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Although intestinal parasites are no longer considered a significant public health concern in Korea, tissue-invading parasites continue to pose clinical challenges. The diagnosis of tissue helminthiasis by recovering worms or larvae from tissues is invasive; therefore, serodiagnosis is widely used to diagnose infections caused by tissue-invading parasites. Among the serological tests, the enzyme-linked immunosorbent assay (ELISA) is the most commonly used, and various antigens, including crude antigens, excretory-secretory antigens of helminths, and cystic fluid of larval tapeworms, are used to detect specific IgGs against parasite antigens in the sera or cerebrospinal fluid of patients. A multi-antigen ELISA was used to diagnose four major tissue parasitic infections: clonorchiasis, paragonimiasis, cysticercosis, and sparganosis. In addition to these four parasitic infections, ELISA remains a valuable diagnostic method for toxocariasis, trichinellosis, fascioliasis, echinococcosis, and other diseases. A comprehensive history of the mode of transmission of the suspected parasites and the patient’s residence in or travel to an endemic area may help in making a definitive diagnosis. For the management of patients with eosinophilia in Korea, it is essential to perform ELISA for the differential diagnosis of toxocariasis. Serological tests have the disadvantage of being unable to differentiate between past and current infections, and the possibility of cross-reactivity requires careful interpretation. It is important to note that the results of serological tests are not necessarily conclusive and should be interpreted in the context of other symptoms, as well as clinical and imaging findings.

Knowledge about mitogenomes has been proven to be essential in human parasite diagnostics and understanding of their diversity. However, the lack of substantial data for comparative analysis is still a challenge in Trichuris trichiura research. To provide high quality mitogenomes, we utilized long-read sequencing technology of Oxford Nanopore Technologies (ONT) to better resolve repetitive regions and to construct de novo mitogenome assembly minimizing reference biases. In this study, we got three de novo assembled mitogenomes of T. trichiura isolated from Korean individuals. These circular complete mitogenomes of T. trichiura are 14,508 bp, 14,441 bp, and 14,440 bp in length. A total of 37 predicted genes were identified consisting of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNAs) genes, two ribosomal RNA (rRNA) genes (rrnS and rrnL), and two non-coding regions. Interestingly, the assembled mitogenome has up to six times longer AT-rich regions than previous reference sequences, thus proving the advantage of long-read sequencing in resolving unreported non-coding regions. Furthermore, variant detection and phylogenetic analysis using concatenated protein coding genes, cox1, rrnL, and nd1 genes confirmed the distinct molecular identity of this newly assembled mitogenome while at the same time showing high genetic relationship with sequences from China or Tanzania. Our study provided a new set of reference mitogenome with better contiguity and resolved repetitive regions that could be used for meaningful phylogenetic analysis to further understand disease transmission and parasite biology.

BackgroundSoil-transmitted helminthiasis (STH) is endemic in Fiji but its prevalence is not known and likely to have changed after a decade of mass drug administration (MDA) for lymphatic filariasis (LF). By linking with LF transmission assessment surveys (LF-TAS), we undertook the first nation-wide assessment of STH in Fijian primary schools, as well as an analysis of factors associated with STH infections.Methodology/principal findingsA cross-sectional assessment for STH was conducted in all four Divisions of Fiji from 2014 to 2015. In the Western, Central, and Northern Divisions, schools were sub-sampled after LF-TAS, while, in the Eastern Division, schools were selected via simple random sampling. For the diagnosis of STH, stool samples were examined by coproscopy with a single Kato-Katz thick smear (KK) and the formol-ether-acetate concentration technique, except for the samples from the Eastern Division where only KK was used. Mean prevalence of any STH among class 1-2 students at the national level was 10.5% (95% CI: 6.9-15.5). Across the three Divisions via LF-TAS, the prevalence levels for ascariasis were 8.7% (95% CI: 4.3-16.6), hookworm 3.9% (95% CI: 2.3-6.6) and trichuriasis 0%. In the Eastern Division, ascariasis prevalence was 13.3% (95% CI: 6.4-25.6), and hookworm 0.7% (95% CI: 0.2-2.5), with one case of trichuriasis. Among class 3-8 students, ascariasis prevalence was lower. Lower risk of any STH was associated with wearing shoes (adjusted OR 0.54, 95% CI: 0.32-0.90) and having piped water from the Fiji Water Authority at home (adjusted OR 0.48, 95% CI: 0.25-0.92).ConclusionsAfter a decade of community-based LF-MDA, STH in school-age children in Fiji is now close to 10%, but localities of endemicity remain. Preventive chemotherapy should be maintained in areas with elevated STH prevalence alongside targeted delivery of integrated WASH interventions. LF-TAS has provided an opportunity to develop future public health surveillance platforms.

Objectives This study aimed to investigate the current status of infectious disease research in North Korea by analyzing recent trends in medical journals from North Korea in comparison with research from South Korea. Methods Three medical journals (Preventive Medicine, Basic Medicine, and Chosun Medicine) were analyzed from 2012 to 2016. Articles on tuberculosis (TB), malaria, and parasitic diseases were selected and classified by their subtopics and study areas. Two medical journals published in the South Korea were selected for a comparative analysis of research trends. Results Of the 2792 articles that were reviewed, 93 were extracted from North Korea journals. TB research in North Korea was largely focused on multi-drug resistant TB and extrapulmonary TB, whereas research in South Korea more frequently investigated non-tuberculous mycobacteria. Research on parasitic diseases in North Korea was focused on protozoan and intestinal nematodes, while the corresponding South Korea research investigated various species of parasites. Additionally, the studies conducted in North Korea were more likely to investigate the application of traditional medicine to diagnosis and treatment than those conducted in South Korea. Conclusions This study presents an analysis of research trends in preventive medicine in North Korea focusing on infectious diseases, in which clear differences were observed between South and North Korea. Trends in research topics suggest a high prevalence of certain parasitic diseases in North Korea that are no longer widespread in South Korea. The large proportion of studies examining traditional medicine implies a lack of affordable medicine in North Korea.

BACKGROUND:Clonorchis sinensis is a group I bio-carcinogen responsible for cholangiocarcinoma (CHCA) in humans. However, the mechanism by which C. sinensis promotes carcinogenesis is unclear. METHODOLOGY:Using the human cholangiocyte line H69, we investigated cell proliferation and gap junction protein expression after stimulation with the hepatotoxin N-nitrosodimethylamine (NDMA) and/or excretory-secretory products (ESP) of C. sinensis, which induce inflammation. NDMA and ESP treatment increased proliferation by 146% and the proportion of cells in the G2/M phase by 37%. Moreover, the expression of the cell proliferation-related proteins E2F1, Ki-67, and cancer related protein cytokeratin 19 and Cox-2 increased in response to combined treatment with NDMA and ESP. The gap-junction proteins connexin (Cx) 43 and Cx26 increased. In contrast, Cx32 expression decreased in cells treated with NDMA and ESP. Silencing of Cx43 reduced cell proliferation and significantly suppressed Cx26 and Cox-2 expression. CONCLUSIONS:These results suggest that Cx43 is an important factor in CHCA induced by C. sinensis ESP and NDMA and further investigations targeting this pathway may allow prevention of this deadly disease.

We report an anti-reflective cover glass for Cu(In,Ga)Se2 (CIGS) thin film solar cells. Subwavelength structures (SWSs) were fabricated on top of a cover glass using one-step self-masked etching. The etching method resulted in dense whiskers with high aspect ratio. The produced structure exhibited excellent anti-reflective properties over a broad wavelength range, from the ultraviolet to the near infrared. Compared to a flat-surface glass, the average transmittance of the glass integrated with the SWSs improved from 92.4% to 95.2%. When the cover glass integrated with the SWSs was mounted onto the top of a CIGS device, the short-circuit current and the efficiency of the solar cell were enhanced by 4.38 and 6%, respectively, compared with a CIGS solar cell without cover glass.

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

Ocular toxoplasmosis is mediated by monocytes infected with Toxoplasma gondii that are disseminated to target organs. Although infected monocytes can easily access to outer blood-retinal barrier due to leaky choroidal vasculatures, not much is known about the effect of T. gondii-infected monocytes on outer blood-retinal barrier. We prepared human monocytes, THP-1, infected with T. gondii and human retinal pigment epithelial cells, ARPE-19, grown on transwells as an in vitro model of outer blood-retinal barrier. Exposure to infected monocytes resulted in disruption of tight junction protein, ZO-1, and decrease in transepithelial electrical resistance of retinal pigment epithelium. Supernatants alone separated from infected monocytes also decreased transepithelial electrical resistance and disrupted tight junction protein. Further investigation revealed that the supernatants could activate focal adhesion kinase (FAK) signaling in retinal pigment epithelium and the disruption was attenuated by FAK inhibitor. The disrupted barrier was partly restored by blocking CXCL8, a FAK activating factor secreted by infected monocytes. In this study, we demonstrated that monocytes infected with T. gondii can disrupt outer blood-retinal barrier, which is mediated by paracrinely activated FAK signaling. FAK signaling can be a target of therapeutic approach to prevent negative influence of infected monocytes on outer blood-retinal barrier.

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

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses.

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

BACKGROUND: Stool examination by counting eggs per gram of feces (EPGs) is the best method to estimate worm burden of Clonorchis sinensis in infected humans. The present study investigated a correlation between EPGs and worm burden in human clonorchiasis. METHODS AND FINDINGS: A total of 60 residents, 50 egg-positive and 10 egg-negative, in Sancheong-gun, Korea, participated in this worm collection trial in 2006-2009. They were diagnosed by egg positivity in feces using the Kato-Katz method. After administration of praziquantel, they were purged with cathartics on the next day, and then discharged adult worms were collected from their feces. Their EPGs ranged from 0 to 65,544. Adult worms of C. sinensis were collected from 17 egg-positive cases, and the number of worms ranged from 1 to 114 in each individual. A positive correlation between EPGs and numbers of worms was demonstrated (r = 0.681, P

BACKGROUND: A pilot clonorchiasis control project was implemented to evaluate the efficacies of various chemotherapy strategies on prevalence, incidence and re-infection in Heilongjiang Province, China. METHODS AND FINDINGS: Seven intervention groups (14,139 residents, about 2000 in each group) in heavily or moderately endemic areas were subjected to repeated praziquantel administration from 2001 to 2004. In the selective chemotherapy groups, residents were examined for fecal eggs, and those who tested positive were treated with three doses of 25 mg/kg praziquantel at 5-hour-intervals in one day. However, all residents were treated in the mass chemotherapy groups. In heavily endemic areas, two mass treatments of all residents in 2001 and 2003 reduced the prevalence from 69.5% to 18.8%, while four annual mass treatments reduced the prevalence from 48.0% in 2001 to 8.4% in 2004. Selective annual treatments for egg-positive subjects reduced the egg-positive rates from 54.9% in 2001 to 15.0% in 2004 or from 73.2% in 2001 to 12.3% in 2004. Selective treatments every 6 months significantly reduced the prevalence from 59.5% in 2001 to 7.5% in 2004. All of the repeated treatments reduced EPG (eggs per gram of feces) significantly. The annual mass treatment and selective treatment every 6 months produced lower prevalence and re-infection rates and higher egg reduction rate than annual selective treatments did. In the moderate endemic areas, egg positive rates were 24.8% and 29.7% in 2001 but were 1.9% and 1.3% after 2 or 3 selective treatments. The prevalence, incidence, re-infection rates in a moderately endemic area were significantly lower than those of heavy endemic areas. CONCLUSIONS: Repeated mass treatment or selective treatment with praziquantel every 6 to 12 months is highly effective for clonorchiasis control in heavily endemic areas. In contrast, one or two selective treatments with health education is effective in moderately endemic areas.

Helminth infections are prevalent in Lao People's Democratic Republic (Lao PDR). This study aimed at determining the prevalence and risk factors of intestinal helminthiasis in remote mountainous villages of northern Lao PDR. During the dry season in January 2017, a cross-sectional survey was conducted in 3 remote mountainous villages in Oudomxay province, Lao PDR. Villagers older than 18 years of age who agreed to submit stool samples or undergo an interview, were recruited. Stool samples from 198 individuals were examined by the Kato-Katz method, and a questionnaire surveyed 161 individuals among them. Univariable and multivariable logistic regression analyses were used to identify risk factors associated with the intestinal helminthiasis. An overall prevalence of intestinal helminthiasis was 75.8%. Hookworm infection was the most common (63.1%), followed by Opisthorchis viverrini/minute intestinal flukes (17.7%), Taenia spp. (15.2%), Trichuris trichiura (2.0%), Ascaris lumbricoides (1.5%), and Enterobius vermicularis (1.0%). Questionnaire analysis revealed sex (male) and absence of latrine to be significant risk factors for hookworm infection and consumption of raw meat for taeniasis. These results suggest that the mountainous area in northern Lao PDR has a different composition of helminth infections from other studies conducted in Lao PDR; a high prevalence of hookworm infection and taeniasis and low prevalence of T. trichiura and A. lumbricoides infections were observed. Also, liver flukes or intestinal flukes were similarly prevalent in the mountainous area. [ABSTRACT FROM AUTHOR]

Eosinophilia occurs commonly in many diseases including allergic diseases and helminthic infections. Toxocariasis has been suggested as one cause of eosinophilia. The present study was undertaken to examine the prevalence of toxocariasis in patients with eosinophilia and to identify the risk factors for toxocariasis. This prospective cohort study recruited a total of 81 patients with eosinophilia (34 males and 47 females) who visited the outpatient clinic at Seoul National University Hospital from January 2017 to February 2018 and agreed to participate in this study. The prevalence of toxocariasis was examined by T. canis-specific ELISA, and the various risk factors for toxocariasis were evaluated by a questionnaire survey. Among 81 patients with eosinophilia, 18 were positive for anti-T. canis antibodies (22.2%); 88.9% were male (16/18) and 11.1% were female (2/18). Multivariate statistical analysis revealed that males (OR 21.876, 95% CI: 1.667-287.144) with a history of consuming the raw meat or livers of animals (OR 5.899, 95% CI: 1.004-34.669) and a heavy alcohol-drinking habit (OR 8.767, 95% CI: 1.018-75.497) were at higher risk of toxocariasis in patients with eosinophilia. Toxocariasis should be considered a potential cause of eosinophilia when the patient has a history of eating the raw meat or livers of animals in Korea. A single course of albendazole is recommended to reduce the migration of Toxocara larvae in serologically positive cases with eosinophilia. [ABSTRACT FROM AUTHOR]

A 23-year-old Korean woman with a residence history in Kenya and Malawi for about 2 years presented with gross hematuria for 1 month. Blood tests were within normal range except eosinophilia. Asymmetrically diffuse wall thickening and calcification were observed at the urinary bladder on CT. Multiple erythematous nodular lesions were observed in the cystoscopy and transurethral resection was done. Numerous eggs of Schistosoma haematobium with granulomatous inflammation were observed in the submucosal layer of the bladder. The patient was diagnosed with schistosomiasis- related cystitis and treated with praziquantel (40 mg/kg/day) twice before and after transurethral resection. This case suggests that S. haematobium infection should be considered as a cause of hematuria in Korea when the patient had a history of traveling endemic areas of schistosomiasis. [ABSTRACT FROM AUTHOR]

A complicated case of echinococcosis with multiple organ involvement is reported in a 53-year-old businessman who frequently traveled overseas, including China, Russia, and Kazakhstan from 2001 to 2007. The patient was first diagnosed with a large liver cyst during a screening abdomen ultrasonography in 2011, but he did not follow up on the lesion afterwards. Six years later, dizziness, dysarthria, and cough developed, and cystic lesions were found in the brain, liver and lungs. The clinical course was complicated when the patient went through multiple surgeries and inadequate treatment with a short duration of albendazole without a definite diagnosis. The patient visited our hospital for the first time in August 2018 due to worsening symptoms; he was finally diagnosed with echinococcosis using imaging and serologic criteria. He is now on prolonged albendazole treatment (400 mg twice a day) with gradual clinical and radiological improvement. A high index of suspicion is warranted to early diagnose echinococcosis in a patient with a travel history to endemic areas of echinococcosis. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) signaling plays an important role in tumor progression in patients with certain gastrointestinal tract cancers. In addition to lowering cholesterol in serum, statins have pleiotropic effects, including anti-oxidative, anti-inflammatory or anti-neoplastic effects. Therefore, the present study investigated whether statins could induce the apoptosis of colon cancer cells and regulate the expression of IGF-1R and its associated signaling pathways in the present study. It was demonstrated that simvastatin and pravastatin suppressed cell proliferation and induced cell death in human HT-29 cells, but simvastatin was more potent than pravastatin. Simvastatin induced apoptosis in a concentration-dependent manner. In addition, simvastatin suppressed the expression of IGF-1R and inhibited the activity of phosphorylated-extracellular signal-regulated kinase (ERK)1/2 and phosphorylated-Akt activated by IGF-1. Simvastatin and IGF-1 each stimulated the activity of phosphorylated ERK1/2. However, simvastatin inhibited cell proliferation and IGF-1 stimulated cell proliferation. Mevalonic acid and PD98059 reversed the ERK activation and apoptosis induced by treatment with simvastatin. It was concluded that simvastatin induces the apoptosis of human colon cancer cells and inhibits IGF-1-induced ERK and Akt expression via the downregulation of IGF-1R expression and proapoptotic ERK activation. Simvastatin may be beneficial for the treatment of colon cancer. The present study suggested that statin may possess therapeutic potential for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

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

Background/Aims: Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression. Methods: Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis. Results: Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation. Conclusions: Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is one of the most widespread zoonotic helminthiases, which can last an asymptomatic infection for several years. The purpose of this study was to demonstrate serum antibody prevalence of CE among asymptomatic people in Uzbekistan using ELISA. A total of 2,547 serum samples were collected, 66 from confirmed CE patients and 2,481 of patients with other diseases than CE at a hospital in Tashkent, Uzbekistan. The serum samples were screened for CE specific IgG antibodies by ELISA using cystic fluid antigen obtained from sheep. The serum antibody positive rate was 89.4% (59/66) in CE and 3.6% (89/2,481) in other disease patients. The present ELISA recognized 89.4% sensitivity and 96.4% specificity. The ELISA absorbance of positive samples was distributed 0.271- 0.971 for CE and 0.273-0.887 for other disease patients. The other disease patients with high absorbance over 0.3 were 50 (2.0%) who were presumed to be active CE patients. The patients in their 40s showed the highest positive rate of 5.2% (P=0.181), and women were 4.4% while men were 3.1% positive (P=0.136). The data confirmed that there are many asymptomatic patients of CE in Tashkent. It is indicated that CE is an endemic disease of public health importance in Uzbekistan. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia is an ubiquitous aerobic Gram-negative bacillus. Hospitalization and prior antibiotic therapy are risk factors for S. maltophilia infection. This organism is isolated with increasing frequency from hospitalized patients and may cause therapeutic problems because of its intrinsic resistance to common antibiotics and the immunodeficiency status of the affected host. S. maltophilia has been reported to be commonly associated with pneumonia and urinary tract infection. However, biliary infection caused by S. maltophilia is very rare. Herein, we report on a case of acute cholecystitis that developed secondary to S. maltophilia bacteremia in a patient with hepatitis-B related liver cirrhosis and gallbladder stone. [ABSTRACT FROM AUTHOR]

The mature domain of a cysteine protease of Spirometra erinacei plerocercoid larva (i.e., sparganum) was expressed in Escherichia coli, and its value as an antigen for the serodiagnosis of sparganosis was investigated. The recombinant protein (rSepCp-1) has the molecular weight of 23.4 kDa, and strongly reacted with the sparganum positive human or mice sera but not with negative sera by immunoblotting. ELISA with rSepCp-1 protein or sparganum crude antigen (SeC) was evaluated for the serodiagnosis of sparganosis using patient's sera. The sensitivity and specificity of ELISA using rSepCp-1 protein were 95.0% (19/20) and 99.1% (111/112), respectively. In contrast, the sensitivity and specificity of ELISA with SeC were 100% (20/20) and 96.4% (108/112), respectively. Moreover, in experimentally infected mice, the sensi- tivity and specificity of both ELISA assays were 100% for the detection of anti-sparganum IgG. It is suggested that the rSepCp-1 protein-based ELISA could provide a highly sensitive and specific assay for the diagnosis of sparganosis. [ABSTRACT FROM AUTHOR]

Toxocariasis is a worldwide zoonosis caused by larvae of ascarid nematodes of dogs or cats, Toxocara canis or T. cati. Diagnosis of human toxocariasis currently relies on serology that uses T. canis excretory-secretory antigen to detect specific IgG antibodies by ELISA. We investigated the serodiagnostic efficacy of ELISA using crude antigen of T. canis larvae (TCLA). Serum specimens of 64 clinically confirmed toxocariasis, 115 healthy controls, and 119 other tissue-invading helminthiases were screened by ELISA using TCLA. The ELISA using TCLA showed 92.2% (59/64 patient samples) sensitivity and 86.6% (103/119) specificity. Its positive diagnostic predictivity was 78.7% and negative predictivity was 97.8%. No serum of healthy controls reacted but that of anisakiasis (45.5%), gnathostomiasis (19.2%), clonorchiasis (15.8%), sparganosis (11.1%), and cysticercosis (6.3%) cross-reacted. Immunoblot analysis on TCLA recognized antigenic proteins of 28- and 30-kDa bands in their dominant protein quantity and strong blotting reactivity. The present results indicate that the ELISA using our TCLA antigen is acceptable by the sensitivity and specificity for serodiagnosis of human toxocariasis. ELISA with TCLA is recommended to make differential diagnosis for patients with any sign of organ infiltration and eosinophilia. [ABSTRACT FROM AUTHOR]

Background/Aims: Colonoscopic polypectomy is an effective tool for the treatment of colonic polyps. With the recent widespread use of colonoscopic polypectomy, there is a growing concern about iatrogenic complications, such as bleeding and perforation. The aim of this study is to analyze the clinical presentation and management of complications during colonoscopic polypectomy. Methods: We retrospectively reviewed the medical records of colonoscopic examinations performed at 5 hospitals of Hallym University Medical Center between June 2005 and June 2008. Results: A total of 26,773 colonoscopies and 4,123 colonoscopic polypectomy were performed. The overall rate of complication was 1.04% (43/4,123). Perforation occurred in 0.19% (8/4,123) of cases, and bleeding occurred in 0.85% (35/4,123) of cases. Perforation occurred in 0.05% of snare polypectomies, 1.09% of endoscopic mucosal resections (EMR), and 7.14% of endoscopic submucosal dissections (ESD). Bleeding occurred in 0.8% of snare polypectomies, 1.09% of EMRs, and 3.57% of ESDs. The complication rate of ESDs was higher than in EMRs and snare polypectomies (P<0.001). Endoscopic clippings were performed in 25% of perforation and 66.7% of bleeding cases. Medical treatment was successful in 75% of perforation and 100% of bleeding cases. Conclusions: Colonoscopic polypectomy is a safe procedure for the treatment of colonic polyps, but rarely, serious complications occur. Compared to a snare polypectomy or an EMR, the complication of an ESD occurs more frequently. Endoscopic treatment and further conservative management seems to be appropriate in most cases with complication. [ABSTRACT FROM AUTHOR]

Human sparganosis is caused by the larval tapeworm of genus Spirometra. This parasite commonly invades subcutaneous tissues and muscles. However, infection in the pleural cavity is rare. A 65-year-old male patient, who had undergone surgical excision of subcutaneous masses due to a parasite infection (presumed to have been sparganosis) approximately 10 years ago, showed pleural effusion and peripheral eosinophilia. The anti-sparganum specific IgG antibody levels in the serum and pleural fluid were significantly higher than the normal control levels. Three consecutive doses of praziquantel (75 mg/kg/day) were administered for control of pleural effusion and peripheral eosinophilia. In this patient, sparganosis was suspected, and the probable cause of the infection was ingestion of raw snakes and frogs. Immunoserologic tests using ELISA can be helpful in diagnosis of pleural sparganosis and praziquantel is suggested as an alternative treatment for surgically unresectable cases. [ABSTRACT FROM AUTHOR]

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

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

In gallbladder epithelial cells (GBEC), PPARalpha and PPARgamma ligands modulate inflammation by suppression of TNFalpha production and prevent excessive accumulation of cholesterol by ABCA1 activation. Recently, HMG-CoA reductase inhibitors (statins) were shown to activate PPARalpha and PPARgamma in various cells but no studies of their effects in GBEC have been conducted. The objective of this study was, therefore, to determine the effects of statins on PPAR and ABCA1 expression and the anti-inflammatory effect of statins in GBEC. Canine GBEC were cultured on Petri dishes. Expression of the proteins PPARalpha, PPARgamma, and ABCA1 was measured by western blotting analysis after treatment with simvastatin, pravastatin, NO-pravastatin, PPARalpha ligand, or PPARgamma ligand in the culture media. Expression of ABCA1 and LXRalpha mRNAs was estimated by RT-PCR. Expression of TNFalpha mRNA was measured by RT-PCR after 24 h pre-treatment with the statins, preceding 1 h of lipopolysaccharide (LPS) loading. Simvastatin, pravastatin, and NO-pravastatin increased expression of the proteins PPARalpha, PPARgamma, and ABCA1, and expression of the mRNA of ABCA1 and LXRalpha in GBEC. Pre-treatment with simvastatin, pravastatin, and NO-pravastatin suppressed the production of TNFalpha mRNA induced by LPS. In conclusion, statins probably contribute to the preservation of GBEC function by activation of PPARalpha and PPARgamma, which have anti-inflammatory effects by suppression of pro-inflammatory cytokines, and ABCA1 activation mediated by LXRalpha, which prevents the accumulation of cholesterol in GBEC. [ABSTRACT FROM AUTHOR]

The microbial production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae involves the formation of various by-products, which are synthesized through the oxidative pathway. To eliminate the by-products synthesis, the oxidative branch of glycerol metabolism was inactivated by constructing two mutant strains. In one of the mutant strains, the structural genes encoding glycerol dehydrogenase and dihydroxyacetone kinase were deleted from the chromosomal DNA, whereas in the second mutant strain dhaR, which is a putative transcription factor that activates, gene expression was deleted from the chromosomal DNA. In the resultant mutant strains lacking the dhaT gene encoding 1,3-PD oxidoreductase, which was simultaneously deleted while replacing the native promoter with the lacZ promoter, the by-product formation except for acetate was eliminated, but it still produced 1,3-PD at a lower level, which might be due to a putative oxidoreductase that catalyzes the production of 1,3-PD. The recombinant strains in which the reductive pathway was recovered produced slightly lower amount of 1,3-PD as compared to the parent strain, which might be due to the reduced activity of DhaB caused by the substitution of the promoter. However, the production yield was higher in the recombinant strain (0.57 mol mol−1) than the wild type Cu strain (0.47 mol mol−1). [ABSTRACT FROM AUTHOR]

This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-γ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/ A), TNF-α (-308 G/A), and TGF-β1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-γ intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-α low- producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-γ and TNF-α genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-γ and low producing TNF-α), moderate, and low (low-producing IFN-γ and high producing TNF-α,) risk groups. The incidence of IHDD was significantly different among these groups (P= 0.022); 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-γ and TNF-α, genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients. [ABSTRACT FROM AUTHOR]

Abstract  Infection by Clonorchis sinensis, the Chinese or oriental liver fluke, is a significant risk factor for the development of cholangiocarcinoma, a human epithelial carcinoma of the intrahepatic bile duct. Parthenolide is a sesquiterpene lactone that has strong anticancer properties and is also known to induce apoptosis in cholangiocarcinoma cells. Many investigators have reported that excretory–secretory (ES) products of C. sinensis as well as Opisthorchis viverrini promote the development of cholangiocarcinomas. However, the intrinsic mechanism is not clearly understood. Therefore, we investigated the biological roles of the ES products in a cholangiocarcinoma cell line, HuCCT1. The ES products of C. sinensis increased proliferation of HuCCT1 cells and augmented the expression of cyclooxygenase (COX)-2. To determine whether cells treated with ES products would respond differently to parthenolide, HuCCT1 cells were treated with parthenolide alone or parthenolide after pretreatment with ES products. Cells pretreated with ES products were resistant to parthenolide-induced apoptosis. Because parthenolide has been reported to be a COX-2 inhibitor, we hypothesize that COX-2 might be a key factor that promotes resistance of cholangiocarcinoma cancer cells to parthenolide-induced apoptosis. These results suggest that chemotherapy treatment regimens in cholangiocarcinoma patients with C. sinensis infection should be modulated to account for ES products excreted by the liver fluke. [ABSTRACT FROM AUTHOR]

We measured changes in sonographic findings of patients with clonorchiasis after a treatment in a highly endemic area. A total of 347 residents showed positive stool results for Clonorchis sinensis eggs in a village in northeastern China, and were treated with praziquantel. Of them, 132 patients underwent abdominal sonography both before and 1 year after treatment, and the changes in sonographic findings of 83 cured subjects were compared. Diffuse dilatation of intrahepatic bile ducts (DDIHD) was found in 82 patients (98.2%) before and 80 (96.4%) after treatment, which was improved in 3, aggravated in 1, and unchanged in 79 patients. Increased periductal echogenicity (IPDE) was observed in 42 patients (50.6%) before and 45 (54.2%) after treatment, which was improved in 5, aggravated in 8, and unchanged in 70 patients. Floating echogenic foci in the gallbladder (FEFGB) was detected in 32 patients (38.6%) before and 17 (20.5%) after treatment, which was improved in 20, aggravated in 5, and unchanged in 58 patients. Improvement of FEFGB only was statistically significantly (P = 0.004). The present results confirm that DDIHD and IPDE persist but FEFGB decreases significantly at 1 year after treatment. In a heavy endemic area, the sonographic finding of FEFGB may suggest active clonorchiasis 1 year after treatment. [ABSTRACT FROM AUTHOR]

This study investigated freshwater fish for their current infection status with metacercariae of Clonorchis sinensis in Korea. Twenty-one species of freshwater fish (n = 677) were collected from 34 regions nationwidely from February 2007 to June 2008. They were individually examined by digestion technique. Eight species of freshwater fish from 17 different regions were recognized positive for the metacercariae of C. sinensis. The positive rates (range of metacercariae number per fish) of fish by the species were as follows: 48% (1-1,142) in Pseudorasbora parva, 60% (1-412) in Pungtungia herzi, 15.7% (1-23) in Pseudogobio esocinus, 29% (1-7) in Acheilognathus intermedia, 21% (1-4) in Odontobutis interrupta, 33% (1-6) in Zacco temmincki, 3.6% (1-4) in Zacco platypus, and 26.3% (1) in Hemibarbus labeo. The two species, P. parva and P. herzi, are able to be the index fish for estimation of C. sinensis transmission in a certain locality. Still several species of freshwater fish are briskly transmitting C. sinensis infection in many riverside areas of southern Korea. [ABSTRACT FROM AUTHOR]

Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins. [ABSTRACT FROM AUTHOR]

Abstract  Rats develop resistance to re-infection by Clonorchis sinensis while humans do not. We investigated factors involved in the development of resistance to re-infection and super-infection in rats. Sprague–Dawley rats were infected by C. sinensis metacercariae and treated with praziquantel, then re-infected after immune modulation. The rats were also subjected to super-imposed infection after primary infection. Resistance to re-infection was observed by lowered rates of worm recovery after various durations from treatment; 1% at 5days and 24.4% at 11months vs 56.2% in the control. Similar significant resistance was observed in the super-infected rats after 3weeks of primary infection. The re-infected or super-infected worms grew very slowly and remained immature. Resistance disappeared in immune-suppressed and nude rats but not in splenectomized rats. Immunization with antigens of C. sinensis produced no resistance. Local tissue reaction and immune response in the infected bile duct may play an important role in the resistance, although the crowding effect may also be implicated in resistance in super-infected rats. [ABSTRACT FROM AUTHOR]

Rats develop strong resistance to re-infection and super-infection by Clonorchis sinensis. The present study investigated the antibodies present in the sera and bile juice of rats that were primary infected and re-infected with C. sinensis. The serum level of specific IgG antibodies, which were elevated 2 wk of the primary infection, peaked at 4 wk and subsequently remained unchanged even during re-infection. The total IgE level in serum increased slowly from 388 ng / ml to 3,426 ng / ml beginning 2 wk after the primary infection, and remained high up to 8 wk but dropped to a normal level (259 ng / ml) after treatment. In resistant re-infected rats, the serum IgE level increased rapidly and peaked within 1 wk, whereas no increase was observed in immunosuppressed rats. The serum level of specific IgA antibodies was elevated beginning 1 wk after infection, and decreased 4 wk after treatment. The total bile IgA level unchanged during the primary infection but increased in treated and re-infected rats. The elevated levels of serum IgE and bile IgA indicate that these immunoglobulins may be correlated with the development of resistance to re-infection by C. sinensis in rats. [ABSTRACT FROM AUTHOR]

Abstract   Clonorchis sinensis is one of the most prevalent parasitic helminths of humans in East Asia. Although several complications in bile duct epithelial cells are caused by C. sinensis infection, the mechanism is not clearly understood. To clarify the effects of C. sinensis excretory–secretory products (ES products) on bile duct epithelial cells, we investigated their effects on the human embryonic kidney epithelial cell line HEK293 in vitro. Our results show that ES products alter the proportion of cells in each stage of the cell cycle and induce HEK293 cell proliferation. Among cell cycle-related proteins, the expression of cyclin E increased markedly after treatment with ES products, indicating that the G1/S transition occurred. In addition, the expression of the transcription factor E2F1 was up-regulated by the addition of ES products. Small interfering RNA (siRNA) was used to demonstrate that the transcription factor E2F1 is a key factor in the control of cell proliferation in HEK293 cells. The present results demonstrate that ES products from C. sinensis stimulate cell proliferation by inducing E2F1 expression. We suggest that the ES products released from C. sinensis during infection may play an important role in the development of cholangiocarcinoma via the overgrowth of the bile duct epithelium. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess testicular rupture, scrotal haematoma, penile fracture and penile injury, comparing the prognoses of surgery and conservative management, as trauma to male external genital organs can cause devastating effects on patients and their partners. PATIENTS AND METHODS We reviewed the medical records of 156 male patients who presented to our emergency centre with trauma to the external genital organs between January 1996 and March 2006. RESULTS In all, 74 patients had testicular rupture, 32 penile fracture, 26 a penile injury and 24 a scrotal haematoma (mean age 27.8 years). The main cause of trauma was assault (52, 33%). Four of 14 patients with penile trauma who were managed conservatively had complications. Of 20 patients, 17 had a partial orchidectomy and were followed for a month after surgery; scrotal ultrasonography showed three cases of testicular atrophy. The mean hospital stay was less for patients with surgical intervention, at 6.4 days, than for those managed conservatively, at 8.7 days ( P < 0.05). A visual analogue pain scale showed less pain in patients who were surgically treated ( P < 0.05). CONCLUSION Prompt surgical intervention is crucial; it should be considered by urologists, and is strongly recommended. Ultrasonography was highly sensitive and specific, and should be used in all patients with trauma to the external genital organs, to aid diagnosis and evaluation before surgery. [ABSTRACT FROM AUTHOR]

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

Abstract  WD40-repeat proteins have four to eight repeat units, which have Gly–His (GH) and Trp–Asp (WD) at both termini and fold into a beta-propeller. In particular, the WD40-repeat protein of Clonorchis sinensis (CsWD1) has seven WD-repeat units and is expressed stage-specifically in metacercariae. By yeast two-hybrid screening, putative interacting protein cDNAs were cloned from a C. sinensis metacercaria cDNA library and purified further by higher stringency screening and lacZ colony-lift assay. After assessing their nucleotide and polypeptide sequences, 21 putative partner protein cDNAs were selected and assembled into 14 clones. Using YRG2 strain yeast, 12 putative partner protein clones were confirmed to interact with CsWD1 protein. These 12 proteins were grouped into functional categories, i.e., signal proteins, transporters, proteases, and muscle proteins. These results suggest that CsWD1 protein is associated with intracellular protein translocation and cell cycle control in C. sinensis metacercaria. [ABSTRACT FROM AUTHOR]

The WD40-repeat proteins serve as a platform coordinating partner proteins and are involved in a range of regulatory cellular functions. A WD40-repeat protein (CsWD1) of Clonorchis sinensis previously cloned is expressed stage-specifically in the tegumental syncytium of C. sinensis metacercariae. In the present study, interacting proteins with the CsWD1 protein was purified by immunoprecipitation and 2 dimension gel electrophoresis from the C. sinensis metacercaria soluble extract, and tryptic peptides were analyzed by LC/ESI-MS. Putative partner proteins were annotated to be actin-2, glyceraldehyde-3-phosphate dehydrogenase, and hypothetical and unmanned proteins. The CsWD1 protein was predicted to contain 3 conserved actin-interacting residues on its functional surface. With these results, the CsWD1 protein is suggested to be an actin-interacting protein of C. sinensis. [ABSTRACT FROM AUTHOR]

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

We investigated a small-scale serological survey to screen tissue-parasitic helminthiases of North Koreans as one of research programs for re-unification of Korea. Soil-transmitted helminthiases were found highly prevalent among North Korean residents at the border with China. ELISA using 4 tissue-parasitic helminth antigens was applied to 137 residents living in Cheongjin-shi, Hamgyeongbuk-do, North Korea and 133 female refugees in South Korea in 2004-2005. Among a total of 270 samples, 31 (11.5%), 25 (9.3%), and 11 (4.1%) were positive for specific IgG antibodies to antigens of Clonorchis sinensis, Taenia solium metacestode, and sparganum, respectively. The overall positive rate was 21.5%; 38.2% in males and 15.8% in females. The present finding suggests that tissue parasites, such as C. sinensis, T. solium metacestode and sparganum are highly prevalent in some limited areas of North Korea. These foodborne tissue-parasitic helminthiases should be considered for future control measures of parasitic diseases in North Korea. [ABSTRACT FROM AUTHOR]