Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.

BACKGROUND: Countries in the Southeast Asia region have a high prevalence of soil-transmitted helminth, such as roundworm, whipworm, and hookworms [Ancylostoma duodenale, Necator americanus, Ancylostoma ceylanicum]. Recent molecular-based surveys have revealed that A. ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in that part of the world, while others have noted that this infection is an emerging public health risk not only for indigenous people but also for visitors from other countries. CASE PRESENTATION: We recently encountered four cases of A. ceylanicum infection in Japanese individuals who returned from Southeast Asia and Papua New Guinea. Case 1 was a 25-year-old male who stayed in a rainforest in Malaysia for 4 weeks, where he developed abdominal pain and diarrhea in the third week. Eleven adult worms (five males, six females) were expelled after treatment with pyrantel pamoate and identified as A. ceylanicum based on morphological characteristics and DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Case 2 was a 26-year-old male who spent 2 years as an overseas cooperation volunteer for agriculture in Papua New Guinea. He did not note any symptoms at that time, though eggs were detected in feces samples at a medical check-up examination after returning. Although collection of adult worms was unsuccessful, DNA analysis of the eggs for cox1 and the ribosomal internal transcribed spacer (ITS)-1 and ITS-2 genes demonstrated that they were A. ceylanicum. Case 3 was a 47-year-old male who spent 1 month in a rural village in Lao People's Democratic Republic and began suffering from watery diarrhea from the third week. A total of nine adult worms (three males, six females) were collected by endoscopic procedures and following treatment with pyrantel pamoate. Morphological examination and molecular analyses of the cox1 gene showed that they were A. ceylanicum. Case 4 was a 27-year-old male who participated in group travel to India for 5 days. Three weeks after returning, he developed abdominal pain and diarrhea. Hookworm eggs were found in feces samples and developed into larvae in culture, which were identified as A. ceylanicum based on molecular analysis of the cox1 gene. Eosinophilia was observed in all of the cases prior to treatment. CONCLUSIONS: A. ceylanicum should be recognized as an important etiologic pathogen of hookworm diseases in travelers to countries in the Southeast Asia and West Pacific Ocean regions.

Successful surgical rescue of delayed onset diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma.

Radiofrequency ablation (RFA) has been established as the mainstay therapy for hepatocellular carcinoma (HCC) in patients deemed unsuitable for surgical resection. However, delayed diaphragmatic hernia can occur as a result of this procedure. There have been only seven other cases reported on this complication in the literature. Considering the recent growth in the popularity of the procedure, it is predictable that the incidence of the diaphragmatic hernia, due to RFA, will definitely increase. This case report is therefore vitally important as it increases clinical awareness of this currently rare complication, which could lead to improved survival rates in these patients. This case concerns an 81-year-old Asian man with a past medical history of cirrhosis and HCC (segment IV and VIII) who presented with a delayed, right diaphragmatic hernia and strangulated ileus 18 months after his original RFA procedure. It is important to implement extra measures to limit the risk of diaphragmatic, thermal injuries when RFA is performed. In particular, gastroenterologists, surgeons and accident and emergency staff should all be aware of this complication proceed with rapid diagnosis and management when patients, who previously underwent RFA, present with acute abdominal pain.

[A case of hypervascular hyperplastic nodule in chronic alcoholic liver disease with corona-like enhancement in the late phase image of CT during hepatic arteriography].

A 46-year-old woman was admitted to our hospital with hepatic encephalopathy due to alcoholic liver disease. A hepatic nodule (20 mm in diameter) in S7 was enhanced in the early phase of contrast CT. No significant findings were observed in the late phase of contrast CT and SPIO MRI. The late phase of CT during hepatic arteriography showed corona-like enhancement of the nodule. The nodule was diagnosed as a hypervascular hyperplastic nodule, based on histological examinations and immunohistochemical results with antibodies against CD68 and CD34.

Non-prescription supplement-induced hepatitis with hyperferritinemia and mutation (H63D) in the HFE gene.

A 55-year-old Japanese woman was hospitalized because liver function tests showed an abnormality. Transaminases and biliary enzymes were markedly elevated with hyperferritinemia. Her imaging tests revealed no significant abnormality. She had been taking various non-prescription supplements for over approximately 6 months. After the supplements were discontinued her liver function gradually improved. This clinical course was suggestive of supplement-induced hepatitis. She had no history of taking supplements containing iron, so it was interesting that she had hyperferritinemia. We examined C282Y and H63D, which are important mutations in theiron-metabolizing gene, HFE. She was found to be heterozygous for the H63D mutation. The interaction between hyperferritinemia and supplements is unknown, but it can be speculated that some interaction between iron overload and supplements may have underlain the pathogenesis of her liver injury.

Lack of evidence for leukocyte maternal microchimerism in primary biliary cirrhosis.

AIM: It is reasonable to assume that microchimerism could also be involved in the induction of primary biliary cirrhosis (PBC). However, previous reports investigated only fetus-microchimerism in women patients. Maternal microchimerism has not been investigated until now. The current study aimed to clear either maternal microchimerism was involved in the pathogenesis of PBC or not. METHODS: We used fluorescence in situ hybridization on paraffin-embedded tissue (We called "Tissue-FISH".) to determine whether maternal cells infiltrated in male patients who were diagnosed as having PBC. Tissue-FISH was performed by using both X and Y specific probes on the biopsy liver sample of 3 male PBC patients. RESULTS: Infiltrating lymphocytes demonstrated both X and Y signals in all 3 male patients. CONCLUSION: Maternal microchimerism dose not play a significant role in PBC. PBC may not relate to fetus and maternal microchimerism.

Insulin resistance/beta-cell function and serum ferritin level in non-diabetic patients with hepatitis C virus infection.

BACKGROUND/AIMS: Since impaired glucose tolerance and iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases, in this study we investigated insulin resistance, pancreatic beta-cell function, i.e., insulin secretion, and serum ferritin levels in patients with HCV infection, especially non-diabetic patients. METHODS: Homeostasis model assessments for insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) were performed in 92 HCV-infected patients. RESULTS: The levels of plasma immunoreactive insulin (IRI), HOMA-IR, and HOMA-beta were significantly correlated with fasting plasma glucose (FPG) levels. Among the 86 non-diabetics (with an FPG of <126 mg/dl), IRI, HOMA-IR, and HOMA-beta were significantly higher in patients with liver cirrhosis than in patients with persistently normal alanine aminotransferase levels. The IRI and HOMA-IR values, but not the HOMA-beta values, were correlated with both serum transaminase and ferritin levels in the 65 non-diabetic chronic hepatitis patients. CONCLUSION: Insulin resistance was connected with impaired glucose tolerance and the severity of liver diseases in non-diabetic patients with HCV infection. Iron overload may be responsible for insulin resistance, or vice versa. Pancreatic beta-cell function was unrelated to the patients' serum ferritin levels.

Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX in patients with nonalcoholic steatohepatitis (NASH) or simple steatosis. METHODS: Serum TRX levels were determined using an enzyme-linked immunosorbent assay kit in 25 patients with NASH, 15 patients with simple steatosis, and 17 healthy volunteers. RESULTS: Serum TRX levels (medians and (ranges), ng/ml) were significantly elevated in patients with NASH (60.3 (17.6-104.7)), compared to those in patients with simple steatosis (24.6 (16.6-69.7), P=0.0009) and in healthy controls (23.5 (1.3-50.7), P<0.0001). Serum ferritin levels in patients with NASH were also significantly higher than the levels in patients with simple steatosis. The receiver operating characteristic curve confirmed that serum TRX and ferritin levels were predictors for distinguishing NASH from simple steatosis. Higher grades of histological iron staining were observed in NASH than in simple steatosis. Serum TRX tended to increase in accordance with hepatic iron accumulation and the histological severity in patients with NASH. CONCLUSIONS: The pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from simple steatosis as well as a predictor of the severity of NASH.

Effects of nitric oxide on the redox status of liver microsomes-electron spin resonance monitoring using nitroxide probes.

Nitroxide radicals (nitroxides) are reduced to the corresponding hydroxylamines and lose their electron spin resonance (ESR) signals, but these hydroxylamines are easily reoxidized to nitroxides and regain the ESR signals. In the present study the effects of nitric oxide (NO) on the reduction/oxidation (redox) status of hepatic microsomes were investigated by ESR spectroscopy using nitroxide probes. Rat hepatic microsomes were treated with an NO donor, NOR3 or NOC7, and then labeled with a water-soluble nitroxide, 2,2,6,6-tetramethyl-4-hydroxy-1-piperidinyloxy (Tempol), or a lipid-soluble nitroxide, 5-doxyl stearic acid (5-DSA). The reduction of Tempol was facilitated under hypoxic conditions in control microsomes. In NOR3 or NOC7-treated microsomes, the reduction of Tempol and the reoxidation of the corresponding hydroxylamine hardly occurred under both normoxic and hypoxic conditions. The ESR signals of 5-DSA changed just as those of Tempol did in control and NO-treated microsomes. The concentrations of total thiol and cytochrome P-450, and the activity of mixed function amine oxidase were reduced in NOR3 or NOC7-treated microsomes. In conclusion, NO affects not only the reduction of nitroxides but also the oxidation of hydroxylamines in hepatic microsomes, suggesting that the microsomal capability of redox regulation was lost by NO.

Effects of glycyrrhizin on glucocorticoid signaling pathway in hepatocytes.

The cytoprotective effects of glycyrrhizin (GL) are similar to glucocorticoids. We investigated the effects of GL on the glucocorticoid receptor (GR) and on the enzyme activity of tyrosine aminotransferase (TAT), an hepatocyte-specific marker of glucocorticoid action, in rat hepatocytes. Pretreatment with GL significantly decreased the affinity of GRs for dexamethasone (DEX) and increased the period of time required for TAT activity to reach a peak after the addition of DEX. GL did not affect the amount of GR, but significantly decreased the amount of heat-shock protein 90 (HSP90) and HSP90-associated GR. Alternatively, TAT activity and TAT mRNA levels increased significantly after the addition of GL to hepatocytes pretreated with DEX. In conclusion, GL reduces the affinity of GRs for ligands through the decreased HSP90 expression, but significantly enhances the glucocorticoid-induced TAT-gene expression at the transcriptional level in rat hepatocytes.