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Sample records for adult liver flukes

  1. [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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

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

  4. Progress in development of liver fluke vaccines.

    PubMed

    Spithill, T W; Dalton, J P

    1998-12-01

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

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

    PubMed

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

    2016-09-15

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

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

    PubMed

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

    2015-08-01

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

  7. 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.

  8. 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

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

    PubMed

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

    2013-08-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2015-04-01

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

  12. Citrate synthase from the liver fluke Fasciola hepatica.

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    1997-07-01

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

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

    PubMed

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

    2016-01-15

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

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

    PubMed

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

    2016-01-15

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

  16. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2015-09-01

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

  20. 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

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-09-01

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

  5. 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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-01-01

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

  8. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Foreyt, W J; Todd, A C

    1976-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2015-07-01

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

  19. 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.

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

    PubMed Central

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

    2014-01-01

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

  1. 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

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

    PubMed Central

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

    2014-01-01

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

  3. 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

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

    PubMed

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

    2015-06-01

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

  5. 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

  6. 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.

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

    PubMed

    Kim, Jung Man

    1965-12-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Saleha, A A

    1991-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. 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

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

    PubMed

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

    2009-05-01

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

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

    PubMed

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

    2016-09-01

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

  16. 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

  17. 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

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-15

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

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

    PubMed

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

    2008-02-01

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

  2. 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

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2008-11-01

    A total of 8 calves approximately 6 months old and 22 lambs of similar age were infected with metacercariae of Fasciola hepatica of various laboratory-maintained isolates including: Cullompton (sensitive to triclabendazole) and Sligo, Oberon and Leon (reported as resistant to triclabendazole). Ten to 16 weeks after infection, flukes were harvested from these experimental animals and the histology of the testis tissue was examined in a representative sample of flukes from each population. Adult wild-type flukes were also collected from 5 chronically infected cattle and 7 chronically infected sheep identified at post-mortem inspection. The testis tissue of these flukes was compared with that of the various laboratory-maintained isolates. Whilst the testes of the wild-type, Oberon and Leon flukes displayed all the usual cell types associated with spermatogenesis in Fasciola hepatica (spermatogonia, spermatocytes, spermatids and mature sperm), the Cullompton flukes from both cattle and sheep showed arrested spermatogenesis, with no stages later than primary spermatocytes represented in the testis profiles. The presence of numerous eosinophilic apoptotic bodies and nuclear fragments suggested that meiotic division was anomalous and incomplete. In contrast to the wild-type flukes, no mature spermatozoa were present in the testes or amongst the shelled eggs in the uterus. A high proportion of the eggs collected from these flukes hatched to release normal-appearing miracidia after an appropriate incubation period, as indeed was the case with all isolates examined and the wild-type flukes. It is concluded that the eggs of Cullompton flukes are capable of development without fertilization, i.e. are parthenogenetic. The implications of this for rapid evolution of resistant clones following an anthelmintic selection event are discussed. Amongst the Sligo flukes examined, two subtypes were recognised, namely, those flukes with all stages of spermatogenesis and mature

  5. 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.

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

    PubMed

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

    2012-03-01

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

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

    PubMed

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

    2012-02-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    MANSOUR, T E

    1957-12-01

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

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

    PubMed

    Keiser, Jennifer; Morson, Gianni

    2008-02-01

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

  14. 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.

  15. 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

  16. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2003-09-30

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

  20. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-05-01

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

  3. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

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

    PubMed

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

    2012-03-01

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

  5. 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.

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2015-03-01

    Leloir pathway enzyme uridine diphosphate (UDP)-galactose 4'-epimerase from the common liver fluke Fasciola hepatica (FhGALE) was identified and characterized. The enzyme can be expressed in, and purified from, Escherichia coli. The recombinant enzyme is active: the K(m) (470 μM) is higher than the corresponding human enzyme (HsGALE), whereas the k(cat) (2.3 s(-1)) is substantially lower. FhGALE binds NAD(+) and has shown to be dimeric by analytical gel filtration. Like the human and yeast GALEs, FhGALE is stabilized by the substrate UDP-galactose. Molecular modelling predicted that FhGALE adopts a similar overall fold to HsGALE and that tyrosine 155 is likely to be the catalytically critical residue in the active site. In silico screening of the National Cancer Institute Developmental Therapeutics Program library identified 40 potential inhibitors of FhGALE which were tested in vitro. Of these, 6 showed concentration-dependent inhibition of FhGALE, some with nanomolar IC50 values. Two inhibitors (5-fluoroorotate and N-[(benzyloxy)carbonyl]leucyltryptophan) demonstrated selectivity for FhGALE over HsGALE. These compounds also thermally destabilized FhGALE in a concentration-dependent manner. Interestingly, the selectivity of 5-fluoroorotate was not shown by orotic acid, which differs in structure by 1 fluorine atom. These results demonstrate that, despite the structural and biochemical similarities of FhGALE and HsGALE, it is possible to discover compounds which preferentially inhibit FhGALE.

  10. 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

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

    PubMed

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

    1988-01-01

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

  12. 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

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

    PubMed

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

    2014-02-24

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

  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. Split liver transplantation in adults.

    PubMed

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

    2016-09-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  16. Split liver transplantation in adults

    PubMed Central

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

    2016-01-01

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

  17. Split liver transplantation in adults

    PubMed Central

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

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  18. Split liver transplantation in adults.

    PubMed

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

    2016-09-01

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

  19. General Information about Adult Primary Liver Cancer

    MedlinePlus

    ... Primary Liver Cancer Treatment (PDQ®)–Patient Version General Information About Adult Primary Liver Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

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

    PubMed Central

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

    2003-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  3. Systems Biology Studies of Adult Paragonimus Lung Flukes Facilitate the Identification of Immunodominant Parasite Antigens

    PubMed Central

    McNulty, Samantha N.; Fischer, Peter U.; Townsend, R. Reid; Curtis, Kurt C.; Weil, Gary J.; Mitreva, Makedonka

    2014-01-01

    Background Paragonimiasis is a food-borne trematode infection acquired by eating raw or undercooked crustaceans. It is a major public health problem in the far East, but it also occurs in South Asia, Africa, and in the Americas. Paragonimus worms cause chronic lung disease with cough, fever and hemoptysis that can be confused with tuberculosis or other non-parasitic diseases. Treatment is straightforward, but diagnosis is often delayed due to a lack of reliable parasitological or serodiagnostic tests. Hence, the purpose of this study was to use a systems biology approach to identify key parasite proteins that may be useful for development of improved diagnostic tests. Methodology/Principal Findings The transcriptome of adult Paragonimus kellicotti was sequenced with Illumina technology. Raw reads were pre-processed and assembled into 78,674 unique transcripts derived from 54,622 genetic loci, and 77,123 unique protein translations were predicted. A total of 2,555 predicted proteins (from 1,863 genetic loci) were verified by mass spectrometric analysis of total worm homogenate, including 63 proteins lacking homology to previously characterized sequences. Parasite proteins encoded by 321 transcripts (227 genetic loci) were reactive with antibodies from infected patients, as demonstrated by immunoaffinity purification and high-resolution liquid chromatography-mass spectrometry. Serodiagnostic candidates were prioritized based on several criteria, especially low conservation with proteins in other trematodes. Cysteine proteases, MFP6 proteins and myoglobins were abundant among the immunoreactive proteins, and these warrant further study as diagnostic candidates. Conclusions The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species. These data provide a powerful foundation for translational research to develop improved diagnostic tests. Similar integrated approaches may be useful for identifying novel

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.

    PubMed

    McCusker, Paul; McVeigh, Paul; Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O'Connor, Anna; Marks, Nikki J; Mousley, Angela; Brennan, Gerard P; Halton, David W; Spithill, Terry W; Maule, Aaron G

    2016-09-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study

  9. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.

    PubMed

    McCusker, Paul; McVeigh, Paul; Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O'Connor, Anna; Marks, Nikki J; Mousley, Angela; Brennan, Gerard P; Halton, David W; Spithill, Terry W; Maule, Aaron G

    2016-09-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study

  10. Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro

    PubMed Central

    Rathinasamy, Vignesh; Toet, Hayley; McCammick, Erin; O’Connor, Anna; Marks, Nikki J.; Mousley, Angela; Brennan, Gerard P.; Halton, David W.; Spithill, Terry W.; Maule, Aaron G.

    2016-01-01

    Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving ‘molecular toolbox’ for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the “neoblast” stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. 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

  15. 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.

  16. Identity of rumen fluke in deer.

    PubMed

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

    2014-11-01

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

  17. Identity of rumen fluke in deer.

    PubMed

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

    2014-11-01

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

  18. 2D-PAGE analysis of the soluble proteins of the tropical liver fluke, Fasciola gigantica and biliary amphistome, Gigantocotyle explanatum, concurrently infecting Bubalus bubalis.

    PubMed

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

    2016-09-01

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

  19. 2D-PAGE analysis of the soluble proteins of the tropical liver fluke, Fasciola gigantica and biliary amphistome, Gigantocotyle explanatum, concurrently infecting Bubalus bubalis.

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2011-06-10

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2016-01-30

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

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

    PubMed Central

    2010-01-01

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

  5. 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.

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

    PubMed

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

    2012-12-01

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

  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.

  8. Tuberculosis as an Etiological Factor in Liver Abscess in Adults

    PubMed Central

    Dey, Jaideep; Venugopal, Shwetha; Mirdha, Bijay Ranjan

    2016-01-01

    Background. Tuberculosis of the liver without active pulmonary or miliary tuberculosis is considered as an uncommon diagnosis. The aim of the present study was to determine the etiological role of tuberculosis in adult patients presenting with features of liver abscess. Methods. A total of 40 patients with liver abscess were included in the study. The liver abscess aspirate was subjected to microscopy, culture, and polymerase chain reaction to determine the role of tuberculosis as an etiological factor in liver abscess. Results. Of the 40 patients enrolled, 25% (10/40) were diagnosed with having tubercular liver abscess. In a total of 40 specimens, 2.5% (1/40) were positive for acid fast bacilli by Ziehl-Neelsen method, while 10% (4/40) were positive for M. tuberculosis by culture using BACTEC 460 and the yield increased to 25% (10/40) by polymerase chain reaction for M. tuberculosis. Conclusion. 25% of the patients presenting with liver abscess had tubercular etiology without features of active pulmonary or miliary tuberculosis. Liver can act as the primary site of involvement in the absence of activity elsewhere in the body. Tuberculosis should be considered as an important differential diagnosis of liver abscess irrespective of evidence of active tuberculosis elsewhere in the body. PMID:27595021

  9. Tuberculosis as an Etiological Factor in Liver Abscess in Adults.

    PubMed

    Dey, Jaideep; Gautam, Hitender; Venugopal, Shwetha; Porwal, Chhavi; Mirdha, Bijay Ranjan; Gupta, Naresh; Singh, Urvashi B

    2016-01-01

    Background. Tuberculosis of the liver without active pulmonary or miliary tuberculosis is considered as an uncommon diagnosis. The aim of the present study was to determine the etiological role of tuberculosis in adult patients presenting with features of liver abscess. Methods. A total of 40 patients with liver abscess were included in the study. The liver abscess aspirate was subjected to microscopy, culture, and polymerase chain reaction to determine the role of tuberculosis as an etiological factor in liver abscess. Results. Of the 40 patients enrolled, 25% (10/40) were diagnosed with having tubercular liver abscess. In a total of 40 specimens, 2.5% (1/40) were positive for acid fast bacilli by Ziehl-Neelsen method, while 10% (4/40) were positive for M. tuberculosis by culture using BACTEC 460 and the yield increased to 25% (10/40) by polymerase chain reaction for M. tuberculosis. Conclusion. 25% of the patients presenting with liver abscess had tubercular etiology without features of active pulmonary or miliary tuberculosis. Liver can act as the primary site of involvement in the absence of activity elsewhere in the body. Tuberculosis should be considered as an important differential diagnosis of liver abscess irrespective of evidence of active tuberculosis elsewhere in the body. PMID:27595021

  10. [Living donor liver transplantation in adults].

    PubMed

    Neumann, U P; Neuhaus, P; Schmeding, M

    2010-09-01

    The worldwide shortage of adequate donor organs implies that living donor liver transplantation represents a valuable alternative to cadaveric transplantation. In addition to the complex surgical procedure the correct identification of eligible donors and recipients plays a decisive role in living donor liver transplantation. Donor safety must be of ultimate priority and overrules all other aspects involved. In contrast to the slightly receding numbers in Europe and North America, in recent years Asian programs have enjoyed constantly increasing living donor activity. The experience of the past 15 years has clearly demonstrated that technical challenges of both bile duct anastomosis and venous outflow of the graft significantly influence postoperative outcome. While short-term in-hospital morbidity remains increased compared to cadaveric transplantation, long-term survival of both graft and patient are comparable or even better than in deceased donor transplantation. Especially for patients expecting long waiting times under the MELD allocation system, living donor liver transplantation offers an excellent therapeutic alternative. Expanding the so-called "Milan criteria" for HCC patients with the option for living donor liver transplantation is currently being controversially debated.

  11. Fetal and adult liver stem cells for liver regeneration and tissue engineering.

    PubMed

    Fiegel, H C; Lange, Claudia; Kneser, U; Lambrecht, W; Zander, A R; Rogiers, X; Kluth, D

    2006-01-01

    For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2016-06-01

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

  14. Hepatic haemangioendothelioma in adults: excellent outcome following liver transplantation.

    PubMed

    Lerut, Jan P; Orlando, Giuseppe; Sempoux, Christine; Ciccarelli, Olga; Van Beers, Bernard E; Danse, Etienne; Horsmans, Yves; Rahier, Jacques; Roggen, Francine

    2004-05-01

    Hepatic epithelioid haemangioendotheliomas (HEHEs) are rare, low-grade vascular tumours. Five adults with HEHEs and one adult with a vascular tumour showing combined features of haemangioma and haemangioendothelioma underwent liver transplantation. Two HEHE patients had extrahepatic metastases at the time of transplantation. Median survival time following diagnosis was 10.7 years (range 40 months to 195 months). One patient needed resection of a HEHE in the breast 13 years post-transplantation. All six patients are surviving free from disease 22 to 166 months after transplantation (median 77 months). One HEHE-patient who had been treated for 8 years for vertebral and cerebral localisations is free of disease without immunosuppression 56 months after transplantation. We can conclude that liver transplantation is a valuable treatment for hepatic haemangioendothelioma, even in cases of extrahepatic localisation of the disease. PMID:15114438

  15. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  16. Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis

    PubMed Central

    Tang, An; Chen, Joshua; Le, Thuy-Anh; Changchien, Christopher; Hamilton, Gavin; Middleton, Michael S.; Loomba, Rohit; Sirlin, Claude B.

    2014-01-01

    Purpose To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. Methods In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. Results Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R2 = 0.735, P < 0.001). Conclusion Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial. PMID:25015398

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

    PubMed

    Hassl, Andreas R

    2010-10-01

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

  18. Liver graft regeneration in right lobe adult living donor liver transplantation.

    PubMed

    Cheng, Y-F; Huang, T-L; Chen, T-Y; Tsang, L L-C; Ou, H-Y; Yu, C-Y; Concejero, A; Wang, C-C; Wang, S-H; Lin, T-S; Liu, Y-W; Yang, C-H; Yong, C-C; Chiu, K-W; Jawan, B; Eng, H-L; Chen, C-L

    2009-06-01

    Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

  19. [Comparison of serum trace element spectrum of liver cancer patients and healthy adults].

    PubMed

    Yin, D Z

    1990-05-01

    The contents of 15 trace elements in the sera of 30 liver cancer patients and 30 healthy adults were assayed by ICP-AES method. The data obtained were analysed by routine statistical tests, multi-variate discrimination analysis, multi-variate stepwise regression analysis and non-linear mapping algorithm. The results showed that the contents of copper, vanadium, cadmium, stannum, cobalt, nickel in liver cancer patients were significantly higher than those in healthy adults. The serum trace element spectrum of liver cancer patients was different from that of healthy adults. Hence, the liver cancer patients could be differentiated from healthy adults by serum trace element spectrum. PMID:2249593

  20. Adult to adult living related liver transplantation: where do we currently stand?

    PubMed

    Carlisle, Erica M; Testa, Giuliano

    2012-12-14

    Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers. PMID:23239910

  1. Changes in liver and spleen volumes after living liver donation: a report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL).

    PubMed

    Emond, Jean C; Fisher, Robert A; Everson, Gregory; Samstein, Benjamin; Pomposelli, James J; Zhao, Binsheng; Forney, Sarah; Olthoff, Kim M; Baker, Talia B; Gillespie, Brenda W; Merion, Robert M

    2015-02-01

    Previous reports have drawn attention to persistently decreased platelet counts among liver donors. We hypothesized an etiologic association between altered platelet counts and postdonation splenomegaly and sought to explore this relationship. This study analyzed de-identified computed tomography/magnetic resonance scans of 388 donors from 9 Adult-to-Adult Living Donor Liver Transplantation Cohort Study centers read at a central computational image analysis laboratory. Resulting liver and spleen volumes were correlated with time-matched clinical laboratory values. Predonation liver volumes varied 2-fold in healthy subjects, even when they were normalized by the body surface area (BSA; range = 522-1887 cc/m(2) , n = 346). At month 3 (M3), postdonation liver volumes were, on average, 79% of predonation volumes [interquartile range (IQR) = 73%-86%, n = 165] and approached 88% at year 1 (Y1; IQR = 80%-93%, n = 75). The mean spleen volume before donation was 245 cc (n = 346). Spleen volumes greater than 100% of the predonation volume occurred in 92% of donors at M3 (n = 165) and in 88% at Y1 after donation (n = 75). We sought to develop a standard spleen volume (SSV) model to predict normal spleen volumes in donors before donation and found that decreased platelet counts, a younger age, a higher predonation liver volume, higher hemoglobin levels, and a higher BSA predicted a larger spleen volume (n = 344, R(2)  = 0.52). When this was applied to postdonation values, some large volumes were underpredicted by the SSV model. Models developed on the basis of the reduced sample of postdonation volumes yielded smaller underpredictions. These findings confirm previous observations of thrombocytopenia being associated with splenomegaly after donation. The results of the SSV model suggest that the biology of this phenomenon is complex. This merits further long-term mechanistic studies of liver donors with an investigation of the role of

  2. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

    PubMed

    Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

    2014-04-01

    Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

  3. Drug-induced liver injury in older adults

    PubMed Central

    Mitchell, Sarah J.

    2010-01-01

    Drug-induced liver injury (DILI) is an important cause of hospitalisation and of medication deregistration. In old age, susceptibility to DILI is affected by changes in physiology and increased interindividual variability, compounded by an increased prevalence of disease and the frailty syndrome. While dose-related or predictable DILI reactions are often detected in preclinical trials, the occurrence of rare hypersensitivity or idiosyncratic reactions cannot be reliably predicted from preclinical studies or even by clinical trials. The limited participation of older adults in clinical trials means that the susceptibility of this population to DILI is largely unknown. Vigilance during clinical trials and postmarketing surveillance must be universally practised. A systematic approach should be taken to determine not only which medicines are hepatotoxic and should be removed from the market, but also the hepatotoxicity risks from marketed drugs to consumers with different characteristics, many of whom are older people. PMID:25083196

  4. Metabolic aspects of adult patients with nonalcoholic fatty liver disease.

    PubMed

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-08-21

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  5. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  6. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Differences in Liver Impairment Between Adults and Children with Dengue Infection.

    PubMed

    Martínez Vega, Rosario; Phumratanaprapin, Weerapong; Phonrat, Benjaluck; Dhitavat, Jittima; Sutherat, Maleerat; Choovichian, Vorada

    2016-05-01

    Dengue infection (DI) is a major vector-borne disease in southeast Asia and an important cause of morbidity. The complications such as hepatic impairment are common, and because the physiology of the liver differs between children and adults, the DI-associated liver impairments might be expected to differ as well. This study aims to compare the differences in liver impairment between adults and children with DI. We retrospectively studied 158 adults and 79 children with serologically confirmed DI admitted to the Bangkok Hospital for Tropical Diseases from 2008 to 2012. In total, 93% of adults and 87% of children exhibited abnormal liver enzyme levels during hospitalization. Overall, 76 (42.4%) adults and 16 (20.3%) children had dengue hemorrhagic fever (DHF). Compared with children, adults with dengue fever (DF) presented a significantly higher incidence of liver function impairment (alanine transaminase [ALT] > 2 × upper limit of normal [ULN]) (47.1% versus 25.5%), hepatitis (ALT > 4 × ULN) (29.4% versus 12.8%), and severe hepatitis (aspartate transaminase [AST]/ALT > 10 × ULN) (16.5% versus 4.3%). Children with DHF showed a significantly higher incidence of liver function impairment due to AST derangement than did adults (100% versus 73%). There were no differences in the total bilirubin, albumin, or total protein levels between adults and children. Liver enzymes normalized significantly more slowly in adults, and AST recovery was faster than ALT. In conclusion, liver function impairment was more common among adults than children with DF. As the severity progressed to DHF, liver injury became more common in children.

  11. Enrichment of a bipotent hepatic progenitor cell from naive adult liver tissue

    SciTech Connect

    Wright, Natasha; Samuelson, Lisa; Walkup, Maggie H.; Chandrasekaran, Prakash; Gerber, David A.

    2008-02-08

    Background/Aim: Recent interest in the liver stem cell field has led to the identification and characterization of several hepatic progenitor cell populations from fetal and adult tissues. We isolated a hepatic progenitor cell from naive adult liver and the current studies focus on differentiation and growth. Results: A Sca-1{sup +} hepatic progenitor cell was identified within the liver parenchyma. This cell expresses numerous liver related genes and transcription found in the developing and/or adult liver. It is located in the peri-portal region and expresses markers associated with undifferentiated hepatic cell populations, mature hepatocytes and biliary cells which distinguish it from the Sca-1{sup -} fraction. Conclusion: This hepatic progenitor cell from uninjured liver has features of both hepatocytic and biliary populations and demonstrates proliferative potential. Further studies will focus on sca-HPC subsets and conditions that regulate differentiation towards hepatic or biliary lineages.

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

    ClinicalTrials.gov

    2015-03-25

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

  13. Undifferentiated embryonal sarcoma of the liver in an adult patient

    PubMed Central

    Lee, Kyu Ho; Maratovich, Mussin Nadiar; Lee, Kyoung-Bun

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is rare primary hepatic sarcoma and is known to occur in pediatric patients. This case is the UESL occurred in a 51-year old male patient. Multilocular cystic lesion was composed of primitive spindle cells without specific differentiation. This rare case would help to review differential diagnosis of primary sarcoma in liver and cystic neoplasm of the liver. PMID:27377912

  14. Liver Retransplantation in Adults: The Largest Multicenter Italian Study

    PubMed Central

    Maggi, Umberto; Andorno, Enzo; Rossi, Giorgio; De Carlis, Luciano; Cillo, Umberto; Bresadola, Fabrizio; Mazzaferro, Vincenzo; Risaliti, Andrea; Bertoli, Paolo; Consonni, Dario; Barretta, Francesco; De Feo, Tullia; Scalamogna, Mario

    2012-01-01

    This study is the largest Italian survey on liver retransplantations (RET). Data report on 167 adult patients who received 2 grafts, 16 who received 3 grafts, and one who received 4 grafts over a 11 yr period. There was no statistically significant difference in graft survival after the first or the second RET (52, 40, and 29% vs 44, 36, and 18% at 1,5,and 10 yr, respectively: Log-Rank test, p = 0.30). Survivals at 1, 5, and 10 years of patients who underwent 2 (n = 151) or 3 (n = 15) RETs, were 65, 48,and 39% vs 59, 44, and 30%, respectively (p = 0.59). Multivariate analysis of survival showed that only the type of graft (whole vs reduced) was associated with a statistically significant difference (HR = 3.77, Wald test p = 0. 05); the donor age appeared to be a relevant factor as well, although the difference was not statistically significant (HR = 1.91, Wald test p = 0.08). Though late RETs have better results on long term survival relative to early RETs, no statistically significant difference can be found in early results, till three years after RET. Considering late first RETs (interval>30 days from previous transplantation) with whole grafts the difference in graft survival in RETs due to HCV recurrence (n = 17) was not significantly different from RETs due to other causes (n = 53) (65–58 and 31% vs 66–57 and 28% respectively at 1–5 and 10 years, p = 0.66). PMID:23071604

  15. Foodborne Intestinal Flukes in Southeast Asia

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  18. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study

    PubMed Central

    Gad, Emad Hamdy; Alsebaey, Ayman; Lotfy, Maha; Eltabbakh, Mohamed; Sherif, Ahmed Alshawadfy

    2015-01-01

    Background and aims Living donor liver transplantation (LDLT) is widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation of the procedure, both complications and mortality of LDLT are annoying problems. The aim of this study was to analyze complications and mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. Methods: Between April 2003 and November 2013, 167 (A-ALDLT) recipients in National Liver Institute, Egypt were included. We retrospectively analyzed complications and mortality in them. Results The overall incidence of complications was 86.2% (n = 144) and classified as biliary 43.7% (n = 73), vascular 21.6% (n = 36), Small for size syndrome (SFSS) 12.6% (n = 21), Gastrointestinal tract (GIT) 19.8% (n = 33), wound 12.6% (n = 21), chest 19.8% (n = 33), neurological 26.3% (n = 44), renal 21% (n = 35), intra abdominal collection 21.6% (n = 36), recurrent hepatitis C virus (HCV) 16.8% (n = 28), recurrent hepatocellular carcinoma (HCC) 2.4% (n = 4), acute rejection 19.2% (n = 32). 65 (45.1%) of 144 complicated patients died, while 10 (43.5%) of 23 non complicated died. The incidence of whole, in hospital and late mortalities were 44.9%, 28.7% and 16.2% respectively. Conclusions: Mortality was higher among complicated cases where vascular complications and SFSS had significant effect on it so prevention and treatment of them is required for improving outcome. PMID:26005570

  19. Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice

    PubMed Central

    Dorrell, Craig; Erker, Laura; Schug, Jonathan; Kopp, Janel L.; Canaday, Pamela S.; Fox, Alan J.; Smirnova, Olga; Duncan, Andrew W.; Finegold, Milton J.; Sander, Maike; Kaestner, Klaus H.; Grompe, Markus

    2011-01-01

    The molecular identification of adult hepatic stem/progenitor cells has been hampered by the lack of truly specific markers. To isolate putative adult liver progenitor cells, we used cell surface-marking antibodies, including MIC1-1C3, to isolate subpopulations of liver cells from normal adult mice or those undergoing an oval cell response and tested their capacity to form bilineage colonies in vitro. Robust clonogenic activity was found to be restricted to a subset of biliary duct cells antigenically defined as CD45−/CD11b−/CD31−/MIC1-1C3+/CD133+/CD26−, at a frequency of one of 34 or one of 25 in normal or oval cell injury livers, respectively. Gene expression analyses revealed that Sox9 was expressed exclusively in this subpopulation of normal liver cells and was highly enriched relative to other cell fractions in injured livers. In vivo lineage tracing using Sox9creERT2-R26RYFP mice revealed that the cells that proliferate during progenitor-driven liver regeneration are progeny of Sox9-expressing precursors. A comprehensive array-based comparison of gene expression in progenitor-enriched and progenitor-depleted cells from both normal and DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine or diethyl1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate)-treated livers revealed new potential regulators of liver progenitors. PMID:21632826

  20. Access to adult liver transplantation in Canada: a survey and ethical analysis.

    PubMed Central

    Mullen, M A; Kohut, N; Sam, M; Blendis, L; Singer, P A

    1996-01-01

    OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and

  1. [Early detection of chronic liver disease in primary care in the apparently health adult population].

    PubMed

    Caballería, Llorenç; Torán, Pere

    2012-12-01

    Liver diseases are highly prevalent and are a major health problem as they progress to more severe forms. In the west, cirrhosis and primitive liver cancer are among the first 10 causes of death in adults. Moreover, chronic liver inflammation, irrespective of cause, is usually asymptomatic. Consequently diagnosis tends to be established when the disease is in the advanced stages and is thus irreversible and with few treatment possibilities. Therefore, ideally, diagnosis would be established in the initial phases of chronic liver inflammation, which would allow the natural history of the disease to be altered by either halting or delaying progression. To date, physicians have been guided by alterations in liver function tests to identify the etiology of liver disease or-depending on the severity of involvement-the presence of liver disease. Abdominal ultrasound findings can also reveal alterations suggesting the presence of chronic liver disease. However, in the last few years, noninvasive methods have been designed. These include serological markers (direct and indirect) of fibrosis and radiological tests (especially elastography) based on measuring liver elasticity, which allow noninvasive quantification of the degree of fibrous tissue in the liver. The use of noninvasive methods may be highly useful in the early detection of liver diseases.

  2. Scar formation and lack of regeneration in adult and neonatal liver after stromal injury.

    PubMed

    Masuzaki, Ryota; Zhao, Sophia R; Csizmadia, Eva; Yannas, Ioannis; Karp, Seth J

    2013-01-01

    Known as a uniquely regenerative tissue, the liver shows a remarkable capacity to heal without scarring after many types of acute injury. In contrast, during chronic liver disease, the liver responds with fibrosis, which can progress to cirrhosis and ultimately liver failure. The cause of this shift from a nonfibrotic to a fibrotic response is unknown. We hypothesized that stromal injury is a key event that prevents restoration of normal liver architecture. To test this, we developed a model of stromal injury using a surgical incision through the normal liver in adult and neonatal mice. This injury produces minimal cell death but locally complete stromal (extracellular matrix) disruption. The adult liver responds with inflammation and stellate cell activation, culminating in fibrosis characterized by collagen deposition. This sequence of events is remarkably similar to the fibrotic response leading to cirrhosis. Studies in neonates reveal a similar fibrotic response to a stromal injury. These findings suggest that extracellular matrix disruption leads not to regeneration but rather to scar, similar to other mammalian organs. These findings may shed light on the pathogenesis of chronic liver disease, and suggest therapeutic strategies. PMID:23228176

  3. Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature.

    PubMed

    Li, Jiang; Cai, Jin-Zhen; Guo, Qing-Jun; Li, Jun-Jie; Sun, Xiao-Ye; Hu, Zhan-Dong; Cooper, David K C; Shen, Zhong-Yang

    2015-05-28

    Mesenchymal hamartomas of the liver (MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography (CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen included intraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg (dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months

  4. Liver transplantation in adults: Choosing the appropriate timing

    PubMed Central

    Siciliano, Maria; Parlati, Lucia; Maldarelli, Federica; Rossi, Massimo; Ginanni Corradini, Stefano

    2012-01-01

    Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation. PMID:22966483

  5. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  6. Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy.

    PubMed

    Duret, Cedric; Moreno, Daniel; Balasiddaiah, Anangi; Roux, Solene; Briolotti, Phillipe; Raulet, Edith; Herrero, Astrid; Ramet, Helene; Biron-Andreani, Christine; Gerbal-Chaloin, Sabine; Ramos, Jeanne; Navarro, Francis; Hardwigsen, Jean; Maurel, Patrick; Aldabe, Rafael; Daujat-Chavanieu, Martine

    2015-01-01

    Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation. PMID:25622096

  7. Right lobe split liver transplantation versus whole liver transplantation in adult recipients: A systematic review and meta-analysis.

    PubMed

    Wan, Ping; Li, Qigen; Zhang, Jianjun; Xia, Qiang

    2015-07-01

    Split liver transplantation (SLT) has proven to be an effective technique to reduce the mortality of children on the waiting list, but whether creating 2 split grafts from 1 standard-criteria whole liver would compromise outcomes of adult recipients remains uncertain. We conducted this meta-analysis to compare outcomes of right lobe SLT and whole liver transplantation (WLT) in adult patients. PubMed, Embase, and the Cochrane Library were searched for relevant articles published before December 2014. Outcomes assessed were patient survival (PS), graft survival (GS), and major surgical complications after transplantation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to synthesize the results. Seventeen studies with a total of 48,457 patients met the full inclusion criteria. PS and GS rates were all found to be equivalent between SLT and WLT recipients. However, SLT was associated with higher rates of overall biliary complications (OR = 1.66; 95% CI = 1.29-2.15; P < 0.001), bile leaks (OR = 4.30; 95% CI = 2.97-6.23; P < 0.001), overall vascular complications (OR = 1.81; 95% CI = 1.29-2.53; P < 0.001), hepatic artery thromboses (OR = 1.71; 95% CI = 1.17-2.50; P = 0.005), and outflow tract obstructions (OR = 4.17; 95% CI = 1.75-9.94; P = 0.001). No significant difference was observed in incidences of biliary stricture, portal vein complications, postoperative bleeding requiring surgical treatments, primary nonfunction, and retransplantations. In subgroup analyses, biliary and vascular complications only increased after ex vivo SLT rather than in situ SLT, and SLT recipients had more retransplantations if they matched with WLT recipients in terms of urgent status. In conclusion, adult right lobe SLT was associated with increased biliary and vascular complications compared with WLT, but it did not show significant inferiority in PSs and GSs. PMID:25832308

  8. Living donor liver transplantation in an adult patient with situs inversus totalis

    PubMed Central

    Yankol, Yücel; Mecit, Nesimi; Kanmaz, Turan; Acarlı, Koray; Kalayoğlu, Münci

    2015-01-01

    Situs inversus totalis (SIT) is a rare congenital anomaly, and liver transplantation (LT) in an adult SIT patient is extremely rare. Liver transplantation in a SIT patient is also technically challenging due to reversed anatomical structures. Here we present the case of an 18-year-old female with SIT in whom left lobe living donor LT was performed. The patient suffered from cirrhosis due to autoimmune hepatitis. The recipient and donor are doing well without complications 20 months after LT. Situs inversus totalis should not be considered a contraindication for LT. If possible, use of a living donor left lobe graft for LT is more feasible than a living donor right lobe graft. It is also technically easier than using deceased donor full-size liver graft in SIT patients who require liver transplantation. PMID:26668533

  9. Quality Improvement Targeting Adherence During the Transition from a Pediatric to Adult Liver Transplant Clinic.

    PubMed

    Fredericks, Emily M; Magee, John C; Eder, Sally J; Sevecke, Jessica R; Dore-Stites, Dawn; Shieck, Victoria; Lopez, M James

    2015-09-01

    The transition from pediatric to adult transplant care is a high risk period for non-adherence and poor health outcomes. This article describes a quality improvement initiative integrated into a pediatric liver transplant program that focused on improving outcomes following the transfer from pediatric to adult liver transplant care. Using improvement science methodology, we evaluated the impact of our center's transition readiness skills (TRS) program by conducting a chart review of 45 pediatric liver transplant recipients who transferred to adult transplant care. Medication adherence, clinic attendance, and health status variables were examined for the year pre-transfer and first year post-transfer. 19 recipients transferred without participating in the TRS program (control group) and 26 recipients participated in the program prior to transferring to the adult clinic (TRS group). The TRS group was significantly older at the time of transfer, more adherent with medications, and more likely to attend their first adult clinic visit compared to the control group. Among the TRS group, better adolescent and parent regimen knowledge were associated with greater adherence to post-transfer clinic appointments. Transition planning should focus on the gradual shift in responsibility for health management tasks, including clinic attendance, from parent to adolescent. There may be support for extending transition support for at least 1 year post-transfer to promote adherence.

  10. The osmotic stability of lysosomes from adult and foetal guinea-pig liver tissue.

    PubMed

    Turnbull, J M; Neil, M W

    1969-02-01

    1. Lysosome-rich fractions were obtained from foetal liver tissues as early as 35 days uterine age. Foetal lysosomes showed the same ;structure-linked latency' and acid hydrolytic potentiality characteristic of their adult counterparts. 2. The osmotic stability of lysosome-rich fraction from foetal guinea-pig liver tissue was greater than that of the corresponding adult lysosome fractions, p-nitrophenyl-phosphatase being used as marker enzyme. 3. The observation was confirmed by using beta-glycerophosphatase and phenolphthalein beta-glucuronidase as alternative marker enzymes. p-Nitrophenyl phosphate and beta-glycerophosphate appear to act as substrates for the same enzyme. 4. By using p-nitrophenylphosphatase activity measurements it was shown that the osmotic stability of foetal lysosomal fractions decreased with increasing foetal age, but at no time achieved the degree of osmotic instability characteristic of adult lysosomal fractions. 5. The correlation of these findings with the intracellular environment of lysosomes is discussed.

  11. Adult liver transplantation in the congenital absence of inferior vena cava.

    PubMed

    Angelico, R; Stonelake, S; Perera, D S; Mirza, D F; Russell, S; Muiesan, P; Perera, M T P R

    2015-10-01

    Whereas congenital absence of inferior vena cava observed in paediatric population more often than not, as an isolated or syndromic variety, this is seldom encountered in adult liver transplant recipients. There appear few sporadic reports in the literature on experience of such anomaly in adults. Given the rarity of situation, surprising encounters of such anomalies may pose challenge to the unprepared transplant surgeon and unfavourable outcomes may even have resulted in under-reportage of this condition. In this brief report we document our recent experience with two such cases and this is supplemented with extensive reference to the literature on classification of such anomalies with the endeavour to document implications of such in the adult liver transplant setting. PMID:26278662

  12. Changes in liver and spleen volumes after living liver donation: A report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

    PubMed Central

    Emond, Jean C.; Fisher, Robert A.; Everson, Gregory; Samstein, Benjamin; Pomposelli, James J.; Zhao, Binsheng; Forney, Sarah; Olthoff, Kim M.; Baker, Talia B.; Gillespie, Brenda W.; Merion, Robert M.

    2014-01-01

    Previous reports have drawn attention to persistently decreased platelet counts among liver donors. We hypothesized an etiologic association between altered platelet counts and post-donation splenomegaly and sought to explore this relationship. This study analyzed de-identified CT/MR scans of 388 donors from 9 A2ALL centers read at a central computational image analysis lab. Resulting liver and spleen volumes were correlated with time-matched clinical lab values. Pre-donation liver volumes varied twofold in healthy subjects, even when normalized by body surface area (BSA) (range: 522 – 1887cc/m2, N=346). At 3 months post-donation liver volumes were, on average, 79% of pre-donation volumes (IQR: 73-86%, N=165) and approached 88% at 1 year (IQR: 80-93%, N=75). The mean spleen volume pre-donation was 245 cc (N=346). Spleen volumes greater than 100% of pre-donation volume occurred in 92% of donors at 3 months (N=165) and 88% at 1 year post-donation (N=75). We sought to develop a standard spleen volume (SSV) model to predict “normal” spleen volumes in donors pre-donation and found that decreased platelet counts, younger age, higher pre-donation liver volume, higher hemoglobin and higher BSA predicted a larger spleen volume (N=344, R2=0.52). When applied to post-donation values some large volumes were under predicted by the SSV model. Models developed on the reduced sample of post-donation volumes yielded smaller under-predictions. These findings confirm previous observations of thrombocytopenia associated with splenomegaly post-donation. The results of the SSV model suggest the biology of this phenomenon is complex. This merits further long term mechanistic studies of liver donors with investigation into the role of other factors such as thrombopoietin, and exposure to viral infections to better understand the evolution of spleen volume after liver donation. PMID:25488878

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

    PubMed

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

    2010-08-01

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

  14. Exome sequencing of liver fluke-associated cholangiocarcinoma.

    PubMed

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

    2012-06-01

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

  15. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells

    PubMed Central

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P.; Walles, Heike

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions. PMID:26488607

  16. Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring.

    PubMed

    Conceição, E P; Peixoto-Silva, N; Pinheiro, C R; Oliveira, E; Moura, E G; Lisboa, P C

    2015-04-01

    Early nicotine exposure causes future obesity and insulin resistance. We evaluated the long-term effect of the maternal nicotine exposure during lactation in liver oxidative status, insulin sensitivity and morphology in adult offspring. Two days after birth, osmotic minipumps were implanted in the dams: nicotine (N), 6 mg/kg/day for 14 days or saline (C). Offspring were killed at 180 days. Protein content of superoxide dismutase, glutathione peroxidase, catalase, nitrotyrosine, 4HNE, IRS1, Akt1 and PPARs were measured. MDA, bound protein carbonyl content, SOD, GPx and catalase activities were determined in liver and plasma. Hepatic morphology and triglycerides content were evaluated. Albumin and bilirubin were determined. In plasma, N offspring had higher catalase activity, and SOD/GPx ratio, albumin and bilirubin levels but lower MDA content. In liver, they presented higher MDA and 4HNE levels, bound protein carbonyl content, SOD activity but lower GPx activity. N offspring presented an increase of lipid droplet, higher triglyceride content and a trend to lower PPARα in liver despite unchanged insulin signaling pathway. Early nicotine exposure causes oxidative stress in liver at adulthood, while protect against oxidative stress at plasma level. In addition, N offspring develop liver microsteatosis, which is related to oxidative stress but not to insulin resistance. PMID:25662863

  17. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells

    PubMed Central

    Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C.

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications. PMID:27403430

  18. Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

    PubMed

    Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

    2013-01-01

    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit. PMID:23430518

  19. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

    PubMed

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

  20. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells.

    PubMed

    Finoli, Anthony; Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.

  1. Tear copper and its association with liver copper concentrations in six adult ewes.

    PubMed Central

    Schoster, J V; Stuhr, C; Kiorpes, A

    1995-01-01

    Tear and liver copper concentrations from 6 clinically healthy adult mixed-breed ewes were measured by Atomic Absorption Electrothermal Atomization (graphite furnace) Spectrometry and Flame Absorption Spectrometry, respectively, 7 times over 227 d to determine if their tears contained copper and if so, whether tear copper concentrations could reliably predict liver copper concentrations. To produce changes in liver copper concentration, the diet was supplemented with copper at concentrations that increased from 23 mg to 45 mg Cu/kg feed/day/sheep during the study. This regimen raised liver copper for all sheep to potentially toxic hepatic tissue concentration of greater than 500 mg/kg dry (DM) matter (tissue). The results of the study showed that copper was present in the tears of all sheep. The mean tear copper concentration showed a positive correlation with liver copper concentration (P = 0.003), increasing from 0.07 mg/kg DM at the start to 0.44 mg/kg DM at the end of the study, but could not reliably predict liver copper concentration (R2 = 0.222). PMID:7648525

  2. Relationships between host species and morphometric patterns in Fasciola hepatica adults and eggs from the northern Bolivian Altiplano hyperendemic region.

    PubMed

    Valero, M A; Darce, N A; Panova, M; Mas-Coma, S

    2001-12-01

    The highest prevalences and intensities of human fasciolosis by Fasciola hepatica are found in the northern Bolivian Altiplano, where sheep and cattle are the main reservoir host species and pigs and donkeys the secondary ones. Morphometric comparisons of many linear measurements, areas and ratios of F. hepatica adults (from sheep, cattle and pigs) and eggs (from sheep, cattle, pigs and donkeys) in natural liver fluke populations of the Bolivian Altiplano, as well as of F. hepatica adults and eggs experimentally obtained in Wistar rats infected with Altiplanic sheep, cattle and pig isolates, were made using computer image analysis and an allometric model. Although morphometric values of adult flukes from natural populations of sheep, cattle, and pigs showed great overlap, there were clear differences in allometric growth. The allometries analyzed were: body area (BA) versus body length (BL), BA versus body width (BW), BA versus perimeter (Pe), BA versus distance between posterior end of body and ventral sucker (P-VS), BL versus BW, BL versus Pe, and BL versus P-VS. These allometries show a good fit in the seven pairs of variables in all the populations examined. Comparative statistical analysis of the allometries shows that fluke adult populations from sheep, cattle and pigs significantly differ in BL versus BW and BL versus P-VS functions. Statistical analysis of F. hepatica egg size shows characteristic morphometric traits in each definitive host species. In experimentally infected rats, fluke adult allometry and egg morphometry do not vary depending on the Altiplanic definitive host species isolate. Our study reveals that the definitive host species decisively influences the size of F. hepatica adults and eggs, and these influences do not persist in a rodent definitive host model.

  3. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs.

  4. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports.

    PubMed

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-02-01

    Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed.

  5. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors

    PubMed Central

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-01-01

    Abstract Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed. PMID:26886643

  6. 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

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

    PubMed Central

    Hanna, Robert

    2015-01-01

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

  8. Long-term culture of genome-stable bipotent stem cells from adult human liver.

    PubMed

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M A; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N M; Nieuwenhuis, Edward E S; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R G; van der Laan, Luc J W; Cuppen, Edwin; Clevers, Hans

    2015-01-15

    Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

  9. Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease.

    PubMed

    Levi Sandri, G B; Lai, Q; Melandro, F; Guglielmo, N; Garofalo, M; Morabito, V; Cirelli, C; Lucatelli, P; Di Laudo, M; Rossi, M; Berloco, P B

    2012-01-01

    Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease. According to Gigot classification, and to the characteristics of haemangioma surgery in these patients can be considered safe. We report the case of a 55 year-old man affected by an adult polycystic liver disease (PCLD) and a contemporaneous symptomatic haemangioma of the III segment. At the preoperative imaging scans, APCLD was classified in a type II grading according to Gigot classification. The patient underwent surgery: a wedge resection of the III segment with the exportation of the haemangioma and a fenestration of a large cyst placed in the VIII segment were performed. Post-operative course was regular and the patient was discharged uneventfully in post-operative 9th day, with a total regress of the initial symptoms. APCLD and haemangioma are two benign conditions that do not require surgery except if they cause important symptoms, such as pain. The good clinical conditions of the patient, the moderate gravity of the APCLD and the particular exofitic localisation of the cavernous haemangioma gave us the possibility to make a safe surgery for the patient. To the best of our knowledge, this is the first case reported in literature in which a liver resection for haemangioma in patient with APCLD was performed. In conclusion, liver resection for haemangioma is not contraindicated, mainly if it is symptomatic, even in the contemporaneous presence of an APCLD.

  10. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    PubMed Central

    Baratta, Francesco; Pastori, Daniele; Polimeni, Licia; Tozzi, Giulia; Violi, Francesco; Angelico, Francesco; Del Ben, Maria

    2015-01-01

    Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis. PMID:26602919

  11. Concealed expansion of immature precursors underpins acute burst of adult HSC activity in foetal liver

    PubMed Central

    Ivanovs, Andrejs; Zhao, Suling; Medvinsky, Alexander

    2016-01-01

    One day prior to mass emergence of haematopoietic stem cells (HSCs) in the foetal liver at E12.5, the embryo contains only a few definitive HSCs. It is thought that the burst of HSC activity in the foetal liver is underpinned by rapid maturation of immature embryonic precursors of definitive HSCs, termed pre-HSCs. However, because pre-HSCs are not detectable by direct transplantations into adult irradiated recipients, the size and growth of this population, which represents the embryonic rudiment of the adult haematopoietic system, remains uncertain. Using a novel quantitative assay, we demonstrate that from E9.5 the pre-HSC pool undergoes dramatic growth in the aorta-gonad-mesonephros region and by E11.5 reaches the size that matches the number of definitive HSCs in the E12.5 foetal liver. Thus, this study provides for the first time a quantitative basis for our understanding of how the large population of definitive HSCs emerges in the foetal liver. PMID:27095492

  12. A Monte Carlo approach to assessing 147Pm in the liver of the adult phantom.

    PubMed

    Bhati, S

    1993-06-01

    A low-background phoswich detector is used to detect small amounts of 147Pm--a pure beta-emitting nuclide--present in the liver of an occupational worker. The assessment was based on the measurement of bremsstrahlung radiation produced by the beta particles in the tissue. Computer programs based on Monte Carlo techniques for photon transport have been developed to calculate the response of an external phoswich detector to 1) a 147Pm point source embedded in tissue-equivalent slabs of various thicknesses; and 2) various source distributions of 147Pm in the liver of an adult phantom. The goal is to theoretically calibrate the phoswich detector for each source distribution and to study the variation of maxima of the spectra with the depth of the source in the adult phantom liver and tissue-equivalent slabs. The initial bremsstrahlung photon distribution of 147Pm in water has been computed using Wyard's and Pratt's methods. These calculations have been compared with experimental measurements using Perspex acrylic sheet slabs. Good agreements have been noted when the initial bremsstrahlung spectrum is obtained by using Wyard's method. These results find applications in monitoring the liver burdens in occupational workers handling 147Pm-based radioluminous paints.

  13. Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

    PubMed Central

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M.A.; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A.; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J.; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N.M.; Nieuwenhuis, Edward E.S.; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R.G.; van der Laan, Luc J.W.; Cuppen, Edwin; Clevers, Hans

    2015-01-01

    Summary Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

  14. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    ClinicalTrials.gov

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  15. Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach

    PubMed Central

    Qiao, Qin; Le Manach, Séverine; Sotton, Benoit; Huet, Hélène; Duvernois-Berthet, Evelyne; Paris, Alain; Duval, Charlotte; Ponger, Loïc; Marie, Arul; Blond, Alain; Mathéron, Lucrèce; Vinh, Joelle; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-01-01

    Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues. PMID:27561897

  16. Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach.

    PubMed

    Qiao, Qin; Le Manach, Séverine; Sotton, Benoit; Huet, Hélène; Duvernois-Berthet, Evelyne; Paris, Alain; Duval, Charlotte; Ponger, Loïc; Marie, Arul; Blond, Alain; Mathéron, Lucrèce; Vinh, Joelle; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-01-01

    Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues. PMID:27561897

  17. Deep sexual dimorphism in adult medaka fish liver highlighted by multi-omic approach.

    PubMed

    Qiao, Qin; Le Manach, Séverine; Sotton, Benoit; Huet, Hélène; Duvernois-Berthet, Evelyne; Paris, Alain; Duval, Charlotte; Ponger, Loïc; Marie, Arul; Blond, Alain; Mathéron, Lucrèce; Vinh, Joelle; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

    2016-08-26

    Sexual dimorphism describes the features that discriminate between the two sexes at various biological levels. Especially, during the reproductive phase, the liver is one of the most sexually dimorphic organs, because of different metabolic demands between the two sexes. The liver is a key organ that plays fundamental roles in various physiological processes, including digestion, energetic metabolism, xenobiotic detoxification, biosynthesis of serum proteins, and also in endocrine or immune response. The sex-dimorphism of the liver is particularly obvious in oviparous animals, as the female liver is the main organ for the synthesis of oocyte constituents. In this work, we are interested in identifying molecular sexual dimorphism in the liver of adult medaka fish and their sex-variation in response to hepatotoxic exposures. By developing an integrative approach combining histology and different high-throughput omic investigations (metabolomics, proteomics and transcriptomics), we were able to globally depict the strong sexual dimorphism that concerns various cellular and molecular processes of hepatocytes comprising protein synthesis, amino acid, lipid and polysaccharide metabolism, along with steroidogenesis and detoxification. The results of this work imply noticeable repercussions on the biology of oviparous organisms environmentally exposed to chemical or toxin issues.

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

    PubMed

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

    2015-10-01

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

  19. Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation

    PubMed Central

    Ikeda, S; Yazaki, M; Takei, Y; Ikegami, T; Hashikura, Y; Kawasaki, S; Iwai, M; Kobayashi, K; Saheki, T

    2001-01-01

    OBJECTIVE—Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to.
METHODS—Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member.
RESULTS—There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work.
CONCLUSIONS—The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

 PMID:11606680

  20. Percutaneous Endovascular Treatment of Hepatic Artery Stenosis in Adult and Pediatric Patients After Liver Transplantation

    SciTech Connect

    Maruzzelli, Luigi; Miraglia, Roberto Caruso, Settimo; Milazzo, Mariapina; Mamone, Giuseppe; Gruttadauria, Salvatore; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2010-12-15

    The purpose of this study was to evaluate the efficacy of percutaneous endovascular techniques for the treatment of hepatic artery stenosis (HAS) occurring after liver transplantation (LT) in adult and pediatrics patients. From February 2003 to March 2009, 25 patients (15 adults and 10 children) whose developed HAS after LT were referred to our interventional radiology unit. Technical success was achieved in 96% (24 of 25) of patients. Percutaneous transluminal angioplasty (PTA) was performed in 13 patients (7 children), and stenting was performed in 11 patients (2 children). After the procedure, all patients were followed-up with liver function tests, Doppler ultrasound, and/or computed tomography. Mean follow-up was 15.8 months (range 5 days to 58 months). Acute hepatic artery thrombosis occurred immediately after stent deployment in 2 patients and was successfully treated with local thrombolysis. One patient developed severe HA spasm, which reverted after 24 h. After the procedure, mean trans-stenotic pressure gradient decreased from 30.5 to 6.2 mmHg. Kaplan-Meyer curve of HA primary patency was 77% at 1 and 2 years. During the follow-up period, 5 patients (20%) had recurrent stenosis, and 2 patients (8.3%) had late thrombosis. Two of 7 patients with stenosis/thrombosis underwent surgical revascularization (n = 1) and liver retransplantation (n = 1). Six (25%) patients died during follow-up, but overall mortality was not significantly different when comparing patients having patent hepatic arteries with those having recurrent stenosis/thrombosis. There were no significant differences in recurrent stenosis/thrombosis and mortality comparing patients treated by PTA versus stenting and comparing adult versus pediatric status. Percutaneous interventional treatment of HAS in LT recipients is safe and effective and decreases the need for surgical revascularization and liver retransplantation. However, the beneficial effects for survival are not clear, probably because

  1. Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells.

    PubMed

    Smalheiser, N R; Costa, E; Guidotti, A; Impagnatiello, F; Auta, J; Lacor, P; Kriho, V; Pappas, G D

    2000-02-01

    Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing alpha-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues.

  2. Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells

    PubMed Central

    Smalheiser, Neil R.; Costa, Erminio; Guidotti, Alessandro; Impagnatiello, Francesco; Auta, James; Lacor, Pascale; Kriho, Virginia; Pappas, George D.

    2000-01-01

    Reelin regulates telencephalic and cerebellar lamination during mammalian development and is expressed in several structures of the adult brain; however, only traces of reelin were believed to be in peripheral tissues. Because reelin structurally resembles extracellular matrix proteins, and because many of these proteins are expressed in blood, we hypothesized that reelin also might be detectable in the circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands (310 and 160 kDa) are expressed in serum and platelet-poor plasma of rats, mice, and humans, but these three bands were not detectable in serum of homozygous reeler (rl/rl) mice. Reelin plasma levels in heterozygous (rl/+) mice were half of those in wild-type littermates. Western blotting and immunocytochemistry using antireelin mAbs indicated that reelin-like immunoreactivity was expressed in a subset of chromaffin cells within the rat adrenal medulla and in a subset of cells coexpressing α-melanocyte-stimulating hormone within the pituitary pars intermedia. However, surgical removal of adrenal or pituitary failed to decrease the amount of reelin (420-kDa band) expressed in serum. Adult liver expressed one-third of the reelin mRNA concentration expressed in adult mouse cerebral cortex. Full-length reelin protein was detectable in liver extracts in situ; acutely isolated liver cells also secreted full-length reelin in vitro. Liver appears to be a prime candidate to produce and maintain the circulating reelin pool. It now becomes relevant to ask whether circulating reelin has a physiologic role on one or more peripheral target tissues. PMID:10655522

  3. Quantitative survival model for short-term survival after adult-to-adult living donor liver transplantation.

    PubMed

    Tsunematsu, Ichiro; Ogura, Yasuhiro; Inoue, Kayoko; Koizumi, Akio; Tanigawa, Nobuhiko; Tanaka, Koichi

    2006-06-01

    Adult-to-adult living donor liver transplantation (ALDLT) has been accepted as an important option for end-stage liver disease, but information regarding the risk factors remains fragmentary. We aimed to establish a predictive model for 90-day survival. In the first step, a total of 286 cases who had received primary ALDLT using a right lobe graft between 1998 and 2004 were randomly divided into 2 cohorts at a ratio of 2:1 (191 vs. 95 recipients). The larger cohort of patients was used to develop a model. The outcome was defined as 90-day survival, and a total of 39 preoperative and operative variables, including the period of surgery (1998-2001 vs. 2002-2004), were included using Cox's proportional hazard regression model. Two mismatches of human leukocyte antigen (HLA) type DR (hazard ratio [HR] = 4.45; confidence interval [CI] = 1.96-10.1), log(e)[blood loss volume] (HR = 2.43; CI = 1.64-3.60), period of surgery (1998-2001 vs. 2002-2004) (HR = 2.41; CI = 1.04-5.57), and log(e)[serum C-reactive protein or CRP] (HR = 1.64; CI = 1.13-2.38) were found to be independent risk factors. In the second step, we tried to establish a realistic survival model. In this step, we created 2 models, 1 that used all 4 variables (model 1) and 1 (model 2) in which blood loss volume was replaced with the past history of upper abdominal surgery and Model for End-Stage Liver Disease (MELD) score (> or =25), both of which showed associations with blood loss volume. These models were applied to the smaller cohort of 95 patients. Receiver operating characteristic analyses demonstrated that both models showed similar significant c-statistics (0.63 and 0.62, respectively). In conclusion, model 2 can provide a rough estimation of the 90-day survival after ALDLT.

  4. Donor Safety in Adult-Adult Living Donor Liver Transplantation: A Single-Center Experience of 356 Cases

    PubMed Central

    Meng, Haipeng; Yang, Jiayin; Yan, Lunan

    2016-01-01

    Background As an important means to tackle the worldwide shortage of liver grafts, adult-adult living donor liver transplantation (A-ALDLT) is the most massive operation a healthy person could undergo, so donor safety is of prime importance. However, most previous research focused on recipients, while complications in donors have not been fully described or investigated. Material/Methods To investigate donor safety in terms of postoperative complications, the clinical data of 356 A-ALDLT donors in our center from January 2002 to September 2015 were retrospectively analyzed. These patients were divided into a pre-2008 group (before January 2008) and a post-2008 group (after January 2008). Donor safety was evaluated with regard to the type, frequency, and severity of postoperative complications. Results There were no donor deaths in our center during this period. The overall complication rate was 23.0% (82/356). The proportion of Clavien I, II, III, and IV complications was 51.2% (42/82), 25.6% (21/82), 22.0% (18/82), and 1.2% (1/82), respectively. In all the donors, the incidence of Clavien I, II, III, and IV complications was 11.8% (42/356), 5.9% (21/356), 5.1% (18/356), and 0.3% (1/356), respectively. The overall complication rate in the post-2008 group was significantly lower than that in the pre-2008 group (18.1% (41/227) vs. 32.6% (42/129), P<0.01). Biliary complications were the most common, with an incidence of 8.4% (30/356). Conclusions The risk to A-ALDLT donors is controllable and acceptable with improvement in preoperative assessment and liver surgery. PMID:27178367

  5. Obesity and the extent of liver damage among adult New Zealanders: findings from a national survey

    PubMed Central

    Miller, J. C.; Gray, A. R.; Schultz, M.; Mann, J. I.; Parnell, W. R.

    2015-01-01

    Summary Objective Non‐alcoholic fatty liver disease (NAFLD), defined as excessive fat accumulation in hepatocytes when no other pathologic causes are present, is an increasingly common obesity‐related disorder. We sought to describe the prevalence of elevated liver enzymes, a marker of liver damage, among New Zealand adults, and high‐risk subgroups including those with an elevated body mass index and those with pre‐diabetes or diabetes, to gain a better understanding of the burden of liver disease. Methods A total of 4,721 New Zealanders aged 15+ years participated in a nationally representative nutrition survey. Liver enzymes, alanine transaminase (ALT) and gamma glutamyl transpeptidase (GGT) were measured in serum. Results were available for 3,035 participants, of whom 10.8% were Māori and 4.5% Pacific. Results Overall, the prevalence of elevated ALT and elevated GGT was 13.1% (95% confidence interval [CI]: 11.2 – 15.0) and 13.7% (95% CI: 12.0 – 15.4), respectively. Odds ratios for an elevated ALT or GGT markedly increased with increasing body mass index. Men with obesity had the highest elevated ALT prevalence (28.5%; 95% CI: 21.7–35.4), and women with diabetes had the highest elevated GGT prevalence (36.5%; 95% CI: 26.0–47.0). Adding alcohol consumption categories to each of the adjusted models did not meaningfully change any results, although for women, heavy alcohol consumption was associated with an elevated GGT (overall p = 0.03). Conclusions Obesity‐related liver disease is likely to increasingly burden the New Zealand health sector and contribute to health disparities unless effective obesity treatment and prevention measures are given high priority. © 2015 The Authors. Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society. PMID:27774250

  6. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  7. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  8. Neurologic complications in adult living donor liver transplant patients: an underestimated factor?

    PubMed

    Saner, Fuat Hakan; Gensicke, Julia; Olde Damink, Steven W M; Pavlaković, Goran; Treckmann, Juergen; Dammann, Marc; Kaiser, Gernot M; Sotiropoulos, Georgios C; Radtke, Arnold; Koeppen, Susanne; Beckebaum, Susanne; Cicinnati, Vito; Nadalin, Silvio; Malagó, Massimo; Paul, Andreas; Broelsch, Christoph E

    2010-02-01

    Liver transplantation is the only curative treatment in patients with end-stage liver disease. Neurological complications (NC) are increasingly reported to occur in patients after cadaveric liver transplantation. This retrospective cohort study aims to evaluate the incidence and causes of NC in living donor liver transplant (LDLT) patients in our transplant center. Between August 1998 and December 2005, 121 adult LDLT patients were recruited into our study. 17% of patients experienced NC, and it occurred significantly more frequently in patients with alcoholic cirrhosis (42%) and autoimmune hepatitis (43%) as compared with patients with hepatitis B or C (9/10%, P = 0.013). The most common NC was encephalopathy (47.6%) followed by seizures (9.5%). The choice of immunosuppression by calcineurin inhibitor (Tacrolimus or Cyclosporin A) showed no significant difference in the incidence of NC (19 vs. 17%). The occurrence of NC did not influence the clinical outcome, since mortality rate, median ICU stay and length of hospital stay were similar between the two groups. Most patients who survived showed a nearly complete recovery of their NC. NCs occur in approximately 1 in 6 patients after LDLT and seem to be predominantly transient in nature, without major impact on clinical outcome. PMID:19727899

  9. Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver.

    PubMed Central

    Lomri, N; Gu, Q; Cashman, J R

    1992-01-01

    Complementary DNA (cDNA) clones encoding the adult human liver flavin-containing monooxygenase (FMO; dimethylaniline N-oxidase, EC 1.14.13.8) were isolated from lambda gt10 and lambda gt11 libraries. The cDNA libraries were screened with three synthetic 36-mer oligonucleotide probes derived from the nucleic acid sequence of the pig liver FMO cDNA. The deduced amino acid sequence for the adult human liver FMO was quite distinct from the pig liver FMO, and adult human liver FMO was designated form II (HLFMO II). The full-length cDNA sequence of HLFMO II [2119 base pairs (bp)] had an open reading frame of 1599 nucleotides, which encoded a 533-amino acid protein of Mr 59,179, a 5'-noncoding region of 136 nucleotides and a 3'-noncoding region of 369 nucleotides excluding the poly(A) tail. The deduced amino acid sequence of HLFMO II had 80% similarity with the rabbit liver FMO II but only a 52%, 55%, and 53% amino acid similarity with the rabbit liver (form I), the pig liver (form I), and fetal human liver (form I) FMOs, respectively. RNA analysis of adult human liver RNA showed that there was one HLFMO II mRNA species. Analysis of genomic DNA indicated that HLFMO II was the product of a single gene. These results indicated that the deduced amino acid sequence for HLFMO II contained highly conserved residues and suggested that FMO enzymes were closely related and, undoubtedly, derived from the same ancestral gene. Images PMID:1542660

  10. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  11. Patterns and Predictors of Sexual Function After Liver Donation: the Adult to Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

    PubMed Central

    DiMartini, AF.; Dew, MA.; Butt, Z.; Simpson, MA.; Ladner, DP.; Smith, AR.; Hill-Callahan, P.; Gillespie, BW.

    2015-01-01

    Although sexual functioning is an important facet of living donor quality of life, it has not received extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year postdonation. Donors (n=208) and a comparison group of non-donors (n=155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the three time points, donor sexual functioning was lower at the evaluation phase and 3 months postdonation than at one year postdonation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm (OR = 3.98, 95% CI 1.30–12.16), concerns over appearance with lower sexual desire (OR = 4.14, 95% CI 1.02–16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR 3.58, 95% CI 1.43–8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning. PMID:25779554

  12. Brief Report: The Deletion of the Phosphatase Regulator NIPP1 Causes Progenitor Cell Expansion in the Adult Liver.

    PubMed

    Boens, Shannah; Verbinnen, Iris; Verhulst, Stefaan; Szekér, Kathelijne; Ferreira, Monica; Gevaert, Thomas; Baes, Myriam; Roskams, Tania; van Grunsven, Leo A; Van Eynde, Aleyde; Bollen, Mathieu

    2016-08-01

    The Ppp1r8 gene encodes NIPP1, a nuclear interactor of protein phosphatase PP1. The deletion of NIPP1 is embryonic lethal at the gastrulation stage, which has hampered its functional characterization in adult tissues. Here, we describe the effects of a conditional deletion of NIPP1 in mouse liver epithelial cells. Ppp1r8(-/-) livers developed a ductular reaction, that is, bile-duct hyperplasia with associated fibrosis. The increased proliferation of biliary epithelial cells was at least partially due to an expansion of the progenitor cell compartment that was independent of liver injury. Gene-expression analysis confirmed an upregulation of progenitor cell markers in the liver knockout livers but showed no effect on the expression of liver-injury associated regulators of cholangiocyte differentiation markers. Consistent with an inhibitory effect of NIPP1 on progenitor cell proliferation, Ppp1r8(-/-) livers displayed an increased sensitivity to diet-supplemented 3,5-diethoxycarbonyl-1,4-dihydrocollidine, which also causes bile-duct hyperplasia through progenitor cell expansion. In contrast, the liver knockouts responded normally to injuries (partial hepatectomy, single CCl4 administration) that are restored through proliferation of differentiated parenchymal cells. Our data indicate that NIPP1 does not regulate the proliferation of hepatocytes but is a suppressor of biliary epithelial cell proliferation, including progenitor cells, in the adult liver. Stem Cells 2016;34:2256-2262. PMID:27068806

  13. A study on endocrine dysfunction in adult males with liver cirrhosis.

    PubMed

    Bandyopadhyay, Sanjay K; Moulick, Avijit; Saha, Manjari; Dutta, Anita; Bandyopadhyay, Ramtanu; Basu, Asish Kumar

    2009-12-01

    Over a period of two years, 72 adult males with liver cirrhosis of different aetiologies were studied in terms of clinical and biochemical evidence of endocrine dysfunctions related to hypothalamic-pituitary-gonadal axis and the thyroid status, and compared with 40 age-matched control subjects. With more advanced disease, a progressive fall in testosterone, leutinising hormone and triiodothyronine and a rise in oestradiol was observed. Severity of the liver disease determined by Child-Turcotte-Pugh class, rather than aetiology (alcoholic or postviral), was the chief determinant of such dysfunctions. The involvement was both central and peripheral, with only peripheral defects at gonadal level in early state but dysfunctions at both the levels in late stage of cirrhosis.

  14. Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes

    PubMed Central

    Tarlow, Branden D.; Pelz, Carl; Naugler, Willscott E.; Wakefield, Leslie; Wilson, Elizabeth M.; Finegold, Milton J.; Grompe, Markus

    2014-01-01

    Summary Adult liver progenitor cells are biliary-like epithelial cells that emerge only under injury conditions in the periportal region of the liver. They exhibit phenotypes of both hepatocytes and bile ducts. However, their origin and their significance to injury repair remain unclear. Here, we used a chimeric lineage tracing system to demonstrate that hepatocytes contribute to the progenitor pool. RNA-sequencing, ultrastructural analysis, and in vitro progenitor assays revealed that hepatocyte-derived progenitors were distinct from their biliary-derived counterparts. In vivo lineage tracing and serial transplantation assays showed that hepatocyte-derived proliferative ducts retained a memory of their origin and differentiated back into hepatocytes upon cessation of injury. Similarly, human hepatocytes in chimeric mice also gave rise to biliary progenitors in vivo. We conclude that human and mouse hepatocytes can undergo reversible ductal metaplasia in response to injury, expand as ducts and subsequently contribute to restoration of the hepatocyte mass. PMID:25312494

  15. Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation

    PubMed Central

    Fayed, Nirmeen; Mourad, Wessam; Yassen, Khaled; Görlinger, Klaus

    2015-01-01

    Background The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. Methods The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. Results Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. Conclusion Preoperative thromboelastometric analysis is

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Liver.

    PubMed

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

    2016-01-01

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

  19. Metabolic alterations in liver and testes of adult and newborn rats following cadmium administration

    SciTech Connect

    Agarwal, A.K.

    1988-04-01

    A large number of studies have been conducted to understand the effect of cadmium on cellular intermediary metabolism. Although, most of the metal is stored in liver and kidney, the organ affected most in acute toxicity is testis. Increased lipid peroxidation and decreased mitochondrial respiration along with other cellular enzyme activities have been reported to take place due to cadmium administration. The present experiment was designed to study the effect of acute cadmium administration on the activities of some of the tissue enzyme systems that provide the reducing equivalent NADPH. The levels of NADH and NADPH were also measured. All the measurements were conducted in two tissues: liver and testes. The effect of simultaneous administration of zinc on cadmium induced changes was also determined. Newborn animals have been found to be resistant to many effects of cadmium. The present studies were also conducted in newborn rat liver and testes. The purpose of the study is to compare the effects of cadmium on adult and new born rats.

  20. Undifferentiated embryonal sarcoma of the liver in a middle-aged adult with systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Adult primary undifferentiated embryonal sarcoma of the liver (UESL) is a rare disease. While the etiology of UESL remains largely unknown, association with systemic inflammatory disorders has been observed. Here, we report a case of UESL in a 46-year-old woman with systemic lupus erythematosus (SLE) and without chronic hepatitis or liver cirrhosis. Systematic review of the publicly available English language medical literature identified only 27 cases of UESL in patients aged >45 years and none with SLE. Our patient presented with abdominal pain and had a 2-year history of SLE. Abdominal ultrasonography and enhanced computed tomography revealed a solid mass in the right lobe of the liver. Presumptive diagnosis of atypical hepatocellular carcinoma was made and the patient was treated with segmentectomy of S5 and S4a and cholecystectomy. The final diagnosis of UESL was made according to the pathology results. Since SLE patients may be at increased risk of malignancy, it is possible that the SLE pathogenesis may have contributed to the development of UESL in our patient. According to this case, UESL should be considered when SLE patients present with hepatic space-occupying lesions. PMID:24073982

  1. Vascular complications after adult living donor liver transplantation: Evaluation with ultrasonography

    PubMed Central

    Ma, Lin; Lu, Qiang; Luo, Yan

    2016-01-01

    Living donor liver transplantation (LDLT) has been widely used to treat end-stage liver disease with improvement in surgical technology and the application of new immunosuppressants. Vascular complications after liver transplantation remain a major threat to the survival of recipients. LDLT recipients are more likely to develop vascular complications because of their complex vascular reconstruction and the slender vessels. Early diagnosis and treatment are critical for the survival of graft and recipients. As a non-invasive, cost-effective and non-radioactive method with bedside availability, conventional gray-scale and Doppler ultrasonography play important roles in identifying vascular complications in the early postoperative period and during the follow-up. Recently, with the detailed vascular tracing and perfusion visualization, contrast-enhanced ultrasound (CEUS) has significantly improved the diagnosis of postoperative vascular complications. This review focuses on the role of conventional gray-scale ultrasound, Doppler ultrasound and CEUS for early diagnosis of vascular complications after adult LDLT. PMID:26819527

  2. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    PubMed

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  3. Adult-onset liver disease and hepatocellular carcinoma in S-adenosylhomocysteine hydrolase deficiency

    PubMed Central

    Stender, Stefan; Chakrabarti, Rima S.; Xing, Chao; Gotway, Garrett; Cohen, Jonathan C.; Hobbs, Helen H.

    2016-01-01

    Background The etiology of liver disease remains elusive in some adults presenting with severe hepatic dysfunction. Methods and results Here we describe a woman of Pakistani descent who had elevated aminotransferases at age 23. She developed muscle weakness in her mid-20s, and was diagnosed with hepatocellular carcinoma at age 29. She died without a diagnosis at age 32 after having a liver transplant. Exome sequencing revealed that she was homozygous for a missense mutation (R49H) in AHCY, the gene encoding S-adenosylhomocysteine (SAH) hydrolase. SAH hydrolase catalyzes the final step in conversion of methionine to homocysteine and inactivating mutations in this enzyme cause a rare autosomal recessive disorder, SAH hydrolase deficiency, that typically presents in infancy. An asymptomatic 7-year old son of the proband is also homozygous for the AHCY-R49H mutation and has elevated serum aminotransferase levels, as well as markedly elevated serum levels of SAH, S-adenosylmethionine (SAM), and methionine, which are hallmarks of SAH hydrolase deficiency. Conclusion This report reveals several new aspects of SAH hydrolase deficiency. Affected women with SAH hydrolase deficiency can give birth to healthy children. SAH hydrolase deficiency can remain asymptomatic in childhood, and the disorder can be associated with early onset hepatocellular carcinoma. The measurement of serum amino acids should be considered in patients with liver disease or hepatocellular carcinoma of unknown etiology. PMID:26527160

  4. Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma.

    PubMed

    Lee, Nikki P Y; Leung, Kar-wai; Cheung, Nicole; Lam, Brian Y; Xu, Michelle Z; Sham, Pak C; Lau, George K; Poon, Ronnie T P; Fan, Sheung Tat; Luk, John M

    2008-05-01

    To identify potential oncofetal biomarkers that distinguish hepatocellular carcinoma (HCC) from healthy liver tissues, we compared and analyzed the proteomic profiles of mouse livers at different developmental stages. Fetal (E13.5, E16.5), newborn (NB), postnatal (3-week) and adult (3-month) livers were isolated and profiled by 2-D PAGE. Statistical analysis using linear regression and false discovery rate (FDR) revealed that 361 protein spots showed significant changes. Unsupervised hierarchical tree analysis segregated the proteins into fetal, NB, and postnatal-adult clusters. Distinctive protein markers were identified by MALDI-TOF/MS and the corresponding mRNA profiles were further determined by Q-PCR. Fetal markers (hPCNA, hHSP7C, hHEM6) and postnatal-adult markers (hARGI1, hASSY, hBHMT, hFABPL) were selected for testing against a panel of seven human hepatocyte/HCC cell lines and 59 clinical specimens. The fetal proteins were found to be overexpressed in the metastatic HCC cell lines and the tumor tissues, whereas the postnatal-adult proteins were expressed in non-tumor tissues and normal hepatocytes. This "Ying-Yang" pattern, as orchestrated by distinct fetal and adult markers, is hypothesized to indicate the progressive change of the liver from a growing, less-differentiated organ into a functional metabolic center. Thus, embryogenesis and tumorigenesis share certain oncofetal markers and adult "hepatic" phenotypes are lost in HCC.

  5. The Association between Sarcopenia and the Risk of Serious Infection among Adults Undergoing Liver Transplantation

    PubMed Central

    Krell, Robert W.; Kaul, Daniel R.; Martin, Andrew R.; Englesbe, Michael J.; Sonnenday, Christopher J.; Cai, Shijie; Malani, Preeti N.

    2013-01-01

    Background While sarcopenia (muscle loss) is associated with increased mortality after liver transplant, its influence on other complications is less well understood. We examined the association between sarcopenia and the risk of severe post-transplant infections among adult liver transplant recipients. Methods We assessed sarcopenia among 207 liver transplant recipients by calculating total psoas area (TPA) on preoperative computed tomography scans. The presence or absence of severe post-transplant infection was determined by review of the medical chart. The influence of post-transplant infection on overall survival was also assessed. Results We identified 196 episodes of severe infections among 111 patients. Fifty-six patients had more than one infection. The median time to development of infection was 27 days (range 13–62). When grouped by tertiles, patients in the lowest tertile had a more than four-fold higher odds of developing severe infection compared to patients in the highest tertile; OR 4.6, CI 95 2.3–9.5). In multivariable analysis, recipient age (hazard ratio 1.04, p=0.02), pre-transplant TPA (hazard ratio 0.38, p<0.01) and pre-transplant total bilirubin level (hazard ratio 1.05, p=0.02) were independently associated with the risk of developing severe infections. Patients with severe post-transplant infections had worse 1-year survival compared to patients without infection (76% vs. 92%, p=0.003). Conclusions Among patients undergoing liver transplantation, lower TPA was associated with heightened risk for post-transplant infectious complications and mortality. Future efforts should focus on approaches to assess and mitigate vulnerability among patients undergoing transplantation. PMID:24151041

  6. First-in-Human Case Study: Multipotent Adult Progenitor Cells for Immunomodulation After Liver Transplantation.

    PubMed

    Soeder, Yorick; Loss, Martin; Johnson, Christian L; Hutchinson, James A; Haarer, Jan; Ahrens, Norbert; Offner, Robert; Deans, Robert J; Van Bokkelen, Gil; Geissler, Edward K; Schlitt, Hans J; Dahlke, Marc H

    2015-08-01

    Mesenchymal stem cells and multipotent adult progenitor cells (MAPCs) have been proposed as novel therapeutics for solid organ transplant recipients with the aim of reducing exposure to pharmacological immunosuppression and its side effects. In the present study, we describe the clinical course of the first patient of the phase I, dose-escalation safety and feasibility study, MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I). After receiving a living-related liver graft, the patient was given one intraportal injection and one intravenous infusion of third-party MAPC in a low-dose pharmacological immunosuppressive background. Cell administration was found to be technically feasible; importantly, we found no evidence of acute toxicity associated with MAPC infusions.

  7. Assessment of methyl methanesulfonate using the repeated-dose liver micronucleus assay in young adult rats.

    PubMed

    Muto, Shigeharu; Yamada, Katsuya; Kato, Tatsuya; Wako, Yumi; Kawasako, Kazufumi; Iwase, Yumiko; Uno, Yoshifumi

    2015-03-01

    A repeated-dose liver micronucleus assay using young adult rats was conducted with methyl methanesulfonate (MMS) as a part of a collaborative study supported by the Collaborative Study Group for the Micronucleus Test/the Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. MMS is a classical DNA-reactive carcinogen, but it is not a liver carcinogen. In the first experiment (14-day study), MMS was administered per os to 6-week-old male Crl:CD (SD) rats every day for 14 days at a dose of 12.5, 25, or 50mg/kg/day. In the second experiment (28-day study), 6-week-old male SD rats were treated with MMS at 7.5, 15, or 30mg/kg/day for 28 days, because the highest dose used in the 14-day study (50mg/kg/day) caused mortality. Hepatocyte and bone marrow cell specimens were prepared on the day after the final dose. The frequency of micronucleated hepatocytes (MNHEPs) in the liver and that of micronucleated immature erythrocytes (MNIMEs) in the bone marrow were evaluated. Exposure to 50mg/kg/day MMS for 14 days resulted in an increased frequency of MNHEPs, but MMS had no effect on the frequency of MNHEPs in the rats exposed to the chemical for 28 days at doses up to 30mg/kg/day. MMS induced MNIMEs production at doses of 25 and 50mg/kg/day in the 14-day study and at doses of 15 and 30mg/kg/day in the 28-day study. Overall, the effect of MMS on the frequency of MNHEPs was considered to be equivocal.

  8. Social barriers to listing for adult liver transplantation: their prevalence and association with program characteristics.

    PubMed

    Flattau, Anna; Olaywi, Manhal; Gaglio, Paul J; Marcus, Paula; Meissner, Paul; L Dorfman, Emily B; Reinus, John F

    2011-10-01

    Social barriers to effective medical care are mandated to be routinely assessed as part of an evaluation for liver transplantation. This study explores how frequently liver transplant programs encounter these barriers in patients undergoing an evaluation and whether programs with higher proportions of Medicaid patients, historically disadvantaged minority patients, and rural patients encounter social barriers more frequently. A survey for assessing patient demographics and social barriers was electronically completed by representatives of 61 of 104 eligible US adult liver transplant programs (59%). Fifty-eight of the 61 programs identified themselves, and their characteristics were similar to those of all 104 US programs according to publicly available data from the Organ Procurement and Transplantation Network. Social barriers were reported to be encountered sometimes (10%-30%) or frequently (>30%) by the 61 programs as follows: inadequate or unstable health insurance (68.9% of the programs), a chaotic social environment (63.9%), a lack of a care partner (60.7%), an inability to obtain transportation (49.2%), a low educational level (36.1%), inadequate housing (23.0%), a language barrier (19.7%), no reliable way of contacting the patient (16.4%), difficulty in obtaining child care (11.5%), and food insecurity (8.2%). The frequencies of perceived social barriers did not differ significantly between programs reporting higher or lower proportions of Medicaid, minority, or rural patients. Our analysis suggests that program-level operational planning for addressing social barriers to transplant listing should be considered regardless of the proportions of Medicaid-insured, racial or ethnic minority, and rural patients in the population.

  9. Acute Liver Failure in Adults: An Evidence-Based Management Protocol for Clinicians

    PubMed Central

    Misel, Michael; Gish, Robert G.

    2012-01-01

    With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes. PMID:22675278

  10. Laminin alpha 5, a major transcript of normal and malignant rat liver epithelial cells, is differentially expressed in developing and adult liver.

    PubMed

    Seebacher, T; Medina, J L; Bade, E G

    1997-11-25

    The laminin family of extracellular matrix glycoproteins plays a major role in cell migration and differentiation and in tumor cell invasion. As previously shown, the laminin deposited by normal and malignant rat liver epithelial cells in their extracellular matrix (ECM) and into their ECM migration tracks does not contain a typical (EHS-like) alpha 1 heavy chain. By RT-PCR screening we have now identified two alpha chains among a total of five additional laminin chains produced by these cells. Three of the newly identified chains were not previously known for the rat. Their sequences have been deposited in the EMBL nucleotide sequence data bank. The alpha 5 chain now identified is expressed at comparably high levels by both the normal and the malignant liver epithelial cells. The chain is also expressed in fetal liver together with the alpha 2 and beta 2 chains, but it is only vestigially expressed in the mature organ as shown by RT-PCR. These results suggest for alpha 5 a role in development and production of the chain by only a small subset of cells in adult liver. At the level of detection used, no changes were observed in regenerating liver after partial hepatectomy. In addition to the alpha 5 chain, the cultured cells express the beta 1 and beta 2 light chains, indicating the expression of more than one laminin isoform by the same cell line. The expression of the alpha 5 chain and of the other new non-EHS isoform chains was also analyzed in various tissues. The malignant liver epithelial cells, but not their nontumorigenic parental cells, also express, in addition to the alpha 5 chain the alpha 2 chain, which is expressed at high level by the NBT II bladder carcinoma cell line, suggesting a relationship with malignancy. PMID:9417868

  11. Restoration of portal flow using a pericholedochal varix in adult living donor liver transplantation for patients with total portosplenomesenteric thrombosis.

    PubMed

    Moon, Deok-Bog; Lee, Sung-Gyu; Ahn, Chul-Soo; Hwang, Shin; Kim, Ki-Hun; Ha, Tae-Yong; Song, Gi-Won; Park, Gil-Chun; Jung, Dong-Hwan; Namkoong, Jung-Man; Park, Hyung-Woo; Park, Yo-Han

    2014-05-01

    In total portosplenomesenteric thrombosis patients, cavoportal hemitransposition (CPHT) is indicated but rarely applicable for adult-to-adult (A-to-A) living donor liver transplantation (LDLT) because partial liver graft requires splanchno-portal inflow for liver graft regeneration. If intra- & peri-pancreatic collaterals draining into pericholedochal varix were present, pericholedochal varix may provide splanchnic blood flow to the transplanted liver and also relieve recipient's portal hypertension. To date, however, there is no successful report using pericholedochal varix in liver transplantation (LT). We successfully performed A-to-A LDLTs using pericholedochal varix for those 2 patients. The surgical strategies are followings: (a) dissection of hepatic hilum to isolate left hepatic artery using for arterial reconstruction of implanted right lobe graft, (b) en-mass clamping of the undissected remaining hilum if we can leave adequate length of stump from the clamping site, and then hilum is divided, (c) delay the donor hepatectomy until the feasibility of the recipient operation is confirmed. Portal flow was established between the sizable pericholedochal varix (caliber > 1cm) and graft portal vein, but the individually designed approaches were used for each patients. Currently, they have been enjoying normal life on posttransplant 92 and 44 months respectively. In conclusion, enlarged pericholedochal varix in patients with totally obliterated splanchnic veins might be an useful inflow to restore portal flow and secure good outcome in A-to-A LDLT. AASLD.

  12. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

    PubMed

    Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

    2014-03-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies.

  13. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

    PubMed

    Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

    2014-03-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  14. Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice

    PubMed Central

    Zhang, Xiuqi; Garcia, Oscar A.; Wang, Rebecca F.; Stevenson, Mary C.; Threadgill, David W.; Russell, William E.

    2014-01-01

    Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies. PMID:24407590

  15. Greater serum carotenoid levels associated with lower prevalence of nonalcoholic fatty liver disease in Chinese adults

    PubMed Central

    Cao, Yi; Wang, Cheng; Liu, Jun; Liu, Zhao-min; Ling, Wen-hua; Chen, Yu-ming

    2015-01-01

    Previous studies have suggested that serum carotenoids may be inversely associated with liver injury, but limited data are available from population-based studies. We examined the relationship between serum carotenoid levels and the prevalence of nonalcoholic fatty liver disease (NAFLD) in Chinese adults. A total of 2935 participants aged 40–75 years were involved in this community-based cross-sectional study. General information, lifestyle factors, serum levels of carotenoid and the presence and degree of NAFLD were determined. After adjusting for potential covariates, we observed a dose-dependent inverse association between NAFLD risk and each individual serum carotenoid and total carotenoids (all p-values < 0.001). The ORs of NAFLD for the highest (vs. lowest) quartile were 0.44 (95% CI 0.35, 0.56) for α-carotene, 0.32 (95% CI 0.25, 0.41) for β-carotene, 0.62 (95% CI 0.49, 0.79) for β-cryptoxanthin, 0.54 (95% CI 0.42, 0.68) for lycopene, 0.56 (95% CI 0.44, 0.72) for lutein + zeaxanthin and 0.41 (95% CI 0.32, 0.53) for total carotenoids. Higher levels of α-carotene, β-carotene, lutein + zeaxanthin and total carotenoids were significantly associated with a decrease in the degree of NAFLD (p-trend: < 0.001 to 0.003). Serum carotenoids are inversely associated with prevalence of NAFLD in middle aged and elderly Chinese. PMID:26256414

  16. Acute lethal graft-versus-host disease stimulates cellular proliferation in the adult rat liver.

    PubMed

    Klein, R M; Clancy, J; Stuart, S

    1982-11-01

    The present investigation was designed to analyse the effects of acute lethal graft-versus-host disease (GVHD) in adult (DA x LEW)F1 rats on cellular proliferation within the liver. The influence of the host thymus on GVHD-induced proliferation was also assessed. From 1-28 days after initiation of GVHD [3H]thymidine ([3H]-TdR) was injected i.v. and rats were killed one hour later. Percentage labelled cells (LI) of periportal infiltrating cells (PIC), hepatocytes (H), and sinusoidal lining cells (SC) were counted. Mean values for control rats were 0.3 +/- 0.1% (H), 0.4 +/- 0.1% (SC) and 0.2 +/- 0.1% (PIC). GVHD rats demonstrated a significant increase in LI of PIC (days 1-21), SC (days 2-17) and H (days 2-17). Most labelled cells in PIC were large lymphocytes. Peak LI values were 7.0 +/- 1.0% PIC (day 17), 6.8 +/- 0.9% SC (day 17), and 5.2 +/- 0.9% H (day 7), with all cellular compartments returning to near normal LI values by day 28. Stimulation of cellular proliferation occurred in all three liver cell compartments in neonatally thymectomized (TXM) rats. The intensity of GVHD-induced cell proliferation was significantly decreased at day 7 in all compartments and PIC was dramatically decreased at day 21 in TXM-GVHD rats as compared to non-TXM-GVHD rats. It is hypothesized that the general stimulation of hepatocyte cell proliferation in GVHD is related to the secretion of lymphokines by primarily donor and secondarily host T cells in the periportal infiltrate. PMID:7172201

  17. Neonatal androgenization exacerbates alcohol-induced liver injury in adult rats, an effect abrogated by estrogen.

    PubMed

    Ellefson, Whitney M; Lakner, Ashley M; Hamilton, Alicia; McKillop, Iain H; Bonkovsky, Herbert L; Steuerwald, Nury M; Huet, Yvette M; Schrum, Laura W

    2011-01-01

    Alcoholic liver disease (ALD) affects millions of people worldwide and is a major cause of morbidity and mortality. However, fewer than 10% of heavy drinkers progress to later stages of injury, suggesting other factors in ALD development, including environmental exposures and genetics. Females display greater susceptibility to the early damaging effects of ethanol. Estrogen (E2) and ethanol metabolizing enzymes (cytochrome P450, CYP450) are implicated in sex differences of ALD. Sex steroid hormones are developmentally regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which controls sex-specific cycling of gonadal steroid production and expression of hepatic enzymes. The aim of this study was to determine if early postnatal inhibition of adult cyclic E2 alters ethanol metabolizing enzyme expression contributing to the development of ALD in adulthood. An androgenized rat model was used to inhibit cyclic E2 production. Control females (Ctrl), androgenized females (Andro) and Andro females with E2 implants were administered either an ethanol or isocalorically-matched control Lieber-DeCarli diet for four weeks and liver injury and CYP450 expression assessed. Androgenization exacerbated the deleterious effects of ethanol demonstrated by increased steatosis, lipid peroxidation, profibrotic gene expression and decreased antioxidant defenses compared to Ctrl. Additionally, CYP2E1 expression was down-regulated in Andro animals on both diets. No change was observed in CYP1A2 protein expression. Further, continuous exogenous administration of E2 to Andro in adulthood attenuated these effects, suggesting that E2 has protective effects in the androgenized animal. Therefore, early postnatal inhibition of cyclic E2 modulates development and progression of ALD in adulthood.

  18. Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques.

    PubMed

    Mabrouk Mourad, Moustafa; Liossis, Christos; Kumar, Senthil; Gunson, Bridget K; Mergental, Hynek; Isaac, John; Bramhall, Simon R; Muiesan, Paolo; Mirza, Darius F; Thamara P R Perera, M

    2015-01-01

    Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I-IV), and biliary reconstruction was classified into 2 groups [duct-to-duct (DD) anastomosis and Roux-en-Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high-risk reconstructive techniques. PMID:25302412

  19. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. PMID:27405894

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

    PubMed

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

    2013-01-01

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

  1. Metabolic alterations in liver and testes of adult and newborn rats following cadmium administration

    SciTech Connect

    Agarwal, A.K. )

    1988-05-01

    Cadmium is a well known toxic heavy metal responsible for many toxic manifestations. A large number of studies have been conducted to understand the effect of cadmium on cellular intermediary metabolism. Although, most of the metal is stored in liver and kidney, the organ affected most in acute toxicity is testis. Cadmium has been shown to have high affinity to sulfhydryl groups. Reducing equivalents such as NADH or NADPH are important for keeping the sulfhydryl groups at a reduced state and maintaining the cellular integrity. The present experiment was designed to study the effect of acute cadmium administration on the activities of some of the tissue enzyme systems that provide the reducing equivalent NADPH. The levels of NADH and NADPH were measured. The effect of simultaneous administration of zinc on cadmium-induced changes was also determined. Because newborn animals have been found to be resistant to many effects of cadmium, the studies were also conducted to compare the effects of cadmium on adult and newborn rats.

  2. A Milestone: Approval of CEUS for Diagnostic Liver Imaging in Adults and Children in the USA.

    PubMed

    Seitz, K; Strobel, D

    2016-06-01

    The approval of microbubbles with the inert gas sulfur hexafluoride (SF6) and a palmitic acid shell (SonoVue(®), Bracco Geneva, CH) for the diagnostic imaging of liver tumors in adults and children by the FDA in the United States represents a milestone for contrast-enhanced ultrasound (CEUS).This warrants a look back at the history of the development of CEUS. The first publications based on echocardiographic observations of right ventricular contrast phenomena caused by tiny air bubbles following i. v. injection of indocyanine green appeared around 1970 1 2 3. A longer period of sporadic publications but no real progress then followed since, in contrast to X-ray methods, ultrasound works quite well without a contrast agent.It is noteworthy that the foundations for further development were primarily laid in Europe. The development and approval (1991) of the contrast agent Echovist(®) by a German contrast manufacturer for echocardiography unsuitable for passing through lungcapillaries 4 5 resulted in the first extracardiac indications, e. g. for detecting retrovesical reflux and tubal patency, in the mid-1980 s 6 7 8. The sensitivity of color Doppler was not able to compensate for the lack of an ultrasound contrast agent compared to CT with its obligatory contrast administration.Studies of SHU 508 - microbubbles of air moderately stabilized with galactose and palmitic acid - began in 1990 9 10 11 12 13 14 15 and the contrast agent was then introduced in 1995 in Germany as Levovist(®). The most important publications by Blomley, Cosgrove, Leen, and Albrecht are named here on a representative basis 16 17 18 19 20.SHU 508 along with other US contrast agents provided impressive proof of the superiority of CEUS for the diagnosis of liver metastases. However, practical application remained complicated and required skill and technical know-how because of a lack of suitable software on US units 21 22 23 24 25. The monograph regarding the use of contrast agent in

  3. Liver function parameters, cholesterol, and phospholipid α-linoleic acid are associated with adipokine levels in overweight and obese adults.

    PubMed

    Gray, Belinda; Steyn, Frederik; Davies, Peter Stephen Wynford; Vitetta, Luis

    2014-05-01

    Dysregulation of adipose hormones in obesity has been associated with the hastened development of metabolic syndrome and associated chronic disease sequalae including cardiovascular disease and type 2 diabetes mellitus. This study aims to identify common biochemical and anthropometric markers that impact adipose hormones, including adiponectin and leptin. Based on previous literature, it was hypothesized that these would be adversely impacted by liver function parameters, and adiponectin levels would be positively correlated with phospholipid Ω-3 fatty acids. Forty nondiabetic adult subjects (body mass index, ≥ 25.0 kg/m(2)) were recruited. Fasting plasma samples were taken to assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and blood lipids. Basic anthropometric measurements were also recorded. Adiponectin levels were positively correlated with high-density lipoprotein cholesterol and negatively correlated with anthropometric measures, insulin, liver enzymes, triglycerides, and very low-density lipoprotein cholesterol but not body mass index. Conversely, plasma leptin levels were positively correlated with anthropometric measures, C-reactive protein, high-density lipoprotein cholesterol, and plasma phospholipid proportions of Ω-3 α linoleic acid but inversely correlated with creatinine levels. These results support other data regarding correlations between adiponectin and relative adipose distribution. Correlations with specific liver enzymes may indicate that adiponectin levels are tied to fatty acid deposition in the liver; however, liver/kidney damage though further mechanistic clarification is required. Leptin levels were associated with measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids, may serve as potential future therapeutic targets for the prevention and management of obesity and related comorbidities. PMID:24916550

  4. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes

    PubMed Central

    2011-01-01

    Background Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders. Methods We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease) was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII) modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OH)vitamin D was measured by colorimetric method. Results Patients with NAFLD (n = 162,61.8%) had reduced serum 25(OH) vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p < 0.001, OR 0.95, IC 95% 0.92-0.98). The relationship between NAFLD and reduced 25(OH)vitamin D levels was independent from age, sex, triglycerides, high density lipoproteins (HDL) and glycaemia (p < 0.005) and Fatty Liver Index inversely correlated with low 25(OH) vitamin D regardless sex, age and HOMA-IR (p < 0.007). Conclusions Low 25(OH)vitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile. PMID:21749681

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

    PubMed Central

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

    2016-01-01

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

  6. Liver transplantation versus conservative treatment for adult-onset type II citrullinemia: our experience and a review of the literature.

    PubMed

    Kimura, N; Kubo, N; Narumi, S; Toyoki, Y; Ishido, K; Kudo, D; Umehara, M; Yakoshi, Y; Hakamada, K

    2013-11-01

    Adult-onset type II citrullinemia (CTLN2), an autosomal recessive disorder caused by a mutation in the SLC25A13 gene, is characterized by increased serum citrulline and ammonia levels. Patients with CTLN2 also display various neuropsychiatric symptoms. Many individuals with CTLN2 are fond of protein-rich and/or lipid-rich foods with an aversion to carbohydrate-rich foods. We herein report two cases of CTLN2 treated with living donor liver transplantation (LDLT) and provide a review of the pertinent literature. Case 1 was a 43-year-old man admitted to our hospital for repetitive episodes of consciousness disturbance. Case 2 was a 37-year-old man admitted to our hospital because of abnormal behavior associated with hyperammonemia. A definitive diagnosis of CTLN2 was accomplished by DNA analysis in both patients, who successfully underwent LDLT using liver segments from donor siblings with confirmed heterozygous gene expression. Case 2 also underwent conservative therapy with arginine and a high-fat, carbohydrate-restricted diet prior to LDLT. Postoperative recovery was uneventful and food was unrestricted in both patients. We also identified 77 cases of CTLN2 in the literature and reviewed them in terms of outcome of both liver transplantation and conservative therapy. The survival rate in patients treated by liver transplantation was 100%, whereas that in patients treated by conservative treatment showed improvement from 39.5% to 76.5% over the years. Liver transplantation is a practical treatment that fundamentally improves patient quality of life after transplantation. However, recent studies have suggested that arginine and sodium pyruvate administration combined with intensive nutritional support is also an effective therapy for CTLN2. Further development of conservative therapy may provide a safer, more affordable alternative to liver transplantation in the near future.

  7. Risk factors for liver disease and associated knowledge and practices among Mexican adults in the US and Mexico.

    PubMed

    Flores, Yvonne N; Lang, Cathy M; Salmerón, Jorge; Bastani, Roshan

    2012-04-01

    Latinos in the US are disproportionately affected by chronic liver disease, which is the sixth most common cause of death among this group. In Mexico, cirrhosis and other liver diseases are the fourth leading cause of general mortality. The objective of this study was to contrast the liver disease risk factors, knowledge, and prevention practices reported among separate samples of Mexicans living in Los Angeles, CA and in Cuernavaca, Mexico. We assessed the prevalence of specific risk factors (body mass index, waist circumference, and alcohol consumption), the level of knowledge about liver disease in general, hepatitis B (HBV), and hepatitis C (HCV), as well as prevention activities such as screening and vaccination. Data were collected from in-person interviews and anthropometric measures obtained from Mexican adults aged 18-70 years. Chi-square and t tests were used to compare the results between groups. Numerous similarities were observed in the bi-national samples, including high prevalence of obesity, abdominal obesity, and high levels of alcohol consumption. Most participants in both countries recognized that excessive alcohol consumption is a risk factor for liver disease, but only 60% correctly identified hepatitis C, being overweight or obese, or having diabetes as risk factors. Few participants reported having been screened for HBV or HCV, vaccinated for HBV, or having the intention of getting screened for HBV or HCV. US participants reported significantly higher levels of prevention activities and screening intentions than those in Mexico. Identifying the specific risk factors, levels of knowledge and prevention activities that affect specific racial/ethnic populations is important in order to effectively target efforts to prevent liver disease.

  8. Uptake and distribution of hepatocyte growth factor in normal and regenerating adult rat liver.

    PubMed Central

    Liu, M. L.; Mars, W. M.; Zarnegar, R.; Michalopoulos, G. K.

    1994-01-01

    We have previously shown that systemically injected hepatocyte growth factor (HGF) is primarily taken up by the liver. The present study shows that HGF injected systemically or through the portal circulation is retained primarily at periportal sites. The periportal retention of HGF seems to persist longer in regenerating liver. The percentage of the total HGF injected that was retained within the liver at 1 minute after injection varied with the dose. A maximal amount of 0.157 +/- 0.012 microgram of HGF per gram liver tissue is retained by normal liver. Analysis of the circulating form of HGF in the plasma showed a relative enrichment with time for the heterodimeric form of HGF. A portion of portally injected HGF, composed of both single chain and two chain (heterodimeric) form was excreted intact in the bile. This was found in both normal and regenerating liver. These studies show that the liver can sequester large amounts of HGF and that the sequestration occurs primarily at periportal sites. Our studies support the hypothesis that a nonlysosomal processing pathway for HGF is present in the liver. Images Figure 1 Figure 3 Figure 4 Figure 6 PMID:8291602

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

    PubMed

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

    1986-11-01

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

  10. PET-CT in Determining the Radioembolization Dose Delivered to Patients With Liver Metastasis, Primary Liver Cancer, or Biliary Cancer

    ClinicalTrials.gov

    2016-03-01

    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. A model of donors' decision-making in adult-to-adult living donor liver transplantation in Japan: having no choice.

    PubMed

    Fujita, Misao; Akabayashi, Akira; Slingsby, Brian Taylor; Kosugi, Shinji; Fujimoto, Yasuhiro; Tanaka, Koichi

    2006-05-01

    This study examined the decision-making processes of donors in adult-to-adult living donor liver transplantation. Twenty-two donors were interviewed using a semi-structured format. Interview contents were transcribed verbatim and analyzed qualitatively using grounded theory. A decision-making model was developed consisting of 5 stages: (1) recognition, (2) digestion, (3) decision-making, (4) reinforcement, and (5) resolution. The second and the third stages described donors' experiences of "reaching a decision"; the fourth and fifth stages described those of "facing transplantation." The central theme of this model was "having no choice," which consisted of 4 codes: (1) priority of life, (2) only LDLT, (3) for family, and (4) only me. In conclusion, this model can help health care professionals to understand the donor experience and, based on that understanding, to provide sufficient support to the donor.

  12. Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults

    PubMed Central

    Yang, Chao-Qun; Shu, Long; Wang, Shuai; Wang, Jia-Jia; Zhou, Yu; Xuan, Yu-Jie; Wang, Su-Fang

    2015-01-01

    Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day−1 in men and 10 g day−1 in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the

  13. Disseminated Gonococcal Infection Presenting as Bacteremia and Liver Abscesses in a Healthy Adult

    PubMed Central

    Byun, Jongkyu; Yang, John Jeongseok

    2015-01-01

    Herein, we describe a bacteremia caused by Neisseria gonorrhoeae that presented as liver abscesses. The patient had no risk factors for disseminated gonococcal infection. Periodic fever, skin rashes, and papules were present and the results of an abdominal computed tomography scan indicated the presence of small liver abscesses. The results of blood culture and 16S rRNA sequencing of the bacterial isolates confirmed the presence of N. gonorrhoeae. The patient improved with antibiotic therapy. PMID:25844265

  14. Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver.

    PubMed

    Harmon, Cathal; Robinson, Mark W; Fahey, Ronan; Whelan, Sarah; Houlihan, Diarmaid D; Geoghegan, Justin; O'Farrelly, Cliona

    2016-09-01

    The adult human liver is enriched with natural killer (NK) cells, accounting for 30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell subpopulations, distinct from peripheral blood NK cells. In murine liver, a subset of liver-resident hepatic NK cells have altered expression of the two highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here, we investigate the heterogeneity of T-bet and Eomes expression in NK cells from healthy adult human liver with a view to identifying human liver-resident populations. Hepatic NK cells were isolated from donor liver perfusates and biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic CD56(bright) NK cells were Eomes(hi) T-bet(lo) , a phenotype virtually absent from peripheral blood. These NK cells express the chemokine receptor CXCR6 (chemokine (C-X-C motif) receptor 6), a marker of tissue residency, which is absent from hepatic CD56(dim) and blood NK cells. Compared to blood populations, these hepatic CD56(bright) NK cells have increased expression of activatory receptors (NKp44, NKp46, and NKG2D). They show reduced ability to produce IFN-γ but enhanced degranulation in response to challenge with target cells. This functionally distinct population of hepatic NK cells constitutes 20-30% of the total hepatic lymphocyte repertoire and represents a tissue-resident immune cell population adapted to the tolerogenic liver microenvironment.

  15. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    PubMed

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery.

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

    PubMed

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

    2016-03-30

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

  17. Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.

    PubMed

    Zimmermann, Esther; Berentzen, Tina L; Gamborg, Michael; Sørensen, Thorkild I A; Baker, Jennifer L

    2016-03-15

    Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.

  18. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    PubMed

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  19. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  20. Informed consent and decision-making about adult-to-adult living donor liver transplantation: a systematic review of empirical research.

    PubMed

    Gordon, Elisa J; Daud, Amna; Caicedo, Juan Carlos; Cameron, Kenzie A; Jay, Colleen; Fryer, Jonathan; Beauvais, Nicole; Skaro, Anton; Baker, Talia

    2011-12-27

    Adult-to-adult living donor liver transplantation (LDLT) is a complex procedure that poses serious health risks to and provides no direct health benefit for the donor. Because of this uneven risk-benefit ratio, ensuring donor autonomy through informed consent is critical. To assess the current knowledge pertaining to informed consent for LDLT, we conducted a systematic review of the empirical literature on donors' decision-making process, comprehension about risks and outcomes, and information needs for LDLT. Of the 1423 identified articles, 24 met final review criteria, representing the perspective of approximately 2789 potential and actual donors. As donors' decisions to donate often occur before evaluation, they often make uninformed decisions. The review found that 88% to 95% of donors reported understanding information clinicians disclosed about risks and benefits. However, donors reported unmet information needs, knowledge gaps regarding risks, and unanticipated complications. Few donors reported feeling pressure to donate. Most studies were limited by cultural differences, small sample sizes, inconsistent measures, and poor methodological approaches. This systematic review suggests that informed consent for LDLT is sub-optimal as donors do not adequately appreciate disclosed information during the informed consent process, despite United Network for Organ Sharing/CMS regulations requiring formal psychological evaluation of donor candidates. Interventions are needed to improve donor-clinician communication during the LDLT informed consent process such as through the use of comprehension assessment tools and e-health educational tools that leverage adult learning theory to effectively convey LDLT outcome data. PMID:22143436

  1. Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion.

    PubMed

    Hwang, Shin; Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2016-08-01

    After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases. PMID:27621745

  2. Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion

    PubMed Central

    Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2016-01-01

    After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases. PMID:27621745

  3. Standardized surgical techniques for adult living donor liver transplantation using a modified right lobe graft: a video presentation from bench to reperfusion.

    PubMed

    Hwang, Shin; Ha, Tae-Yong; Ahn, Chul-Soo; Moon, Deok-Bog; Kim, Ki-Hun; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2016-08-01

    After having experienced more than 2,000 cases of adult living donor liver transplantation (LDLT), we established the concepts of right liver graft standardization. Right liver graft standardization intends to provide hemodynamics-based and regeneration-compliant reconstruction of vascular inflow and outflow. Right liver graft standardization consists of the following components: Right hepatic vein reconstruction includes a combination of caudal-side deep incision and patch venoplasty of the graft right hepatic vein to remove the acute angle between the graft right hepatic vein and the inferior vena cava; middle hepatic vein reconstruction includes interposition of a uniform-shaped conduit with large-sized homologous or prosthetic grafts; if the inferior right hepatic vein is present, its reconstruction includes funneling and unification venoplasty for multiple short hepatic veins; if donor portal vein anomaly is present, its reconstruction includes conjoined unification venoplasty for two or more portal vein orifices. This video clip that shows the surgical technique from bench to reperfusion was a case presentation of adult LDLT using a modified right liver graft from the patient's son. Our intention behind proposing the concept of right liver graft standardization is that it can be universally applicable and may guarantee nearly the same outcomes regardless of the surgeon's experience. We believe that this reconstruction model would be primarily applied to a majority of adult LDLT cases.

  4. The genome of the blood fluke Schistosoma mansoni

    PubMed Central

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

    2009-01-01

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

  5. Retinoid Homeostatic Gene Expression in Liver, Lung and Kidney: Ontogeny and Response to Vitamin A-Retinoic Acid (VARA) Supplementation from Birth to Adult Age

    PubMed Central

    Owusu, Sarah A.; Ross, A. Catharine

    2016-01-01

    Vitamin A (VA, retinol) metabolism is homeostatically controlled, but little is known of its regulation in the postnatal period. Here, we determined the postnatal trajectory of VA storage and metabolism in major compartments of VA metabolism–plasma, liver, lung, and kidney from postnatal (P) day 1 to adulthood. We also investigated the response to supplementation with VARA, a combination of VA and 10% all-trans-retinoic acid that previously was shown to synergistically increase retinol uptake and storage in lung. Nursling pups of dams fed a VA-marginal diet received an oral dose of oil (placebo) or VARA on each of four neonatal days: P1, P4, P7, and P10; and again as adults. Tissues were collected 6 h after the final dosing on P1, P4, P10, and at adult age. Gene transcripts for Lrat and Rbp4 in liver and Raldh-1 and Raldh-3 in lung, did not differ in the neonatal period but were higher, P<0.05, in adults, while Cyp26B1, Stra6, megalin, and Raldh-2 in lung did not differ from perinatal to adult ages. VARA supplementation increased total retinol in plasma, liver and lung, with a dose-by-dose accumulation in neonatal liver and lung, while transcripts for Lrat in liver, megalin in kidney, Cyp26A1/B1 in liver and lung, respectively, and Stra6 in lung, were all increased, suggesting pathways of VA uptake, storage and RA oxidation were each augmented after VARA. VARA decreased hepatic expression of Rbp4, responsible for VA trafficking from liver to plasma, and, in lung, of Raldh-1 and Raldh-2, which function in RA production. Our results define retinoid homeostatic gene expression from neonatal and adult age and show that while supplementation with VARA acutely alters retinol content and retinoid homeostatic gene expression in neonatal and adult lung, liver and kidney, VARA supplementation of neonates increased adult-age VA content only in the liver. PMID:26731668

  6. Priming of hepatocytes enhances in vivo liver transduction with lentiviral vectors in adult mice.

    PubMed

    Pichard, Virginie; Boni, Sébastien; Baron, William; Nguyen, Tuan Huy; Ferry, Nicolas

    2012-02-01

    Lentiviral vectors are promising tools for liver disease gene therapy, because they can achieve protracted expression of transgenes in hepatocytes. However, the question as to whether cell division is required for optimal hepatocyte transduction has still not been completely answered. Liver gene-transfer efficiency after in vivo administration of recombinant lentiviral vectors carrying a green fluorescent protein reporter gene under the control of a liver-specific promoter in mice that were either hepatectomized or treated with cholic acid or phenobarbital was compared. Phenobarbital is known as a weak inducer of hepatocyte proliferation, whereas cholic acid has no direct effect on the cell cycle. This study shows that cholic acid is able to prime hepatocytes without mitosis induction. Both phenobarbital and cholic acid significantly increased hepatocyte transduction six- to ninefold, although cholic acid did not modify the mitotic index or cell-cycle entry. However, the effect of either compound was weaker than that observed after partial hepatectomy. In no cases was there a correlation between the expression of cell-cycle marker and transduction efficiency. We conclude that priming of hepatocytes should be considered a clinically applicable strategy to enhance in vivo liver gene therapy with lentiviral vectors.

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

    PubMed

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

    2007-11-01

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

  8. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    PubMed Central

    Poley, Rachel A.; Snowdon, Jaime F.; Howes, Daniel W.

    2011-01-01

    Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated. PMID:24826316

  9. Neutrophils and lymphoid chimerism after adult living-related liver transplantation from a homozygous donor.

    PubMed

    Hajeer, A H; Issa, S; Alaskar, A; Abdullah, K; Awad, M; Tbakhi, A; Alabdulkareem, A

    2005-12-01

    Chimerism and graft-versus-host disease (GVHD) pose significant risks to liver transplant patients. The risk of chimerism and GVHD is higher among cases of living-related liver transplant (LRLT). Donors homozygous at all HLA loci carry a higher risk for GVHD. Herein we present a case of LRLT. The recipient suffered from end-stage liver disease and received a right lobe graft from his son. After 8 months posttransplant, the patient developed profound bone marrow depression. The patient was negative for CMV, Brucella, HHV6, HHV8, HBV, HCV, and parvovirus. No skin or GI signs of GVHD were noted. The patient and donor were HLA typed by SSP. The donor was homozygous for all HLA loci while the patient shared the class II homozygosity and was class I heterozygous. Chimerism studies were prompted after noting that the neutrophil compartment of the patient was homozygous for all HLA loci. This initiated further studies of the PMN and lymphocytes by microsatellite analysis. A total 15 microsatellites were analyzed. The results suggest that the majority (75%) of the PMNs and 45% of the lymphocytes were of donor origin. The patient was treated with G-CSF; his WBC counts returned to normal. At 2.5 years posttransplant the patient had not developed GVHD, despite the large number of donor lymphocytes circulating in his bloodstream. The only complaint he had was severe arthritis, which was treated with steroids. It must be investigated whether this was the result of GVHD.

  10. Reliability and validity of the Chronic Liver Disease Questionnaire (CLDQ) in adults with non-alcoholic steatohepatitis (NASH)

    PubMed Central

    Chawla, Kashmira S; Talwalkar, Jayant A; Keach, Jill C; Malinchoc, Michael; Lindor, Keith D; Jorgensen, Roberta

    2016-01-01

    Introduction Significant impairments in health-related quality of life (HRQL) in patients with non-alcoholic fatty liver disease have been previously described. The disease-specific HRQL among patients with non-alcoholic steatohepatitis (NASH), however, remains unknown. Aim To determine the degree of construct validity of the Chronic Liver Disease Questionnaire (CLDQ) in adults with NASH. Methods Participants referred for the evaluation of histology-proven NASH at Mayo Clinic, Rochester, between 1996 and 2000, were evaluated. HRQL assessment by the Short-Form 36 (SF-36) Health Survey and CLD) was performed. The primary outcome was to determine the level of correlation between overall and subscale scores for the CLDQ and SF-36 instruments. Results Among 79 participants (70%) with NASH completing both questionnaires (mean age, 51.2 years with 64% female gender), excellent reliability was noted for the CLDQ instrument. Significant reductions in all SF-36 domains (p<0.05 for all) including PCS and MCS scores (p<0.02 for both) among participants with NASH compared with normative data from an age-matched and sex-matched US general population sample was observed. Highly significant correlations were observed between overall CLDQ score with SF-36 PCS (r=0.82, p<0.0001) and SF-36 MCS (r=0.67, p<0.0001) scores. Similar degrees of correlation were observed between relevant subscales of the CLDQ and SF-36 as well. Discussion The CLDQ has excellent reliability and validity of construct for HRQL assessment in adults with NASH when compared with the SF-36. Future investigations among participants with NASH require assessing the responsiveness of the CLDQ to medical therapies and disease progression. PMID:27110379

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

    PubMed Central

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

    2015-01-01

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

  12. Reversal of parenteral nutrition-associated liver disease with a fish oil-based lipid emulsion (Omegaven) in an adult dependent on home parenteral nutrition.

    PubMed

    Burns, David L; Gill, Brian M

    2013-03-01

    Patients with intestinal failure and short bowel syndrome usually require chronic parenteral nutrition (PN). PN is associated with risks, including infections, vascular thrombosis, and liver disease. PN-associated liver disease (PNALD) can progress from steatosis to chronic hepatitis and ultimately to cirrhosis. The etiology of PNALD is not completely understood. Therapies for PNALD include carbohydrate or lipid calorie reduction, antibiotics, or the use of ursodeoxycholic acid. When these efforts fail, therapeutic options are limited and liver transplantation may be required. The transition from a soybean- to a fish oil-based lipid formulation, such as the ω-3 parenteral lipid formulation (Omegaven), has shown a dramatic reversal of PNALD within the pediatric population. This is the first report of a PN-dependent adult in the United States complicated by PNALD and hepatic failure who had improvement of liver disease with an ω-3 fish oil-based parenteral formulation.

  13. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation

    PubMed Central

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review. PMID:27708510

  14. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.

    PubMed

    Broutier, Laura; Andersson-Rolf, Amanda; Hindley, Christopher J; Boj, Sylvia F; Clevers, Hans; Koo, Bon-Kyoung; Huch, Meritxell

    2016-09-01

    Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments. Personnel with basic scientific training can conduct this protocol. PMID:27560176

  15. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.

    PubMed

    Broutier, Laura; Andersson-Rolf, Amanda; Hindley, Christopher J; Boj, Sylvia F; Clevers, Hans; Koo, Bon-Kyoung; Huch, Meritxell

    2016-09-01

    Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments. Personnel with basic scientific training can conduct this protocol.

  16. A quantitative model to predict blood use in adult orthotopic liver transplantation.

    PubMed

    Liu, Chang; Vachharajani, Neeta; Song, Shuang; Cooke, Rhonda; Kangrga, Ivan; Chapman, William C; Grossman, Brenda J

    2015-12-01

    To identify preoperative predictors for the use of any blood component during and after orthotopic liver transplantation (OLT), we performed a retrospective analysis on 602 OLT patients who were randomly split into a training set (n = 482) and a validation set (n = 120). Hemoglobin and calculated MELD score were identified as independent predictors for blood use using bootstrap aggregation. A logistic regression model constructed using both variables showed comparable performance in the training and validation sets. Predictive scores can be obtained from a nomogram, and a score above -2.328 predicted transfusion of any blood component with a positive predictive value of 97% and 96% in the training and validation sets, respectively. PMID:26297190

  17. Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case.

    PubMed

    Yu, Young-Dong; Park, Gil-Chun; Park, Pyoung-Jae; Choi, Young-Il; Hwang, Shin; Song, Gi-Won; Jung, Dong-Hwan; Ahn, Chul-Soo; Kim, Ki-Hun; Moon, Deog-Bok; Ha, Tae-Yong; Lee, Sung-Gyu

    2013-04-01

    Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.

  18. Ligation of left renal vein for large spontaneous splenorenal shunt to prevent portal flow steal in adult living donor liver transplantation.

    PubMed

    Lee, Sung-Gyu; Moon, Deok-Bog; Ahn, Chul-Soo; Kim, Ki-Hun; Hwang, Shin; Park, Kwang-Min; Ha, Tae-Yong; Ko, Gi-Young; Sung, Kyu-Bo; Song, Gi-Won; Jung, Dong-Hwan; Moon, Ki-Myung; Kim, Bum-Soo; Cho, Yong-Pil

    2007-01-01

    Persistance of a large spontaneous splenorenal shunt (SRS) may result in graft failure in adult living donor liver transplantation (LDLT) because it reduces the effective portal perfusion to the partial liver graft by diversion of hepatotrophic portal flow into this hepatofugal pathway. We performed a prospective study to evaluate the efficacy of ligation of left renal vein (LRV) to prevent portal flow steal and the safety of this procedure to the renal function in adult LDLT patients with SRS. Between October 2001 and January 2005, 44 cirrhotic patients with large SRS underwent LDLT with ligation of LRV. Each patient received pre- and postoperative computed tomography and Doppler USG to assess the changes of collaterals and portal flow, as well as serial renal and liver function tests. Portal flow after ligation of LRV was statistically and significantly increased when compared with pre-operative value (P = 0.001). Whereas four patients (9.1%) demonstrated sustained, elevated serum creatinine levels after operation, the renal function tests returned to normal in 40 patients. All patients recovered with satisfactory regeneration of the partial liver graft and there was no procedure-related permanent renal dysfunction. In conclusion, ligation of LRV to prevent a 'portal steal phenomenon' seems to be a safe and effective graft salvage procedure for large spontaneous SRS (>10-mm diameter) in adult LDLT.

  19. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    PubMed

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  20. Prevalence and factors associated with the presence of non alcoholic fatty liver disease in an apparently healthy adult population in primary care units

    PubMed Central

    Caballería, Llorenç; Auladell, Ma Antonia; Torán, Pere; Miranda, Dolores; Aznar, Jesús; Pera, Guillem; Gil, Dolors; Muñoz, Laura; Planas, Jaume; Canut, Santiago; Bernad, Jesús; Aubà, Josep; Pizarro, Gregorio; Aizpurua, Miren Maite; Altaba, Anna; Tibau, Albert

    2007-01-01

    Background Fatty liver disease is characterized by the accumulation of fat vacuoles inside of the hepatocytes. Non alcoholic fatty liver is associated with obesity, type 2 diabetes, dyslipemia, the intake of certain drugs and with the so-called metabolic syndrome. However, there is little information on the clinical relevance of this disorder as a healthcare problem in the general population, since the studies published generally include a limited number of patients and the diagnosis is established on the basis of clear biochemical alterations and liver biopsy. Methods/Design The aim of the study is the prevalence of non-alcoholic fatty liver disease in a general adult population by hepatic ultrasonography. A population-based, descriptive, transversal, multicentre study. Eighteen primary care centres of the north of Barcelona and the Maresme Areas of Healthcare Management attending an urban and semi-urban population of 360.000 inhabitants. A randomized sample of 786 subjects of 15 years or older were selected from the population and assigned to the participating centres according to the Primary Care Information System (SIAP): This population is practically the same as the general population of the area. The following determinations will be carried out in all the participants: hepatic ultrasonography to detect fatty liver, a questionnaire concerning liver diseases, alcohol intake, smoking and drug use, physical examination including abdominal perimeter and body mass index and biochemical analysis including liver function tests and parameters related to the metabolic syndrome and the HAIR score. Ultrasonographic diagnosis of fatty liver will be made according to established criteria (American Gastroenterology Association) and diagnosis of metabolic syndrome according to the criteria of the European Group for the Study of Insulin Resistance. Discussion This study will attempt to determine the prevalence of non alcoholic fatty liver disease, as well as, the factors

  1. BMS-247550 in Treating Patients With Liver or Gallbladder Cancer

    ClinicalTrials.gov

    2014-05-13

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  2. The functional role of some tomato products on lipid profile and liver function in adult rats.

    PubMed

    Ibrahim, Hoda Salama; Ahmed, Lamiaa Ali; El-din, Maha Mohamed Essam

    2008-09-01

    This study was carried out to investigate the functional role of lycopene obtained from powder prepared from fresh tomato, tomato paste, and ketchup that contained equal amounts of lycopene based on levels of intake on body weight gain (BWG), feed intake, feed efficiency ratio (FER), lipid profiles, atherogenic index, and liver enzymes of hyperlipidemic rats. Forty-eight male albino rats were divided into two main groups: the first group (n = 6 rats) was kept on the basal diet as a normal control, while the second group (n = 42 rats) was fed a hyperlipidemic diet for 5 weeks to induce hyperlipidemia. The latter group was divided into seven subgroups: the first subgroup was the positive control group, while the others were supplemented with one of the tomato products at one of two levels (10 or 20 mg of lycopene/kg of diet). BWG, feed intake, and FER were calculated, and blood samples were collected to determine total lipids, total cholesterol, triglycerides, lipoprotein fractions, atherogenic index, and liver function in sera. Relative organ weights were also calculated. Results revealed that administration of various tomato products produced a significant reduction in feed intake except for the hyperlipidemic group that supplemented with the lower lycopene level from tomato paste. In addition, BWG and FER were not influenced by addition of tomato products at any level of intake. Hyperlipidemic rats supplemented with tomato powder, tomato paste, or ketchup showed significant improvement in almost all the parameters studied compared to the positive control group. Results showed that the higher lycopene level from tomato paste produced significant improvement in all lipid parameters, followed by 10 mg of lycopene/kg from tomato paste, which caused significant elevation in high-density lipoprotein cholesterol comparable to that of the negative control group. The lowest atherogenic index was achieved by addition of the lower lycopene level from tomato paste followed by

  3. Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats.

    PubMed

    El Golli, Narges; Jrad-Lamine, Aicha; Neffati, Hajira; Rahali, Dalila; Dallagi, Yosra; Dkhili, Houssem; Ba, Nathalie; El May, Michele V; El Fazaa, Saloua

    2016-07-01

    This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.

  4. Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats.

    PubMed

    El Golli, Narges; Jrad-Lamine, Aicha; Neffati, Hajira; Rahali, Dalila; Dallagi, Yosra; Dkhili, Houssem; Ba, Nathalie; El May, Michele V; El Fazaa, Saloua

    2016-07-01

    This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state. PMID:27484987

  5. Relationship between grip strength and newly diagnosed nonalcoholic fatty liver disease in a large-scale adult population

    PubMed Central

    Meng, Ge; Wu, Hongmei; Fang, Liyun; Li, Chunlei; Yu, Fei; Zhang, Qing; Liu, Li; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Bao, Xue; Su, Qian; Gu, Yeqing; Yang, Huijun; Bin Yu; Wu, Yuntang; Sun, Zhong; Niu, Kaijun

    2016-01-01

    Enhanced muscle strength is often related to improved insulin sensitivity and secretion, control of lipid metabolism, and increased secretion of myokines. These factors have emerged as important mechanisms involved in the development and progression of nonalcoholic fatty liver disease (NAFLD), implying that muscle strength may be a useful predictor for NAFLD. We aimed to assess the relationship between grip strength (GS) and NAFLD in a large-scale adult population. GS was assessed using an electronic hand-grip dynamometer, and NAFLD was diagnosed by the liver ultrasonography. Multiple logistic regression analysis was used to assess the relationship between the quartiles of GS per body weight and the prevalence of NAFLD. After adjusting for potentially confounding factors, the odds ratios (95% confidence interval) for overall NAFLD, NAFLD with normal alanine aminotransferase levels, and NAFLD with elevated alanine aminotransferase levels across the quartiles of GS were 1.00 (reference), 0.89 (0.78, 1.01), 0.77 (0.67, 0.89), and 0.67 (0.57, 0.79); 1.00 (reference), 0.91 (0.80, 1.04), 0.79 (0.68, 0.92), and 0.72 (0.61, 0.85); 1.00 (reference), 0.77 (0.61, 0.98), 0.67 (0.51, 0.86), and 0.53 (0.40, 0.71) (all P for trend < 0.01), respectively. This is the first study shows that increased GS is independently associated with lower prevalence of NAFLD. PMID:27616599

  6. Relationship between grip strength and newly diagnosed nonalcoholic fatty liver disease in a large-scale adult population.

    PubMed

    Meng, Ge; Wu, Hongmei; Fang, Liyun; Li, Chunlei; Yu, Fei; Zhang, Qing; Liu, Li; Du, Huanmin; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Bao, Xue; Su, Qian; Gu, Yeqing; Yang, Huijun; Bin Yu; Wu, Yuntang; Sun, Zhong; Niu, Kaijun

    2016-01-01

    Enhanced muscle strength is often related to improved insulin sensitivity and secretion, control of lipid metabolism, and increased secretion of myokines. These factors have emerged as important mechanisms involved in the development and progression of nonalcoholic fatty liver disease (NAFLD), implying that muscle strength may be a useful predictor for NAFLD. We aimed to assess the relationship between grip strength (GS) and NAFLD in a large-scale adult population. GS was assessed using an electronic hand-grip dynamometer, and NAFLD was diagnosed by the liver ultrasonography. Multiple logistic regression analysis was used to assess the relationship between the quartiles of GS per body weight and the prevalence of NAFLD. After adjusting for potentially confounding factors, the odds ratios (95% confidence interval) for overall NAFLD, NAFLD with normal alanine aminotransferase levels, and NAFLD with elevated alanine aminotransferase levels across the quartiles of GS were 1.00 (reference), 0.89 (0.78, 1.01), 0.77 (0.67, 0.89), and 0.67 (0.57, 0.79); 1.00 (reference), 0.91 (0.80, 1.04), 0.79 (0.68, 0.92), and 0.72 (0.61, 0.85); 1.00 (reference), 0.77 (0.61, 0.98), 0.67 (0.51, 0.86), and 0.53 (0.40, 0.71) (all P for trend < 0.01), respectively. This is the first study shows that increased GS is independently associated with lower prevalence of NAFLD. PMID:27616599

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

    PubMed

    Orélis-Ribeiro, Raphael; Bullard, Stephen A

    2016-06-01

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

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

    PubMed

    Orélis-Ribeiro, Raphael; Bullard, Stephen A

    2016-06-01

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

  9. Prenatal Arsenic Exposure Alters Gene Expression in the Adult Liver to a Proinflammatory State Contributing to Accelerated Atherosclerosis

    PubMed Central

    States, J. Christopher; Singh, Amar V.; Knudsen, Thomas B.; Rouchka, Eric C.; Ngalame, Ntube O.; Arteel, Gavin E.; Piao, Yulan; Ko, Minoru S. H.

    2012-01-01

    The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE−/−) mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE−/− mice exposed to 49 ppm arsenic in utero from gestational day (GD) 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND) 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). Gene ontology (GO) annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes containing

  10. PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity12

    PubMed Central

    Mondul, Alison; Mancina, Rosellina M; Merlo, Andrea; Dongiovanni, Paola; Rametta, Raffaela; Montalcini, Tiziana; Valenti, Luca; Albanes, Demetrius; Romeo, Stefano

    2015-01-01

    Background: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. Objective: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. Methods: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m2) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. Results: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = −0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = −0.043, P = 0.04). Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. PMID:26136587

  11. Health status in young adults two decades after pediatric liver transplantation.

    PubMed

    Mohammad, S; Hormaza, L; Neighbors, K; Boone, P; Tierney, M; Azzam, R K; Butt, Z; Alonso, E M

    2012-06-01

    We conducted a cross-sectional study of patients who underwent pediatric liver transplant (LT) between 1988 and 1992 to evaluate long-term health status. Survivors completed socio-demographic, medical and Health-Related Quality of Life (HRQOL) surveys by mail including the SF-36v2, PedsQL™4.0 Generic Core Scale, PedsQL™ Cognitive Functioning Scale and PedsQL™3.0 Transplant Module. SF-36 scores were converted to SF6D-based utilities and risk factors for lower outcomes were assessed. Eighty-five of 171 patients had survived. Fifty-six were contacted with a response rate of 66%. Median age at LT was 0.86 years (IQR 0.58-3.0) and 64.3% had biliary atresia. Mean age at survey was 23.0 ± 4.4 years: 62% attended college, 68% lived with parents and 80% of those over 23 were employed. Patient health utilities were lower than norms (0.75 ± 0.12 vs. 0.82 ± 0.18, p < 0.01) and correlated with unemployment (p < 0.042), hospitalizations (p < 0.005) and lower education level (p < 0.016). Lower PedsQL™3.0 Transplant Module and PedsQL™ 4.0 Generic Core Scale scores correlated with unemployment (p = 0.006, p = 0.009) and hospitalizations (p = 0.006, p = 0.02). Pediatric transplant recipients who survive to adulthood have lower physical HRQOL, measurable transplant-related disability and lower health utility. Transplantation is life saving; however, physical and psychological sequelae continue to affect health status up to two decades later.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2012-01-01

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

  17. Neuropathologic and biochemical changes during disease progression in liver X receptor beta-/- mice, a model of adult neuron disease.

    PubMed

    Bigini, Paolo; Steffensen, Knut R; Ferrario, Anna; Diomede, Luisa; Ferrara, Giovanni; Barbera, Sara; Salzano, Sonia; Fumagalli, Elena; Ghezzi, Pietro; Mennini, Tiziana; Gustafsson, Jan-Ake

    2010-06-01

    In amyotrophic lateral sclerosis (ALS), there is selective degeneration of motor neurons that leads to paralysis and death. Although the etiology of ALS is unclear, its heterogeneity suggests that a combination of factors (endogenous and/or environmental) may induce progressive motor neuron stress that results in the activation of different cell death pathways. Alterations of brain cholesterol homeostasis have recently been considered as possible cofactors in many neurodegenerative disorders, including ALS. The liver X receptor beta (LXRbeta) receptor is involved in lipogenesis and cholesterol metabolism, and we previously found that adult-onset motor neuron pathology occurs in LXRbeta mice. Here, we investigated neuromuscular alterations of LXRbeta mice from ages 3 to 24 months. Increased cholesterol levels, gliosis, and inflammation preceded motor neuron loss and clinical disease onset; the mice showed progressivemotor neuron deficits starting from age 7 months. The numbers ofmotor neurons and neuromuscular junctions were decreased in 24-month-old mice, but neither paralysis nor reduced life span was observed. Moreover, other spinal neurons were also lost in these mice. These results suggest that LXRbeta may inhibit neuroinflammation and maintain cholesterol homeostasis, and that LXRbeta mice represent a potential model for investigating the role of cholesterol in ALS and other neurodegenerative disorders.

  18. The lack of protective effects of tea supplementation on liver and jejunal epithelium in adult rats exposed to cadmium and lead.

    PubMed

    Tomaszewska, Ewa; Winiarska-Mieczan, Anna; Dobrowolski, Piotr

    2015-11-01

    Adult rats at the age of 12 weeks were divided into the control group and groups supplemented with green (GT), black (BT), red (RT), or white (WT) tea extracts. The diet (except that for the control) was mixed with 7 mg Cd/kg and 50 mg Pb/kg. The experiment lasted 12 weeks. Basal haematology and plasma biochemical parameters as well as the histomorphometrical parameters of jejunal epithelium and liver were determined. The lowest body mass was found in the RT and WT groups. Some functional (increased plasma ALT and AST, and the de Ritis coefficient) and structural changes in the liver (slight fatty degenerative changes, an increase in the intercellular space) were evident irrespective of the type of tea in the Cd and Pb poisoned rats. This toxic effect was visible especially in rats drinking black or red tea. However, the rats had no elevated LDH and ALT activities. The highest content of Cd and Pb in the liver and blood plasma was found in rats drinking red tea. Based on the results obtained, it is clear that long-term exposure of adult rats with a mature intestinal barrier to Cd and Pb contamination, under higher exposure conditions than the current estimates of weekly exposure of the general population to Cd and Pb through diet, causes a toxic effect, especially in the liver, and can change the structure of intestinal mucosa, irrespective of tea administration.

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

    PubMed Central

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

    2009-01-01

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

  20. Low Vitamin D Status Is Associated with Nonalcoholic Fatty Liver Disease Independent of Visceral Obesity in Korean Adults

    PubMed Central

    Seo, Ji A.; Eun, Chai Ryoung; Cho, Hyunjoo; Lee, Seung Ku; Yoo, Hye Jin; Kim, Sin Gon; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Yim, Hyung Joon; Shin, Chol; Kim, Nan Hee

    2013-01-01

    Objective To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity in Koreans and to examine whether the associations differ according to the presence of diabetes or insulin resistance. Research Design and Methods A total of 1081 adults were enrolled from a population-based cohort in Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver attenuation index (LAI, the difference between the mean hepatic and splenic attenuation) was <5 Hounsfield Units. Results In subjects with diabetes (n = 282), 25(OH)D levels were negatively associated with waist circumference, fasting insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were positively associated with LAI after adjusting for age, sex, season, exercise, and vitamin supplementation. In subjects without diabetes, only triglyceride level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5 (95% CI:1.0–6.2)]. In contrast, no significant difference in OR was observed in subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR, an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was observed in the high HOMA-IR (≥2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4–10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3–1.9)]. Conclusions Low vitamin D status is closely associated with NAFLD, independent of visceral obesity in subjects with diabetes or insulin resistance. PMID:24130687

  1. Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in overweight and obese adults: a pilot study.

    PubMed

    Parker, Helen M; O'Connor, Helen T; Keating, Shelley E; Cohn, Jeffrey S; Garg, Manohar L; Caterson, Ian D; George, Jacob; Johnson, Nathan A

    2015-09-14

    Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status - the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.

  2. Liver metastases

    MedlinePlus

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

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

    PubMed

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

    2016-08-01

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

  4. 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.

  5. Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

    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; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  6. Acute Liver Failure in an Adult, a Rare Complication of Alagille Syndrome: Case Report and Brief Review.

    PubMed

    Frongillo, F; Bianco, G; Silvestrini, N; Lirosi, M C; Sanchez, A M; Nure, E; Gaspari, R; Avolio, A W; Sganga, G; Agnes, S

    2015-09-01

    Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function. PMID:26361673

  7. Intrauterine metabolic programming alteration increased susceptibility to non-alcoholic adult fatty liver disease in prenatal caffeine-exposed rat offspring.

    PubMed

    Wang, Linlong; Shen, Lang; Ping, Jie; Zhang, Li; Liu, Zhongfen; Wu, Yong; Liu, Yansong; Huang, Hegui; Chen, Liaobin; Wang, Hui

    2014-01-30

    An increase in susceptibility to metabolic syndromes (MetS) in rat offspring that experienced prenatal caffeine exposure (PCE) has been previously demonstrated. The present study aimed to clarify this increased susceptibility and elucidate the mechanism of foetal origin that causes or contributes to adult non-alcoholic fatty liver disease (NAFLD) as a result of PCE. Based on the results from both foetal and adult studies of rats that experienced PCE (120 mg/kgd), the foetal weight and serum triglyceride levels decreased significantly and hepatocellular ultrastructure was altered. Foetal livers exhibited inhibited insulin-like growth factor-1 (IGF-1), enhanced lipogenesis and reduced lipid output. In adult female offspring of PCE+lab chow, lipid synthesis, oxidation and output were enhanced, whereas lipogenesis was inhibited in their male conterparters. Furthermore, in adult offspring of PCE+ high-fat diet, catch-up growth appeared obvious with enhanced hepatic IGF-1, especially in females. Both males and females showed increased lipid synthesis and reduced output, which were accompanied by elevated serum triglyceride. Severe NAFLD appeared with higher Kleiner scores. Gluconeogenesis was continuously enhanced in females. Therefore, increased susceptibility to diet-induced NAFLD in PCE offspring was confirmed, and it appears to be mediated by intrauterine glucose and alterations in lipid metabolic programming. This altered programming enhanced foetal hepatic lipogenesis and reduced lipid output in utero, which continued into the postnatal phase and reappeared in adulthood with the introduction of a high-fat diet, thereby aggravating hepatic lipid accumulation and causing NAFLD.

  8. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    PubMed

    Lupp, A; Lau, K; Trautmann, A K; Krausse, T; Klinger, W

    1999-01-01

    In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens

  9. B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation.

    PubMed

    Egawa, Hiroto; Ohmori, Katsuyuki; Haga, Hironori; Tsuji, Hiroaki; Yurugi, Kimiko; Miyagawa-Hayashino, Aya; Oike, Fumitaka; Fukuda, Akinari; Yoshizawa, Jun; Takada, Yasutsugu; Tanaka, Koichi; Maekawa, Taira; Ozawa, Kazue; Uemoto, Shinji

    2007-04-01

    Although the effectiveness of rituximab has been reported in ABO blood group (ABO)-incompatible (ABO-I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO-I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B-cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO-I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B-cell study of the spleen, another 4 patients undergoing ABO-I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO-compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti-donor blood-type antibody titer was lower, and clinical and pathological antibody-mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody-mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO-I LDLT patients.

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

    PubMed

    Nakao, Minoru

    2015-10-01

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

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

    PubMed

    Nakao, Minoru

    2015-10-01

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

  12. Imaging in liver transplantation

    PubMed Central

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

    2009-01-01

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

  13. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  14. Immunocytochemical localization of the nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen.

    PubMed

    Luo, M; Faure, R; Tong, Y A; Dussault, J H

    1989-04-01

    A monoclonal antibody was used for the localization of the nuclear T3 receptor in different tissues of the adult rat: the liver, kidney, heart, lung, spleen, testis, and pituitary. In the liver, the immunoreactivity was found uniformly distributed in the nuclei of hepatocytes. Sections incubated with a control ascitic fluid or with the same ascitic fluid pre-adsorbed with purified receptor showed no specific staining. In the kidney, the immunoreactivity was higher in the epithelial cell of the proximal convoluted tubes and juxtaglomerular cells. In the heart, only the myocardial cells were stained. In the lung, the immunoreactivity was confined to type II pneumocytes and alveolar macrophages. In the spleen, only a few mature lymphocyte and macrophage cell nuclei were stained. These results show that: 1) the abundance of the nuclear T3 correlates with previous studies using hormone binding techniques; 2) the nuclear T3 receptor is selectively located in certain cell types, which possess a precise local function.

  15. Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells

    PubMed Central

    Vondráček, Jan; Machala, Miroslav

    2016-01-01

    The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, β-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β-catenin and TGF-β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion. PMID:27274734

  16. Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells.

    PubMed

    Vondráček, Jan; Machala, Miroslav

    2016-01-01

    The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, β-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β-catenin and TGF-β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion.

  17. Crowding effect on adult growth, pre-patent period and egg shedding of Fasciola hepatica.

    PubMed

    Valero, M A; De Renzi, M; Panova, M; Garcia-Bodelon, M A; Periago, M V; Ordoñez, D; Mas-Coma, S

    2006-10-01

    Fascioliasis pathogenesis depends on fluke burden. In human hyperendemic zones, individual infection intensities reach very high levels and the majority of infected subjects should be in the advanced chronic phase. The rat model offers a useful approach for pathological research in the advanced chronic period. The influence of infection intensity per rat on fluke development, pre-patent period and egg shedding (eggs/g faeces/worm) was analysed in 3 groups (I: 1-3 worms/rat; II: 4-6; III: 7-9). Ontogenetic trajectories of fluke body measures followed a logistic model. Results showed that when the burden increases, the maximum values of fluke measures decrease. The crowding effect is manifest when fluke measures approximate their maximums in the advanced chronic stage. The pre-patent period and egg production decrease when the burden increases. This means that measurements of eggs per gramme of faeces tend to underestimate the fluke burden. The present study demonstrates how to quantify the fascioliasis experimental rat model crowding effect on adult growth, pre-patent period and egg production. This quantification may be of great interest in epidemiological studies and in experimental research on the in vivo actions of different anthelminthic drugs and vaccines, pathology, immunology and resistance studies.

  18. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  19. Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure.

    PubMed

    Zhang, Tao; Gan, Zhiwei; Gao, Chuanzi; Ma, Ling; Li, Yanxi; Li, Xiao; Sun, Hongwen

    2016-09-14

    In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 μg per kg bw per day, respectively. PMID:27383923

  20. Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure.

    PubMed

    Zhang, Tao; Gan, Zhiwei; Gao, Chuanzi; Ma, Ling; Li, Yanxi; Li, Xiao; Sun, Hongwen

    2016-09-14

    In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 μg per kg bw per day, respectively.

  1. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  2. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects. PMID:27194488

  3. Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population-based cohort study.

    PubMed

    Asdahl, Peter Haubjerg; Winther, Jeanette Falck; Bonnesen, Trine Gade; De Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Holmqvist, Anna Sällfors; Malila, Nea; Tryggvadottir, Laufey; Wesenberg, Finn; Dahlerup, Jens Frederik; Olsen, Jørgen Helge; Hasle, Henrik

    2016-10-01

    Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.

  4. Evaluation of the repeated dose liver micronucleus assay using young adult rats with cyclophosphamide monohydrate: a report of a collaborative study by CSGMT/JEMS.MMS.

    PubMed

    Matsumoto, Kazumi; Zaizen, Kazuyo; Miyamoto, Atsushi; Wako, Yumi; Kawasako, Kazufumi; Ishida, Hisao

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect liver carcinogens, and this assay could be integrated into general toxicological studies. In this study, in order to assess the performance of the assay, cyclophosphamide monohydrate (CP) was tested in a 14-day RDLMN assay. Based on the results of the 4-day repeated dose-finding study, 10 mg/kg/day of CP was selected as the highest dose and the lower doses were set at 5, 2.5, 1.25, and 0.625 mg/kg/day for the 14-day RDLMN assay. On the day after the completion of the dosing period, specimens of hepatocytes and bone marrow cells were prepared and the induction of micronuclei was assessed. No changes were observed in the incidences of micronucleated hepatocytes. Nevertheless, the incidences of micronucleated immature erythrocytes in the bone marrow were increased significantly at CP doses of 1.25 mg/kg/day or more. These findings are consistent with reports that CP induces tumors in various tissues but it does not induce liver tumors.

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

    PubMed

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

    2012-01-01

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

  6. Fibrosing Cholestatic Hepatitis in a Complicated Case of an Adult Recipient After Liver Transplantation: Diagnostic Findings and Therapeutic Dilemma

    PubMed Central

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Patient: Male, 66 Final Diagnosis: Fibrosing cholestatic hepatitis Symptoms: Prolonged jaundice and intractable ascites Medication: Steroid pulse therapy and direct-acting antivirals Clinical Procedure: Liver transplantation Specialty: Transplantology Objective: Challenging differential diagnosis Background: Hepatitis C recurrence is a serious matter after liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV) positive recipients develop fibrosing cholestatic hepatitis (FCH). FCH rapidly results in graft loss. Currently, direct-acting antivirals (DAAs) are effective and safe for hepatitis C, even after LT. However, only a few cases of successfully treated FCH after LT have been reported. We present FCH in a complicated case with sepsis and portal flow obstruction after LT. Case Report: A 66-year-old man underwent cadaveric LT. Liver function disorders were observed from post-operative day (POD) 22. Sepsis repeated on POD 38, 74, and 101. Steroid pulse therapy was given from POD 40 to 54. The infectious focus was surgically removed on POD 89. Interventional radiology for portal venous obstruction was completed on POD 96. To make a real-time diagnosis and to investigate the graft condition, repeat liver needle biopsies (LNBs) were taken. Although there was a combined impact of sepsis, portal flow decrease, and recurrent hepatitis C on graft failure, it was interesting that recurrent hepatitis C was consistently detectable from the first LNB. HCV-ribonucleic acid increased on POD 68. Liver function disorders peaked on POD 71 and 72. Jaundice peaked on POD 82. DAA induction was regrettably delayed because of a reluctance to introduce DAAs under conditions of graft dysfunction. DAAs were administered after hospital discharge. Conclusions: A real-time and precise diagnosis based on histopathological examination and viral measurement is important for FCH treatment. Well-considered therapy with DAAs should be aggressively introduced for potentially fatal

  7. In vitro investigation of a standardized dried extract of Citrullus colocynthis on liver toxicity in adult rats.

    PubMed

    Barth, Astrid; Müller, Dieter; Dürrling, Katrin

    2002-11-01

    A standardized extract of Citrullus colocynthis used as an oral natural laxative in folk medicine was tested for its influence on liver function parameters in vitro. Cytochrome P450 (CYP) dependent production of reactive oxygen species (ROS) under the influence of Citrullus colocynthis extract was investigated by means of stimulated lipid peroxidation (LPO), H2O2 formation and amplified chemiluminescence in rat liver microsomes. In rat liver 9000 x g supernatants 4 monooxygenase reactions mediated by different CYP forms were measured. Putative hepatotoxic effects of Citrullus colocynthis extract were measured by means of potassium and GSH concentrations in and LDH leakage from precision-cut rat liver slices. For possible hepatoprotective effects the influence of the extract on carbon tetrachloride-induced changes of these parameters was investigated. Citrullus colocynthis extract in concentrations higher than 10 microg/ml incubation mixture proved to inhibit lipid peroxidation and ROS-production as well as CYP1A-, 2B- and 3A-dependent reactions with typical substrates. In contrast, H2O2 production was not reduced under the influence of the extract, a slight but significant increase was seen. Citrullus colocynthis extract was found to be free of hepatotoxic effects in concentrations up to 100 microg/ml incubation mixture when liver slices were incubated in William's medium E for 22 hours. All viability parameters used were not influenced by the extract of Citrullus colocynthis. Carbon tetrachloride induced hepatotoxicity could not be prevented or alleviated. Moreover, the damage was sometimes enhanced by higher extract concentrations.

  8. Normal liver stiffness in healthy adults assessed by real-time shear wave elastography and factors that influence this method.

    PubMed

    Huang, Zeping; Zheng, Jian; Zeng, Jie; Wang, Xiaoli; Wu, Tao; Zheng, Rongqin

    2014-11-01

    Real-time shear wave elastography (SWE) is a novel two-dimensional elastographic method that is used to estimate the severity of liver fibrosis. However, the normal range of liver stiffness (LS) and the possible factors that influence SWE are not well understood. The aims of the current study are to define the normal range of LS in healthy subjects and to explore the factors that may affect SWE. A total of 509 healthy subjects underwent SWE to determine the stiffness of their livers, and the effects of gender, age and body mass index (BMI) on LS were analyzed. The effects of different factors on SWE, including the testing position, measurement depth and size of the region of interest (ROI), were analyzed in 137 subjects. SWE imaging was successfully performed in 502 healthy subjects (98.6%, 502/509). The mean value of the SWE measurements in 502 individuals was 5.10 ± 1.02 kPa, and the 95% confidence interval was 5.02-5.19 kPa (range: 2.4-8.7 kPa). We found that the detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V. LS was greater at a depth >5 cm (5.78 ± 1.66 kPa) compared with depths ≤5 cm (4.66 ± 0.77 kPa, p < 0.001); LS was also greater in men than in women (5.45 ± 1.02 kPa vs. 4.89 ± 0.96 kPa, p < 0.001). However, there were no significant differences in the LS values regarding the size of the ROI, age or BMI (all p > 0.05). The mean LS value in all 502 healthy subjects was 5.10 ± 1.02 kPa. The mean LS value obtained by SWE was not influenced by the size of the ROI, age or BMI, but the mean value was significantly influenced by the different segments of the liver, the detection depth and gender.

  9. Normal liver stiffness in healthy adults assessed by real-time shear wave elastography and factors that influence this method.

    PubMed

    Huang, Zeping; Zheng, Jian; Zeng, Jie; Wang, Xiaoli; Wu, Tao; Zheng, Rongqin

    2014-11-01

    Real-time shear wave elastography (SWE) is a novel two-dimensional elastographic method that is used to estimate the severity of liver fibrosis. However, the normal range of liver stiffness (LS) and the possible factors that influence SWE are not well understood. The aims of the current study are to define the normal range of LS in healthy subjects and to explore the factors that may affect SWE. A total of 509 healthy subjects underwent SWE to determine the stiffness of their livers, and the effects of gender, age and body mass index (BMI) on LS were analyzed. The effects of different factors on SWE, including the testing position, measurement depth and size of the region of interest (ROI), were analyzed in 137 subjects. SWE imaging was successfully performed in 502 healthy subjects (98.6%, 502/509). The mean value of the SWE measurements in 502 individuals was 5.10 ± 1.02 kPa, and the 95% confidence interval was 5.02-5.19 kPa (range: 2.4-8.7 kPa). We found that the detective position within the liver had a significant impact on the liver stiffness measurement (LSM), and the lowest coefficient of variation (CV = 8%) was obtained for LSMs made at segment V. LS was greater at a depth >5 cm (5.78 ± 1.66 kPa) compared with depths ≤5 cm (4.66 ± 0.77 kPa, p < 0.001); LS was also greater in men than in women (5.45 ± 1.02 kPa vs. 4.89 ± 0.96 kPa, p < 0.001). However, there were no significant differences in the LS values regarding the size of the ROI, age or BMI (all p > 0.05). The mean LS value in all 502 healthy subjects was 5.10 ± 1.02 kPa. The mean LS value obtained by SWE was not influenced by the size of the ROI, age or BMI, but the mean value was significantly influenced by the different segments of the liver, the detection depth and gender. PMID:25282481

  10. Xenobiotic biotransformation in livers and lungs of adult black-tailed deer: comparison with domestic goat and sheep.

    PubMed

    Helferich, W G; Silva, M H; Flueck, W T; Hammock, B D; Shull, L R

    1987-01-01

    1. The capacity of liver and lung tissue of black-tailed dear (Odocoileus hemionus columbianus) to biotransform xenobiotics was compared in vitro to the domestic sheep and goat. Donor animals were all females of varying ages. Tissues from the black-tailed deer were collected in the wild. A variety of biotransformation enzymes were measured in both microsomal and cytosolic fractions. 2. Deer liver was lower in total cytochrome P450 concentration, but mono-oxygenase activities were greater compared to sheep and goat. The opposite was true for the lung. 3. Epoxide hydrolase activities were significantly different in deer vs sheep and goat. 4. In general, both hepatic and pulmonary activities were more similar between sheep and goat than either species compared to the deer, however, the magnitude of the hepatic differences did not exceed 5-fold. 5. Based on these limited results, there is no reason to discredit the sheep or goat as a toxicity testing model for deer.

  11. Acute liver failure in children.

    PubMed

    Devictor, Denis; Tissieres, Pierre; Afanetti, Mickael; Debray, Dominique

    2011-06-01

    The management of children with acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but clinical studies have mainly concerned adult patients. There are no specific medical therapies, except for a few metabolic diseases presenting with acute liver failure. Liver transplantation still remains the only definitive therapy in most instances. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to liver transplantation, for providing metabolic support during liver failure and for replacing liver transplantation in certain metabolic liver diseases.

  12. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  13. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  14. 9 CFR 311.25 - Parasites not transmissible to man; tapeworm cysts in sheep; hydatid cysts; flukes; gid bladder...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  15. Natural trematode infection in liver of water buffalo (Bubalus bubalis): histopathological investigation.

    PubMed

    Haque, Masoodul; Mohan, Chandra; Ahmad, Imtiaz

    2011-06-01

    This study reports the infection of liver and bile ducts, carried out from November 2008 to April 2010, on 730 randomly selected water buffaloes-Bubalusbubalis, infected with the amphistome trematode parasite Explanatum explanatum (Creplin, 1847) Fukui, 1929. Macroscopic examination revealed massive infection of adult fluke in bile ducts and intrahepatic ductules in 131 (18%) cases. The predominant features were multifocal granulomatous nodules throughout the luminal surface of the bile ducts. Histopathological study of 4 μm thick tissue sections cut adjacent to and through the site of attachment of individual worm and stained with hematoxylin and eosin revealed intense infiltration of inflammatory cells such as lymphocytes, macrophages, plasma cells, eosinophils as well as fibrocytes. This was associated with fibrosis and thickening of the bile ducts. Due to high level of prevalence and intensity of natural infection, amphistomiasis appears to be endemic in this geographical region and probably represent one of the most important animal health problems. It is hoped that the study may draw attention to the need for educating farmers, regarding the economic importance of infection of these amphistome parasites and also for the development of control strategies to prevent the spread of infection to ruminants.

  16. Xenogeneic transfer of fetal liver and adult bone marrow-derived haemopoietic cells in rodents: changes in spleen colony differentials with increased doses of cells.

    PubMed

    Gulya, E; Gábor Szabó, L; Kelemen, E

    1997-01-01

    The effect of very high haemopoietic cell doses were investigated on the composition of splenic cell colonies/clusters in irradiated animals under xenogeneic circumstances. Differential cluster/colony counts from serial histological sections of the spleen were investigated before, and 9-12 days after transplantation of fetal liver- or adult bone marrow-derived haemopoietic cells following 5.0 to 8.5 Gy total body irradiation. Syngeneic as well as xenogeneic (mouse to rat and rat to mouse) transplantations were carried out. Cluster/colony differentials changed with the increase of the injected cell mass from 10(5) to 10(6) and 10(7) or more, i.e. the overwhelming erythroid pattern became trilinear even with xenogeneic transplants.

  17. Effect of methionine replacement by homocystine in cultures containing both malignant rat breast carcinosarcoma (Walker-256) cells and normal adult rat liver fibroblasts.

    PubMed

    Halpern, B C; Ezzell, R; Hardy, D N; Clark, B R; Ashe, H; Halpern, R M; Smith, R A

    1975-01-01

    When malignant W-256 rat breast carcinosarcoma cells are mixed with an equal number of normal adult rat liver fibroblasts and allowed to grow in a medium containing sufficient L-methionine and an excess of vitamin B12 and of folic acid, the malignant cells outgrow the normal cells, and within 2 weeks the tissue culture flasks contain only neoplastic cells. However, when ample DL-homocystine or homocysteine replaces methionine in the medium containing the same amount of vitamin B12 and folic acid, and seeded with the same type and number of malignant and normal cells, the malignant cells die and the normal cells thrive. Substantiating this conclusion are the results of injections into rats of comparable numbers of cells from each group after 3 weeks of growth in tissue culture. Fatal malignancies are produced by the homocystein-cultivated cells.

  18. Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

    PubMed

    Bayomy, Naglaa A; Soliman, Gehan M; Abdelaziz, Eman Z

    2016-09-01

    Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc.

  19. Effect of Potassium Bromate on the Liver of Adult Male Albino Rat and A Possible Protective Role of Vitamin C: Histological, Immunohistochemical, and Biochemical Study.

    PubMed

    Bayomy, Naglaa A; Soliman, Gehan M; Abdelaziz, Eman Z

    2016-09-01

    Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Group 2: received 30 mg/Kg/day vitamin C orally for 4 weeks, Group 3: received 20 mg/Kg/dose KBrO3 orally twice weekly for 4 weeks and Group 4: received both KBrO3 and vitamin C. Liver specimens were processed for histological study by light and electron microscopes and stained immunohistochemically to detect glial fibriller acidic protein (GFAP). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated as well as the levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities in all dissected tissues were determined. KBrO3 induced histological alterations in the form of degeneration, cellular infiltration and significant increase in collagen deposition in portal tracts with a significant increase in immunoexpression of GFAP. Significant rise in serum levels of AST, ALT, and MDA in liver tissues were recorded. However, levels of GSH and SOD were significantly decreased. Most of these changes were improved by vitamin C treatment. In conclusion, vitamin C ameliorates the histological and biochemical alterations of the liver induced by KBrO3 . Anat Rec, 299:1256-1269, 2016. © 2016 Wiley Periodicals, Inc. PMID:27373450

  20. Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach

    SciTech Connect

    Eveillard, Alexandre; Lasserre, Frederic; Tayrac, Marie de; Polizzi, Arnaud; Claus, Sandrine; Canlet, Cecile; Mselli-Lakhal, Laila; Gotardi, Gaelle; Paris, Alain; Guillou, Herve; Martin, Pascal G.P.; Pineau, Thierry

    2009-05-01

    Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPAR{alpha} targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erb{alpha} pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erb{alpha} target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erb{alpha} pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.

  1. MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

    ClinicalTrials.gov

    2015-10-14

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage 0 Adult Hepatocellular Carcinoma; BCLC Stage A Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma

  2. Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

    SciTech Connect

    McCallum, Gordon P.; Siu, Michelle; Sweeting, J. Nicole; Wells, Peter G.

    2011-01-15

    In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.

  3. Waist Gain Is Associated with a Higher Incidence of Nonalcoholic Fatty Liver Disease in Korean Adults: A Cohort Study

    PubMed Central

    Lim, Jisun; Park, Hye Soon; Chang, Yoosoo; Jung, Hyun-Suk; Kim, Chan-Won; Ko, Byung-Joon; Chung, Eun Chul; Shin, Hocheol; Ryu, Seungho

    2016-01-01

    Background We examined the relationship between changes in waist circumference (WC) and the incidence of nonalcoholic fatty liver disease (NAFLD). Methods A cohort study of 37,130 men and women were followed-up annually or biennially. Differences in WC between baseline and subsequent measurements were categorized in quartiles: first (WC loss), second (no change in WC as the reference), third and highest quartiles (WC gain). The presence of fatty liver was determined using ultrasound. Parametric Cox modeling was used to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) of the incidence of NAFLD. Results During 127,324.4 person-years of follow-up, 6249 participants developed NAFLD. Despite adjusting for possible confounders, the risk of development of NAFLD increased with increasing quartiles of WC change in a dose-response manner (p for trend < 0.001). Compared with the reference, WC loss was associated with a lower risk of NAFLD (men: aHR 0.79 [95% CI: 0.73–0.87]; women: 0.72 [0.63–0.81]), and the highest quartile (WC gain) was associated with a higher risk of NAFLD (men: 1.30 [1.19–1.42]; women: 1.48 [1.31–1.67]). Conclusion Waist gain appears to increase the risk of developing NAFLD, independently of the baseline body mass index and WC. PMID:27420035

  4. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Auer, Herbert; Aspöck, Horst

    2014-10-01

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

  7. 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.

  8. 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

  9. Comparative effects of nodularin and microcystin-LR in zebrafish: 2. Uptake and molecular effects in eleuthero-embryos and adult liver with focus on endoplasmic reticulum stress.

    PubMed

    Faltermann, Susanne; Grundler, Verena; Gademann, Karl; Pernthaler, Jakob; Fent, Karl

    2016-02-01

    . In contrast to adult liver, MC-LR and nodularin did not result in detectable changes of mRNA levels of selected target genes involved in ER-stress in zebrafish eleuthero-embryos, nor was the abundance of transcripts belonging to the MAPK and pro-apoptosis pathways altered. In conclusion, our data indicate that MC-LR and nodularin have similar transcriptional effects. They lead to changes in mRNA levels of genes that suggest induction of ER-stress, and furthermore, lead to increased level of tnfα mRNA in the adult liver, which suggests a novel (transcriptional) mode of action in fish. However, although taken up by eleuthero-embryos, no transcriptional changes induced by these cyanobacterial toxins were detected. This is probably due to action to specific organs such as liver and kidneys that could not be identified by whole-embryo sampling. PMID:26748408

  10. Comparative effects of nodularin and microcystin-LR in zebrafish: 2. Uptake and molecular effects in eleuthero-embryos and adult liver with focus on endoplasmic reticulum stress.

    PubMed

    Faltermann, Susanne; Grundler, Verena; Gademann, Karl; Pernthaler, Jakob; Fent, Karl

    2016-02-01

    . In contrast to adult liver, MC-LR and nodularin did not result in detectable changes of mRNA levels of selected target genes involved in ER-stress in zebrafish eleuthero-embryos, nor was the abundance of transcripts belonging to the MAPK and pro-apoptosis pathways altered. In conclusion, our data indicate that MC-LR and nodularin have similar transcriptional effects. They lead to changes in mRNA levels of genes that suggest induction of ER-stress, and furthermore, lead to increased level of tnfα mRNA in the adult liver, which suggests a novel (transcriptional) mode of action in fish. However, although taken up by eleuthero-embryos, no transcriptional changes induced by these cyanobacterial toxins were detected. This is probably due to action to specific organs such as liver and kidneys that could not be identified by whole-embryo sampling.

  11. Imaging in pediatric liver transplantation.

    PubMed

    Monti, L; Soglia, G; Tomà, P

    2016-05-01

    Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors. PMID:26909515

  12. Sero-epidemiology of Hepatitis B Surface Antigenaemia among Adult Nigerians with Clinical Features of Liver Diseases Attending a Primary-Care Clinic in a Resource-Constrained Setting of Eastern Nigeria

    PubMed Central

    Iloh, Gabriel Uche Pascal; Ikwudinma, Austin Obiora

    2013-01-01

    Background: Hepatitis-B infection is not commonly perceived as a serious medical problem in Nigeria. However, chronic hepatitis-B infection, which is a subject of global concern, may lead to lethal liver diseases. Aim: The study was to determine the sero-epidemiology of hepatitis-B surface antigenaemia among adult Nigerians with clinical features of liver diseases attending a primary-care clinic in a resource-constrained setting of Eastern Nigeria. Materials and Methods: A cross-sectional study was carried out on 140 adult Nigerians with clinical features of liver diseases at the primary-care clinic of Federal Medical Centre, Owerri. They made up three groups: 44 patients, 62 patients and 34 patients with clinical features of hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. Hepatitis-B surface antigen (HBsAg) was assayed using an immunochromatographic method. Demographic variables were collected. Results: The overall sero-positivity rate was 50.7%. The sero-positivity rates for these patients were 23.9%, 39.5% and 36.6% for hepatitis, liver cirrhosis and hepatocellular carcinoma, respectively. The age group 40-60 years (P = 0.048) and artisans (P = 0.019) were significantly infected. Abdominal swelling (86.4%) and ascites (67.1%) were the most common symptoms and signs, respectively. Conclusion: HBsAg prevalence was high and has significant association with age and occupation. PMID:23724405

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

    PubMed

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

    2016-04-01

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

  14. Higher estimated net endogenous Acid production may be associated with increased prevalence of nonalcoholic Fatty liver disease in chinese adults in Hong Kong.

    PubMed

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto's method and potential renal acid load (PRAL) was calculated using Remer's method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

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

    PubMed

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

    2015-05-30

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

  16. Liver Facts

    MedlinePlus

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

  17. 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

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

    PubMed

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

    2015-08-01

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

  19. Optimization of an experimental model for the recovery of adult Haplorchis pumilio (Heterophyidae: Digenea).

    PubMed

    Kay, Helle; Murrell, K Darwin; Hansen, Axel Kornerup; Madsen, Henry; Trang, Nguyen Thi Thu; Hung, Nguyen Manh; Dalsgaard, Anders

    2009-06-01

    Recent studies in Vietnam and other Asian countries have shown that fish-borne zoonotic intestinal trematodes (FZT) occur very frequently in humans. The dominant intestinal FZT in Vietnamese fish are species of Haplorchis, in particular H. pumilio. However, basic studies on the biology and pathology of adult H. pumilio are difficult because of the lack of a standardized experimental animal model. The objective of this study was to establish and optimize such an animal-infection model for H. pumilio. Using metacercariae isolated from naturally infected fish, experiments were conducted to identify a suitable experimental animal host species, as well as the optimum metacercariae infection dose, and to determine the post-infection interval for patency. In a series of experiments, mice (Mus musculus) and chickens (Gallus gallus dom.) were infected with different numbers of metacercariae, and worm recoveries were made at varying intervals post-infection (PI). Based on the mean number of adult flukes recovered/number of metacercariae inoculated and the percent of hosts infected, mice were significantly more susceptible to infection than were chickens. The proportion of metacercariae developing to the adult stage increased with dose size. The peak worm recovery (geometric mean) was found to be day 7, although not all recovered flukes were gravid until day 9 PI. These results describe a mouse infection model with good predictability for intestinal flukes, such as H. pumilio, results which could facilitate investigations on important biological and pathological aspects of intestinal fluke infections.

  20. Biologically active substances-enriched diet regulates gonadotrope cell activation pathway in liver of adult and old rats.

    PubMed

    Oszkiel, Hanna; Wilczak, Jacek; Jank, Michał

    2014-09-01

    According to the Hippocrates' theorem "Let food be your medicine and medicine be your food", dietary interventions may induce changes in the metabolic and inflammatory state by modulating the expression of important genes involved in the chronic disorders. The aim of the present study was to evaluate the influence of long-term (14 months) use of biologically active substances-enriched diet (BASE-diet) on transcriptomic profile of rats' liver. The experiment was conducted on 36 Sprague-Dawley rats divided into two experimental groups (fed with control or BASE-diet, both n = 18). Control diet was a semi-synthetic diet formulated according to the nutritional requirements for laboratory animals. The BASE-diet was enriched with a mixture of polyphenolic compounds, β-carotene, probiotics, and n-3 and n-6 polyunsaturated fatty acids. In total, n = 3,017 differentially expressed (DE) genes were identified, including n = 218 DE genes between control and BASE groups after 3 months of feeding and n = 1,262 after 14 months. BASE-diet influenced the expression of genes involved particularly in the gonadotrope cell activation pathway and guanylate cyclase pathway, as well as in mast cell activation, gap junction regulation, melanogenesis and apoptosis. Especially genes involved in regulation of GnRH were strongly affected by BASE-diet. This effect was stronger with the age of animals and the length of diet use. It may suggest a link between the diet, reproductive system function and aging. PMID:25156242

  1. Comparative Analysis of AhR-Mediated TCDD-Elicited Gene Expression in Human Liver Adult Stem Cells

    PubMed Central

    Kim, Suntae; Dere, Edward; Burgoon, Lyle D.; Chang, Chia-Cheng; Zacharewski, Timothy R.

    2009-01-01

    Time course and dose-response studies were conducted in HL1-1 cells, a human liver cell line with stem cell–like characteristics, to assess the differential gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) compared with other established models. Cells were treated with 0.001, 0.01, 0.1, 1, 10, or 100nM TCDD or dimethyl sulfoxide vehicle control for 12 h for the dose-response study, or with 10nM TCDD or vehicle for 1, 2, 4, 8, 12, 24, or 48 h for the time course study. Elicited changes were monitored using a human cDNA microarray with 6995 represented genes. Empirical Bayes analysis identified 144 genes differentially expressed at one or more time points following treatment. Most genes exhibited dose-dependent responses including CYP1A1, CYP1B1, ALDH1A3, and SLC7A5 genes. Comparative analysis of HL1-1 differential gene expression to human HepG2 data identified 74 genes with comparable temporal expression profiles including 12 putative primary responses. HL1-1–specific changes were related to lipid metabolism and immune responses, consistent with effects elicited in vivo. Furthermore, comparative analysis of HL1-1 cells with mouse Hepa1c1c7 hepatoma cell lines and C57BL/6 hepatic tissue identified 18 and 32 commonly regulated orthologous genes, respectively, with functions associated with signal transduction, transcriptional regulation, metabolism and transport. Although some common pathways are affected, the results suggest that TCDD elicits species- and model-specific gene expression profiles. PMID:19684285

  2. Changes of liver metabolite concentrations in adults with disorders of fructose metabolism after intravenous fructose by 31P magnetic resonance spectroscopy.

    PubMed

    Boesiger, P; Buchli, R; Meier, D; Steinmann, B; Gitzelmann, R

    1994-10-01

    A novel 31P magnetic resonance spectroscopy procedure allows the estimation of absolute concentrations of certain phosphorus-containing compounds in liver. We have validated this approach by measuring ATP, phosphomonesters, and inorganic phosphate (Pi) during fasting and after an i.v. fructose bolus in healthy adults and in three adults with disorders of fructose metabolism and by comparing results with known metabolic concentrations measured chemically. During fasting, the ATP concentration averaged 2.7 +/- 0.3 (SD, n = 9) mmol/L, which, after due correction for other nucleoside triphosphates, was 2.1 mmol/L and corresponded well with known concentrations. Fructose-1-phosphate (F-1-P) could not be measured during fasting; its concentration after fructose was calculated from the difference of the phosphomonester signals before (2.9 +/- 0.2 mmol/L) and after fructose. Pi was 1.4 +/- 0.3 mmol/L and represented the one fourth of Pi visible in magnetic resonance spectra. In the three healthy controls after fructose (200 mg/kg, 20% solution, 2.5 min), the fructokinase-mediated increase of F-1-P was rapid, reaching 4.9 mmol/L within 3 min, whereas the uncorrected ATP decreased from 2.7 to 1.8 mmol/L and the Pi from 1.4 to 0.3 mmol/L. The subsequent decrease of F-1-P, mediated by fructaldolase, was accompanied by an overshooting rise of Pi to 2.7 mmol/L. In the patient with essential fructosuria, the concentrations of F-1-P, ATP, and Pi remained unchanged, confirming that fructokinase was indeed inactive. In the patient with hereditary fructose intolerance, initial metabolic changes were the same as in the controls, but baseline concentrations were not yet reestablished after 7 h, indicating weak fructaldolase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Venous Outflow Reconstruction in Adult Living Donor Liver Transplant: Outcome of a Policy for Right Lobe Grafts without the Middle Hepatic Vein

    PubMed Central

    Badawy, Mohamad T.; Soliman, Hosam El-Din; El-Gendy, Magdy; Ibrahim, Tarek; Davidson, Brian R.

    2013-01-01

    Introduction. The difficulty and challenge of recovering a right lobe graft without MHV drainage is reconstructing the outflow tract of the hepatic veins. With the inclusion or the reconstruction of the MHV, early graft function is satisfactory. The inclusion of the MHV or not in the donor's right lobectomy should be based on sound criteria to provide adequate functional liver mass for recipient, while keeping risk to donor to the minimum. Objective. Reviewing the results of a policy for right lobe grafts transplant without MHV and analyzing methods of venous reconstruction related to outcome. Materials and Methods. We have two groups Group A (with more than one HV anast.) (n = 16) and Group B (single HV anast.) (n = 24). Both groups were compared regarding indications for reconstruction, complications, and operative details and outcomes, besides describing different modalities used for venous reconstruction. Results. Significant increase in operative details time in Group A. When comparison came to complications and outcomes in terms of laboratory findings and overall hospital stay, there were no significant differences. Three-month and one-year survival were better in Group A. Conclusion. Adult LDLT is safely achieved with better outcome to recipients and donors by recovering the right lobe without MHV, provided that significant MHV tributaries (segments V, VIII more than 5 mm) are reconstructed, and any accessory considerable inferior right hepatic veins (IRHVs) or superficial RHVs are anastomosed. PMID:24489434

  4. Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

    PubMed

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  5. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation. PMID:25892856

  6. Soluble factor(s) produced by adult bone marrow stroma inhibit in vitro proliferation and differentiation of fetal liver BFU-E by inducing apoptosis.

    PubMed Central

    Roy, V; Verfaillie, C M

    1997-01-01

    Hematopoiesis occurs in different organs during fetal development. Several studies suggest that the growth of hematopoietic progenitors at one stage of ontogenic maturation may not be supported by a microenvironment from a different ontogenic stage. To determine if human fetal liver (FL) clonogenic progenitors can develop in an adult bone marrow (ABM) microenvironment, we compared growth of BFU-E and CFU-GM from 7-14-wk-old FL, 11-20-wk-old fetal bone marrow (FBM), umbilical cord blood (UCB), or ABM in clonogenic medium with or without ABM stroma. In contrast to BFU-E from FBM, UCB, or ABM, soluble factor(s) produced by ABM stroma severely suppressed growth of 98% of FL BFU-E by inducing apoptosis of cells beyond early erythroblast stage. The nature of the soluble factor remains unknown, although we have evidence that it is heat labile with molecular mass < 10 kD. Antibody neutralization studies indicate that TGF-beta1, IL-1, TNF-alpha, macrophage inflammatory protein (MIP)-1alpha, or IFN-gamma are not responsible. The observation that FL progenitors may not be capable of differentiating when transferred to an ABM microenvironment may have important implications for FL transplantation into postnatal recipients. Further, this demonstrates that ontogenic stage-specific interactions between hematopoietic progenitors and their microenvironment are important for the normal development of hematopoiesis. PMID:9259591

  7. Nutritional recovery with a soybean diet after weaning reduces lipogenesis but induces inflammation in the liver in adult rats exposed to protein restriction during intrauterine life and lactation.

    PubMed

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPARγ as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNFα mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-κB mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNFα-mediated inflammation.

  8. Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of Adult-Onset Still's Disease with Liver Failure with No Response to Tocilizumab Therapy

    PubMed Central

    Tamechika, Shinya; Iwagaitsu, Shiho; Maeda, Shinji; Togawa, Hiroyuki

    2013-01-01

    A 21-year-old woman with refractory systemic flare of adult-onset Still's disease with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus, and tocilizumab, was successfully treated with additional use of etanercept. Etanercept at a dose of 50 mg weekly was partially effective but could not reduce the dose of concomitant betamethasone from 5 mg/day. Etanercept at a dose of 75 mg weekly could lead her to clinical remission and enabled successful tapering off the corticosteroids and discontinuation of etanercept. Normalization of serum C-reactive protein and interleukin 6 and persistent elevation of serum tumor necrosis factor α under the treatment with high-dose corticosteroids and immunosuppressants suggest that tumor necrosis factor α was more deeply involved than at least interleukin 6 in the pathogenesis of refractoriness of the disease in this patient, and these findings might be indicative of potential efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an interleukin 6 inhibitor. PMID:24455384

  9. EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells.

    PubMed

    Martínez-Palacián, A; del Castillo, G; Herrera, B; Fernández, M; Roncero, C; Fabregat, I; Sánchez, A

    2012-02-01

    Liver progenitor cells rise as potential critical players in hepatic regeneration but also carcinogenesis. It is therefore mandatory to define the signals controlling their activation and expansion. Recently, by using a novel in vitro model of oval cell lines expressing a mutant tyrosine kinase-inactive form of c-Met we demonstrated that autocrine c-Met signalling plays an essential role in promoting oval cell survival. Here, we investigated the significance of the epidermal growth factor receptor (EGFR) signalling in oval cell proliferation and survival, as well as a potential functional crosstalk between the c-Met and the EGFR pathways. We found an autocrine activation of the EGFR-triggered pathway in Met(flx/flx) and Met(-/-) oval cells as judged by constitutive expression of the EGFR ligands, transforming growth factor-alpha (TGF-α) and heparin-binding EGF like growth factor (HB-EGF), and activation of EGFR. On the other hand, treatment with AG1478, a specific inhibitor of EGFR, effectively blocked endogenous and EGF-induced proliferation, while increased serum withdrawal and transforming growth factor-beta (TGF-β)-induced apoptosis. These results suggest that constitutively activated EGFR might promote oval cell proliferation and survival. We found that hepatocyte growth factor (HGF) does not transactivate EGFR nor EGF transactivates c-Met. Furthermore, treatment with AG1478 or EGFR gene silencing did not interfere with HGF-mediated activation of target signals, such as protein kinase B (AKT/PKB), and extracellular signal-regulated kinases 1/2 (ERK 1/2), nor did it have any effect on HGF-induced proliferative and antiapoptotic activities in Met(flx/flx) cells, showing that HGF does not require EGFR activation to mediate such responses. EGF induced proliferation and survival equally in Met(flx/flx) and Met(-/-) oval cells, proving that EGFR signalling does not depend on c-Met tyrosine kinase activity. Together, our results provide strong evidence that in

  10. 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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2012-01-01

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

  13. Liver transplantation: current concepts.

    PubMed Central

    Wall, W J

    1988-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  18. Acute liver failure and liver transplantation.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

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

  19. Liver Wellness

    MedlinePlus

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

  20. Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

    ClinicalTrials.gov

    2013-06-03

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  1. Association between Dietary Vitamin C Intake and Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study among Middle-Aged and Older Adults

    PubMed Central

    Wei, Jie; Lei, Guang-hua; Fu, Lei; Zeng, Chao; Yang, Tuo; Peng, Shi-fang

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disease all over the world. The objective of this study was to evaluate the association between dietary vitamin C intake and NAFLD. Method Subjects were diagnosed with NAFLD by abdominal ultrasound examination and the consumption of alcohol was less than 40g/day for men or less than 20g/day for women. Vitamin C intake was classified into four categories according to the quartile distribution in the study population: ≤74.80 mg/day, 74.81–110.15 mg/day, 110.16–146.06 mg/day, and ≥146.07 mg/day. The energy and multi-variable adjusted odds ratio (OR), as well as their corresponding 95% confidence interval (CI), were used to determine the relationship between dietary vitamin C intake and NAFLD through logistic regression. Result The present cross-sectional study included 3471 subjects. A significant inverse association between dietary vitamin C intake and NAFLD was observed in the energy-adjusted and the multivariable model. The multivariable adjusted ORs (95%CI) for NAFLD were 0.69 (95%CI: 0.54–0.89), 0.93 (95%CI: 0.72–1.20), and 0.71 (95%CI: 0.53–0.95) in the second, third and fourth dietary vitamin C intake quartiles, respectively, compared with the lowest (first) quartile. The relative odds of NAFLD was decreased by 0.71 times in the fourth quartile of dietary vitamin C intake compared with the lowest quartile. After stratifying data by sex or the status of obesity, the inverse association remained valid in the male population or non-obesity population, but not in the female population or obesity population. Conclusion There might be a moderate inverse association between dietary vitamin C intake and NAFLD in middle-aged and older adults, especially for the male population and non-obesity population. PMID:26824361

  2. Higher Estimated Net Endogenous Acid Production May Be Associated with Increased Prevalence of Nonalcoholic Fatty Liver Disease in Chinese Adults in Hong Kong

    PubMed Central

    Chan, Ruth; Wong, Vincent Wai-Sun; Chu, Winnie Chiu-Wing; Wong, Grace Lai-Hung; Li, Liz Sin; Leung, Jason; Chim, Angel Mei-Ling; Yeung, David Ka-Wai; Sea, Mandy Man-Mei; Woo, Jean; Chan, Francis Ka-Leung; Chan, Henry Lik-Yuen

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been associated with reduced growth hormone levels and signaling. Such hormonal changes also occur in metabolic acidosis. Since mild metabolic acidosis can be diet induced, diet-induced acid load may constitute a nutritional factor with possible influence on NAFLD development. This study explored whether a higher diet-induced acid load is associated with an increased likelihood of NAFLD. Apparently healthy Chinese adults (330 male, 463 female) aged 19-72 years were recruited through population screening between 2008 and 2010 in a cross-sectional population-based study in Hong Kong. Estimated net endogenous acid production (NEAP) was calculated using Frassetto’s method and potential renal acid load (PRAL) was calculated using Remer’s method based on dietary data from a food frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content at >5% by proton-magnetic resonance spectroscopy. Possible advanced fibrosis was defined as liver stiffness at >7.9 kPa by transient elastography. Multivariate logistic regression models were used to examine the association between each measure of dietary acid load and prevalent NAFLD or possible advanced fibrosis with adjustment for potential anthropometric and lifestyle factors. 220 subjects (27.7%) were diagnosed with NAFLD. Estimated NEAP was positively associated with the likelihood of having NAFLD after adjustment for age, sex, body mass index, current drinker status and the presence of metabolic syndrome [OR (95% CI) = 1.25 (1.02-1.52), p = 0.022]. The association was slightly attenuated but remained significant when the model was further adjusted for other dietary variables. No association between PRAL and NAFLD prevalence was observed. Both estimated NEAP and PRAL were not associated with the presence of possible advance fibrosis. Our findings suggest that there may be a modest association between diet-induced acid load and NAFLD. More studies are needed to

  3. Spontaneous liver fibrosis induced by long term dietary vitamin D deficiency in adult mice is related to chronic inflammation and enhanced apoptosis.

    PubMed

    Zhu, Longdong; Kong, Ming; Han, Yuan-Ping; Bai, Li; Zhang, Xiaohui; Chen, Yu; Zheng, Sujun; Yuan, Hong; Duan, Zhongping

    2015-05-01

    Epidemiological studies have revealed an association between vitamin D deficiency and various chronic liver diseases. However, it is not known whether lack of vitamin D can induce spontaneous liver fibrosis in an animal model. To study this, mice were fed either a control diet or a vitamin D deficient diet (VDD diet). For the positive control, liver fibrosis was induced with carbon tetrachloride. Here we show, for the first time, that liver fibrosis spontaneously developed in mice fed the VDD diet. Long-term administration of a VDD diet resulted in necro-inflammation and liver fibrosis. Inflammatory mediators including tumor necrosis factor-α, interleulin-1, interleukin-6, Toll-like-receptor 4, and monocyte chemotactic protein-1 were up-regulated in the livers of the mice fed the VDD diet. Conversely, the expression of Th2/M2 markers such as IL-10, IL-13, arginase 1, and heme oxygenase-1 were down-regulated in the livers of mice fed the VDD diet. Transforming growth factor-β1 and matrix metalloproteinase 13, which are important for fibrosis, were induced in the livers of mice fed the VDD diet. Moreover, the VDD diet triggered apoptosis in the parenchymal cells, in agreement with the increased levels of Fas and FasL, and decreased Bcl2 and Bclx. Thus, long-term vitamin D deficiency can provoke chronic inflammation that can induce liver apoptosis, which consequently activates hepatic stellate cells to initiate liver fibrosis.

  4. Liver biopsy

    MedlinePlus

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

  5. Liver Diseases

    MedlinePlus

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

  6. Liver Transplant

    MedlinePlus

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

  7. Liver disease

    MedlinePlus

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  10. Hepatitis C: liver transplantation.

    PubMed

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

    2014-12-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-02-01

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

  14. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  15. Induction of digitoxigenin monodigitoxoside UDP-glucuronosyltransferase activity by glucocorticoids and other inducers of cytochrome P-450p in primary monolayer cultures of adult rat hepatocytes and in human liver.

    PubMed

    Schuetz, E G; Hazelton, G A; Hall, J; Watkins, P B; Klaassen, C D; Guzelian, P S

    1986-06-25

    We have recently proposed that glucocorticoids induce cytochrome P-450p, a liver microsomal hemoprotein originally isolated from rats treated with the antiglucocorticoid pregnenolone 16 alpha-carbonitrile (PCN), through a mechanism that involves a stereospecific recognition system clearly distinguishable from the classic glucocorticoid receptor (Schuetz, E. G., Wrighton, S. A., Barwick, J. L., and Guzelian, P. S. (1984) J. Biol. Chem. 259, 1999-2012). We now report that digitoxigenin monodigitoxoside UDP-glucuronosyltransferase (DIG UDP-glucuronosyltransferase), a liver microsomal enzyme activity induced by PCN in rats, is also inducible, as is P-450p, in primary monolayer cultures of adult rat hepatocytes. DIG UDP-glucuronosyltransferase activity closely resembled reported characteristics of induction of P-450p in its time course of induction, concentration-response relationships, exclusivity of induction by steroids with glucocorticoid properties, unusual rank order of potency of glucocorticoid agonists, unusually high ED50 for induction by glucocorticoids, enhanced induction rather than inhibition by anti-glucocorticoids in the presence of glucocorticoids, and finally, induction by nonsteroidal inducers of P-450p. DIG UDP-glucuronosyltransferase activity was also readily detected in human liver microsomes and was elevated in two patients who had received inducers of P-450p. We conclude that the liver enzymes controlled by the postulated PCN recognition system include not only P-450p but also one or more UDP-glucuronosyltransferases.

  16. Liver regeneration.

    PubMed

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

    2014-04-01

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

  17. 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

  18. Fasting Plasma Insulin Concentrations Are Associated With Changes in Hepatic Fatty Acid Synthesis and Partitioning Prior to Changes in Liver Fat Content in Healthy Adults.

    PubMed

    Pramfalk, Camilla; Pavlides, Michael; Banerjee, Rajarshi; McNeil, Catriona A; Neubauer, Stefan; Karpe, Fredrik; Hodson, Leanne

    2016-07-01

    Resistance to the action of insulin affects fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver, and triglyceride export from the liver. To understand the metabolic consequences of hepatic fatty acid synthesis, partitioning, oxidation, and net liver fat content in the fasted and postprandial states, we used stable-isotope tracer methodologies to study healthy men and women with varying degrees of insulin resistance before and after consumption of a mixed meal. Subjects were classified as being normoinsulinemic (NI) (fasting plasma insulin <11.2 mU/L, n = 18) or hyperinsulinemic (HI) (fasting plasma insulin >11.2 mU/L, n = 19). Liver fat content was similar between HI and NI individuals, despite HI subjects having marginally more visceral fat. However, de novo lipogenesis was higher and fatty acid oxidation was lower in HI individuals compared with NI subjects. These data suggest that metabolic pathways promoting fat accumulation are enhanced in HI but, paradoxically, without any significant effect on liver fat content when observed in healthy people. This is likely to be explained by increased triglyceride secretion as observed by hypertriglyceridemia. PMID:27207513

  19. American Liver Foundation

    MedlinePlus

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

  20. 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...

  1. Liver Biopsy

    MedlinePlus

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

  2. Obesity, inflammation, and liver cancer.

    PubMed

    Sun, Beicheng; Karin, Michael

    2012-03-01

    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  3. Isolation and characterization of a mutant liver aldolase in adult hereditary fructose intolerance. Identification of the enzyme variant by radioassay in tissue biopsy specimens

    PubMed Central

    Cox, Timothy M.; O'Donnell, Martin W.; Camilleri, Michael; Burghes, Arthur H.

    1983-01-01

    Hereditary fructose intolerance (HFI) is a metabolic disorder caused by enzymic deficiency of aldolase B, a genetically distinct cytosolic isoenzyme expressed exclusively in liver, kidney, and intestine. The molecular basis of this enzyme defect has been investigated in three affected individuals from a nonconsanguineous kindred, in whom fructose-l-phosphate aldolase activities in liver or intestinal biopsy samples were reduced to 2-6% of mean control values. To identify a putative enzyme mutant in tissue extracts, aldolase B was purified from human liver by affinity chromatography and monospecific antibodies were prepared from antiserum raised in sheep. Immunodiffusion gels showed a single precipitin line common to pure enzyme and extracts of normal liver and intestine, but no reaction with extracts of brain, muscle, or HFI liver. However, weak positive staining for aldolase in hepatocyte and enterocyte cytosol was demonstrated by indirect immunofluorescence of HFI tissues. This was abolished by pretreatment with pure enzyme protein. Accordingly, a specific radioimmunoassay (detection limit 7.5 ng) was established to quantify immunoreactive aldolase B in human biopsy specimens. Extracts of tissue from affected patients gave 10-25% immunoreactive enzyme in control samples; immunoreactive aldolase in intestinal extracts from four heterozygotes was reduced (to 55%) when compared with seven samples from normal control subjects (P < 0.05). In extracts of HFI tissues, there was a sevenfold reduction in apparent absolute specific activity (1.02 vs. 8.82 U/mg) of immunoreactive fructose-l-phosphate aldolase B, but the apparent specific activity in heterozygotes (7.71 U/mg) was only slightly impaired. Displacement radioimmunotitration of aldolase B in liver supernatants showed a significant (P < 0.005) decrease in antibody avidity for immunoreactive protein in HFI tissue when compared with the pure enzyme or extract of normal control liver. Immunoaffinity chromatography on

  4. 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

  5. Population Pharmacokinetic Modeling of Tribendimidine Metabolites in Opisthorchis viverrini-Infected Adults

    PubMed Central

    Penny, Melissa A.; Duthaler, Urs; Odermatt, Peter; Sayasone, Somphou; Keiser, Jennifer

    2016-01-01

    There is a pressing need for alternative treatments against the liver fluke Opisthorchis viverrini. Oral tribendimidine is a promising candidate, but its population pharmacokinetic properties are unknown. Two phase IIa trials were conducted in Laos in O. viverrini-infected adults receiving single oral doses of 25 to 600 mg tribendimidine administered as different formulations in each study (study 1 used 200-mg tablets, and study 2 used 50-mg tablets). Venous whole blood, plasma, and capillary dried blood spots were sampled frequently from 68 adults, and concentrations of the tribendimidine metabolites dADT (deacetylated amidantel) and adADT (acetylated dADT) were measured. Population pharmacokinetics were assessed by using nonlinear mixed-effects modeling. The relationship between drug exposure and cure (assessed at 21 days posttreatment) was evaluated by using univariable logistic regression. A six-transit compartment absorption model with a one-disposition compartment for each metabolite described the data well. Compared to the 50-mg formulation (study 2), the 200-mg formulation (study 1) had a 40.1% higher mean transit absorption time, a 113% higher dADT volume of distribution, and a 364% higher adADT volume of distribution. Each 10-year increase in age was associated with a 12.7% lower dADT clearance and a 21.2% lower adADT clearance. The highest cure rates (≥55%) were observed with doses of ≥100 mg. Higher dADT, but not adADT, peak concentrations and exposures were associated with cure (P = 0.004 and 0.003, respectively). For the first time, population pharmacokinetics of tribendimidine have been described. Known differences in the 200-mg versus 50-mg formulations were captured by covariate modeling. Further studies are needed to validate the structural model and confirm covariate relationships. (This study has been registered with the ISRCTN Registry under no. ISRCTN96948551.) PMID:27431233

  6. 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.

  7. The quantification of liver anatomical changes and assessment of occupant liver injury patterns.

    PubMed

    Parenteau, Chantal S; Ehrlich, Peter; Ma, Linda; Su, Grace L; Holcombe, Sven; Wang, Stewart C

    2013-11-01

    Liver injuries can be significant in vehicle crashes. In this study, the liver anatomy was quantified in both adult and pediatric populations as a function of gender and age. Five anatomical liver measurements were determined using CT scans of 260 normal livers. These measurements include the area and volume, and the length, width, and girth of the liver (IRB HUM00041441). To characterize geometrical shape, an inscribed sphere and circumscribed ellipsoid were fitted on the measurements. In the pediatric population the liver area and volume continuously increased with age. When normalized by patient weight, volume measurements show a decrease in volume with age, suggesting that the liver occupies a smaller proportion of the body with age. In the adult population, liver measurements varied with gender. The superior and inferior locations of the liver were also recorded with respect to the spine. The lower portion was at the L3 in small children and at L2 as children approached puberty. It stayed in that area through the 60+ group, offering more ribcage protection. Liver injury patterns were also assessed in crash occupants. Seventy-two occupants with moderate to severe (AIS 2+) liver injuries were investigated. A new methodology was presented and consisted of quantifying blood volumes. The results were compared to overall liver volume and injury scales. No clear distinction on the injury pattern was observed by age group. Liver injuries were more commonly associated with AIS 2+ thoracic injuries in adults than in children. Most injuries occurred in the right lobe. PMID:24435735

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

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

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

  9. 21 CFR 520.462 - Clorsulon drench.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of body weight). (2) Indications for use. For the treatment of immature and adult liver fluke... established, do not use in female dairy cattle of breeding age. Consult your veterinarian for assistance...

  10. Current Management of Neonatal Liver Tumors.

    PubMed

    Langham, Max R; Furman, Wayne L; Fernandez-Pineda, Israel

    2015-01-01

    This review is focused on the special issues and challenges confronting physicians and surgeons caring for an unborn child, or a newborn with a liver tumor. Liver tumors at this age are very rare and they make it difficult for pediatric surgeons to gain experience necessary to obtain good results. On the other hand, adult hepatobiliary surgeons faced with a fetus or infant with a liver mass are ill equipped to care for the patient even if they have done a high volume of adult liver surgery and are expert in the field. Often a team approach is the best solution. PMID:26168944

  11. Phenological and liver antioxidant profiles of adult Nile tilapia (Oreochromis niloticus) exposed to toxic live cyanobacterium (Microcystis aeruginosa Kützing) cells.

    PubMed

    Khairy, Hanan M; Ibrahim, Marwa A; Ibrahem, Mai D

    2012-01-01

    Blue-green algae (cyanobacteria) constitute the greater part of the phytoplankton. Microcystis aeruginosa is amongst the most ubiquitously distributed cyanobacterial species, and almost invariably produces cyclic heptapeptide toxins called microcystins (MCs). The present study was designed to investigate the phenological and liver antioxidant profiles of the Nile tilapia Oreochromis niloticus chronically exposed to toxic live M. aeruginosa cells. Fish were grown in the absence and presence of M. aeruginosa in three different concentrations for seven days, and subsequently reared for another 30 days in the absence of the cyanobacteria. While cyanobacteria did not cause any fish mortality, there was a progressive development of yellowish discolouration in the livers of exposed fish. In the livers, the activities and levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), glutathione (GSH), and lipid peroxidation products like malondialdehyde (MDA) were elevated in response to the concentration of M. aeruginosa. Moreover, DNA fragmentation and DNA-protein crosslinks were measured. These parameters can thus be considered potential biomarkers for the fish exposure to M. aeruginosa. The present study sheds light on cyanobacterial blooms like health, environmental, and economic problem, respectively. PMID:23413757

  12. Interventional Radiology in Liver Transplantation

    SciTech Connect

    Karani, John B. Yu, Dominic F.Q.C.; Kane, Pauline A.

    2005-04-15

    Radiology is a key specialty within a liver transplant program. Interventional techniques not only contribute to graft and recipient survival but also allow appropriate patient selection and ensure that recipients with severe liver decompensation, hepatocellular carcinoma or portal hypertension are transplanted with the best chance of prolonged survival. Equally inappropriate selection for these techniques may adversely affect survival. Liver transplantation is a dynamic field of innovative surgical techniques with a requirement for interventional radiology to parallel these developments. This paper reviews the current practice within a major European center for adult and pediatric transplantation.

  13. Autoantibodies in autoimmune liver diseases.

    PubMed

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  14. Liver spots

    MedlinePlus

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

  15. Aromatase deficiency in a Chinese adult man caused by novel compound heterozygous CYP19A1 mutations: Effects of estrogen replacement therapy on the bone, lipid, liver and glucose metabolism

    PubMed Central

    Chen, Zhike; Wang, Ou; Nie, Min; Elison, Kathleen; Zhou, Dujin; Li, Mei; Jiang, Yan; Xia, Weibo; Meng, Xunwu; Chen, Shiuan; Xing, Xiaoping

    2015-01-01

    Objectives Aromatase deficiency is a rare disorder resulting in estrogen insufficiency in humans. It has been reported in remarkably few men with loss-of-function mutations in the CYP19A1 gene encoding the aromatase, a cytochrome P450 enzyme that plays a crucial role in the biosynthesis of estrogens from androgens. We investigated a non-consanguineous family including an adult man with clinical features of aromatase deficiency, and studied the effects of estrogen replacement in the man. Methods We investigated the clinical and biochemical phenotype, performed CYP19A1 mutational analysis in the family and 50 unrelated persons, studied the effects of CYP19A1 mutations on aromatase protein structure, functionally characterized the mutations by cell-based aromatase activity assays, and studied the effects of estrogen replacement on the bone, lipid, liver and glucose metabolism. Results The man with clinical features of aromatase deficiency had novel compound heterozygous CYP19A1 mutations (Y81C and L451P) that were not found in 50 unrelated persons. Three-dimensional modeling predicted that Y81C and L451P mutants disrupted protein structure. Functional studies on the basis of in vitro expression showed that Y81C and L45P mutants significantly decreased the aromatase activity and catalytic efficiency. Estrogen replacement in the man increased bone mineral density, accelerated bone maturation, improved lipid profile and liver steatosis, and improved glucose levels but not insulin resistance. Conclusions We have identified two novel CYP19A1 missense mutations in an aromatase-deficient man. Estrogen replacement in the man shows great impact on recovering the impairments in the bone, lipid, liver and glucose metabolism, but fails to improve insulin resistance. PMID:25301327

  16. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.

    PubMed

    Miyakawa, Hiroshi; Kawashima, Yumi; Kitazawa, Eriko; Kawaguchi, Naomi; Kato, Takashi; Kikuchi, Kentaro; Imai, Erika; Fujikawa, Hirotoshi; Hashimoto, Etsuko; Schlumberger, Wolfgang

    2003-08-01

    Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.

  17. Equal overall rejection rate in pre-transplant flow-cytometric cross-match negative and positive adult recipients in liver transplantation.

    PubMed

    Matinlauri, Irma H; Höckerstedt, Krister A; Isoniemi, Helena M

    2005-10-01

    T cell IgG flow-cytometric cross-matches (FCXM) using 48 stored pre-transplant patient serum samples and 40 stored serum samples collected 3 wk after liver transplantation and frozen spleen cells of cadaveric donors in 48 consecutive liver transplantations were performed retrospectively. T cell IgG FCXM using pre-transplant serum samples was compared with 46 complement-dependent lymphocytotoxic cross-matches (CDCXM) performed at the time of transplantation. Clinical relevance of these tests was evaluated in relation to acute rejection, 1-, 3- and 5-yr graft and patient survival. The incidence of positive FCXM was 33% (16 of 48) and 13% (six of 46) by CDCXM. The median time of acute rejection was 29 d after transplantation in FCXM positive group (range 13-101 d) and 22 d in FCXM negative group (range 7-157 d, NS). Rejection rate was similar in 16 pre-transplant FCXM positive patients (eight of 16, 50%) compared with six pre-transplant CDCXM positive patients (three of six, 50%; NS). Recipients having graft rejection tended to be more often pre-transplant FCXM positive (eight of 21, 38%) than CDCXM positive (three of 21, 14%), but the difference was not significant (p > 0.1). No difference was found in the positive predictive value in relation to acute rejection between positive FCXM and CDCXM (69% vs. 50%; NS). Furthermore there was no correlation between post-transplant positive FCXM and acute rejection. No difference was found between pre-transplant T cell IgG FCXM positive and negative recipients in relation to graft or patient survival. Our findings are supportive for little risk associated with preformed donor-specific antibodies in liver transplantation.

  18. Clinical implications of advances in liver regeneration.

    PubMed

    Kwon, Yong Jin; Lee, Kyeong Geun; Choi, Dongho

    2015-03-01

    Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

  19. Possible discovery of Chinese lung fluke, Paragonimus skrjabini in Manipur, India.

    PubMed

    Singh, Shantikumar T; Singh, Deven L; Sugiyama, Hiromu

    2006-01-01

    To obtain more information about Paragonimus species prevalent in Manipur, India, hundreds of freshwater crabs, Potamiscus manipurensis, were captured from mountain streams in the Motbung Mountains in Senapati District, from December 1997 to January 1998. Crab extracts were prepared by digestion, differential filtration, and sedimentation. The filtered sediments were critically examined under a stereomicroscope. Isolated Paragonimus metacercariae were used for morphological study and animal experimentation. Forty-seven metacercariae were fed orally to a 3-month-old male puppy of local breed; at autopsy 155 days after inoculation, 12 adult worms were recovered; 2 were free in the thoracic cavity and 5 pairs were in lung cysts. Two adult worms were flattened and fixed in 70% ethanol and the remaining worms were put directly into 70% ethanol and preserved until July 2005. The former 2 worms were stained with borax carmine for morphological study at Sikkim Manipal Institute of Medical Sciences, Sikkim, India. Two adult worms in the latter group were sent to the National Institute of Infectious Diseases, Tokyo, Japan, for morphological identification and DNA sequencing. The morphological features of the borax carmine-stained worms were characteristic of P. skrjabini, although no genetic material for PCR amplification and sequencing could be extracted from the worm.

  20. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer.

    PubMed

    Katoh, Yuriko; Katoh, Masaru

    2007-03-01

    Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate FGF20, JAG1, DKK1, WISP1, CCND1 and MYC genes for cell-fate determination, while non-canonical WNT signals are transduced through FZD family receptor and ROR2/PTK7/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NLK and NFAT signaling cascades for the regulation of tissue polarity, cell movement, and adhesion. We previously reported molecular cloning and characterization of human FZD5, which showed six amino-acid substitutions with human Hfz5. FZD5, functioning as WNT5A receptor, is the key molecule in the fields of oncology, regenerative medicine, cardiology, rheumatology, diabetology, and gastroenterology. Here, comparative integromics analyses on FZD5 orthologs were performed by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD5 and cow Fzd5 genes were identified within NW_104292.1 and AC166656.2 genome sequences, respectively. FZD5 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser523 and Ser529 around the DVL-binding motif of FZD5 orthologs were putative aPKC phosphorylation sites. POU5F1 (OCT4)-binding site linked to SP1-binding site within the 5'-promoter region of human FZD5 gene was evolutionarily conserved among mammalian FZD5 orthologs. POU5F1 was more related to POU2F and POU3F subfamily members. POU5F1 was preferentially expressed in undifferentiated human embryonic stem (ES) cells, pancreatic islet, and diffuse-type gastric cancer. POU2F1 (OCT1) was expressed in ES cells, fetal liver/spleen, adult colon, POU2F2 in ES cells, fetal liver/spleen, and POU2F3 in diffuse-type gastric cancer. Multiple SP1/KLF family members, other than KLF2 or KLF4, were expressed in undifferentiated human ES cells. Together, these facts indicate that POU5F1 and POU2F subfamily members

  1. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

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

  2. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    PubMed Central

    dos Santos, Bruno; Estadella, Debora; Hachul, Ana Cláudia Losinskas; Okuda, Marcos Hiromu; Moreno, Mayara Franzoi; Oyama, Lila Missae; Ribeiro, Eliane Beraldi; Oller do Nascimento, Claudia Maria da Penha

    2013-01-01

    This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver. PMID:24027356

  3. Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A.

    PubMed

    van Esterik, J C J; Vitins, A P; Hodemaekers, H M; Kamstra, J H; Legler, J; Pennings, J L A; Steegenga, W T; Lute, C; Jelinek, J; Issa, J P J; Dollé, M E T; van der Ven, L T M

    2015-01-01

    Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0-3000μg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000μg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.

  4. What Is Liver Cancer?

    MedlinePlus

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

  5. Benign Liver Tumors

    MedlinePlus

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

  6. Living related liver transplantation.

    PubMed

    Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M

    1992-01-01

    Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

  7. Technical Skills Required in Split Liver Transplantation.

    PubMed

    Liu, Huanqiu; Li, Ruijun; Fu, Jinling; He, Qianyan; Li, Ji

    2016-01-01

    The number of liver grafts obtained from a cadaver can be greatly increased with the application of split liver transplantation. In the last 10 years, pediatric waiting list mortality has been reduced significantly with the use of this form of liver transplantation, which has 2 major forms. In its most commonly used form, the liver can be transplanted into 1 adult and 1 child by splitting it into a right extended and a left lateral graft. For adult and pediatric recipients, the results of this procedure are comparable to those of whole-organ techniques. In another form, 2 hemi-grafts are obtained by splitting the liver, which can be transplanted into a medium-sized adult (the right side) and a large child/small adult (the left side). The adult liver graft pool is expanded through the process of full right/full left splitting; but it is also a critical technique when one considers the knowledge required of the potential anatomic variations and the high technical skill level needed. In this review, we provide some basic insights into the technical and anatomical aspects of these 2 forms of split liver transplantation and present an updated summary of both forms. PMID:27363540

  8. Liver Panel

    MedlinePlus

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

  9. Liver transplant

    MedlinePlus

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

  10. Liver cirrhosis.

    PubMed Central

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

    1998-01-01

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

  11. Effects of Mirazid® and myrrh volatile oil on adult Fasciola gigantica under laboratory conditions

    PubMed Central

    Massoud, AM; Shalaby, HA; El Khateeb, RM; Mahmoud, MS; Kutkat, MA

    2012-01-01

    Objective To evaluate the effects of Mirazid® and myrrh volatile oil on adult Fasciola gigantica (F. gigantica ) under laboratory conditions. Methods The effects of oleoresin extract of myrrh (Mirazid®) and myrrh volatile oil on the surface morphology of adult F. gigantica following treatment in vitro had been determined by scanning electron microscopy. The results were compared with those observed in the fluke tegument following incubation in triclabendazole sulphoxide (TCBZ-SO), active form, (Fasinex®, Ciba-Geigy). Results Observations of the efficacy of Mirazid® oleoresin extract and myrrh volatile oil indicated that both products showed dose-dependent anthelmintic efficacy. The anterior half of the fluke was consistently more severely affected than the posterior half. The surface changes induced by Mirazid® oleoresin extract were less severe than those observed after exposure to either myrrh volatile oil or TCBZ-SO. Flukes showed swelling after these treatments, but its level and blebbing were much greater with myrrh volatile oil; in which patches of tegumental sloughing were observed in the apical cone and the posterior mid-body region of flukes. This was not observed after treatment with Mirazid® oleoresin extract. Conclusions The comparatively more disruption, observed in myrrh volatile oil exposed specimens, compared to that exposed to Mirazid® oleoresin extract might suggest that the anthelmintic activity of Mirazid® oleo resin extract was attributed to its content of volatile oil. So, increasing the concentration of myrrh volatile oil in Mirazid® might possibly help to developing its anthelmintic activity. PMID:23569864

  12. 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

  13. Biomarkers in Pediatric Liver Disease.

    PubMed

    Kyrana, Eirini; Fitzpatrick, Emer; Dhawan, Anil

    2016-01-01

    The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

  14. Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies.

    PubMed

    Ferlemi, Anastasia-Varvara; Katsikoudi, Antigoni; Kontogianni, Vassiliki G; Kellici, Tahsin F; Iatrou, Grigoris; Lamari, Fotini N; Tzakos, Andreas G; Margarity, Marigoula

    2015-07-25

    Our aim was to investigate the possible effects of regular drinking of Rosmarinus officinalis L. leaf infusion on behavior and on AChE activity of mice. Rosemary tea (2% w/w) phytochemical profile was investigated through LC/DAD/ESI-MS(n). Adult male mice were randomly divided into two groups: "Rosemary-treated" that received orally the rosemary tea for 4weeks and "control" that received drinking water. The effects of regular drinking of rosemary tea on behavioral parameters were assessed by passive avoidance, elevated plus maze and forced swimming tests. Moreover, its effects on cerebral and liver cholinesterase (ChE) isoforms activity were examined colorimetricaly. Phytochemical analysis revealed the presence of diterpenes, flavonoids and hydroxycinnamic derivatives in rosemary tea; the major compounds were quantitatively determined. Its consumption rigorously affected anxiety/fear and depression-like behavior of mice, though memory/learning was unaffected. ChE isoforms activity was significantly decreased in brain and liver of "rosemary treated" mice. In order to explain the tissue ChE inhibition, principal component analysis, pharmacophore alignment and molecular docking were used to explore a possible relationship between main identified compounds of rosemary tea, i.e. rosmarinic acid, luteolin-7-O-glucuronide, caffeic acid and known AChE inhibitors. Results revealed potential common pharmacophores of the phenolic components with the inhibitors. Our findings suggest that rosemary tea administration exerts anxiolytic and antidepressant effects on mice and inhibits ChE activity; its main phytochemicals may function in a similar way as inhibitors.

  15. Application of a Bayesian simulation model to a database for split liver transplantation on two adult recipients in the environment of WinBUGS (Bayesian Inference Using Gibbs Sampling).

    PubMed

    Santori, G; Valente, R; Andorno, E; Ghirelli, R; Valente, U

    2007-01-01

    A Bayesian simulation model has been applied to a database developed for split liver transplantation on two adult recipients (SLT A/A) in the context of a macroregional project funded by the Italian Ministry of Health. The model was entered within Bayesian inference Using Gibbs Sampling (WinBUGS), a free software for Bayesian analysis of complex statistical models using Markov chain Monte Carlo techniques developed by the MRC Biostatistics Unit Cambridge jointly with the Imperial College School of Medicine at St Mary's, London. The model was built by using data entry performed from January 1, 2005 to August 5, 2005. In that period, 20 potential donors suitable for the SLT A/A procedure were entered into the database. We only selected the continuous and dichotomous donor-related variables (DRV, n = 62) for which almost one data entry procedure. The model assumed that a database user learned during data entry procedures for each donor, and that the probability of a successful input may depend on the number of previous errors and corrections. After binary transformation of the DRV (value 0 for each input record, value 1 for each no input record), we calculated an overall value of 0.28 +/- 0.27 (median: 0.3; 95% confidence interval: from 0.18 to 0.629). The transformed DRV were entered within the WinBUGS environment after model specification, assuming as success (y = 1) each procedure of input record, and as failure (y = 0) each procedure of no input record. A unequivocal convergence was obtained after 10,000 iterations, and a simulation run was launched for a further 10,000 updates. We obtained a negligible Monte Carlo error and a fine profile in the kernel density plot. This study supported the application of simulation models to databases concerning liver transplantation as a useful strategy to identify a critical state in the data entry process. PMID:17692652

  16. Liver transplantation in Spain.

    PubMed

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  17. Comparison of liver mitochondrial proteins derived from newborn cloned calves and from cloned adult cattle by two-dimensional differential gel electrophoresis.

    PubMed

    Takeda, Kumiko; Tasai, Mariko; Akagi, Satoshi; Watanabe, Shinya; Oe, Mika; Chikuni, Koichi; Ohnishi-Kameyama, Mayumi; Hanada, Hirofumi; Nakamura, Yoshiaki; Tagami, Takahiro; Nirasawa, Keijiro

    2011-04-01

    Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. The inability to establish functional interactions between donor nucleus and recipient mitochondria is also likely responsible for such a developmental deficiency. However, detailed knowledge of protein expression during somatic cell nuclear transfer (SCNT) in cattle is lacking. In the present study, variations in mitochondrial protein levels between SCNT-derived and control cattle, and from calves derived by artificial insemination were investigated. Mitochondrial fractions were prepared from frozen liver samples and subjected to two-dimensional (2-D) fluorescence differential gel electrophoresis (DIGE) using CyDye™ dyes. Protein expression changes were confirmed with a volume ratio greater than 2.0 (P < 0.05). 2D-DIGE analysis revealed differential expression of three proteins for SCNT cattle (n = 4) and seven proteins for SCNT calves (n = 6) compared to controls (P < 0.05). Different protein patterning was observed among SCNT animals even if animals were generated from the same donor cell source. No differences were detected in two of the SCNT cattle. Moreover, there was no novel protein identified in any of the SCNT cattle or calves. In conclusion, variation in mitochondrial protein expression concentrations was observed in non-viable, neonatal SCNT calves and among SCNT individuals. This result implicates mitochondrial-related gene expression in early developmental loss of SCNT embryos. Comparative proteomic analysis represents an important tool for further studies on SCNT animals.

  18. Identification and characterization of microRNAs in the zoonotic fluke Fasciolopsis buski.

    PubMed

    Chen, Mu-Xin; Hu, Wei; Li, Juan; He, Jun-Jun; Ai, Lin; Chen, Jia-Xu

    2016-06-01

    Fasciolopsis buski is a food-borne zoonotic parasite which is transmitted by aquatic plants, with pigs and humans as the definitive hosts. The objective of the present study was to characterize the microRNA (miRNA) profiles of this parasite by Solexa deep sequencing and bioinformatic analysis. Approximately 12 million high-quality reads were obtained from adult F. buski. A total of 286 miRNA candidates were found and 24 miRNA candidates were conserved miRNAs in the miRBase database. Three novel miRNAs were identified and confirmed by stem-loop reverse transcriptase polymerase chain reaction (RT-PCR). The miRNAs found in the present study belong to 13 families whose members showed high bias. The guanine (G) was the dominant nucleotide at the beginning and middle of the conserved miRNAs, particularly at the positions of 2nd, 6th, and 13th. To our knowledge, this is the first report of the miRNA profiles of F. buski, which would lay a foundation for further functional studies of miRNAs of F. buski.

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

    PubMed

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

    2008-01-01

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

  20. Corset liver

    SciTech Connect

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

    1985-08-01

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

  1. Liver cancer - hepatocellular carcinoma

    MedlinePlus

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

  2. Liver disease - resources

    MedlinePlus

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

  3. Tests for Liver Cancer

    MedlinePlus

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

  4. Blood flukes (Digenea: Aporocotylidae) infecting body cavity of South American catfishes (Siluriformes: Pimelodidae): two new species from rivers in Bolivia, Guyana and Peru with a re-assessment of Plehniella Szidat, 1951.

    PubMed

    Orelis-Ribeiro, Raphael; Bullard, Stephen A

    2015-01-01

    Plehniella Szidat, 1951 is emended based on new collections from South American long-whiskered catfishes. It is clearly differentiated from Sanguinicola Plehn, 1905 by lacking lateral tegumental body spines and by having 6 asymmetrical caeca. Plehniella sabajperezi sp. n. infects body cavity of Pimelodus albofasciatus (Mees) from the Demerara and Rupununi Rivers (Guyana) and Pimelodus blochii (Valenciennes) from Lake Tumi Chucua (Bolivia) and Napo River (Peru). It differs from Plehniella coelomicola Szidat, 1951 (type species) by having a thin-walled vas deferens that greatly exceeds the length of cirrus-sac and that joins the cirrus-sac at level of ovovitelline duct and ootype, an internal seminal vesicle that is absent or diminutive, and a cirrus-sac that is spheroid, nearly marginal, and envelops the laterally-directed distal portion of the male genitalia. Plehniella armbrusteri sp. n. infects body cavity of P. blochii from Lake Tumi Chucua (Bolivia). It differs from P. coelomicola and P. sabajperezi by having a relatively ovoid body, a massive intestine comprising caeca that are deeply-lobed to diverticulate and terminate in the posterior half of the body, a testis that flanks the distal tips of the posteriorly-directed caeca, and a proximal portion of the vas deferens that loops ventral to the testis. Small adults (Plehniella sp.) collected from body cavity of Pimelodus grosskopfii (Steindachner) from Cienega de Jobo and Canal del Dique (Colombia) differ from congeners by having a posteriorly-constricted body region, an anterior sucker with concentric rows of minute spines, an elongate anterior oesophageal swelling, short and wide caeca, and a male genital pore that opens proportionally more anteriad. This study nearly doubles the number of aporocotylids documented from South America Rivers and comprises the first record of a fish blood fluke from P. blochii, P. albofasciatus and P. grosskopfii as well as from Bolivia, Colombia, Guyana or Peru. PMID:26373332

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

    PubMed

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

    2008-01-01

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

  6. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice.

    PubMed

    Lepus, Christin M; Gibson, Thomas F; Gerber, Scott A; Kawikova, Ivana; Szczepanik, Marian; Hossain, Jaber; Ablamunits, Vitaly; Kirkiles-Smith, Nancy; Herold, Kevan C; Donis, Ruben O; Bothwell, Alfred L; Pober, Jordan S; Harding, Martha J

    2009-10-01

    Immunodeficient mice bearing components of a human immune system present a novel approach for studying human immune responses. We investigated the number, phenotype, developmental kinetics, and function of developing human immune cells following transfer of CD34(+) hematopoietic stem cell (HSC) preparations originating from second trimester human fetal liver (HFL), umbilical cord blood (UCB), or granulocyte colony-stimulating factor-mobilized adult blood (G-CSF-AB) delivered via intrahepatic injection into sublethally irradiated neonatal NOD-scid/gammac(-/-), Balb/c-Rag1(-/-)gammac(-/-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/gammac(-/-) and Balb/c-Rag1(-/-)gammac(-/-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/gammac(-/-) mice harbored higher levels of human T cells. NOD-scid/gammac(-/-) mice engrafted with HFL CD34(+) HSC demonstrated human immunological competence evidenced by white pulp expansion and increases in total human immunoglobulin following immunization with T-dependent antigens and delayed-type hypersensitivity-infiltrating leukocytes in response to antigenic challenge. In conclusion, we describe an encouraging base system for studying human hematopoietic lineage development and function utilizing human HFL or UCB HSC-engrafted NOD-scid/gammac(-/-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model.

  7. Stem cells versus plasticity in liver and pancreas regeneration.

    PubMed

    Kopp, Janel L; Grompe, Markus; Sander, Maike

    2016-03-01

    Cell replacement in adult organs can be achieved through stem cell differentiation or the replication or transdifferentiation of existing cells. In the adult liver and pancreas, stem cells have been proposed to replace tissue cells, particularly following injury. Here we review how specialized cell types are produced in the adult liver and pancreas. Based on current evidence, we propose that the plasticity of differentiated cells, rather than stem cells, accounts for tissue repair in both organs.

  8. Stem cells versus plasticity in liver and pancreas regeneration.

    PubMed

    Kopp, Janel L; Grompe, Markus; Sander, Maike

    2016-03-01

    Cell replacement in adult organs can be achieved through stem cell differentiation or the replication or transdifferentiation of existing cells. In the adult liver and pancreas, stem cells have been proposed to replace tissue cells, particularly following injury. Here we review how specialized cell types are produced in the adult liver and pancreas. Based on current evidence, we propose that the plasticity of differentiated cells, rather than stem cells, accounts for tissue repair in both organs. PMID:26911907

  9. 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.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2015-11-01

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

  13. In vitro models for liver toxicity testing

    PubMed Central

    Soldatow, Valerie Y.; LeCluyse, Edward L.; Griffith, Linda G.; Rusyn, Ivan

    2013-01-01

    Over the years, various liver-derived in vitro model systems have been developed to enable investigation of the potential adverse effects of chemicals and drugs. Liver tissue slices, isolated microsomes, perfused liver, immortalized cell lines, and primary hepatocytes have been used extensively. Immortalized cell lines and primary isolated liver cells are currently most widely used in vitro models for liver toxicity testing. Limited throughput, loss of viability, and decreases in liver-specific functionality and gene expression are common shortcomings of these models. Recent developments in the field of in vitro hepatotoxicity include three-dimensional tissue constructs and bioartificial livers, co-cultures of various cell types with hepatocytes, and differentiation of stem cells into hepatic lineage-like cells. In an attempt to provide a more physiological environment for cultured liver cells, some of the novel cell culture systems incorporate fluid flow, micro-circulation, and other forms of organotypic microenvironments. Co-cultures aim to preserve liver-specific morphology and functionality beyond those provided by cultures of pure parenchymal cells. Stem cells, both embryonic- and adult tissue-derived, may provide a limitless supply of hepatocytes from multiple individuals to improve reproducibility and enable testing of the individual-specific toxicity. This review describes various traditional and novel in vitro liver models and provides a perspective on the challenges and opportunities afforded by each individual test system. PMID:23495363

  14. 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

  15. 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

  16. Evaluation of the repeated-dose liver micronucleus assay using N-nitrosomorpholine in young adult rats: report on collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study (MMS) Group.

    PubMed

    Hayashi, Aya; Kosaka, Mizuki; Kimura, Aoi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    The present study was conducted to evaluate the suitability of a repeated-dose liver micronucleus (LMN) assay in young adult rats as a collaborative study by the Mammalian mutagenicity study (MMS) group. All procedures were performed in accordance with the standard protocols of the MMS Group. Six-week-old male Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N-nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14 days. Control animals received vehicle (water). Hepatocytes were collected from the liver 24h after the last dose, and the number of micronucleated hepatocytes (MNHEPs) was determined by microscopy. The number of micronucleated immature erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver was examined using histopathologic methods after formalin fixation. The results showed statistically significant and dose-dependent increases in the number of MNHEPs in the liver at doses of 10mg/kg and greater when compared with the vehicle control. However, no significant increase was noted in the number of MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg and above. These results showed that the induction of micronuclei by NMOR was detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow micronucleus assay.

  17. Genetic Polymorphism of Cytochrome P450 4F2, Vitamin E Level and Histological Response in Adults and Children with Nonalcoholic Fatty Liver Disease Who Participated in PIVENS and TONIC Clinical Trials

    PubMed Central

    Athinarayanan, Shaminie; Wei, Rongrong; Zhang, Min; Bai, Shaochun; Traber, Maret G.; Yates, Katherine; Cummings, Oscar W.; Molleston, Jean; Liu, Wanqing; Chalasani, Naga

    2014-01-01

    Vitamin E improved liver histology in children and adults with NAFLD who participated in TONIC and PIVENS clinical trials, but with significant inter-individual variability in its efficacy. Cytochrome P450 4F2 (CYP4F2) is the major enzyme metabolizing Vit E, with two common genetic variants (V433M, rs2108622 and W12G, rs3093105) found to alter its activity. We investigated the relationship between CYP4F2 genotypes, α-tocopherol levels and histological improvement in these two trials. V433M and W12G variants were genotyped in TONIC (n = 155) and PIVENS (n = 213) DNA samples. The relationships between CYP4F2 genotypes, plasma α-tocopherol levels at baseline and weeks 48 (w48) and 96 (w96) and histological end points (overall improvement in liver histology and resolution of NASH) were investigated. As a result, the V433M genotype was significantly associated with baseline plasma α-tocopherol in the TONIC trial (p = 0.004), but not in PIVENS. Among those receiving Vit E treatment, CYP4F2 V433M genotype was associated with significantly decreased plasma α-tocopherol levels at w48 (p = 0.003 for PIVENS and p = 0.026 for TONIC) but not at w96. The w96 α-tocopherol level was significantly associated with resolution of NASH (p = 0.006) and overall histology improvement (p = 0.021)in the PIVENS, but not in the TONIC trial. There was no significant association between CYP4F2 genotypes and histological end points in either trial. Our study suggested the a moderate role of CYP4F2 polymorphisms in affecting the pharmacokinetics of Vit E as a therapeutic agent. In addition, there may be age-dependent relationship between CYP4F2 genetic variability and Vit E pharmacokinetics in NAFLD. PMID:24759732

  18. 21 CFR 520.38a - Albendazole suspension.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver...) body weight (10 mg/kilogram (kg)) as a single oral dose using dosing gun or dosing syringe. (ii) Indications for use. For removal and control of adult liver flukes (Fasciola hepatica); heads and segments...

  19. 21 CFR 520.45a - Albendazole suspension.