Kawasaki disease with dilatation of the common bile duct: A case report and review of literature.

BACKGROUND: Kawasaki disease (KD) is a syndrome that results in acute systemic vasculitis and is a major cause of acquired heart disease in developed countries. KD is diagnosed based on certain characteristic symptoms and echocardiogram results. It has been reported that abdominal ultrasound is of value in supporting the diagnosis of KD. Nevertheless, abdominal ultrasound is not a routine procedure in KD. Moreover, dilatation of the common bile duct (CBD) has been rarely reported in previous cases. CASE PRESENTATION: A 4-year-old boy presented with fever and markedly high transaminase level (aspartate aminotransferase, 5323 U/L; alanine aminotransferase, 1554 U/L). The patient was diagnosed as having KD based on characteristic symptoms and echocardiogram findings. Ultrasound revealed dilatation of the CBD as well as cervical lymphadenopathy resembling a cluster of grapes, thickening of the gallbladder wall, and increased periportal echogenicity throughout the liver parenchyma. The patient received initial treatment with intravenous immunoglobulin at day 4 of fever and second-line treatment with intravenous immunoglobulin and prednisolone because of recurrent fever on day 6. Dilatation of the CBD was improved from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). CONCLUSION: This case highlights the usefulness of abdominal ultrasound and the importance of considering dilatation of the CBD as one of the complications of KD.

Substance-P prevents the cholestatic liver injury by regulating inflammatory responses.

Substance-P (SP) is a neuropeptide that modulates immune responses and accelerates tissue repair in critical inflammatory disease. Liver fibrosis and cirrhosis are the ultimate outcomes of almost all chronic liver diseases caused by viral infection, steatohepatitis, autoimmune, and cholestatic injury. Despite the development of new drugs, liver transplantation is still the only fundamental treatment; thus, new therapeutic approaches to mitigate liver fibrosis and chronic inflammation are constantly being needed. The aim of this study was to examine the effect of SP on liver damage due to cholestatic stress. To induce cholestatic injury, common bile duct ligation (CBDL) was attempted, followed by systemic application of SP. SP treatment increased IL-10 and decreased TNF-α in serum with increasing levels of circulating regulatory T cells (Tregs) from the early stage of CBDL. Moreover, SP decreased CBDL-induced TGF-ß1 expression in the circulation. This could create anti-inflammatory/anti-fibrotic environment under CBDL, which might ameliorate the progression of liver fibrosis in CBDL. Histological and molecular analysis revealed that SP treatment reduced ductular reaction, hepatic damage, and apoptotic hepatocytes, accompanied by diminishing type I collagen and upregulating MMP-9. These studies found that SP is a promising therapeutic candidate for immune-related liver disease as well as cholestatic liver disease, by providing hepatic protective effects via immune suppression.

Safety Evaluation of Paclitaxel-Eluting Biliary Metal Stent with Sodium Caprate in Porcine Biliary Tract.

Background/Aims: Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxeleluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. Methods: MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. Results: Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPM-III were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPM-III stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. Conclusions: In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.

Nucleos(t)ide Analogs Do Not Independently Influence Hepatic Fibrosis and Portal Hypertension beyond Viral Suppression in CBDL-Induced Cirrhotic Rat.

Chronic hepatitis is the major cause of liver cirrhosis and portal hypertension. Several factors affect portal pressure, including liver fibrosis, splanchnic vasodilatation, and pathologic angiogenesis. Nucleos(t)ide analogs (NUCs), the oral antiviral agents, effectively attenuate chronic hepatitis B-related liver cirrhosis and portal hypertension via viral suppression and alleviation of hepatitis. On the other hand, NUCs affect tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and nitric oxide, which participate in fibrogenesis, vasodilatation, and angiogenesis. However, whether NUCs independently influence liver fibrosis and portal hypertension beyond viral suppression is unknown. This study thus aimed to evaluate the influences of three frequently used NUCs in rats with nonviral cirrhosis. Male Sprague-Dawley rats received common bile duct ligation (CBDL) to induce cholestatic cirrhosis and portal hypertension. The rats were randomly allocated into four groups, treated by mouth with lamivudine (30 mg/kg per day), entecavir (0.09 mg/kg per day), tenofovir (50 mg/kg per day), or distilled water (vehicle control) from the 15th day after CBDL. On the 29th day, liver cirrhosis- and portal hypertension-related parameters were evaluated. The results showed that chronic NUCs treatment did not affect hemodynamic parameters, plasma TNF-α concentration, and hepatic fibrogenesis protein expressions in rats with nonviral cirrhosis. Though the mesenteric VEGF receptor 2 phosphorylation was downregulated in NUCs-treated groups, the splanchnic angiogenesis was not influenced. In conclusion, lamivudine, entecavir, and tenofovir had no additional effects on liver cirrhosis and portal hypertension in rats with nonviral cirrhosis.

CXCR2 is involved in pulmonary intravascular macrophage accumulation and angiogenesis in a rat model of hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is a lung complication in various liver diseases, with high incidence, poor prognosis and no effective non-surgical treatments in patients with hepatocirrhosis. Therefore, assessing HPS pathogenesis to explore proper therapy strategies is clinically relevant. In the present study, male Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL). Two weeks post-surgery, the following groups were set up for 2 weeks of treatment: sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + tumour necrosis factor α (TNF-α) antagonist PTX and CBDL + normal saline groups. Liver and lung tissues were collected after mean arterial pressure (MAP) and portal venous pressure (PVP) measurements. Haematoxylin and eosin (H&E) staining (lung) and Masson staining (liver) were performed for pathological analyses. Finally, pulmonary tissue RNA and total protein were assessed for target effectors. The mRNA and protein levels of CXCR2 were significantly increased in the pulmonary tissue of CBDL rats. What's more, CXCR2 inhibition by SB225002 reduced the expression of CD68 and von Willebrand factor (vWf) in CBDL rats. Importantly, CXCR2 inhibition suppressed the activation of Akt and extracellular signal-regulated kinase (ERK) in CBDL rats. Antagonization of TNF-α with PTX down-regulated the expression of CXCR2. During HPS pathogenesis in rats, CXCR2 might be involved in the accumulation of pulmonary intravascular macrophages and angiogenesis, possibly by activating Akt and ERK, with additional regulation by TNF-α that enhanced pulmonary angiogenesis by directly acting on the pulmonary tissue. Finally, the present study may provide novel targets for the treatment of HPS.

[IMPACT OF RONCOLEUKIN ON BALANCE OF CYTOKINS IN COMPLEX TREATMENT OF OBTURATION JAUNDICE OF NONTUMORAL GENESIS].

The results of surgical treatment of 137 patients, suffering obturation jaundice of non-tumoral etiology, were analyzed. In all the patients the cause of obturation jaundice was choledocholithiasis. Roncoleukin was infused intravenously additionally in a complex of therapy. A degree of hepatic dysfunction was determined, taking into account the cholestasis markers. In 23 patients purulent cholangitis have occurred on background of obturation jaundice. Concentration of cytokins TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10 in sera were determined, using immunoassay analysis. The cytokins dysbalance severity preoperatively and dynamics of its changes have depended upon the hepatic dysbalance degree and presence of purulent cholangitis; a dysbalance is deeper, when the hepatic dysfunction is higher. Application of pathogenetically substantiated purposeful cytokinotherapy, including roncoleukin, have promoted the cytokins dysbalance elimination and improvement of the patients treatment results.

The angiogenic related functions of bone marrow mesenchymal stem cells are promoted by CBDL rat serum via the Akt/Nrf2 pathway.

Hepatopulmonary syndrome (HPS) is a complication of severe liver disease. It is characterized by an arterial oxygenation defect. Recent studies have demonstrated that pulmonary angiogenesis contributes to the abnormal gas exchange found in HPS. Additionally, mesenchymal stem cells (MSCs) are considered the stable source of VEGF-producing cells and have the potential to differentiate into multiple cell types. However, it has not been determined whether bone marrow mesenchymal stem cells (BM-MSCs) are mobilized and involved in the pulmonary angiogenesis in HPS. In this study, a CFU-F assay showed that the number of peripheral blood MSCs was increased in common bile duct ligation (CBDL) rats; however, there was no significant difference found in the number of BM-MSCs. In vitro, CBDL rat serum induced the overexpression of CXCR4 and PCNA in BM-MSCs. Consistently, the directional migration as well as the proliferation ability of BM-MSCs were enhanced by CBDL rat serum, as determined by a transwell migration and MTT assays. Moreover, the secretion of VEGF by BM-MSCs increased after treatment with CBDL rat serum. We also found that the expression of phospho-Akt, phospho-ERK, and Nrf2 in BM-MSCs was significantly up-regulated by CBDL rat serum in a time dependent manner, and the blockage of the Akt/Nrf2 signalling pathway with an Akt Inhibitor or Nrf2 siRNA, instead of an ERK inhibitor, attenuated the migration, proliferation and paracrine capacity of BM-MSCs. In conclusion, these findings indicated that the number of MSCs increased in the peripheral blood of CBDL rats, and the Akt/Nrf2 pathway plays a vital role in promoting the angiogenic related functions of BM-MSCs, which could be a potent contributor to pulmonary angiogenesis in HPS.

[ОPTIMIZATION OF PREOPERATIVE PREPARATION AND CONSERVATIVE TREATMENT OF OBTURATION JAUNDICE, OCCURRING ON BACKGROUND OF BILIARY CALCULOUS DISEASE].

Оbturation jaundice (ОJ) on background of biliary calculous disease (BCD) was diagnosed in 61 patients. There was studied the impact of L­lysine escinate and glutargin on the treatment results, which were included in complex of standard preoperative preparation, and what had transformed into conservative treatment and disappearing of ОJ without operative intervention. In accordance to the biochemical investigations results, which characterize a functional state of the liver, OJ had disappeared more rapidly while application of the treatment proposed. Positive results of treatment had witnessed actuality of the trend choosed and necessity of its further studying.

Effects of thienorphine on contraction of the guinea pig sphincter of Oddi, choledochus and gall bladder.

Opioid analgesics are widely believed to cause spasm of the bile duct sphincter and so impede bile flow. Thienorphine is a partial opioid agonist that is a good candidate for the treatment of opioid dependence; however, to date, no studies have reported the effects of thienorphine on the function of the biliary tract. This study examined the in vivo effects of thienorphine on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder and on bile flow. The area under the curve (AUC) of isolated sphincter of Oddi was not influenced by thienorphine or buprenorphine, whereas morphine increased the AUC of the isolated sphincter of Oddi in a concentration-dependent manner. Thienorphine and buprenorphine concentration-dependently decreased the AUC of isolated choledochus, while morphine increased the AUC of isolated choledochus. Thienorphine had no effect on the contractile amplitude or basal tension of isolated gall bladder muscle strips. In contrast, buprenorphine and morphine increased the contractile basal tension of isolated gall bladder muscle strips in a concentration-dependent manner. Thienorphine (0.01-1.0mg/kg) had no significant inhibitory effect on bile flow. However, morphine (1.0-10mg/kg) and buprenorphine (1.0mg/kg) significantly inhibited bile flow. The maximum inhibition of bile flow by buprenorphine was 63.9±12.9% and by morphine was 74.1±11.3%. In summary, thienorphine has little influence on the guinea pig isolated sphincter of Oddi, choledochus and gall bladder or on bile flow, which may result in a lack of adverse biliary colic effects.