ß2-Adrenergic Receptor Enhances the Alternatively Activated Macrophages and Promotes Biliary Injuries Caused by Helminth Infection.

The autonomic nervous system has been studied for its involvement in the control of macrophages; however, the mechanisms underlying the interaction between the adrenergic receptors and alternatively activated macrophages (M2) remain obscure. Using FVB wild-type and beta 2 adrenergic receptors knockout, we found that ß2-AR deficiency alleviates hepatobiliary damage in mice infected with C. sinensis. Moreover, ß2-AR-deficient mice decrease the activation and infiltration of M2 macrophages and decrease the production of type 2 cytokines, which are associated with a significant decrease in liver fibrosis in infected mice. Our in vitro results on bone marrow-derived macrophages revealed that macrophages from Adrb2-/- mice significantly decrease M2 markers and the phosphorylation of ERK/mTORC1 induced by IL-4 compared to that observed in M2 macrophages from Adrb2+/+ . This study provides a better understanding of the mechanisms by which the ß2-AR enhances type 2 immune response through the ERK/mTORC1 signaling pathway in macrophages and their role in liver fibrosis.

Severe hepatobiliary morbidity is associated with Clonorchis sinensis infection: The evidence from a cross-sectional community study.

Clonorchis sinensis infection is highly prevalent in Asia. Diverse hepatobiliary morbidity has been documented for C. sinensis infection. This study aimed to assess the association between C. sinensis infection and hepatobiliary morbidity, taking into consideration of the control, confounders and infection intensity. A cross-sectional community survey was implemented in Hengxian county, southeastern China. Helminth infections were detected by fecal examination. Physical examination and abdominal ultrasonography were then conducted. After excluding confounding effects from gender, age and alcohol drinking, quantitative association between C. sinensis infection and hepatobiliary morbidity was assessed, and the effect from infection intensity was also evaluated, through adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). 696 villagers older than 10 years were enrolled. The prevalence and infection intensity of C. sinensis were higher in male, elder people and the individuals consuming alcohol. Light C. sinensis infection was associated with the increase of diarrhoea (aOR: 2.2, 95% CI: 1.1-4.5). C. sinensis infection was associated with the increase of fatty liver (aOR: 2.7, 95% CI: 1.4-5.2), and the effect was similar in different infection intensities. Moderate C. sinensis infection was associated with the increase of gallbladder stone (aOR: 3.0, 95% CI: 1.1-8.6), while moderate and heavy infections with the increase of intrahepatic bile duct dilatation (aOR: 2.2, 95% CI: 1.0-4.9 and aOR: 4.3, 95% CI: 1.9-9.9, respectively). C. sinensis infection had an effect on the development of periductal fibrosis (aOR: 3.2, 95% CI: 2.1-4.9), which showed increasing trend by infection intensity. The length and width of gallbladder in those with C. sinensis infection were enlarged, especially in those over 30 years old. C. sinensis infection is significantly associated with hepatobiliary morbidity. The occurrence of some morbidity was strongly related to the infection intensity. Awareness on harm of clonorchiasis should be raised both for policy-makers and villagers to adopt effective interventions.

[Survey on Clonorchis sinensis infection and bile component of gallstone patients from the Pearl River Delta region in Guangdong Province].

OBJECTIVE: To evaluate the prevalence of Clonorchis sinensis and bile components of gallstone patients from the Pearl River Delta region in Guangdong Province. METHODS: From June 2011 to November 2012, 406 gallstone patients from the Pearl River Delta region in Guangdong Province were enrolled in the study. Fecal specimens, bile and gallbladder stone samples were examined for the presence of C. sinensis eggs by the Kato-Katz method, centrifuged sediment smear microscopy, and triturated stone microscopy, respectively. The blood samples were detected for the antibody against C. sinensis by using colloidal gold immunochromatographic assay. Total calcium, ionized calcium, HCO3-, magnesium, pH, total bilirubin (TBIL), total bile acid (TBA), total cholesterol (CHO), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were analyzed quantitatively in bile of gall bladder. RESULTS: The overall C. sinensis infection rate was 52.2% (212/406). The proportion of males infected with C. sinensis was 64.7% (130/201), higher than that of females (40.0%, 82/205). The content of TBIL [(1 458.0 +/- 681.0) micromol/L], CHO [(4.1 +/- 1.3) mmol/L] and magnesium [(4.8 +/- 1.8) mmol/L] in the bile from the patients under 30 years old, total calcium [(3.0 +/- 1.3) mmol/L], ionized calcium [(1.5 +/- 0.7) mmol/L], TBA [(114.6 +/- 54.5) mmol/L], CHO [(5.1 +/- 1.7) mmol/L], TBIL [(1 396.0 +/- 615.0) micromol/L], GGT [(1 562.0 +/- 583.0) U/L] and ALP [(263.0 +/- 94.0) U/L] in 31-40 years-old, or CHO [(5.4 +/- 2.2) mmol/L] in 41-50 years-old in egg-positive group was lower than that of the corresponding negative groups [(2 759.0 +/- 969.0) micromol/L, (7.5 +/- 2.5), (7.5 +/- 2.2), (3.8 +/- 1.6), (1.9 +/- 1.0), (144.1 +/- 63.4), and (9.9 +/- 2.5) mmol/L, (1 892.0 +/- 584.0) micromol/L, (2457.0 +/- 988.0) and (535.0 +/- 196.0) U/L, and (7.9 +/- 2.3) mmol/L], respectively (P < 0.05). While, the content of HCO3- [(22.7 +/- 5.1) mmol/L], pH (7.6 +/- 0.4) in 31-40 years-old group and pH (7.6 +/- 0.4) in the patients aged above 50 years-old was higher than that of the negatives [(17.3 +/- 6.9) mmol/L, 7.4 +/- 0.2, and 7.5 +/- 0.3] (P < 0.05). CONCLUSION: In the Pearl River Delta region in Guangdong Province, C. sinensis prevalence is high in the gallstone patients. There are differences in bile components between C. sinensis-infected and non-infected patients.

[Serum level of intercellular adhesion molecule-1 in patients with clonorchiasis and its impact on liver function].

OBJECTIVE: To investigate the serum level of intercellular adhesion molecule-1 (ICAM-1) in patients with clonorchiasis, and the relationship between ICAM-1 and liver function. METHODS: Fifty untreated clonorchiasis patients and 20 normal controls were subjected in the present study. Plasma levels of total bilirubin (TBIL), albumin (ALB) and alanine aminotransferase (ALT) were determined by automatic biochemical analyzer. The patients were divided into three experiment groups (I, II, and III) by Child-Pugh classification. Serum level of sICAM-1 was determined by double-antibody sandwich ELISA. Radioimmunoassay was used to detect the content of interleukin-4(IL-4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in serum. LAL tripeptide substrate staining quantitative method was used to detect the level of bacterial lipopolysaccharide (LPS) in plasma. RESULTS: The level of sICAM-1, LPS, IL-4, IL-6, TNF-alpha, TBIL, and ALT [(729.34 +/- 75.67) microg/ml, (0.18 +/- 0.08) Eu/ml, (3.46 +/- 0.38) ng/ml, (223.48 +/- 46.90) pg/ml, (1.39 +/- 0.62) ng/ml, (15.45 +/- 10.81) micromol/L, and (39.25 +/- 8.82)IU/L, respectively] in serum or plasma of clonorchiasis patients were significantly higher than that of the control group [(269.15 +/- 38.21) microg/ml, (0.07 +/- 0.03) Eu/ml, (0.74 +/- 0.22) ng/ml, (106.06 +/- 32.96) pg/ml, (0.56 +/- 0.14) ng/ml, (6.31 +/- 4.70) micromol/L, (18.43 +/- 9.81) IU/L](P < 0.05 or P < 0.01). Plasma level of ALB [(28.35 +/- 5.38) g/L] was significantly lower than that of the control [(39.43 +/- 7.91) g/L] (P < 0.05). Correlation test showed that the sICAM-1 level in patients' sera was positively correlated with TBIL, ALT, and LPS (r = 0.662, 0.514, 0.499, P < 0.01), while negatively correlated with ALB (r = -0.423, P < 0.01). IL-4 level did not correlate with liver function parameters (P > 0.05). According to the Child-Pugh classification, the more serious the liver function damaged, the higher level of sICAM-1, LPS, IL-6 and TNF-alpha in the experiment groups. Significant differences were found between groups III and I (P < 0.01). CONCLUSION: Higher serum levels of sICAM-1, LPS, IL-6, and TNF-alpha in patients with clonorchiasis take part in the process of liver injury induced by Clonorchis sinensis.

Clonorchiasis: a key foodborne zoonosis in China.

The oriental liverfluke, Clonorchis sinensis, is of major socioeconomic importance in parts of Asia, including China, Japan, Korea, Taiwan, and Vietnam. The parasite is transmitted via snails to freshwater fish, and then to human beings and other piscivorous mammals, and causes substantial clinical or subclinical disease, known as clonorchiasis. There is considerable evidence for an aetiological relation between clonorchiasis and cholangiocarcinoma in human beings. It is estimated that about 35 million people are infected globally, of whom approximately 15 million are in China. Although very little information from China has been published in the English language, recent analyses of epidemiological data sets suggest that clonorchiasis is having an increased human-health impact due to the greater consumption of raw freshwater fish. To gain an improved insight into clonorchiasis in China, this review provides a background on the parasite and its life cycle, summarises key aspects regarding the pathogenesis, diagnosis, and treatment of clonorchiasis, describes the geographic distribution and prevalence of clonorchiasis, and makes some recommendations for future research and the control of this important disease.

[Studies on the relationship between the level of cytokine and liver function in patients with clonorchiasis sinensis].

OBJECTIVE: To explore the relationship between cytokine level and liver function among patients infected with Clonorchis sinensis. METHODS: 47 patients were divided into three groups according to the degree of Child-Pugh liver function grade: 20 in group A (3-4 scores), 15 in group B (5-6 scores) and 12 in group C (7-9 scores). Interleukin 2 (IL-2), soluble IL-2 receptor (sIL-2R), interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were examined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). Automatic biochemical analyzer was employed for the determination of serum level of total bilirubin (TBL), albumin (ALB) and alanine aminotransferase (ALT). Data were analyzed with SAS statistic software. RESULTS: Serum levels of sIL-2R, IL-8 and TNF-alpha from patients were significantly higher than those obtained from healthy people (P<0.05, P<0.05, P<0.01), whereas the IL-2 level was significantly lower than the former (P<0.01). With the affected degree of the liver, serum levels of sIL-2R, IL-8 and TNF-alpha increased, in contrast to the decrease of IL-2 level. The differences were significant between groups A and C (P<0.05). The level of sIL-2R and TNF-alpha directly correlated with that of TBL (r=0.331 P<0.05, r=0.518 P<0.01) and ALT (r=0.475 P<0.01, r=0.285 P<0.05) respectively, but inversely correlated with the level of ALB (r=-0.319 P<0.05, r=-0.665 P<0.01). CONCLUSION: The infection of Clonorchis sinensis results in the reduction of cellular immune function of the patients. Certain relationship exists between serum cytokine level and liver function. Two cytokines, sIL-2R and TNF-alpha, are involved in the process of pathology.

Treatment of severe Clonorchiasis sinensis by endoscopic nasobiliary drainage and oral praziquantel.

AIM: To assess the therapeutic value of endoscopic nasobiliary drainage (ENBD) and oral praziquantel for severe Clonorchiasis sinensis infection. METHODS: Of the 84 Clonorchiasis sinensis-infected patients enrolled, 58 were treated with ENBD (as observing group, ENBD group), 26 received operations (control group, operation group). Both of the two groups were comparable in terms of patient's age, body mass index. Before and one week after treatment, the average diameters of common bile ducts were measured by ultrasound, and serum bilirubin, ALP, gamma-GT and ALT were detected by biochemical methods. After ENBD or operation, the patients took praziquantel for two days. RESULTS: Compared with the patients in operation group, ENBD patients in ENBD group had higher recovery rates of abdominal pain and fever as well as jaundice, quicker remission, smaller trauma, fewer complications and lower cost. CONCLUSION: ENBD combined with oral praziquantel is an effective and safe method for the treatment of severe Clonorchiasis sinensis.

Biliary parasites.

Parasitic diseases of the biliary tract occur frequently in tropical and subtropical areas and cause high morbidity and mortality. In general, neither the clinical presentation nor the general laboratory findings are sufficiently unique to raise the possibility of a parasitic biliary infestation in the mind of the surgeon. Once considered, however, the presence of a parasitic biliary infestation is easily confirmed. Most commonly this is accomplished by the identification of the parasite in stools or duodenal contents. Ultrasonography, CT and MRI are not only important in the diagnosis of parasitic biliary diseases but also in the follow-up and surveillance. ERCP is an excellent diagnostic tool for demonstrating the presence of parasites in the biliary tree. Furthermore, ERCP is also used in the therapy of biliary parasitic infestations and carries less morbidity and mortality than the surgical approach. Surgery is only indicated in complicated cases. Mechanisms that may be effective against parasites include: antibodies; cytotoxic T cells; T-cell-induced activated macrophages; natural killer cells, and a variety of cells that mediate antibody-dependent cell-mediated cytotoxicity and modulators of the immune system such as cytokines. Future research has to focus on the importance of these mechanisms for the immune evasion by parasites.

[Parasitic invasions and bronchial obstruction]. / Parazitnye invazii i bronkhoobstruktivnyi sindrom.

The course and outcomes of bronchial obstruction were reviewed for clonorchiasis, metagonimosis, lambliasis. Bronchial obstruction is shown to run more aggressive course in Trematoda infestation with further transformation into bronchial asthma despite dehelminthization. In lambliasis current antiparasitic therapy is able to abolish the obstruction. In combination of lambliasis with bronchial asthma it is feasible to achieve a persistent remission of bronchial asthma.

Acute clonorchiasis.

A 42-year-old Chinese woman developed 3 weeks of swinging fever, rash, malaise, and discomfort at the right upper quadrant of the abdomen. Acute Clonorchis sinensis infection eventually became evident and the patient responded to praziquantel. Although acute infestation is usually asymptomatic, occasional cases suffer severe symptoms and present difficulties in clinical diagnosis. Clonorchiasis is endemic in South East Asia. With the increasing popularity of travel to these countries and the global migration of Asians, physicians need to be aware of the condition. Treatment with praziquantel is effective and prevents the serious sequelae of chronic infection.

Liver function in Clonorchis sinensis-infected rabbits.

Nine rabbits were fed with Clonorchis sinensis metacercariae (MC) and the blood samples chronologically obtained were analyzed biochemically. Rabbits infected by less than 100 flukes were grouped into Group I, and by 100-250 flukes into Group II. The serum level of alanine aminotransferase (ALT) was increased from 3 weeks after the infection of the metacercariae (AIM) and showed a peak at 8 weeks, and decreased from 12 weeks AIM. The serum level of aspartate aminotransferase (AST) was raised to 92.3 +/- 65.4 U/L at 3 weeks AIM and stayed high until 8 weeks, then lowered thereafter. The serum level of gamma-glutamyl transpeptidase (gamma-GT) was increased rapidly to the highest value (18.9 +/- 14.6 U/L) at 16 weeks AIM, and decreased to the control level after 20 weeks. The serum level of alkaline phosphatase (ALP) was headed down from the early infection to 52 weeks AIM. The serum cholesterol level was increased from 8 weeks and reached at a peak 16 weeks AIM, and decreased thereafter to the control level. It is suggested that serum ALT, AST, ALP and gamma-GT tests be useful to diagnose the early infection of C. sinensis.

[The acid-forming function of the stomach and the signs of chronic "restructuring" gastritis in patients with pulmonary tuberculosis combined with clonorchiasis or metagonimiasis]. / Kislotoobrazuiushchaia funktsiia zheludka i priznaki khronicheskogo gastrita "perestroiki" u bol'nykh tuberkulezom legkikh v sochetanii s klonorkhozom ili metagonimozom.

The study has shown that 100% of patients with pulmonary tuberculosis concurrent with clonorchiasis and metagonimiasis develop a symptomatology of type A chronic gastritis with sharply inhibited gastric acid-producing function. The morphological features of this chronic atrophic gastritis are formation of surface microerosions and abrupt mucoidization of tegmental, foveolate, and cervical epitheliocytes.

Secretions of the biliary mucosa in experimental clonorchiasis.

The histological change of the biliary mucosa in clonorchiasis is characterized as adenomatous hyperplasia, and cross-sectioned mucosa looks like intestinal mucosa. In addition to the glandular hyperplasia, the metaplasia of mucin secreting cells is also known. The present study investigated the presence of intestinal secretion from the biliary mucosal cells of rabbits and rats with Clonorchis sinensis infection. The rabbit was infected with 300 and the rat was infected with 100 metacercariae of C. sinensis. A part of the animals were followed up after praziquantel treatment. The rabbit livers were prepared for histochemistry to observe any endocrine secretion and the bile duct mucosa of the mice was processed for the activity of brush border membrane (BBM)-bound enzymes of the small intestine. Immunohistochemistry with the polyclonal antibodies and biotin-streptavidin-peroxidase staining kit showed no positive cells for gastrin and secretin, but a few cells were positive for serotonin. The proliferated biliary mucosa of the mice revealed no activity of disaccharidases and aminopeptidase. Only alkaline phosphatase activity was found both in the control and the infected. The hyperplastic biliary mucosal cells showed no gastrointestinal secretory functions. The serotonin secreting cells may be one of the inflammatory cells.

Hilar cholangiocarcinoma associated with clonorchiasis.

Pathologic and epidemiologic evidence support the relationship between the liver fluke Clonorchis sinensis and the development of bile duct cancer. We report here a case of cholangiocarcinoma in a Laotian immigrant originally diagnosed with clonorchiasis. This case demonstrates the importance of early recognition and treatment of this disease to prevent subsequent morbidity and mortality. Diagnosis and treatment of clonorchiasis as well as the possible modes of cancer induction are discussed.