiltration of Liver in Hyperlipidemic Patients

    Microsoft Academic Search

    Nimer Assy; Kelly Kaita; David Mymin; Clifford Levy; Barry Rosser; Gerald Minuk

    2000-01-01

    Hyperlipidemia is a known risk factor for fatty infiltration of the liver, a condition that can progress to cirrhosis and liver failure. The objectives of this study were to document the prevalence of fatty infiltration in the livers of hyperlipidemic patients and to identify the predictor variables associated with this condition. Over an 18-month recruitment period, clinical, biochemical, and radiologic

  20. Preoperative evaluation of patients with liver disease

    Microsoft Academic Search

    A James Hanje; Tushar Patel

    2007-01-01

    Patients with end-stage liver disease often undergo surgery for indications other than liver transplantation. These patients have an increased risk of morbidity and mortality that is related to their underlying liver disease. Assessments of surgical risk provide a basis for discussion of risks and benefits, treatment decision making, and for optimal management of patients for whom surgery is planned. The

  1. Liver Transplant Program Established at OHSU

    E-print Network

    Chapman, Michael S.

    Division Chief of Abdominal Organ Transplant Surgery, Susan Orloff, M.D., F.A.C.S. She explainsLiver Transplant Program Established at OHSU The history of the liver transplant program at Oregon community. Since 1988, liver transplants in the Portland area have only been performed at the OHSU

  2. New insights into liver stem cells

    Microsoft Academic Search

    E. Gaudio; G. Carpino; V. Cardinale; A. Franchitto; P. Onori; D. Alvaro

    2009-01-01

    Hepatic progenitor cells are bi-potential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic and the cholangiocytic lineages. In adult livers, hepatic progenitor cells are quiescent stem cells with a low proliferating rate, representing a reserve compartment that is activated only when the mature epithelial cells of the liver are continuously damaged or

  3. Pathology of nonalcoholic fatty liver disease

    Microsoft Academic Search

    Elizabeth M. Brunt

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a significant complication of obesity and is recognized as the hepatic manifestation of the metabolic syndrome. The process occurs in adults and children and is characterized by the presence of increased amounts of fat in the liver (steatosis). With inflammation, cell death and scarring (fibrosis), the process may result in end-stage liver disease, or

  4. Liver transplantation for hepatocellular carcinoma

    Microsoft Academic Search

    VANESSA DE VILLA; S.-T. Fan

    2004-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death, particularly in Asia where the major eti- ology, chronic hepatitis B virus infection, is endemic. The tumor frequently develops in a background of cir- rhosis, and liver transplantation offers a chance to cure both the tumor and the underlying cirrhosis. The Milan criteria based on tumor size and number as

  5. Metallothionein and Liver Cell Regeneration

    Microsoft Academic Search

    M. GEORGE CHERIAN; Y. JAMES KANG

    2006-01-01

    Hepatocytes in adults are in a nonproliferative state but they have high capacity to regenerate within few hours after an injury. After partial hepatectomy or chemical injury, hepatocytes undergo a synchronized multistep process consisting of priming\\/initiation, proliferation, and termination. These distinct steps are essential for restoring the structure and functions of liver. The mechanisms involved in each of these steps

  6. Liver Transplantation and Hepatitis C

    PubMed Central

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko

    2012-01-01

    Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation. PMID:22900194

  7. Advances in Alcoholic Liver Disease

    PubMed Central

    Beier, Juliane I.; Arteel, Gavin E.

    2013-01-01

    Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD. PMID:21088999

  8. [Pulmonary hypertension in liver diseases].

    PubMed

    Savale, Laurent; Sattler, Caroline; Sitbon, Olivier

    2014-09-01

    Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ? 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH. PMID:25148949

  9. Multidisciplinary imaging of liver hydatidosis.

    PubMed

    Marrone, Gianluca; Crino', Francesca; Caruso, Settimo; Mamone, Giuseppe; Carollo, Vincenzo; Milazzo, Mariapina; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2012-04-01

    Liver hydatidosis is a parasitic endemic disease affecting extensive areas in our planet, a significant stigma within medicine to manage because of its incidence, possible complications, and diagnostic involvements. The diagnosis of liver hydatidosis should be as fast as possible because of the relevant complications that may arise with disease progression, involving multiple organs and neighboring structures causing disruption, migration, contamination. The aim of this essay is to illustrate the role of imaging as ultrasonography (US), multi detector row computed tomography, and magnetic resonance imaging (MRI) in the evaluation of liver hydatidosis: the diagnosis, the assessment of extension, the identification of possible complications and the monitoring the response to therapy. US is the screening method of choice. Computed tomography (CT) is indicated in cases in which US is inadequate and has high sensitivity and specificity for calcified hydatid cysts. Magnetic resonance is the best imaging procedure to demonstrate a cystic component and to show a biliary tree involvement. Diagnostic tests such as CT and MRI are mandatory in liver hydatidosis because they allow thorough knowledge regarding lesion size, location, and relations to intrahepatic vascular and biliary structures, providing useful information for effective treatment and decrease in post-operative morbidity. Hydatid disease is classified into four types on the basis of their radiologic appearance. PMID:22509075

  10. Management in Acute Liver Failure

    PubMed Central

    Shalimar; Acharya, Subrat K.

    2014-01-01

    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.

  11. 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

  12. Management in acute liver failure.

    PubMed

    Shalimar; Acharya, Subrat K

    2015-03-01

    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

  13. Adherence in liver transplant recipients.

    PubMed

    Burra, Patrizia; Germani, Giacomo; Gnoato, Francesca; Lazzaro, Silvia; Russo, Francesco Paolo; Cillo, Umberto; Senzolo, Marco

    2011-07-01

    Adherence to a medical regimen has been defined as the extent to which a patient's behavior coincides with clinical prescriptions. In liver transplant patients, adherence to immunosuppressive therapy and to medical indications in general is crucial for short- and long-term outcomes. Nonadherence to immunosuppression carries a risk of graft rejection and potential graft loss, whereas nonadherence to general medical indications (eg, avoiding alcohol intake and smoking after transplantation) may be associated with other complications such as de novo tumors and increasing health care costs. Among adult liver transplant patients, the rate of nonadherence to immunosuppressive drugs ranges from 15% to 40%, whereas the rate of nonadherence to clinical appointments ranges from 3% to 47%. The wide range of reported rates is due to different definitions of the term nonadherence and the variety of methods used to measure adherence in the medical literature. Nonadherence seems to be nearly 4 times higher in pediatric and adolescent patients versus adult transplant recipients. Several nonadherence risk factors, such as high medication costs, psychiatric disorders, the conviction that the medication is harmful, and side effects of immunosuppressive therapy, have been described among adult liver transplant patients. The risk factors for nonadherence in pediatric and adolescent liver transplant patients are psychological distress, the functional status of their families, and the impact of immunosuppressive side effects on their physical appearance. A single approach to promoting adherence to general medical prescriptions has been proved to be ineffectual, so a multidisciplinary strategy should be adopted to achieve significant improvements in this field. The aim of this review is to analyze the published literature on adherence in liver transplant patients with a particular focus on the reported prevalence and the identified risk factors. Patients have been split into 2 age groups (adults and children/adolescents) because the scale of the problem and the potential risk factors differ in the 2 groups. PMID:21384527

  14. Correlation of ammonia clearance with classical liver function tests in normal and liver-damaged sheep 

    E-print Network

    Hansson, Lucille Ann

    1984-01-01

    function, Hypoalbuminemia is associated with severe chronic liver disease. Hypergammaglobulinemia, seen in acute hepatitis and portasystemic vascular shunting, is due to the liver's failure to remove antigens from portal circulation but is more commonly... found in chronic hepatitis. (1, 2, 3, 7) Liver biopsy is the single most important procedure for the accurate evaluation of hepatic disease. However, liver biopsy is the most dangerous and traumatic diagnostic technique for liver disease. (1 2 ~ 3...

  15. Platelet Transfusion can be Related to Liver Regeneration After Living Donor Liver Transplantation

    Microsoft Academic Search

    Joohyun Kim; Nam-Joon Yi; Woo Young Shin; Taehoon Kim; Kuhn Uk Lee; Kyung-Suk Suh

    2010-01-01

    Background  Although liver regeneration is a fundamental aspect of living donor liver transplantation (LDLT), the factors that affect\\u000a liver regeneration during the early post-transplantation period have not been thoroughly investigated. Recently it was suggested\\u000a that platelets contribute to liver regeneration. The aim of the present study was to identify the major factors that affect\\u000a liver graft regeneration during the early post-transplantation

  16. Nonalcoholic Fatty Liver Disease and Psoriasis

    PubMed Central

    Prussick, Lisa; Nussbaum, Dillon

    2015-01-01

    Psoriasis is a systemic inflammatory disease associated with a variety of comorbidities. It has been shown that psoriasis patients have an increased incidence of nonalcoholic fatty liver disease over controls. Patients with nonalcoholic fatty liver disease and psoriasis have more severe skin disease and are at higher risk of severe liver fibrosis than patients without psoriasis. The authors will review the diagnosis of nonalcoholic fatty liver disease and also discuss lifestyle changes and treatments for psoriasis that may benefit or worsen nonalcoholic fatty liver disease. PMID:25852814

  17. Liver bioengineering: Current status and future perspectives

    PubMed Central

    Booth, Christopher; Soker, Tom; Baptista, Pedro; Ross, Christina L; Soker, Shay; Farooq, Umar; Stratta, Robert J; Orlando, Giuseppe

    2012-01-01

    The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate. PMID:23322990

  18. Relationship between liver lipid and liver dry matter in slaughtered ruminants

    PubMed Central

    Tajik, Hossein; Ramin, Aligholi; Nozad, Shahram; Jelodari, Babak; Ashtab, Ghazaleh; Eftekhari, Zohreh; Ramin, Sina

    2012-01-01

    Lipids in liver wet and dry matter, liver moist and dry matter and their relationships were investigated based on species, sex and age in cows, buffaloes, sheep and goats. Mean percentage of lipids in liver wet and dry matter and liver dry matter in cows were 3.60%, 1.10%, 29.70%, and for buffaloes were 5.30%, 1.55%, 29.20%, sheep 3.00%, 0.83%, 27.90%, and goats 2.910%, 1.55% and 28.40%, respectively. The highest and lowest percentage of lipids in liver wet and dry matter was observed in buffaloes and sheep, and for the liver dry matter was recorded in cows and sheep, respectively. Analyses showed significant differences in liver parameters among ruminants (p < 0.01). Gender, except for goats, did not affect the animals' liver parameters. In overall 15.00% of buffaloes and 3.50% of cows showed over 10.00% lipids in liver, while none of small ruminants appeared to have over 6.00% lipids in liver. There was no correlation between liver lipid and liver dry matter. In conclusion mean percentage of lipid in liver dry matter in small ruminants was less than large ruminants. Liver dry matter was high in cows and low in sheep. Mean differences in liver parameters was significant, while the age and sex of the animals were not. Liver lipidosis in buffaloes seems greater than in cows, and in small ruminants it was negligible. No correlation was expected between liver parameters. Finally, on the basis of liver dry matter, the liver in ruminants ranked from cows to buffaloes, goats and sheep. PMID:25653771

  19. Relationship between liver lipid and liver dry matter in slaughtered ruminants.

    PubMed

    Tajik, Hossein; Ramin, Aligholi; Nozad, Shahram; Jelodari, Babak; Ashtab, Ghazaleh; Eftekhari, Zohreh; Ramin, Sina

    2012-01-01

    Lipids in liver wet and dry matter, liver moist and dry matter and their relationships were investigated based on species, sex and age in cows, buffaloes, sheep and goats. Mean percentage of lipids in liver wet and dry matter and liver dry matter in cows were 3.60%, 1.10%, 29.70%, and for buffaloes were 5.30%, 1.55%, 29.20%, sheep 3.00%, 0.83%, 27.90%, and goats 2.910%, 1.55% and 28.40%, respectively. The highest and lowest percentage of lipids in liver wet and dry matter was observed in buffaloes and sheep, and for the liver dry matter was recorded in cows and sheep, respectively. Analyses showed significant differences in liver parameters among ruminants (p < 0.01). Gender, except for goats, did not affect the animals' liver parameters. In overall 15.00% of buffaloes and 3.50% of cows showed over 10.00% lipids in liver, while none of small ruminants appeared to have over 6.00% lipids in liver. There was no correlation between liver lipid and liver dry matter. In conclusion mean percentage of lipid in liver dry matter in small ruminants was less than large ruminants. Liver dry matter was high in cows and low in sheep. Mean differences in liver parameters was significant, while the age and sex of the animals were not. Liver lipidosis in buffaloes seems greater than in cows, and in small ruminants it was negligible. No correlation was expected between liver parameters. Finally, on the basis of liver dry matter, the liver in ruminants ranked from cows to buffaloes, goats and sheep. PMID:25653771

  20. Prevalence of liver disease in cystic fibrosis.

    PubMed Central

    Scott-Jupp, R; Lama, M; Tanner, M S

    1991-01-01

    To assess the prevalence, demography, and clinical features of liver disease among patients with cystic fibrosis the case notes of 524 patients of all ages who were attending the cystic fibrosis clinic were studied. Computer databases were used to establish the condition of the liver in a further 576 such patients. The overall prevalence of overt liver disease indicated by the presence of an enlarged liver or spleen (or both) was 4.2%. The age related prevalence rose to a peak in adolescence, and then fell in patients over 20 years old. The implied increase in mortality among those with liver disease was not explained by deaths from liver disease, which were rare. Male patients were significantly more affected than female, the ratio being 3:1 among adolescents. Increasing prevalence of liver disease in patients with cystic fibrosis is, therefore, not just a result of longevity. PMID:2053791

  1. Protective Effect of Salep on Liver

    PubMed Central

    Pourahmad, Morteza; Kargar Jahromi, Hossein; Kargar Jahromi, Zahra

    2015-01-01

    Background: Salep is used for various purposes in food industries and traditional medicine. Therefore, evaluation of its effect on the liver seems to be necessary. Objectives: The aim of this study was to assess salep effect on liver. Materials and Methods: In this experimental study, various concentrations of Salep were intraperitoneally administered to five groups of Wistar rats (control, placebo and 20, 40 and 80 mg/kg salep). After one month, liver enzymes and liver tissue were evaluated and compared between different groups. Results: Significant decreased level of liver enzymes, MDA (Malondialdehyde) and TOC (Total Oxidation Capacity) were found in various concentrations of salep administration. On the other hand, a significant increase was found in TAC (Total Antioxidant Capacity) level with various doses of salep. Conclusions: Elevated level of total protein and albumin and decreased level of liver enzyme by salep extract were found in this study. Therefore, this plant may be a useful medicine for patients with liver diseases.

  2. Chemotherapy induced liver abnormalities: an imaging perspective

    PubMed Central

    Houshyar, Roozbeh; Bhosale, Priya; Choi, Joon-Il; Gulati, Rajesh; Lall, Chandana

    2014-01-01

    Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy. PMID:25320738

  3. 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 where it is alleged that paracetamol hepatotoxicity was enhanced in chronic alcoholics, the reverse should have been the case because alcohol was actually taken at the same time as the paracetamol. Chronic alcoholics are likely to be most vulnerable to the toxic effects of paracetamol during the first few days of withdrawal but maximum therapeutic doses given at this time have no adverse effect on liver function tests. Although the possibility remains that chronic consumption of alcohol does increase the risk of paracetamol hepatotoxicity in man (perhaps by impairing glutathione synthesis), there is insufficient evidence to support the alleged major toxic interaction. It is astonishing that clinicians and others have unquestion-ingly accepted this supposed interaction in man for so long with such scant regard for scientific objectivity. PMID:10759684

  4. 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. PMID:24635786

  5. Alcohol Consumption, One-Carbon Metabolites, Liver Cancer and Liver Disease Mortality

    PubMed Central

    Weinstein, Stephanie J.; Graubard, Barry I.; Freedman, Neal D.; Männistö, Satu; Albanes, Demetrius; McGlynn, Katherine A.

    2013-01-01

    Background Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk. Results Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer. Conclusions The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality. PMID:24205137

  6. Abdominal MR: liver and pancreas

    Microsoft Academic Search

    C. Bartolozzi; R. Lencioni; F. Donati; D. Cioni

    1999-01-01

    .   Following the introduction of rapid, high-quality scan techniques and the development of new, tissue-specific contrast agents,\\u000a the applications of MRI for abdominal imaging are experiencing unprecedented growth. This article examines the current status\\u000a of liver and pancreatic MRI, highlighting technical and methodological approach, use of contrast agents, and main clinical\\u000a applications. The MRI technique appears to be the ideal

  7. Colorectal Liver Metastases: Radiofrequency Ablation

    Microsoft Academic Search

    Andrew McKay; Elijah Dixon; Oliver Bathe

    In North America, colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer\\u000a death (American Cancer Society, 2005). Nearly half of patients will develop liver metastases at some point during the course\\u000a of their disease, with 15–25% having metastases at the time of diagnosis. Even with recent dramatic improvements in systemic\\u000a therapies for

  8. Evaluation of nonmalignant liver masses

    Microsoft Academic Search

    Wojciech Blonski; K. Rajender Reddy

    2006-01-01

    Nonmalignant liver masses are increasingly being recognized with the widespread use of imaging modalities such as ultrasonography,\\u000a computed tomography, and magnetic resonance imaging. The majority of these lesions are detected incidentally in asymptomatic\\u000a patients. Based on the radiologic appearance, benign lesions can be categorized as solid or cystic, single or multiple, hypervascular\\u000a or hypovascular. Based on histologic characteristics, they are

  9. Alcoholic disease: liver and beyond.

    PubMed

    Rocco, Alba; Compare, Debora; Angrisani, Debora; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2014-10-28

    The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world's third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the "necrosis-fibrosis" sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract. PMID:25356028

  10. Detoxification Functions of the Liver

    Microsoft Academic Search

    Udayan Apte; Partha Krishnamurthy

    \\u000a The body is exposed to a variety of chemicals everyday in the form of pharmaceutical agents, household chemicals, dietary\\u000a supplements, and environmental contaminants, many of which are extremely toxic. The primary defense mechanisms against xenobiotics\\u000a in the body are the drug metabolizing enzymes (DMEs) involved in metabolism and excretion of xenobiotics [1]. Liver is the\\u000a primary organ involved in the

  11. Alcoholic disease: Liver and beyond

    PubMed Central

    Rocco, Alba; Compare, Debora; Angrisani, Debora; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2014-01-01

    The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the “necrosis-fibrosis” sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract. PMID:25356028

  12. Stem Cells for Liver Repopulation

    PubMed Central

    Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalu; Yagi, Hiroshi; Yarmush, Martin L.

    2013-01-01

    Purpose of review The capacity of the liver to regenerate and maintain a constant size despite injury is unique. However, the exact mechanisms are not completely clear. Cell transplantation has been proposed as an alternative treatment of liver diseases. Recent progress has been reported on the generation of stem/progenitor cells that may differentiate towards the hepatic lineage. However, it is currently difficult to determine which of the stem/progenitor cell populations are the best for therapy of a given disease. Recent findings The limited access to donor human hepatocytes has opened a great interest on the generation of hepatocyte-like cells. Several potential cell sources have been identified. However, general standardization of the methods to evaluate these cells is particularly important for the promise of stem/progenitor-derived hepatocyte-based therapies. Moreover, innovations aimed at improving hepatocyte delivery, survival and engraftment have recently opened the field of organ engineering that may improve the perspective of liver repopulation. Summary Here we review current evidence reported from the perspective of potential clinical applications of different hepatic cell sources with repopulation capacities and the future perspectives and tools that can facilitate the translation of laboratory work into clinical success. PMID:19779345

  13. Hormonal control of liver regeneration

    PubMed Central

    Thrower, Seán; Ord, Margery G.

    1974-01-01

    Two peaks in cyclic AMP production in rat livers 4 and 12h after partial hepatectomy (MacManus et al., 1972) were confirmed and a third peak established at 22h, which is the peak of DNA synthesis. The increases in cyclic AMP were prevented by ?-adrenergic blocking agents, propranolol and pindolol, without affecting ornithine decarboxylase induction or DNA synthesis. The ?-blocking agents, phenoxybenzamine and phentolamine, given at the time of partial hepatectomy, delayed the rise in ornithine decarboxylase normally found 4h after operation, but did not affect DNA synthesis. If the ?-blocking agents were given at 9–12h or 18h, the onset of DNA synthesis was delayed. Phenoxybenzamine did not affect the induction of ornithine decarboxylase in intact rat livers by glucagon or growth hormone, but did inhibit induction by dexamethasone. The induction of ornithine decarboxylase produced by dexamethasone was inhibited by 17?-hydroxy-progesterone; this compound also blocked the induction of ornithine decarboxylase in livers of partially hepatectomized rats. PMID:4156833

  14. Live Donors in Liver Transplantation

    PubMed Central

    Brown, Robert S.

    2008-01-01

    Living donor liver transplantation (LDLT) has been controversial since its inception. Begun in response to deceased donor organ shortage and waiting list mortality, LDLT was initiated in 1989 in children, grew rapidly after its first general application in adults in the US in 1998, and has declined since 2001. There are significant risks to the living donor, including the risk of death and substantial morbidity, and two highly publicized donor deaths are thought to have contributed to decreased enthusiasm for LDLT. Significant improvements in outcomes have been seen over recent years and data, including from the NIH-funded Adult-to-Adult Living Donor Liver Transplantation Cohort Study, A2ALL, has established a survival benefit from pursuing LDLT. Despite this, LDLT still comprises less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors comprise approximately 40% of all transplant performed. The ethics, optimal utility and application of LDLT remain to be defined. In addition, most studies to date have focused on post-transplant outcomes and not included the effect of the learning curve on outcome or the potential impact of LDLT on waiting list mortality. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers. PMID:18471556

  15. 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 cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

  16. Liver and diabetes. A vicious circle

    PubMed Central

    Loria, Paola; Lonardo, Amedeo; Anania, Frank

    2013-01-01

    The complex and bi-directional relationship linking the liver and diabetes has recently gained intense new interest. This critical review of the published work aims to highlight the most recent basic and clinical data underlying the development of type 2 diabetes, in those with non-alcoholic fatty liver disease. Moreover, the potentially detrimental effects of type 2 diabetes in liver injury are also discussed in each of the two sections of the present paper. Fatty liver and diabetes share insulin resistance as their chief pathogenic determinant. The roles of the hypothalamus, the intestinal microbiome, white adipose tissue and inflammation are discussed in detail. Molecular insights into hepatocyte insulin resistance as the initiator of systemic insulin resistance are also presented with full coverage of the danger of fatty acids. Lipotoxicity, apoptosis, lipoautophagy, endoplasmic reticular stress response and recent developments in genetics are discussed. Closing the circle, special emphasis is given to biochemical pathways and clinical evidence supporting the role of type 2 diabetes as a risk factor for the development of progressive liver disease, including non-alcoholic steatohepatitis, cirrhosis and primary liver cancer. In conclusion, data support non-alcoholic fatty liver disease as a risk factor for the development of type 2 diabetes which is, in turn, a major contributor to progressive liver disease. This pathway leading from fatty liver to type 2 diabetes and back from the latter to the progressive liver disease is a vicious circle. PMID:23332087

  17. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios. PMID:24090941

  18. Using old liver grafts for liver transplantation: where are the limits?

    PubMed

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-08-21

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

  19. Using old liver grafts for liver transplantation: Where are the limits?

    PubMed Central

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-01-01

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

  20. Indications and Contraindications for Liver Transplantation

    PubMed Central

    Varma, Vibha; Mehta, Naimish; Kumaran, Vinay; Nundy, Samiran

    2011-01-01

    Patients with chronic liver disease and certain patients with acute liver failure require liver transplantation as a life-saving measure. Liver transplantation has undergone major improvements, with better selection of candidates for transplantation and allocation of scarce deceased donor organs (according to more objective criteria). Living donor liver transplantation came into existence to overcome the shortage of donor organs especially in countries where there was virtually no deceased donor programme. Advances in the technical aspects of the procedure, the intraoperative and postoperative care of both recipients and donors, coupled with the introduction of better immunosuppression protocols, have led to graft and patient survivals of over 90% in most high volume centres. Controversial areas like transplantation in alcoholic liver disease without abstinence, acute alcoholic hepatitis, and retransplantation for recurrent hepatitis C virus infection require continuing discussion. PMID:22007310

  1. Liver resection for colorectal cancer metastases

    PubMed Central

    Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

    2013-01-01

    Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung metastases should be seen in consultation with a thoracic surgeon. Combined or staged metastasectomy is recommended when, taking into account anatomic and physiologic considerations, the assessment is that all pulmonary metastases can also be completely removed. Furthermore, liver resection may be indicated in patients who have had a prior lung resection, and vice versa. 1(b). Routine liver resection is not recommended in patients with portal nodal disease. This group includes patients with radiologically suspicious portal nodes or malignant portal nodes found preoperatively or intraoperatively. Liver plus nodal resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—in cases with limited nodal involvement and with metastases that can be completely resected. 1(c). Routine liver resection is not recommended in patients with nonpulmonary ehms. Liver plus extrahepatic resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—for metastases that can be completely resected. 2(a). Perioperative chemotherapy, either before and after resection, or after resection, is recommended in patients with resectable liver metastatic disease. This recommendation extends to patients with ehms that can be completely resected (R0). Risks and potential benefits of perioperative chemotherapy should be discussed for patients with resectable liver metastases. The data on whether patients with previous oxaliplatin-based chemotherapy or a short interval from completion of adjuvant therapy for primary crc might benefit from perioperative chemotherapy are limited. 2(b). Liver resection is recommended in patients with initially unresectable metastatic liver disease who have a sufficient downstaging response to conversion chemotherapy. If complete resection has been achieved, postoperative chemotherapy should be considered. 3. Surgical resection of all lesions, including lesions with rcr, is recommended when technically feasible and wh

  2. A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

    PubMed Central

    Li, R; Barton, HA; Maurer, TS

    2015-01-01

    Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions.

  3. European Guidelines in Liver Contrast Ultrasound

    Microsoft Academic Search

    Riccardo Lencioni; Clotilde Della Pina; Dania Cioni; Laura Crocetti; Carlo Bartolozzi

    Despite the improvement in detection and characterization of focal liver lesions that can be achieved using contrast-enhanced\\u000a US, several issues are still open. First, contrast US will hardly replace CT or MR imaging for preoperative assessment of\\u000a patients with liver tumors, as these techniques still offer a more comprehensive assessment of the liver parenchyma, which\\u000a is mandatory to properly plan

  4. Liver biopsy methods for pediatric oncology patients

    Microsoft Academic Search

    Fredric A. Hoffer

    2000-01-01

    Background. Liver biopsy is a high-risk procedure in oncology patients, and optimal methods for children have not been established.¶Objective. To assess the effectiveness and safety of two methods of performing liver biopsy in pediatric oncology patients.¶Materials and methods. Between May 1997 and July 1999, 51 liver biopsies (22 percutaneous and 29 transjugular) were performed. The 22 percutaneous\\u000a biopsies (13 focal

  5. Pathology of Pyogenic Liver Abscess in Children

    Microsoft Academic Search

    Fausto E. L. Pereira; Carlos Musso; Jane S. Castelo

    1999-01-01

    Little is known about preexisting lesions in livers of children with pyogenic liver abscess (PLA). Study of these lesions\\u000a may elucidate possible predisposing factors for the disease. In Vitória, state of Espirito Santo, Brazil, PLA in children\\u000a is frequently associated with helminthic infections and eosinophilia. We hypothesize that nematode infection with larvae migrating\\u000a through the liver is a predisposing factor

  6. Advances in pediatric liver and intestingal transplantation

    Microsoft Academic Search

    Rafik M Ghobrial; Douglas G Farmer; Farin Amersi; Ronald W Busuttil

    2000-01-01

    Background: Significant progress has been made with liver and intestinal transplantation in pediatric patients. Shortage of whole-organ cadaveric grafts has resulted in a high mortality rate for children awaiting transplantation. New surgical procedures such as split-liver transplantation and living-related liver transplantation have evolved over the last decade to maximize donor utilization in pediatric patients.Methods: In this article we review the

  7. Nonalcoholic fatty liver disease: from pathogenesis to patient care

    Microsoft Academic Search

    Amélie Bigorgne; Anne-Marie Cassard-Doulcier; Sylvie Naveau; Gabriel Perlemuter

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in

  8. Ectopic liver: Different manifestations, one solution

    PubMed Central

    Zonca, Pavel; Martinek, Lubomir; Ihnat, Peter; Fleege, Jan

    2013-01-01

    Developmental abnormalities are rare in the liver. This study presents two case reports of ectopic liver. The first case was a 31-year-old male with clinical indication for laparoscopic appendectomy. Laparoscopy identified a perforated appendix and an unknown tumorous lesion in the ligamentum hepato umbilicalis. The patient underwent a laparoscopic appendectomy, intraoperative lavage of the peritoneal cavity, and extirpation of the lesion in the ligamentum hepato umbilicalis. Histpathological examination of the excised tumor revealed that it comprised liver tissue with fibrinous changes. The tumor was completely separate from the liver with no connection. It was classified as an ectopic liver. No further therapy was required. The second case was a 59-year-old male with a tumor on the upper pole of the spleen, incidentally diagnosed in an ultrasound examination. The biopsy raised suspicion of hepatocellular carcinoma. A positron emission tomography-computed tomography examination revealed accumulation of F-18 fluorodeoxyglucose only in the tumor. The patient underwent a splenectomy with a resection and reconstruction of diaphragm. After the hepatocellular carcinoma was confirmed, adjuvant therapy (sorafenib) was initialized. The operations and postoperative recoveries were uncomplicated in both cases. Despite the low incidence of ectopic liver and rare complications, it is necessary to maintain awareness of this possibility. The potential malignancy risk for ectopic liver tissue is the basis for radical surgical removal. Therapy for hepatocellular carcinoma in an ectopic liver follows the same guidelines as those followed for treating the “mother” liver. PMID:24151369

  9. A liver lesion in primary sclerosing cholangitis.

    PubMed

    Biswas, Sujata; Rajoriya, Neil; Wang, Lai Mun; Collier, Jane

    2015-01-01

    Primary sclerosing cholangitis is associated with an increased risk of cholangiocarcinoma; appropriate surveillance should be undertaken for this. Our case illustrates an unexpected liver lesion in such a patient, which would not have been detected with imaging alone. In suspected cancer, if a patient is not a candidate for liver resection, liver biopsy should be considered in case there is a treatment option for an alternative cause of the liver lesion. This is a careful decision to be made due to the risk of tumour seeding compromising cure and needs to be discussed via the hepatobiliary multidisciplinary team. PMID:25827915

  10. Visualization of liver in 3-D

    NASA Astrophysics Data System (ADS)

    Chen, Chin-Tu; Chou, Jin-Shin; Giger, Maryellen L.; Kahn, Charles E., Jr.; Bae, Kyongtae T.; Lin, Wei-Chung

    1991-05-01

    Visualization of the liver in three dimensions (3-D) can improve the accuracy of volumetric estimation and also aid in surgical planning. We have developed a method for 3-D visualization of the liver using x-ray computed tomography (CT) or magnetic resonance (MR) images. This method includes four major components: (1) segmentation algorithms for extracting liver data from tomographic images; (2) interpolation techniques for both shape and intensity; (3) schemes for volume rendering and display, and (4) routines for electronic surgery and image analysis. This method has been applied to cases from a living-donor liver transplant project and appears to be useful for surgical planning.

  11. Radiocolloid liver imaging in hepatic steatosis

    SciTech Connect

    Lisbona, R.; Rush, C.L.; Derbekyan, V.; Novales-Diaz, J.A.

    1986-03-01

    In a review of 60 patients with fatty infiltration of the liver documented by Xe-133 imaging, 43% had normal radiocolloid liver images, and 57% had abnormal images with various combinations of hepatomegaly, mottling, splenomegaly, and splenic shift of radioactivity. None, however, showed focal defects. Fatty infiltrates do not simulate mass lesions on the radiocolloid study of the liver, and an area of photon deficiency in the presence of hepatic steatosis points to an additional pathologic process. The interpretation of the radiocolloid liver image is unhindered by fatty infiltration when searching for discrete space-occupying lesions.

  12. Endoscopic ultrasound-guided liver biopsy

    PubMed Central

    Parekh, Parth J.; Majithia, Raj; Diehl, David L.; Baron, Todd H.

    2015-01-01

    Liver biopsy remains the cornerstone in the diagnosis and management of liver disorders. Results of liver biopsy can often drive therapeutic decision-making. Unfortunately, studies have shown conventional biopsy techniques to carry significant sampling variability that can potentially impact patient care. Endoscopic ultrasound (EUS) is gaining traction as an alternative method of biopsy. For parenchymal disease, it can decrease sampling variability. It offers a more targeted approach for focal lesions. Its diagnostic yield and limited adverse event profile make it a promising approach for liver biopsy. PMID:26020041

  13. Liver fibrosis markers of nonalcoholic steatohepatitis

    PubMed Central

    Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH.

  14. [Treatment of alcoholic liver diseases. Abstinence, nutritional support, drug therapy, liver transplantation].

    PubMed

    Pár, A

    2000-04-16

    The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis. PMID:10817009

  15. Pattern and profile of chronic liver disease in acute on chronic liver failure.

    PubMed

    Abbas, Zaigham; Shazi, Lubna

    2015-07-01

    The etiology of the chronic liver disease (CLD) in patients with acute on chronic liver failure (ACLF) may vary from region to region. The major cause of underlying CLD is viral (hepatitis B and C) in the East, while it is alcohol related in the West and in some parts of the Indian subcontinent. Autoimmune liver disease and Wilson's disease are the major underlying etiologies in the pediatric age group. The patients with CLD without cirrhosis should be included when defining ACLF. Non-alcoholic fatty liver disease related chronic liver insult in patients with known risk factors for progressive disease should be taken as a chronic liver disease in the setting of ACLF, whereas fatty liver with normal aminotransferases in low risk patients should not. The patients with CLD and previous decompensation should be excluded. Diagnosis of chronic liver disease in the setting of ACLF is made by history, physical examination and previously available or recent laboratory, endoscopic or radiological investigations. A liver biopsy through the transjugular route may help in cases where the presence of underlying CLD or its cause is not clear. The need of liver biopsy in ACLF should, however, be individualized. Standardization of liver biopsy assessment is essential for a uniform approach to the diagnosis and treatment of CLD and acute insult. Tools to measure liver stiffness may aid in identifying patients with advanced fibrosis. Studies are needed to validate the performance of these tests in the setting of ACLF. PMID:26016461

  16. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss

    Microsoft Academic Search

    John B. Dixon; Prithi S. Bhathal; Norman R. Hughes; Paul E. O'Brien

    2004-01-01

    The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable

  17. Immune responses to liver membrane antigens in patients with cystic fibrosis and liver disease.

    PubMed Central

    Mieli-Vergani, G; Psacharopoulos, H T; Nicholson, A M; Eddleston, A L; Mowat, A P; Williams, R

    1980-01-01

    Biliary obstruction by viscid mucus, although important, may not be the only factor for the development of liver disease in some patients with cystic fibrosis. In the present study the relationship between immune responses to liver antigens and the presence of liver damage was investigated using the leucocyte migration test and lymphocyte cytotoxicity to isolated rabbit hepatocytes. Inhibition of leucocyte migration by purified liver-specific lipoprotein, derived from hepatocyte plasma membrane, was found in 9 of 11 children with liver disease, but in only 5 of 14 with cystic fibrosis and no overt liver disease (P < 0.025). Lymphocyte toxicity to isolated rabbit hepatocytes was significantly increased in 10 of 13 children with liver disease, but in only 6 of 29 children without liver disease (P < 0.001). Experiments using lymphocyte subpopulations showed that the cytotoxicity was mediated by a non-T-cell population and could be blocked with liver-specific lipoprotein in 7 out of 10 cases, suggesting that the reaction in these patients was specifically directed against liver-specific lipoprotein. The study suggests that sensitisation against liver membrane antigens, whether arising primarily or secondarily in some way to other hepatic lesions, may contribute to the progression of liver damage in cystic fibrosis. PMID:7436533

  18. The sensitivity and specificity of two methods for detecting Fasciola infections in cattle

    Microsoft Academic Search

    N. Anderson; T. T. Luong; N. G. Vo; K. L. Bui; P. M. Smooker; T. W. Spithill

    1999-01-01

    Counts of Fasciola spp. eggs in faeces and measurements of antibody concentration to the excretory\\/secretory antigens of Fasciola spp. by ELISA were related to the numbers of flukes in the livers of 92 cattle killed in the abattoirs of Hanoi City, Vietnam.In this population, about 22% of the cattle had no flukes, another 22% had between 1 and 10 flukes,

  19. Chronic fascioliasis in farmed and wild greater rheas ( Rhea americana)

    Microsoft Academic Search

    Mauro Pereira Soares; Sergio Silva da Silva; Leandro Quintana Nizoli; Samuel Rodrigues Felix; Ana Lucia Schild

    2007-01-01

    From 50 farmed Rhea americana slaughtered for human consumption, adult forms and eggs of Fasciola hepatica were found in 4. The other three livers were free of flukes but did show lesions caused by larval fluke migration. Histological lesions were similar to those caused by flukes in cattle and sheep. The rheas were from an endemic area of ruminant fascioliasis

  20. Dysfibrinogenemia Associated with Liver Disease

    PubMed Central

    Palascak, Joseph E.; Martinez, Jose

    1977-01-01

    To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of A?, B?, and ? chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient 125I-fibrinogen and normal 131I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization. PMID:874092

  1. ENDOCYTOSIS IN CHANG LIVER CELLS

    PubMed Central

    Wagner, Roger; Rosenberg, Murray; Estensen, Richard

    1971-01-01

    The addition of 0.08 M sucrose to a culture medium containing Chang-strain human liver cells causes intense cytoplasmic vacuolation. Electron microscopy of these cells grown inferritin, time-lapse cinematography, and radioautography reveal that the vacuoles arise by endocytosis and that the sucrose is taken into the cell and localized in the vacuoles. Tracer studies demonstrate that sucrose-3H provides a marker for quantitation of endocytosis and that it neither induces nor stimulates endocytosis. Electron micrographs of vacuolated liver cells show microfilaments in close proximity to the inside of the plasma membrane, in the pseudopodia, and to the cytoplasmic side of the membrane surrounding endocytosis vacuoles. Cytochalasin B (CB), a mold metabolite that inhibits various types of cell motility, has a dose-dependent inhibitory effect on the uptake of sucrose-3H by these cells. This inhibition is accompanied by a cessation of the movement of ruffles and pseudopodia on the surface of the cells and the formation of blebs which arise from the cell's surface. These morphological changes are quickly reversible upon removal of CB. Alterations in the appearance and location of microfilaments are also observed in CB-treated cells. PMID:4329157

  2. Detoxification pathways in the liver.

    PubMed

    Grant, D M

    1991-01-01

    The liver plays an important rôle in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water-soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is their ability to catalyse the oxidation, reduction and hydrolysis (Phase I) and/or conjugation (Phase II) of functional groups on drug and chemical molecules. The broad substrate specificity, isoenzyme multiplicity and inducibility of many of these enzyme systems make them particularly well adapted to handling the vast array of different chemical structures in the environment to which we are exposed daily. However, some chemicals may also be converted to more toxic metabolites by certain of these enzymes, implying that variations in the latter may be important predisposing factors for toxicity. Pharmacogenetic defects of xenobiotic biotransformation enzymes, a subclass of inborn errors of metabolism which are manifested only upon drug challenge, introduce marked variation into human populations for the pharmacokinetics and pharmacodynamics of therapeutic and toxic agents, and thus may have important clinical consequences for drug efficacy and toxicity. PMID:1749210

  3. Pentose pathway in human liver

    SciTech Connect

    Magnusson, I.; Chandramouli, V.; Schumann, W.C.; Kumaran, K.; Wahren, J.; Landau, B.R. (Karolinska Institute at Huddinge Hospital, Stockholm (Sweden))

    1988-07-01

    (1-{sup 14}C)Ribose and (1-{sup 14}C)glucose were given to normal subjects along with glucose loads (1 g per kg of body weight) after administration of diflunisal and acetaminophen, drugs that are excreted in urine as glucuronides. Distributions of {sup 14}C were determined in the carbons of the excreted glucoronides and in the glucose from blood samples drawn from hepatic veins before and after glucagon administration. Eighty percent or more of the {sup 14}C from (1-{sup 14}C)ribose incorporated into the glucuronic acid moiety of the glucuronides was in carbons 1 and 3, with less than 8% in carbon 2. In glucuronic acid from glucuronide excreted when (2-{sup 14}C)glucose was given, 3.5-8.1% of the {sup 14}C was in carbon 1, 2.5-4.3% in carbon 3, and more than 70% in carbon 2. These distributions are in accord with the glucuronides sampling the glucose unit of the glucose 6-phosphate pool that is a component of the pentose pathway and is intermediate in glycogen formation. It is concluded that the glucuronic acid conjugates of the drugs can serve as a noninvasive means of sampling hepatic glucose 6-phosphate. In human liver, as in animal liver, the classical pentose pathway functions, not the L-type pathway, and only a small percentage of the glucose is metabolized via the pathway.

  4. Chronic Liver Disease and Asian Americans/Pacific Islanders

    MedlinePLUS

    ... Population Profiles > Asian American > Chronic Liver Disease Chronic Liver Disease and Asian Americans/Pacific Islanders Among Asian Americans, chronic liver disease is a leading cause of death. While the ...

  5. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    MedlinePLUS

    ... Hawaiian/Other Pacific Islander > Chronic Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/Pacific ... times more likely to be diagnosed with chronic liver disease in 2006. American Samoans were 8 times more ...

  6. Blood flukes (Digenea: Aporocotylidae) of elopomorphs: emendation of Paracardicoloides, supplemental observations of Paracardicoloides yamagutii, and a new genus and species from ladyfish, Elops saurus, (Elopiformes: Elopidae) in the Gulf of Mexico.

    PubMed

    Bullard, Stephen A

    2014-06-01

    Monotypic Paracardicoloides Martin, 1974 is emended based on supplemental observations of 2 voucher specimens of Paracardicoloides yamagutii Martin, 1974 . Features of the anterior sucker, esophagus, and intestine as well as the male and female genitalia previously attributed to, or omitted from the diagnosis and description of, this fluke are resolved and further detailed herein. The holotype of P. yamagutii, originally deposited in the Allan Hancock Parasitology Collection, apparently has been lost, and Queensland Museum voucher G222650 is designated as the neotype. Elopicola nolancribbi n. gen., n. sp. infects the ladyfish, Elops saurus , (Elopiformes: Elopidae) in the north-central Gulf of Mexico. The new genus resembles Paracardicoloides by having the combination of a bowl-shaped anterior sucker, inverse U-shaped intestine, short posterior ceca, post-cecal ovary, pre-ovarian ootype, compact uterus, and prominent excretory arms and vesicle. It differs from Paracardicoloides by lacking robust tegumental body spines and by having a single testis, post-testicular ovary, and primarily post-testicular uterus. The present study is the first confirmed report of an aporocotylid infecting a member of Elopiformes as well as the first report of an infection in an elopomorph outside of Australia and New Zealand or in marine waters. PMID:24467621

  7. Safety of MR liver specific contrast media

    Microsoft Academic Search

    Marie-France Bellin; Judith A. W. Webb; Aart J. Van Der Molen; Henrik S. Thomsen; Sameh K. Morcos

    2005-01-01

    Over the past few years a number of magnetic resonance (MR) liver specific contrast agents have been introduced. In this report the safety issues of these agents are addressed. A literature search was carried out. Based on the available information, simple guidelines on the safety issue of liver specific contrast agents have been produced by the Contrast Media Safety Committee

  8. CT and MRI of diffuse liver disease

    Microsoft Academic Search

    Neil M Rofsky; Haskel Fleishaker

    1995-01-01

    CT and MRI contribute important information to the clinical evaluation of diffuse liver disease. In some cases, these modalities can establish a diagnosis that was not ascertained histologically, which is often the case when sampling errors prevent a definitive tissue diagnosis. Characteristic alterations of liver attenuation on CT, signal changes on MRI, and morphological changes appreciated with both modalities can

  9. Liver resections with or without pedicle clamping

    Microsoft Academic Search

    Gennaro Nuzzo; Felice Giuliante; Ivo Giovannini; Maria Vellone; Germano De Cosmo; Giovanni Capelli

    2001-01-01

    Background: Decreasing operative bleeding during liver resection, and thus extent of transfusions, has become a main criterion to evaluate operative results of hepatectomies. Hepatic pedicle clamping (HPC) is widely used for this purpose. The aim of the study was to evaluate safety, efficacy, technique, and contraindications of HPC during liver resections, comparing results of resections performed with or without HPC.Methods:

  10. Are alcoholics less deserving of liver transplants?

    PubMed

    Brudney, Daniel

    2007-01-01

    When does behavior trigger a lesser claim to medical resources? When does chronic drinking, for example, mean that one has a lesser claim to a liver transplant? Only when one's behavior becomes a callous indifference to others' needs--when one knows the consequences of heavy drinking and knows that by drinking one may end up depriving someone else of a liver. PMID:17348263

  11. EFFECTS OF CORTISONE ON REGENERATING RAT LIVER

    PubMed Central

    Einhorn, Stanley L.; Hirschberg, Erich; Gellhorn, Alfred

    1954-01-01

    The effects of continuous administration of cortisone on the metabolism of regenerating rat liver have been studied. Whereas the restoration of the weight of the liver after partial hepatectomy was not markedly affected by cortisone, the multiplication of cells was reduced to a significant degree after the first 2 days of regeneration. Liver restoration in terms of nucleic acids was similarly inhibited by cortisone. The results are consistent with the interpretation that the inhibition of cell multiplication in this system is dependent on and keeps pace with the inhibition of nucleic acid synthesis by this drug. At almost any time after hepatectomy, the nucleic acid content of the liver cells was the same in treated and in untreated animals. In ancillary studies, it was shown that cortisone caused the cells of regenerating liver to be increased in size and weight through the increased infiltration of lipids. Changes in water, protein, and carbohydrate content of the liver cells did not contribute to this increase in the weight of the cells. Since all animals were treated with cortisone for 5 days before hepatectomy, data were also obtained on the effect of this agent on the resting liver. This course of treatment brought about a significant decrease in the number of cells per unit wet weight and in the water content of the livers. The nucleic acid content of the cells at hepatectomy, on the other hand, was unchanged. PMID:13143188

  12. Strange brew: T cells in the liver

    Microsoft Academic Search

    I. Nicholas Crispe; Wajahat Z. Mehal

    1996-01-01

    The liver is a meeting place for thymus-dependent circulating T cells and thymus-independent T cells with natural-killer (NK)-cell markers. Here, Nick Crispe and Waj Mehal argue that interactions between these two T-cell pools might account for the distinctive immunological role of the liver as a focus of peripheral tolerance induction.

  13. Automatic liver contour segmentation using GVF snake

    Microsoft Academic Search

    Fan Liu; Binsheng Zhao; Peter Kijewski; Michelle S. Ginsberg; Liang Wang; Lawrence H. Schwartz

    2004-01-01

    Liver segmentation is critical for the development of algorithms to detect and define focal lesions. It is also helpful in presurgical planning for hepatic resection and to gauge the results of therapies. The purpose of this study was to develop a computerized method for extraction of liver contours on contrast-enhanced hepatic CT. The method is based on a snake algorithm

  14. COACH syndrome associated with multifocal liver tumors

    Microsoft Academic Search

    Gabriele I. Kirchner; Siegfried Wagner; Peer Flemming; Joerg S. Bleck; Michael Gebel; Ingolf Schedel; Andreas Schüler; Michael Galanski; Michael P. Manns

    2002-01-01

    Here, we describe a 20-yr-old woman with COACH syndome (hypoplasia of Cerebellar vermis, Oligophrenia, congenital Ataxia, Coloboma, and Hepatic fibrosis) developing multiple liver lesions. Epigastric and right upper abdominal pain and lack of appetite led to clinical evaluation. Liver function tests showed an increase in transaminases and cholestatic parameters; ?-fetoprotein was in the normal range. Ultrasound and magnetic resonance imaging

  15. Hepatic progenitors for liver disease: current position

    PubMed Central

    Conigliaro, Alice; Brenner, David A; Kisseleva, Tatiana

    2010-01-01

    Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells) have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s), which in turn give(s) rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics. PMID:24198509

  16. Controversies in patient selection for liver transplantation.

    PubMed Central

    Keeffe, E B; Esquivel, C O

    1993-01-01

    A variety of specific conditions often stimulate controversy regarding candidacy for liver transplantation. We review the published experience with liver transplantation for alcoholic liver disease, fulminant and chronic hepatitis B, and hepatocellular carcinoma and transplantation in older subjects. Liver transplantation for alcoholic liver disease and in subjects older than 60 years is becoming less controversial because recent data demonstrate that these patients have excellent survival and good quality of life after transplantation. Only 10% to 15% of persons with alcoholism return to drinking after transplantation, and most do so only transiently. Liver transplantation for patients with hepatitis B virus infection or primary liver cancer is more problematic because recurrent disease is common in both conditions. After transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection of the allograft and long-term survival is 45% to 50%. Patients receiving transplants for hepatocellular carcinoma have only 20% to 30% long-term survival, but these survivors are cured of malignancy. Data are presented to support continued liver transplantation for chronic hepatitis B and hepatocellular carcinoma; however, patients must be selected based on factors that predict a favorable outcome, and experimental therapies should be employed to explore ways to improve the existing survival rates. PMID:8279156

  17. Study of apoptosis in human liver cancers

    Microsoft Academic Search

    Chang-Min Shan; Juan Li

    2002-01-01

    AIM: To investigate the action of apoptosis in occurrence of liver cacinomas in vivo and the biological effect of Solanum lyratum Thumb on BEL-7404 cell line inducing apoptosis in vitro. METHODS: The apoptosis in the liver carcinoma was detected with terminal deoxynucl neotidyl transferase mediated dUTP nick end labelling (TUNEL); the cancer cells cultured in DMED medium were treated with

  18. Nonalcoholic Fatty Liver Disease: A Clinical Review

    Microsoft Academic Search

    David A. Sass; Parke Chang; Kapil B. Chopra

    2005-01-01

    Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought

  19. Nonalcoholic fatty liver disease and mitochondrial dysfunction

    Microsoft Academic Search

    Yongzhong Wei; R Scott Rector; John P Thyfault; Jamal A Ibdah; Harry S. Truman

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC)

  20. Liver involvement in pediatric celiac disease

    PubMed Central

    Anania, Caterina; De Luca, Ester; De Castro, Giovanna; Chiesa, Claudio; Pacifico, Lucia

    2015-01-01

    Celiac disease (CD) is an intestinal inflammatory disease that manifests in genetically susceptible individuals when exposed to dietary gluten. It is a common chronic disorder, with a prevalence of 1% in Europe and North America. Although the disease primarily affects the gut, the clinical spectrum of CD is remarkably varied, and the disease can affect many extraintestinal organs and systems, including the liver. The hepatic dysfunction presenting in CD ranges from asymptomatic liver enzyme elevations or nonspecific reactive hepatitis (cryptogenic liver disorders), to chronic liver disease. In this article, we review the clinical presentations and possible mechanisms of CD-related liver injury to identify strategies for the diagnosis and treatment of these disorders in childhood. PMID:26019445

  1. Progress toward liver-based gene therapy.

    PubMed

    Suda, Takeshi; Kamimura, Kenya; Kubota, Tomoyuki; Tamura, Yasushi; Igarashi, Masato; Kawai, Hirokazu; Aoyagi, Yutaka; Liu, Dexi

    2009-04-01

    The liver is involved in the synthesis of serum proteins, regulation of metabolism and maintenance of homeostasis and provides a variety of opportunities for gene therapy. The enriched vasculature and blood circulation, fenestrated endothelium, abundant receptors on the plasma membranes of the liver cells, and effective transcription and translation machineries in the hepatocytes are some unique features that have been explored for delivery, and functional analysis, of genetic sequences in the liver. Both viral and non-viral methods have been developed for effective gene delivery and liver-based gene therapy. This review describes the fundamentals of gene delivery, and the preclinical and clinical progress that has been made toward gene therapy using the liver as a target. PMID:19207594

  2. Obesity, Nutrition and Liver Disease in Children

    PubMed Central

    Feldstein, Ariel E.; Patton-Ku, Dana; Boutelle, Kerri N.

    2013-01-01

    Synopsis The prevalence of childhood obesity has reached epidemic proportions in the US and many other parts of the world. With obesity comes a variety of adverse health outcomes and metabolic complications. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several aspects of childhood obesity from epidemiology and associated metabolic complications, to management strategies and therapy with particular attention to the impact of obesity on the liver resulting in non-alcoholic or metabolic fatty liver disease. The deleterious effects of obesity on the liver and health overall can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting pharmacologic, behavioral and dietary interventions for the management of obesity and fatty liver disease in children. PMID:24274876

  3. SHEAR WAVE DISPERSION MEASURES LIVER STEATOSIS

    PubMed Central

    Barry, Christopher T.; Mills, Bradley; Hah, Zaegyoo; Mooney, Robert A.; Ryan, Charlotte K.; Rubens, Deborah J.; Parker, Kevin J.

    2012-01-01

    Crawling waves, which are interfering shear wave patterns, can be generated in liver tissue over a range of frequencies. Some important biomechanical properties of the liver can be determined by imaging the crawling waves using Doppler techniques and analyzing the patterns. We report that the dispersion of shear wave velocity and attenuation, that is, the frequency dependence of these parameters, are strongly correlated with the degree of steatosis in a mouse liver model, ex vivo. The results demonstrate the possibility of assessing liver steatosis using noninvasive imaging methods that are compatible with color Doppler scanners and, furthermore, suggest that liver steatosis can be separated from fibrosis by assessing the dispersion or frequency dependence of shear wave propagations. PMID:22178165

  4. Role of liver transplantation for hepatocellular carcinoma.

    PubMed

    Kumaran, Vinay

    2014-08-01

    This review evaluates the available evidence to establish the role of liver transplantation in the management of hepatocellular carcinoma in India. Most liver transplants in India are living donor transplants due to the paucity of brain dead organ donors. There is sufficient evidence to permit allocation of organs to patients with tumors within the Milan criteria. If the waiting list time is more than 6 months, a down-staging locoregional treatment modality such a trans-arterial chemoembolization, radiofrequency ablation, resection or percutaneous ethanol injection may be used to prevent disease progression. Allocating scarce livers to patients with more advanced tumors may not be justifiable. However, living donor liver transplantation may be offered to medically fit patients with hepatocellular carcinoma with cirrhosis, offering a guarded prognosis to patients beyond the Milan or UCSF criteria. Vascular invasion and extra-hepatic disease should be absolute contraindications to liver transplantation. PMID:25755618

  5. Role of Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Kumaran, Vinay

    2014-01-01

    This review evaluates the available evidence to establish the role of liver transplantation in the management of hepatocellular carcinoma in India. Most liver transplants in India are living donor transplants due to the paucity of brain dead organ donors. There is sufficient evidence to permit allocation of organs to patients with tumors within the Milan criteria. If the waiting list time is more than 6 months, a down-staging locoregional treatment modality such a trans-arterial chemoembolization, radiofrequency ablation, resection or percutaneous ethanol injection may be used to prevent disease progression. Allocating scarce livers to patients with more advanced tumors may not be justifiable. However, living donor liver transplantation may be offered to medically fit patients with hepatocellular carcinoma with cirrhosis, offering a guarded prognosis to patients beyond the Milan or UCSF criteria. Vascular invasion and extra-hepatic disease should be absolute contraindications to liver transplantation. PMID:25755618

  6. Klebsiella pneumoniae liver abscess and endophthalmitis

    PubMed Central

    Abdul-Hamid, Ayeshah; Bailey, Sarah-Jane

    2013-01-01

    A 36-year-old man was referred to the general medical team with endophthalmitis. He was noted to have raised inflammatory markers and deranged liver function tests on admission. Subsequent abdominal ultrasound scan revealed a liver abscess requiring percutaneous drainage. A common human pathogen, Klebsiella pneumoniae, was cultured from multiple sites. K pneumoniae has virulent serotypes (K1 and K2) that can cause primary liver abscess with metastatic infections. Cases have previously been predominantly reported in Southeast Asia but are increasing in prevalence in Europe and North America. The main known risk factor for the disease is diabetes mellitus. Swift antibiotic therapy, ophthalmology review and percutaneous drainage of any liver abscess are essential. Early recognition of the syndrome, despite potentially few initial symptoms, can significantly reduce morbidity and mortality. The authors report the first recorded case of K pneumoniae liver abscess with endophthalmitis in the UK. PMID:23559652

  7. [Acute liver failure. Diagnosis and therapy].

    PubMed

    Streetz, K L; Tacke, F; Koch, A; Trautwein, C

    2013-11-01

    Although acute liver failure is a rare disease with a prevalence of 5 per 1 million people, it has a considerablely high mortality rate of 34?%. The main causes in western civilizations are drug overdose (acetaminophen) and viral hepatitis. Patients are affected by the loss of liver synthesis function and are at risk of developing hepatic encephalopathy and possible multiorgan failure. Specific therapies consisting of the administration of N-acetylcysteine (acetaminophen) or of nucleotide/nucleoside analogs (hepatitis B) are possible, but are often not adequate. Orthotopic liver transplantation is, therefore, frequently the only remaining effective therapy for severe acute liver failure. Due to organ shortage, new prognostic tools, e.g., the Acute Liver Failure Study Group (ALFSG) score, have been developed to improve patient selection using sufficiently stringent selection criteria. PMID:24189846

  8. Liver abnormalities in drug and substance abusers.

    PubMed

    Pateria, Puraskar; de Boer, Bastiaan; MacQuillan, Gerry

    2013-08-01

    Drug and substance abuse remains a major medical problem. Alcohol use, abuse and dependence are highly prevalent conditions. Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis. Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem. While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects. Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure. This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine. PMID:24090944

  9. Uridine Prevents Fenofibrate-Induced Fatty Liver

    PubMed Central

    Le, Thuc T.; Urasaki, Yasuyo; Pizzorno, Giuseppe

    2014-01-01

    Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD) and acyl-CoA oxidase 1 (ACOX1), and induces excessive accumulation of long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA). Uridine co-administration at a daily dosage of 400 mg/kg raises NAD+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver. PMID:24475249

  10. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2014-03-14

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Metastatic Extrahepatic Bile Duct Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Stage D Adult Primary Liver Cancer (BCLC); Unspecified Adult Solid Tumor, Protocol Specific

  11. Cell Metabolism A Quantitative Map of the Liver Mitochondrial

    E-print Network

    Yandell, Brian S.

    Cell Metabolism Resource A Quantitative Map of the Liver Mitochondrial Phosphoproteome Reveals of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological

  12. Anesthesia for Patients With Liver Disease

    PubMed Central

    Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

    2014-01-01

    Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above mentioned rules a safe anesthesia could be achievable in these patients. PMID:25031586

  13. In situ hybridization of albumin mRNA in normal liver and liver tumors: Identification of hepatocellular origin

    Microsoft Academic Search

    Koji Yamaguchi; Michael A. Nalesnik; Brian I. Carr

    1993-01-01

    Summary  In situ hybridization was performed to detect albumin mRNA in normal liver, liver cirrhosis, primary liver tumors and secondary\\u000a liver neoplasms. In areas of normal liver, and liver cirrhosis, signals for albumin mRNA were present in hepatocytes, whereas\\u000a no signals were seen in other cells such as endothelial and Küpffer cells, bile duct epithelium and smooth muscle cells. In\\u000a 53

  14. Left lobe amoebic liver abscess

    PubMed Central

    Rasaretnam, Rudra; Wijetilaka, Shelton E.

    1976-01-01

    For reasons which are not quite clear amoebic liver abscesses in the left lobe are relatively uncommon. On account of the lesser bulk of the left lobe, and the potentially greater space under the left hemidiaphragm, expansive lesions within it remain less obtrusive than corresponding lesions in the right. Sixteen such cases are analysed and five distinct modes of clinical presentation have been found. Eight of the patients presented late with perforation into either the peritoneal or pleural cavities. In seven of eight remaining cases, an abdominal mass suggestive of a left lobe lesion was present. Anaemia, leucocytosis and a raised erythrocyte sedimentation rate were usually present, and in the five cases seen in the last year a positive reaction was obtained to the indirect fluorescent antibody test. Confirmatory radiological features were present only in advanced cases. ImagesFig. 2Fig. 3Fig. 4Fig. 5 PMID:959101

  15. Natural killer T cells in liver injury, inflammation and cancer.

    PubMed

    Wang, Hua; Yin, Shi

    2015-08-01

    The liver is an organ that has the largest amount of natural killer T(NKT) cells, which play critical roles in the pathogenesis of liver diseases. In this article, the authors summarize recent findings about the roles of NKT cells in liver injury, inflammation, fibrosis, regeneration and cancer. In brief, NKT cells accelerate liver injury by producing pro-inflammatory cytokines and directly killing hepatocytes. NKT cells are involved in complex roles in liver fibrogenesis. For instance, NKT cells inhibit liver fibrosis via suppressing hepatic stellate cell activation and can also promote liver fibrosis via enhancing liver inflammation and injury. Inactivated or weakly activated NKT cells play a minimal role in controlling liver regeneration, whilst activated NKT cells have an inhibitory effect on liver regeneration. In liver cancer, NKT cells play both pro-tumor and anti-tumor roles in controlling tumor progress. PMID:26068039

  16. Tivozanib in Treating Patients With Liver Cancer That is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-04-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Stage C Adult Primary Liver Cancer (BCLC); Stage D Adult Primary Liver Cancer (BCLC)

  17. Preoperative liver function assessments to estimate the prognosis and safety of liver resections.

    PubMed

    Mizuguchi, Toru; Kawamoto, Masaki; Meguro, Makoto; Hui, Thomas T; Hirata, Koichi

    2014-01-01

    Liver function assessment is important to ensure safe surgical procedures in patients with hepatocellular disease. Because the liver influences a wide variety of functions, including protein synthesis and metabolic, immune and storage functions, no single parameter is sufficient to adequately address all of these functions. We reviewed the relevant literature concerning the scoring systems, functional tests, plasma parameters and imaging modalities currently used to evaluate the liver function in an attempt to determine which parameters provide the most comprehensive and useful results. While the Child-Pugh scoring system is the gold standard for liver disease assessment, the liver damage grading system recommended by the Liver Cancer Study Group of Japan is also useful. Various models for end-stage liver disease scoring are used for organ allocation. While the indocyanine green clearance test is widely accepted throughout the world, other assessments have not been used routinely for clinical evaluations. The levels of plasma proteins, including albumin, prealbumin, retinol binding protein, apolipoprotein, coagulation factors and antithrombin III, represent the liver productivity. Liver fibrotic markers also correlate with liver function. Imaging modalities such as (99m)Tc-galactosyl serum albumin scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy. PMID:23474700

  18. Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

    SciTech Connect

    Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States)] [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Campbell, Jean S.; Fausto, Nelson [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States)] [Department of Pathology, University of Washington School of Medicine, Seattle, WA (United States); Yeung, Raymond S. [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)] [Department of Surgery, University of Washington School of Medicine, Seattle, WA (United States)

    2013-07-19

    Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/? mice was not enhanced. •The Tsc2+/? livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/? mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/? mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/? mice was not enhanced. Instead, the Tsc2+/? livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

  19. Patients with Chronically Diseased Livers Have Lower Incidence of Colorectal Liver Metastases: A Meta-Analysis

    PubMed Central

    Cai, Bin; Liao, Kai; Song, Xian-qing; Wei, Wei-yuan; Zhuang, Yuan; Zhang, Sen

    2014-01-01

    Background 70 years ago, it was put forward that the diseased liver was not a favorable soil for metastatic tumor cells. In addition, a few studies have demonstrated that rare occurrence of colorectal liver metastases among patients with fatty liver, cirrhosis or chronic hepatitis B and C virus infection. We performed a meta-analysis to verify the association between the incidences of colorectal liver metastases with chronically diseased livers. Methods Relevant studies were identified by a search of electronic database PubMed, Cochrane Library, OVID, Web of Science and CNKI (up to February 24, 2014). Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Meta-analysis and publication bias (Bgger's test) was evaluated with STATA 12.0. Results A total of 10,349 colorectal cancer patients from 10 studies were included. The meta-analysis result showed there was a significant difference in the incidences of colorectal liver metastases between patients with normal and chronically diseased livers (OR?=?0.32; 95% CI 95%: 0.26–0.38, P?=?0.000 fixed-effects model). The result of Begg's test (Pr>|z|?=?0.089; P>0.05) revealed no publication bias. Conclusions The results of this meta-analysis demonstrated that patients with chronically diseased livers had significantly lower incidences of colorectal liver metastases than those with normal livers. PMID:25265536

  20. [Liver function and pathogenetic therapy for echinococcosis].

    PubMed

    Streliaeva, A V; Mamysheva, N O; Abdiev, F T; Sagieva, A T; Iusupova, F Sh; Sadykov, V M; Mukhitdininov, Sh M; Vakhidova, A M

    2013-01-01

    This paper contains the results of examining and treating 64 patients with hepatic echinococcosis, treated at the Surgery Unit of the Samarkand Medical Institute Clinic. Forty-five healthy donors of a blood transfusion station formed a control group. There were a total of 109 examined persons. The liver functional status depended on segmental liver involvement by an echinococcal cyst. The cysts were most frequently located in the 7th-8th segments of the liver (32.31%). The number and sizes of cysts also affected the functional status of the cyst-affected liver. The sizes of hepatic cysts varied from 4 to 2 cm. Hepatoprotective agents should be used in different forms of hydatid disease of the liver to correct its function that is changed in multiple and complicated echinococcosis and giant hepatic cysts. They normalize liver function and enzyme activity in the hepatocytes, reduce energy expenditure in the liver, promote hepatocyte regeneration, and convert neutral fats and cholesterol into easily metabolizing forms. PMID:24003518

  1. Decreasing mitochondrial fission prevents cholestatic liver injury.

    PubMed

    Yu, Tianzheng; Wang, Li; Lee, Hakjoo; O'Brien, Dawn K; Bronk, Steven F; Gores, Gregory J; Yoon, Yisang

    2014-12-01

    Mitochondria frequently change their shape through fission and fusion in response to physiological stimuli as well as pathological insults. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. However, the role of mitochondrial shape change in cholestasis is not defined. In this study, using in vitro and in vivo models of bile acid-induced liver injury, we investigated the contribution of mitochondrial morphology to the pathogenesis of cholestatic liver disease. We found that the toxic bile salt glycochenodeoxycholate (GCDC) rapidly fragmented mitochondria, both in primary mouse hepatocytes and in the bile transporter-expressing hepatic cell line McNtcp.24, leading to a significant increase in cell death. GCDC-induced mitochondrial fragmentation was associated with an increase in reactive oxygen species (ROS) levels. We found that preventing mitochondrial fragmentation in GCDC by inhibiting mitochondrial fission significantly decreased not only ROS levels but also cell death. We also induced cholestasis in mouse livers via common bile duct ligation. Using a transgenic mouse model inducibly expressing a dominant-negative fission mutant specifically in the liver, we demonstrated that decreasing mitochondrial fission substantially diminished ROS levels, liver injury, and fibrosis under cholestatic conditions. Taken together, our results provide new evidence that controlling mitochondrial fission is an effective strategy for ameliorating cholestatic liver injury. PMID:25342755

  2. Diagnostic evaluation of nonalcoholic fatty liver disease.

    PubMed

    Adams, Leon A; Talwalkar, Jayant A

    2006-03-01

    Nonalcoholic fatty liver disease (NAFLD) is a diagnostic consideration among patients with asymptomatic elevated aminotransaminases, patients with radiologic findings of hepatic fatty infiltration, or occasionally in the patient with "cryptogenic" cirrhosis. The diagnosis of NAFLD requires evidence of fatty infiltration of the liver in the absence of excessive alcohol ingestion. Clinical evaluation should examine for metabolic risk factors (central obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol), which are suggestive but not specific for the diagnosis of NAFLD. Secondary causes of NAFLD, such as medications and intestinal bypass surgery, should be excluded as management of these conditions may differ. Confirmation of hepatic steatosis can usually be done by imaging studies, although occasionally liver biopsy is required. Among suspected NAFLD patients with chronically elevated aminotransaminases, clinical evaluation and serological testing should be performed to exclude other causes of chronic liver disease. Liver biopsy is required to stage fibrosis and distinguish between nonalcoholic steatohepatitis and steatosis. This is valuable for providing prognosis, excluding other liver disease, monitoring response to therapy or evaluating disease progression over time. Clinical features, particularly diabetes, obesity, and older age, can aid in stratifying patients at risk for advanced fibrosis but are not sufficiently accurate to replace liver biopsy. PMID:16540765

  3. BIOCONJUGATION OF OLIGONUCLEOTIDES FOR TREATING LIVER FIBROSIS

    PubMed Central

    Ye, Zhaoyang; Hajj Houssein, Houssam S.; Mahato, Ram I.

    2009-01-01

    Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of ?1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed. PMID:18154454

  4. Developmental origins of nonalcoholic fatty liver disease

    PubMed Central

    Brumbaugh, David E.; Friedman, Jacob E.

    2014-01-01

    Obese pregnant women may transmit their metabolic phenotype to offspring, leading to a cycle of obesity and diabetes over generations. Early childhood obesity predicts nonalcoholic fatty liver disease (NAFLD), the most common chronic human liver disease. The fetus may be vulnerable to steatosis because immature fetal adipose depots are not available to buffer the excess transplacental lipid delivery in maternal obesity. In animal models, in utero high-fat diet exposure results in an increase in the accumulation of liver triglycerides in offspring and increased hepatic oxidative stress and apoptosis, perhaps priming the liver for later development of NAFLD. Innate immune dysfunction and necroinflammatory changes have been observed in postnatal offspring liver of animals born to high-fat–fed dams. Postweaning, livers of offspring exposed to maternal high-fat feeding in utero share pathophysiologic features with human NAFLD, including increased de novo lipogenesis and decreased free fatty acid oxidation. Human studies using magnetic resonance imaging have shown that maternal BMI predicts infant intrahepatocellular lipid storage, as seen in animal models. The generational transfer of NAFLD may occur via epigenetic changes in offspring liver. Transmission of micro-biota from mother to infant may impact energy retention and immune function that contribute to a predisposition to NAFLD. PMID:24192698

  5. Automatic liver contour segmentation using GVF snake

    NASA Astrophysics Data System (ADS)

    Liu, Fan; Zhao, Binsheng; Kijewski, Peter; Ginsberg, Michelle S.; Wang, Liang; Schwartz, Lawrence H.

    2004-05-01

    Liver segmentation is critical for the development of algorithms to detect and define focal lesions. It is also helpful in presurgical planning for hepatic resection and to gauge the results of therapies. The purpose of this study was to develop a computerized method for extraction of liver contours on contrast-enhanced hepatic CT. The method is based on a snake algorithm with Gradient Vector Flow (GVF) field as its external force, which uses an edge map and an initial contour as its starting point. A Canny edge algorithm is thus applied to obtain the initial edge map. To suppress edges inside liver parenchyma, a liver template determined by analyzing the histogram of the liver image is employed. Based on the modified edge map, the GVF field is then computed in an iterative manner. Due to the finite iteration step, an area uncovered by the GVF field in the liver can be extracted and serves as an initial contour for the snake algorithm. Preliminary results have shown the potential of separating the liver from its adjacent structures (e.g., kidney and stomach) of similar densities.

  6. Obesity accelerates epigenetic aging of human liver.

    PubMed

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T; Tsai, Pei-Chien; Spector, Tim D; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-10-28

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an "epigenetic clock") to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10(-4) in dataset 1 and r = 0.42, P = 1.2 × 10(-4) in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10(-9)) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer. PMID:25313081

  7. TWEAK induces liver progenitor cell proliferation

    PubMed Central

    Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

    2005-01-01

    Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

  8. Obesity accelerates epigenetic aging of human liver

    PubMed Central

    Horvath, Steve; Erhart, Wiebke; Brosch, Mario; Ammerpohl, Ole; von Schönfels, Witigo; Ahrens, Markus; Heits, Nils; Bell, Jordana T.; Tsai, Pei-Chien; Spector, Tim D.; Deloukas, Panos; Siebert, Reiner; Sipos, Bence; Becker, Thomas; Röcken, Christoph; Schafmayer, Clemens; Hampe, Jochen

    2014-01-01

    Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an “epigenetic clock”) to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver (r = 0.42, P = 6.8 × 10?4 in dataset 1 and r = 0.42, P = 1.2 × 10?4 in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10?9) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer. PMID:25313081

  9. Apoptosis and Necrosis in the Liver

    PubMed Central

    Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

    2013-01-01

    Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

  10. Liver masses with central or eccentric scar.

    PubMed

    Kim, Tonsok; Hori, Masatoshi; Onishi, Hiromitsu

    2009-10-01

    Central or eccentric scar has been described in (most frequently) focal nodular hyperplasia (FNH), large hemangioma, and fibrolamellar hepatocellular carcinoma, and moreover, a central scar may be rarely seen in conventional nonfibrolamellar hepatocellular carcinoma, (peripheral type) cholangiocarcinoma, and some hepatic metastases. Among the liver tumors with central or eccentric scar, differentiating FNH from other solid hepatic tumors is important because FNH usually requires no treatment. Multiphasic computed tomography and magnetic resonance imaging are useful for the differential diagnosis of liver tumors with central or eccentric scar. Liver-specific magnetic resonance contrast media will improve the differentiation between FNH and other solid hepatic tumors. PMID:19842566

  11. Single-incision laparoscopic liver resection

    Microsoft Academic Search

    Sébastien Gaujoux; T. Peter Kingham; William R. Jarnagin; Michael I. D’Angelica; Peter J. Allen; Yuman Fong

    2011-01-01

    Background  Laparoscopic liver surgery has become a safe and effective approach to the surgical management of liver disease. Recently\\u000a developed, single-port-access surgery is of growing interest in an attempt to minimize abdominal wall trauma. Various abdominal\\u000a procedures have already been performed via single-port access, but to date, single-port-access surgery has never been reported\\u000a for liver resection.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  One patient underwent laparoscopic fenestration

  12. Extended-donor criteria liver allografts.

    PubMed

    Alkofer, Barbara; Samstein, Benjamin; Guarrera, James V; Kin, Cindy; Jan, Dominique; Bellemare, Sarah; Kinkhabwala, Milan; Brown, Robert; Emond, Jean C; Renz, John F

    2006-08-01

    Extended-donor criteria liver allografts do not meet traditional criteria for transplantation. Although these organs offer immediate expansion of the donor pool, transplantation of extended-donor criteria liver allografts increases potential short- and long-term risk to the recipient. This risk may manifest as impaired allograft function or donor-transmitted disease. Guidelines defining this category of donor, level of acceptable risk, principles of consent, and post-transplantation surveillance have not been defined. This article reviews the utilization, ethical considerations, and outcomes of extended-donor criteria liver allografts. PMID:16850371

  13. Does human liver contain estrogen receptors?

    Microsoft Academic Search

    H. Bojar; J. Schütte; W. Staib; Ch. Broelsch

    1982-01-01

    Summary A comparative study of specific estrogen-binding components in human and rat liver cytosol was performed. Similar to rat liver, human liver was found to contain high-affinity-low-capacity cytoplasmic estrogen binders. The apparent dissociation constants (KDS) of the [3H]estradiol-17ß-binder complexes were calculated from Scatchard plots and found to be in the range of 0.3–4.3 × 10-9 mol\\/l and 1.0–3.8 × 10-9

  14. Anatomy of liver arteries for interventional radiology.

    PubMed

    Favelier, S; Germain, T; Genson, P-Y; Cercueil, J-P; Denys, A; Krausé, D; Guiu, B

    2015-06-01

    The availability of intra-arterial hepatic therapies (radio and/or chemo-embolisation, intra-arterial hepatic chemotherapy) has convinced radiologists to perfect their knowledge of the anatomy of the liver arteries. These sometimes, complex procedures most often require selective arterial catheterization. Knowledge of the different arteries in the liver and the peripheral organs is therefore essential to optimize the procedure and avoid eventual complications. This paper aims to describe the anatomy of the liver arteries and the variants, applying it to angiography images, and to understand the implications of such variations in interventional radiological procedures. PMID:24534562

  15. Development of a PCR assay and pyrosequencing for identification of important human fish-borne trematodes and its potential use for detection in fecal specimens

    PubMed Central

    2014-01-01

    Background Small liver and minute intestinal flukes are highly prevalent in Southeast Asia. Definitive diagnosis of parasite infection is usually achieved parasitologically by finding the fluke eggs in feces. However, their eggs are difficult to differentiate morphologically in fecal samples, even for experienced technicians. The present study developed a PCR assay coupled with DNA pyrosequencing for identification of the fish-borne trematodes (FBT), Opisthorchis viverrini, Clonorchis sinensis, Haplorchis taichui, H. pumilio and Stellantchasmus falcatus, and to evaluate potential detection in fecal specimens, and identification and differentiation of cercarial and metacercarial stages. Methods Primers targeting the partial 28S large subunit ribosomal RNA gene were designed and about 46–47 nucleotides were selected as the target region for species identification by a PCR assay coupled with a pyrosequencing technique. Results The nucleotide variations at 24 positions, which is sufficient for the identification of the five species of FBT were selected. The method could identify O. viverrini and C. sinensis eggs in feces, cercarial and metacercarial stages of O. viverrini, and metacercarial stage of H. pumilio and H. taichui. The detection limit was as little as a single O. viverrini or C. sinensis egg artificially inoculated in 100 mg of non-infected fecal sample (equivalent to 10 eggs per gram), indicating highly sensitivity. The method was found to be superior to the traditional microscopy method and was more rapid than Sanger DNA sequencing. Conclusions DNA pyrosequencing-based identification is a valuable tool for differentiating O. viverrini and other Opisthorchis-like eggs, and can be applied to epidemiological studies and for molecular taxonomic investigation of FBT in endemic areas. PMID:24589167

  16. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension.

    PubMed

    Seo, Yeon Seok; Shah, Vijay H

    2012-12-01

    Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension. PMID:23323248

  17. Recovery of menstruation and pregnancy after liver transplantation

    Microsoft Academic Search

    T F Cundy; J G OGrady; R Williams

    1990-01-01

    The effect of successful liver transplantation on menstrual function was assessed by questionnaire in 44 women transplanted for various types of end stage liver disease, acute liver failure or malignant disease. Significant amenorrhoea (greater than one year) was present in 48% of women with chronic liver disease before transplantation, and was reversed within 10 months of surgery in all but

  18. Regenerative and fibrotic pathways in canine liver disease

    Microsoft Academic Search

    Bart Spee

    2006-01-01

    Liver diseases occur quite frequently in dogs; the overall incidence in dogs has been estimated around 1-2% of the clinical cases. Most liver diseases are, like in humans, chronic and occur through chronic inflammation due to different causes. In all cases the on-going liver cell damage leads to a reduction of the functional liver cell mass and progressive deposition of

  19. Liver segmentation for CT images using GVF snake

    Microsoft Academic Search

    Fan Liu; Zhao Binsheng; Peter K. Kijewski; Wang Liang; Lawrence H. Schwartz

    2005-01-01

    Accurate liver segmentation on computed tomography (CT) images is a challenging task especially at sites where surrounding tissues (e.g., stomach, kidney) have densities similar to that of the liver and lesions reside at the liver edges. We have developed a method for semiautomatic delineation of the liver contours on contrast-enhanced CT images. The method utilizes a snake algorithm with a

  20. Radiotherapeutic Parameters Predictive of Liver Complications Induced by Liver Tumor Radiotherapy

    SciTech Connect

    Lee, Ik Jae [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)], E-mail: jsseong@yuhs.ac; Shim, Su Jung [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Han, Kwang Hyub [Yonsei Liver Cancer Clinic, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2009-01-01

    Purpose: The purpose of this study was to identify radiotherapeutic parameters for predicting the occurrence of liver complications induced by radiotherapy of a liver tumor. Methods and Materials: From 2001 to 2003, a total of 131 patients with hepatocellular carcinoma received three-dimensional conformal radiotherapy. The total dose was determined by the fraction of nontumor liver receiving 50% of the isocenter dose (V{sub 50%}). We evaluated three sets of published radiation dose guidelines using nontumor liver volume or a combination of nontumor liver volume and hepatic functional reserve. The V{sub 50%} was divided into three intervals (<33%, 33-66%, and >66%) and four categories (<25%, 25-49%, 50-75%, and >75%) according to guidelines by University of Michigan and the Yonsei University, respectively. According to the guideline of Cheng et al., the radiation dose was determined by the indocyanin green retention rate at 15 min (ICG-R15) and the nontumor liver volume. Results: Of the 131 patients, 13 patients (9.9%) presented with liver complications. The incidence was 11.1%, 10.3%, and 18.2%, respectively, for a V{sub 50%} of less than 33%, 33% to 66%, and more than 66%. The observed hepatic toxicity incidence was 10%, 12.1%, and 10.4% respectively for a V{sub 50%} of less than 25%, 25% to 49%, and 50% to 75%, respectively. Nontumor liver volume and ICG-R15 were not predictors of liver complications. The incidence of liver complications was significantly increased in patients with Child-Pugh Class B (p = 0.044). Conclusions: The parameter, V{sub 50%}, can be divided into 4 categories and used to predict acceptable toxicity. Furthermore, indicators of liver functional status like the Child-Pugh class may be more important and useful parameters than ICG-R15 for predicting radiation-related liver disease.

  1. Deficiency in Thrombopoietin Induction after Liver Surgery Is Associated with Postoperative Liver Dysfunction

    PubMed Central

    Haegele, Stefanie; Offensperger, Florian; Pereyra, David; Lahner, Elisabeth; Assinger, Alice; Fleischmann, Edith; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine; Starlinger, Patrick

    2015-01-01

    Background and Aims Thrombopoietin (TPO) has been implicated in the process of liver regeneration and was found to correlate with hepatic function in patients with liver disease. With this investigation we aimed to determine if perioperative TPO levels were associated with postoperative outcome in patients undergoing liver resection. Methods Perioperative TPO was analyzed prior to liver resection as well as on the first and fifth postoperative day in 46 colorectal cancer patients with liver metastasis (mCRC) as well as 23 hepatocellular carcinoma patients (HCC). Serum markers of liver function within the first postoperative week were used to define liver dysfunction. Results While circulating TPO levels significantly increased one day after liver resection in patients without liver cirrhosis (mCRC) (P < 0.001), patients with underlying liver disease (HCC) failed to significantly induce TPO postoperatively. Accordingly, HCC patients had significantly lower TPO levels on POD1 and 5. Similarly, patients with major resections failed to increase circulating TPO levels. Perioperative dynamics of TPO were found to specifically predict liver dysfunction (AUC: 0.893, P < 0.001) after hepatectomy and remained an independent predictor upon multivariate analysis. Conclusions We here demonstrate that perioperative TPO dynamics are associated with postoperative LD. Postoperative TPO levels were found to be lowest in high-risk patients (HCC patients undergoing major resection) but showed an independent predictive value. Thus, a dampened TPO increase after liver resection reflects a poor capacity for hepatic recovery and may help to identify patients who require close monitoring or intervention for potential complications. PMID:25611592

  2. Augmenter of Liver Regeneration (alr) Promotes Liver Outgrowth during Zebrafish Hepatogenesis

    PubMed Central

    Li, Yan; Farooq, Muhammad; Sheng, Donglai; Chandramouli, Chanchal; Lan, Tian; Mahajan, Nilesh K.; Kini, R. Manjunatha; Hong, Yunhan; Lisowsky, Thomas; Ge, Ruowen

    2012-01-01

    Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. The small-liver phenotype in alr morphants results from a reduction of hepatocyte proliferation without affecting apoptosis. When expressed in cultured cells, zebrafish Alr exists as dimer and is localized in mitochondria as well as cytosol but not in nucleus or secreted outside of the cell. Similar to mammalian ALR, zebrafish Alr is a flavin-linked sulfhydryl oxidase and mutation of the conserved cysteine in the CxxC motif abolishes its enzymatic activity. Interestingly, overexpression of either wild type Alr or enzyme-inactive AlrC131S mutant promoted liver growth and rescued the liver growth defect of alr morphants. Nevertheless, alrC131S is less efficacious in both functions. Meantime, high doses of alr MOs lead to widespread developmental defects and early embryonic death in an alr sequence-dependent manner. These results suggest that alr promotes zebrafish liver outgrowth using mechanisms that are dependent as well as independent of its sulfhydryl oxidase activity. This is the first demonstration of a developmental role of alr in vertebrate. It exemplifies that a low-level sulfhydryl oxidase activity of Alr is essential for embryonic development and cellular survival. The dose-dependent and partial suppression of alr expression through MO-mediated knockdown allows the identification of its late developmental role in vertebrate liver organogenesis. PMID:22292055

  3. Raman spectroscopic studies of vitamin A content in the liver: a biomarker of healthy liver.

    PubMed

    Kochan, K; Marzec, K M; Maslak, E; Chlopicki, S; Baranska, M

    2015-04-01

    Confocal Raman microspectroscopy was used in this study to identify hepatic stellate cells (HSCs) from healthy mice and mice with untreated and treated liver steatosis. We have identified the main form of occurrence of vitamin A in healthy liver and confirmed its absence in the pathological state. Additionally, we have reported the reappearance of vitamin A in the tissue after treatment of liver steatosis. PMID:25521614

  4. Hepatitis C: New challenges in liver transplantation.

    PubMed

    Filipec Kanizaj, Tajana; Kunac, Nino

    2015-05-21

    In an era of great achievements in liver transplantation, hepatitis C viral infection (HCV) remains an unsolved problem. As a leading indication for liver transplantation in Western countries, HCV poses a significant burden both before and after transplantation. Post-transplant disease recurrence occurs in nearly all patients with detectable pretransplant viremia, compromising the lifesaving significance of transplantation. Many factors involving the donor, recipient and virus have been evaluated throughout the literature, although few have been fully elucidated and implemented in actual clinical practice. Antiviral therapy has been recognized as a cornerstone of HCV infection control; however, experience and success are diminished following transplantation in a challenging cohort of patients with liver cirrhosis. Current therapeutic protocols surpass those used previously, both in sustained viral response and side-effect profile. In this article we review the most relevant and contemporary scientific evidence regarding hepatitis C infection and liver transplantation, with special attention dedicated to novel, more efficient and safer antiviral regimens. PMID:26019441

  5. Liver Cancer - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Chinese - Traditional (????) Hmong (Hmoob) Korean (???) Laotian (Lao) Spanish (espańol) Tagalog (Tagalog) Vietnamese (Tię?ng Vię?t) Burmese ( ... Korean) PDF Stanford University, Asian Liver Center Laotian (Lao) Know HBV: What Every Asian and Pacific Islander ...

  6. Autophagy and apoptosis in liver injury.

    PubMed

    Wang, Kewei

    2015-06-01

    Apoptosis is a primary characteristic in the pathogenesis of liver disease. Hepatic apoptosis is regulated by autophagic activity. However, mechanisms mediating their interaction remain to be determined. Basal level of autophagy ensures the physiological turnover of old and damaged organelles. Autophagy also is an adaptive response under stressful conditions. Autophagy can control cell fate through different cross-talk signals. A complex interplay between hepatic autophagy and apoptosis determines the degree of hepatic apoptosis and the progression of liver disease as demonstrated by pre-clinical models and clinical trials. This review summarizes recent advances on roles of autophagy that plays in pathophysiology of liver. The autophagic pathway can be a novel therapeutic target for liver disease. PMID:25927598

  7. Paediatric liver transplantation: the surgical view

    PubMed Central

    Vilca-Melendez, H; Heaton, N

    2004-01-01

    Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation. PMID:15466990

  8. Binge ethanol and liver: new molecular developments.

    PubMed

    Shukla, Shivendra D; Pruett, Stephen B; Szabo, Gyongyi; Arteel, Gavin E

    2013-04-01

    Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also to develop therapeutic strategies to control it. This review summarizes these recent developments. PMID:23347137

  9. Risks of Liver (Hepatocellular) Cancer Screening

    MedlinePLUS

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

  10. CELL SIGNALING: Fat Stress and Liver Resistance

    NSDL National Science Digital Library

    Wataru Ogawa (Kobe University Graduate School of Medicine; Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology)

    2008-12-05

    Access to the article is free, however registration and sign-in are required. Communication among immune and fat cells in adipose tissue and liver hepatocytes underlies the pathogenesis of obesity-related insulin resistance.

  11. Dengue and its effects on liver

    PubMed Central

    Samanta, Jayanta; Sharma, Vishal

    2015-01-01

    Dengue has emerged as an important arboviral disease with significant impact on the disease burden in population residing in tropical countries. Dengue is spread by the bite of Aedes mosquito. The virus seems to have some hepatotoxic effects. Affliction of liver in form of derangements in the liver function tests is common and may include mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin. Although asymptomatic in most cases, clinical manifestations like jaundice, and acute liver failure (ALF) may occasionally complicate the clinical picture. Indeed, dengue has been implicated as an important cause of ALF in endemic countries. The present review focuses on the hepatic manifestations and the pathogenesis of the liver injury in dengue. PMID:25685758

  12. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  13. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePLUS

    ... occur with resultant hepatitis called non-alcoholic steatohepatitis (NASH). This condition can lead to liver damage with ... 10-40% of adults in the United States. NASH is present in 2 to 5 percent of ...

  14. Some Observations on Liver Cell Proliferation in the Isolated Perfused Rat Liver

    PubMed Central

    Lloyd, E. A.; Crozier, N.; Pamphlet, G.; Wells, M.; Saunders, S. J.

    1974-01-01

    Experiments were designed to test the hypothesis that in an isolated perfused system a regenerating liver is able to stimulate a normal liver to increase DNA replication after cross-circulation for one hour. The high degree of purity of DNA extracted by the “phenol” technique is demonstrated and the suitability of this technique for rat livers emphasized. The effect of chemiluminescence on tritiated thymidine is presented. The results of experiments presented here, together with other evidence, indicate the improbability of a stimulus being able to induce increased DNA synthesis in a normal liver after an exposure of only one hour. ImagesFig. 1 PMID:4417181

  15. Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure

    PubMed Central

    Zhang, Zhi; Zhao, Yi-Chao; Cheng, Yuan; Jian, Guo-Deng; Pan, Ming-Xin; Gao, Yi

    2014-01-01

    AIM: To evaluate a hybrid bioartificial liver support system (HBALSS) in cynomolgus monkeys with acute liver failure. METHODS: To establish a model of acute liver failure, 0.3 g/kg of D-galactosamine was injected intravenously into cynomolgus monkeys. Chinese human liver cells were introduced into a perfusion bioreactor to carry out hybrid bioartificial liver support treatment. Forty-eight hours after the injection, one group of cynomolgus monkeys received HBALSS care, and a second experimental group received no treatment. Clinical manifestations of all animals, survival time, liver and kidney functions and serum biochemistry changes were recorded. Simultaneous detection of the number, viability and function of hepatocytes in the hybrid bioartificial liver were also performed. RESULTS: Forty-eight hours after the injection of D-galactosamine, serum biochemistry levels were significantly increased, whereas albumin levels and the Fischer index were significantly reduced compared to baseline (all Ps < 0.05). Of the ten monkeys in the HBALSS treatment group, five survived, with an average duration of survival of 128 ± 3 h. All cynomolgus monkeys in the control group died, with a duration of survival of 112 ± 2 h. Survival time was significantly longer with HBALSS treatment (P < 0.05). Moreover, the number, viability and function of hepatocytes were maintained at a high level with HBALSS. CONCLUSION: The novel hybrid bioartificial liver plays a significant role in liver support by significantly reducing serum biochemistry levels and extending animal survival time. PMID:25516651

  16. Liver Damage due to Methotrexate in Patients with Psoriasis

    PubMed Central

    Dahi, M. G. C.; Gregory, M. M.; Scheuer, P. J.

    1971-01-01

    Liver function and histological changes in liver biopsies were studied in 37 patients who had been treated for psoriasis with methotrexate. Cirrhosis was found in seven (19%) and hepatic fibrosis of varying severity in 10 (27%). Minor abnormalities in another 17 (46%) consisted of fatty change, round cell infiltration, and extensive vacuolation of liver cell nuclei. In only three (8%) was hepatic histology entirely normal. The severity of liver damage was related to the duration of methotrexate treatment. Minor abnormalities of liver function tests and liver histology were also found in eight control psoriatic patients. Standard liver function tests were of little value in predicting the degree of liver damage. It appears that methotrexate, in the doses normally used to control psoriasis, may cause cirrhosis if treatment is prolonged and that liver biopsy is necessary for evaluation of liver damage in these patients. ImagesFIG. 2FIG. 3FIG. 4FIG. 5 PMID:5548839

  17. Impact of rapamycin on liver regeneration

    Microsoft Academic Search

    Daniel Palmes; Andree Zibert; Tymotheus Budny; Ralf Bahde; Evgeny Minin; Linus Kebschull; Jens Hölzen; Hartmut Schmidt; Hans-Ullrich Spiegel

    2008-01-01

    The remarkable capacity of the liver to regenerate after injury and the prospects of organ self-renewal have attracted much\\u000a interest in the understanding and modulation of the underlying molecular events. We investigated the effect of mammalian target\\u000a of rapamycin (mTOR) inhibitor rapamycin (RAPA) on liver by correlating intravital microscopy, immunohistochemistry, and reverse\\u000a transcriptase polymerase chain reaction in a rat model

  18. [Application of high technology in liver surgery].

    PubMed

    Astashov, V L; Solontsova, E N; Mukhtarulina, S V

    2013-08-01

    The PlasmaJet, a modem device that provides a high energy flow of ionized gas which seals small blood and lymph vessels has been recently introduced into clinical practice. A comparative retrospective analysis of results of 59 liver surgery with the help of new surgical technologies and standard surgical technique was performed. Liver resection with the use of high technology was accompanied by significantly less intraoperative blood loss, as well as a significant decrease of postoperative complications. PMID:24341019

  19. Aspirin-Induced Acute Liver Injury

    PubMed Central

    Satoskar, Rohit

    2014-01-01

    Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent.

  20. Platelet function in chronic liver disease

    Microsoft Academic Search

    M. H. Rubin; M. J. Weston; P. G. Langley; Yvette White; Roger Williams

    1979-01-01

    Abnormalities of platelet aggregation in response to adenosine diphosphate in 56 patients with chronic liver disease correlated with impairment of hepatocellular function but not with the etiology of the liver disease. Platelet-poor plasma from some patients appeared to contain an inhibitor since, in cross-over studies, it reduced the degree of aggregation of control subjects. However, platelet-poor plasma from some other