[Chronorehabilitation of the patients suffering from chronic cholecystitis with concomitant gallbladder dysfunction and opisthorchiasis]. / Khronoreabilitatsiia bol'nykh khronicheskim kholetsistitom s disfunktsiei zhelchnogo puzyria i opistorkhozom.

The importance of the development of the effective rehabilitative measures for the patients suffering from chronic cholecystitis with concomitant gallbladder dysfunction and opisthorchiasis is beyond question. The adequate methods for the rehabilitation of the patients after an intensive de-worming remain to be developed. It is known that de-worming is not infrequently followed by the immediate amplification of the manifestations of the stagnation of bile in the gallbladder that become even more pronounced than before the de-worming procedure. With the purpose of improving the effectiveness of the spa and health resort-based rehabilitation and prevention of the complications, it is recommended to make use of the modern therapeutic physical factors to be prescribed taking into consideration the characteristics of the biological rhythms in the functional activity of the biliary system in the individual patients. The most effective rehabilitation methods for the treatment of the pathology in question include the application of the therapeutic physical factors known to produce the beneficial effect on the functional state of the biliary system and exert the normalizing influence on the structure of the biological rhythms of the functional activity of various organs and systems. We used a range of approaches for the treatment of 123 patients with chronic cholecystitis and concomitant gallbladder dysfunction plus opisthorchiasis including extremely high-frequency electromagnetic irradiation (EHF therapy) in the combination with the oral intake of the choleretic herbal remedies followed by the transverse galvanization of the epigastric region with due regard for the phase of the rhythm of the functional activity of the gallbladder. The results of such treatment gave evidence of the positive dynamics of all the studied indicators of the functional activity of the biliary system and the organism as a whole which suggests the highest therapeutic effect (87.9%) of the proposed treatment that was maintained during 6 to 12 months.

Carbonyl stress phenomena during chronic infection with Opisthorchis felineus.

Infection with the fish borne liver fluke Opisthorchis felineus is common in the Eastern Europe (Ukraine, European part of Russia), Northern Asia (Siberia) and Central Asia (Northern Kazakhstan). Better understanding of the molecular pathogenesis of the biliary tract and liver during chronic opisthorchiasis can be expected to improve protection against and management of complications of this disease. We hypothesize that infection with O. felineus associates with formation of methylglyoxal and carbonyl stress in the liver and hence here we investigated the glyoxalase system and the receptor for advanced glycated end products (RAGE) in the liver of hamsters infected with this liver fluke. Expression of mRNA encoding glyoxalase 1 decreased at 8weeks of the infection and catalytic activity as well decreased at 8 and 12weeks after infection, and the expression of the glyoxalase 2 decreased until 36week post-infection, which associated with the decreasing activity of the enzyme at 8 and 12weeks post-infection. Glutathione levels in infected livers had decreased at week 8, whereas up-regulation of RAGE at mRNA levels was seen for the extended duration of the experimental infection of the hamsters. This outcome supported the notion of hepatic dicarbonyl stress during chronic opisthorchiasis. The inhibition of the glyoxalase system and accumulation of methylglyoxal at the early stages of the infection may underpin development of insulin resistance during opisthorchiasis.

Infectivity and development of Opisthorchis viverrini metacercariae in immunosuppressed Barbonymus gonionotus fingerlings (Cyprinidae).

Opisthorchiasis caused by Opisthorchis viverrini infection, is a serious public health problem in Lao PDR, Cambodia, Vietnam and Thailand. Cyprinid fish are required for the transmission of O. viverrini metacercariae to fish eating-mammal hosts including humans. The transmission of infective metacerariae is an important event, potentially resulting in the development of cholangiocarcinoma in cases of chronic opisthorchiasis. For a better understanding of the development of O. viverrini metacercariae in the second intermediate host, Barbonymus gonionotus (Cyprinidae), the immune response of infected B. gonionotus through fibrous tissue formation and superoxide dismutase (SOD) activity were investigated. The immunosuppressant (prednisolone) was administered to B. gonionotus infected with O. viverrini cercariae to study infectivity and development of the metacercariae. Additionally, the effects of prednisolone were studied by the investigation of fibrous tissue formation around the metacercariae, as well as SOD activity. In our study, prednisolone administered prior to infection in B. gonionotus had higher metacercarial recovery when compared to the non-administered control group. On the other hand, the administration of prednisolone after the O. viverrini infection allowed metacercariae to develop to the infective stage. Energy consumption from encystation to the infective stage required 443.9-463.7degree-days. The results show that immunosuppression decreases fibrous tissue and SOD activity in infected fish, and also affects the ability of O. viverrini metacercariae to develop to the infective stage. The immune response to metacercarial development of O. viverrini in cyprinid fish should be further studied to gain a greater understanding of this process, and hence, a better understanding of the mechanism(s) involved in metacercarial wall formation.

Multiparasitism and intensity of helminth infections in relation to symptoms and nutritional status among children: a cross-sectional study in southern Lao People's Democratic Republic.

The occurrence and spatial distribution of intestinal helminth infection in children is fairly well understood. However, knowledge on how helminth infections govern intestinal morbidity is scarce. We conducted a cross-sectional study to assess and quantify the relationship between single and multiple species helminth infection with clinical and self-reported morbidity indicators and nutritional status in Champasack province, southern Lao People's Democratic Republic (Lao PDR). A random sample of 1313 children, aged 6 months to 12 years, from villages in nine rural districts were enrolled and examined for helminth infection using duplicate Kato-Katz thick smears. Morbidity was assessed by self-reported symptoms, coupled with clinical examination and appraisal of nutritional status and anaemia. Bivariate and multivariate logistic regression was employed to study associations between helminth infection and morbidity indicators and anaemia. We found considerable morbidity among the surveyed children, including hepatomegaly (13.7%), pale conjunctiva (13.2%) and abdominal pain (10.4%). Anaemia was recorded in 60.4% of the children, whilst signs of stunting and low body mass index (BMI) were observed in 49.8% and 33.3% of the surveyed children, respectively. Hookworm and Opisthorchis viverrini were the predominant helminth species with prevalences of 51.0% and 43.3%, respectively. The prevalence of Schistosoma mekongi in the surveyed children was 5.6%. Multiple species helminth infections were recorded in 40.4% of the study cohort. Morbidity was associated with specific helminth species infection (e.g. S. mekongi with hepatomegaly; adjusted odds ratio (aOR): 9.49, 95% confidence interval (CI): 2.07-43.51) and multiparasitism (e.g. two or more helminth species with abdominal pain; aOR: 2.40, 95% CI: 1.46-3.93). Anaemia was associated with hookworm infection (aOR: 1.64, 95% CI: 1.16-2.34) and multiparasitism (aOR: 1.64, 95% CI: 1.18-2.29). Low BMI was associated with O. viverrini infection (aOR: 1.68, 95% CI: 1.14-2.49) and multiparasitism (aOR: 1.42, 95% CI: 1.01-2.00). The multiple strong associations reported here between helminth infections (single or multiple species) and intestinal morbidity among children in rural parts of southern Lao PDR call for concerted efforts to control helminth infections, which in turn might improve children's health and development.

The Opisthorchis viverrini genome provides insights into life in the bile duct.

Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

[The problem of opisthorchiasis in Ukraine and current approaches to its treatment].

The opisthorchiasis epidemiological situation in Ukraine and the Sumy Region that has the largest natural focus of invasion has been analyzed. Its morbidity rate is 21.6 per 100,000 population, which is more than 20 times greater than that in Ukraine. The clinical course of the disease in the endemic focus, the attribute of which is the high percentage of its latent form, has been examined. Praziquantel is the most effective drug for the etiotropic therapy of opisthorchiasis.

[A case of acute opisthorchiasis concurrent with chronic hereditary hemolytic anemia].

The paper analyzes the clinical and laboratory manifestations of acute Opisthorchis invasion concurrent with chronic hereditary hemolytic anemia before and after antihelminthic therapy. It gives the results of direct clinical observation of a patient in the acute phase of opisthorchiasis in the presence of Minkowsky-Shauffard disease. His examination encompassed conventional laboratory and instrumental studies used in hepatology, such as physical, biochemical, and immunological examinations (tests for viral hepatitismarkers and autoimmune liver diseases), and abdominal ultrasound scanning and magnetic resonance imaging. The patient with acute opisthorchiasis concurrent with hemolytic anemia was found to have a preponderance of clinical and laboratory manifestations of hepatocholangitis in the early stages of the disease and a prevalence of subfebrility with progressive eosinophilia in the presence of regressive symptoms. The clinical and laboratory signs of hereditary microspherocytosis suggest that the process is decompensated. The found clinical and laboratory changes correspond to the natural course of the diseases. The magnitude of changes in laboratory parameters suggests that there is an intercurrent interaction of infectious and somatic diseases, but does not hinder dehelminthization.

[A local case of acute opisthorchiasis in the Moscow Region].

The paper describes a case of acute opisthorchiasis in a 31-year-old female patient after ingestion of dried fish of the family Cyprinidae caught in the Oka River basin on the border of the Moscow and Ryazan Regions. This case could convince of that there was a risk of human Opisthorchis infection despite the zoonotic pattern of circulation of the pathogen in European Russia. The dietary intake of unsterilized fish of the family Cyprinidae caught in the Moscow and neighboring regions may give rise to Opisthorchis invasion and, it a large infectious dose, to acute opisthorchiasis.

Overexpression of PDGFA and its receptor during carcinogenesis of Opisthorchis viverrini-associated cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a crucial health problem in northeastern part of Thailand, which is caused by a combination of Opisthorchis viverrini infection and nitrosamine. A better understanding of its molecular mechanism is an important step to discover and develop the new diagnostics and therapies for CCA. To reveal the involvement of potential genes in the development of CCA, the present study investigated the expression kinetics of platelet-derived growth factor alpha (Pdgfa) and its receptor (Pdgfra) during the tumorigenesis of CCA induced by O. viverrini infection with quantitative RT-PCR, and confirmed the expression with immunohistological staining. The results showed that in the hamster model of opisthorchiasis-associated CCA, the expression of Pdgfa was increased after infection plus N-nitrosodimethylamine (NDMA) administration, reached its peak at 2 months post infection, and remained at the high level until 6 months. Similarly, the expression of Pdgfra was increased time-dependently. The positive immunostaining for PDGFA proteins was observed in the cytoplasm of epithelial tumor cells of hamster CCA. Moreover, the analysis of the expression of these genes in 10 cases of human opisthorchiasis-associated CCA showed that Pdgfa was overexpressed in 80%, and Pdgfra was overexpressed in 40% cases (>3.0 folds, compared with the expressions of adjacent normal tissues). This result suggests that PDGFA is likely involved in the tumorigenesis of opisthorchiasis-associated CCA, and may be a promising candidate biomarker for diagnosis and treatment strategies of CCA.

[Complicated forms of superinvasion opisthorchiasis: pathogenetic aspects].

Superinvasion opisthorchiasis is characterized by host growth retardation and weight reduction, which are due to the cleptoeffect of Opisthorchis felineus; metabolic disturbances, proliferative processes, accelerated collagen biosynthesis and biodegradation in the organs reflect parasite-host interactions as components of the system. The productive reactions of visceral pathology are initiated by the parasite's metabolites located in the liver, lung, heart, and testes.

[Continuous blood coagulation in chronic opisthorchiasis].

Animal experiments have shown that chronic Opisthorchis invasion results in accelerated continuous blood coagulation, by inducing hypercoagulation and platelet activation. The state of hemostasis depends on the degree of infection and undergoes the largest changes during maximum invasion. Irrespective of invasion rates, chronic opisthorchiasis is accompanied by hypofibrinogenemia.

Inflammatory response to liver fluke Opisthorchis viverrini in mice depends on host master coregulator MTA1, a marker for parasite-induced cholangiocarcinoma in humans.

UNLABELLED: Based on the recently established role for the master coregulator MTA1 and MTA1-containing nuclear remodeling complexes in oncogenesis and inflammation, we explored the links between parasitism by the carcinogenic liver fluke Opisthorchis viverrini and this coregulator using both an Mta1(-/-) mouse model of infection and a tissue microarray of liver fluke-induced human cholangiocarcinomas (CCAs). Intense foci of inflammation and periductal fibrosis in the liver and kidneys of wild-type Mta1(+/+) mice were evident at 23 days postinfection with O. viverrini. In contrast, little inflammatory response was observed in the same organs of infected Mta1(-/-) mice. Livers of infected Mta1(+/+) mice revealed strong up-regulation of fibrosis-associated markers such as cytokeratins 18 and 19 and annexin 2, as determined both by immunostaining and by reverse-transcription polymerase chain reaction compared with infected Mta1(-/-) mice. CD4 expression was up-regulated by infection in the livers of both experimental groups; however, its levels were several-fold higher in the Mta1(+/+) mice than in infected Mta1(-/-) mice. Mta1(-/-) infected mice also exhibited significantly higher systemic and hepatic levels of host cytokines such as interleukin (IL)-12p70, IL-10, and interferon-γ compared with the levels of these cytokines in the Mta1(+/+) mice, suggesting an essential role of MTA1 in the cross-regulation of the Th1 and Th2 responses, presumably due to chromatin remodeling of the target chromatin genes. Immunohistochemical analysis of ≈ 300 liver tissue cores from confirmed cases of O. viverrini-induced CCA showed that MTA1 expression was elevated in >80% of the specimens. CONCLUSION: These findings suggest that MTA1 status plays an important role in conferring an optimal cytokine response in mice following infection with O. viverrini and is a major player in parasite-induced CCA in humans.

[Clinical and functional disorders of the stomach-in patients with psoriasis in the presence of chronic opisthorchiasis].

OBJECTIVE: to study the clinical and functional status of the stompach in patients with psoriasis in the presence of chronic opisthorchiasis (CO). Subjects and methods. Ninety patients with psoriasis concurrent with CO (a study group (Group 1)), 70 with psoriasis (a comparison group (Group 2)), 70 with CO (Group 3), and 30 healthy individuals were examined. All the patients underwent fractional gastric secretory studies and esophagogastroduodenoscopy (EGDS). RESULTS: The study group showed a reduction in stimulated hydrochloric acid output (4.25+/-0.38 mmol/hour), which was significantly less than that in Groups 2 and 3 and healthy individuals [5.87+/-0.51 (p<0.001); 6.86+/-0.59 (p<0.05), and 10.73+/-0.84 mmnol/hour (p<0.001), respectively]. In the study group, stimulated pepsin output (4.87+/-0.49 mmol/hour) was also significantly less than that in the other groups. Reduced basal hydrochloric acid output was found in 65.5% of the study group patients, whose number was significantly larger than that in the comparison group [44.3% (p<0.05)] and its stimulated output was less in 80 and 62.9% in the study and comparison groups, respectively (p < 0.05). A reduction in pepsin output in the basal secretion phase was revealed in 57.8 and 37.1% of the patients in the study and comparison groups, respectively (p<0.05) while that in the stimulated phase was in 63.3 and 34.3% (p<0.001). Thus, gastric secretory function in psoriatic patients is characterized by reduced hydrochloric acid and pepsin outputs and it is more impaired in patients with mixed pathology, which necessitates anthelmintic therapy in this category of patients.

[The clinical and functional state of the liver in patients with psoriasis in the presence of chronic opisthorchiasis].

OBJECTIVE: to study the clinical and functional state of the liver in patients with psoriasis concurrent with chronic opisthorchiasis (CO). SUBJECTS AND METHODS: Twenty-eight patients with psoriasis concurrent with CO, 15 patients with CO, 15 patients with the enlarged liver, and 15 healthy individuals were examined. Serum biochemical study and ultrasonography of the liver and gallbladder were used. RESULTS AND DISCUSSION: The patients with comorbidity were found to have hepatomegaly with syndromes of cytolysis, cholestasis, and mesenchymal inflammation of more degrees than those from Groups 2 and 3. CONCLUSION: The found clinical and functional liver changes in patients with psoriasis concurrent with CO make it necessary to perform anthelmintic therapy in this category of patients.

[Gastric secretory function in psoriatic patients with chronic opistorchosis before and after antihelminthic therapy].

The aim of the work was to study secretory function of the stomach in psoriatic patients with chronic opistorchosis (CO) before and after antihelminthic therapy. It included 90 such patients, 70 with psoriasis alone, 70 with CO, and 30 healthy subjects. All patients were examined by oesophagogastroduodenoscopy. Fractional gastric secretion was measured. The secretory function of the stomach was most seriously disturbed in psoriatic patients with CO. It did not further deteriorate after antihelminthic therapy. The disturbance was associated with reduced hydrochloric acid and pepsin levels which confirms the necessity of antihelminthic therapy.

Opisthorchis viverrini excretory/secretory products induce toll-like receptor 4 upregulation and production of interleukin 6 and 8 in cholangiocyte.

Biliary tract infection with the Group I carcinogenic liver fluke Opisthorchis viverrini is associated with severe inflammation leading to cholangiocarcinoma--a major biliary cancer in Southeast Asia. However, mechanism(s) by which the liver fluke induces host mucosal immune/inflammatory responses is unclear. In the present study we address whether a normal immortalized human cholangiocyte cell line (H69 cells) recognizes and responds to O. viverrini excretory/secretory products (OVES). Expression of multiple TLRs, activation of NF-κB, and expression of pro-inflammatory cytokines were monitored in the presence and absence of OVES. Our results showed that OVES induced increased cholangiocyte TLR4 mRNA expression, induced IκB-α degradation in a MyD88-dependent manner, and activated NF-κB nuclear translocation. Moreover, OVES induced expression and secretion of the strong chemoattractant chemokine interleukin 8 (IL-8) and pro-inflammatory cytokine IL-6. These results demonstrate that secreted/excreted products of O. viverrini are recognized by human cholangiocytes and initiate innate mucosal immunity/inflammatory cascades, a primary event in the pathogenesis of opisthorchiasis and cholangiocarcinoma.

[The clinical and functional status of the stomach and small intestine in patients with chronic inflammatory bowel diseases concurrent with chronic opisthorchiasis].

To study the impact of Opisthorchis infestation on the upper digestive tract and small bowel in chronic inflammatory bowel diseases, the authors examined 164 patients with inflammatory bowel diseases, including 71 patients with ulcerative colitis and 45 with Crohn's disease without parasitosis and 48 with chronic opisthorchiasis (31 with ulcerative colitis and 17 with Crohn's disease). A control group consisted of 20 healthy individuals and 20 patients with chronic opisthorchiasis. A diagnosis was established by colonofibroscopy and a morphological study of colonic biopsy specimens. Gastric mucosal atrophic changes and motor evacuatory disorders as duodenogastric reflux were significantly more frequently encountered in inflammatory bowel diseases concurrent with chronic opisthorchiasis. The presence of Opisthorchis infestation significantly worsened fat and carbohydrate malabsorption in the small bowel in inflammatory bowel diseases.

[Myocardial structural and functional changes in patients with chronic viral hepatitis concurrent with chronic opisthorchiasis].

The aim of the investigation was to study the myocardium in patients with chronic viral hepatitis concurrent with chronic opisthorchiasis. Ninety patients with chronic viral hepatitis, including 52 patients with this disease concurrent with chronic opisthorchiasis, were examined. Doppler echocardiography indicated a statistically significant increase in left ventricular mass regardless of the presence of Opisthorchis infestation. Analysis of left ventricular diastolic dysfunction showed its great degree in chronic hepatitis C. Single-photon emission computed tomography with 99mTc-pyrophosphate revealed focal tracer incorporation in the myocardium of most patients with Opisthorchis infestation. A third of patients with chronic viral hepatitis showed moderate diffuse trace accumulation that was significantly more frequently found in chronic hepatitis C. Single photon-emission tomography with labeled leukocytes demonstrated abnormal accumulation in none of the patients; troponin T levels were in the normal allowable range. Myocardial lesion was detected in the chronic course of viral hepatitis C concurrent with chronic opisthorchiasis that was unattended by cardiomyocyte necrosis and that was dystrophic.

[Principles of therapy of hepatobiliary and pancreatic pathology in elderly people with chronic opisthorchiasis].

THE PURPOSE OF RESEARCH: studying of features of clinical current, diagnostics, treatment chronic opisthorchiasis at persons of elderly and senile age. 117 patients are surveyed. In bile in 100% of cases, a sladg-syndrome in 66.6%, infringement of motor function of a bilious bubble in 92.3%, macrobiocenosis in 98.3%, an allergic syndrome--microscopic changes are found out in 93%. The diagnostic importance of triad Paltseva at observable patients is confirmed. It is shown, that chronic [Russian characters: see text] is system disease at which leading value the pathology hepatobiliar and pancreatic system has.

[Left ventricular diastolic dysfunction in patients with psoriasis in the presence of chronic opisthorchiasis].

Left ventricular diastolic function was studied in patients with psoriasis concurrent with chronic opisthorchiasis (CO). Seventy-five patients with psoriasis concurrent with CO, 50 patients with CO, and 20 healthy individuals were examined. Echocardiographic study (EchoCG) in the M-, B-, and Doppler modes was made in all the patients, by using the standard methods. All the examinees were found to have impaired active left ventricular relaxation that manifested itself as a longer isovolumic relaxation time, which was more pronounced in patients with psoriasis concurrent with CO. Left ventricular systolic function in these patients was preserved. In the psoriatic patients, diastolic dysfunction was characterized by impaired relaxation and it was more evident in patients with comorbidity.