bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of lafutidine, a novel histamine H2‐receptor antagonist, on monochloramine‐induced gastric lesions in rats: Role of capsaicin‐sensitive sensory neurons
Authors: Umeda Masakazu , Fujita Akinobu , Nishiwaki Hideyuki , Takeuchi Koji
Published: March 2003

Background
: Lafutidine ((±)‐2‐(furfurylsulfinyl)‐N‐(4‐(4‐(piperidinomethyl)‐2‐pyridyl)oxy‐(Z)‐2‐butenyl)acetamide) is a novel histamine H2‐receptor antagonist and has been shown to exhibit a potent gastroprotective activity in addition to its antisecretory action. In the present study, we examined the effects of lafutidine on the mucosal ulcerogenic and potential difference (PD) responses induced by monochloramine (NH2Cl) in rat stomachs.

Methods
: Oral administration of NH2Cl at 120 mmol/L produced haemorrhagic lesions in the stomach in unanaesthetized rats.

Results
: Lafutidine (3–30 mg/kg), given p.o., showed a dose‐dependent and significant inhibition against damage caused by NH2Cl: the effect was significant at 10 mg/kg or greater but disappeared almost totally in the sensory deafferented animals following capsaicin pretreatment. Likewise, capsaicin (10 mg/kg, p.o.), but not cimetidine (100 mg/kg, p.o.) exhibited a potent protection against NH2Cl‐induced gastric lesions. Topical application of NH2Cl (10 mmol/L) reduced transmucosal PD in ex‐vivo stomachs of anaesthetized rats, but this PD response was also prevented by pre‐exposure to lafutidine, in a dose‐dependent and sensory neuron‐sensitive manner. Mucosal exposure to NH4OH (60 mmol/L) also caused PD reduction in ex‐vivo stomachs made ischaemic by bleeding from the carotid artery (1 mL/100 g bodyweight), resulting in severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischaemia were attenuated by prior application of lafutidine as well as taurine, a scavenger of NH2Cl. The former effect was, again, dependent on the sensory neurons. Intraluminal capsaicin but not cimetidine was also effective in preventing a PD response to NH2Cl.

Conclusions
: These results suggest that lafutidine, but not cimetidine, protects the stomach against NH2Cl, whether occurring endogenously or administered exogenously and that this action may be mediated by capsaicin‐sensitive sensory neurons.
Ethanol intake preceding Helicobacter pylori inoculation promotes gastric mucosal inflammation in Mongolian gerbils
Authors: Suzuki Hidekazu , Mori Mikiji , Seto Koichi , Nagahashi Shoichi , Kawaguchi Chizuko , Kai Akemi , Akiba Yasutada , Suzuki Masayuki , Suematsu Makoto , Miura Soichiro , Ishii Hiromasa
Published: March 2003

Background
: Mongolian gerbils have been reported to be a suitable model for Helicobacter pylori‐associated gastric mucosal injury, including gastric cancer. Although ethanol is known to be one of the harmful substances in the gastric mucosa, the relationship between ethanol and H. pylori infection remains unknown. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury.

Methods
: Male Mongolian gerbils were used for the study. Helicobacter pylori was orally inoculated after 15 h fasting (Hp group). Thirty minutes prior to H. pylori inoculation, a group of gerbils was orally treated with 40% ethanol (20 mL/kg; E + Hp group). Another group of animals was treated either with H. pylori culture media alone (controls) or with 40% ethanol plus culture media (E group). Gerbils were killed 2, 4 or 12 weeks after H. pylori inoculation. Helicobacter pylori infection was confirmed by both histological examination and serological tests. Mucosal damage was evaluated histologically according to the modified Sydney system.

Results
: Although in the controls and E group no significant change to the gastric mucose was observed, persistent H. pylori infection was seen in the mucosa and mucosal leucocyte infiltration and severe epithelial damage was observed in the Hp and E + Hp groups after 4 weeks. The histological scores for polymorphonuclear cell infiltration and myeloperoxidase activity were higher in the E + Hp group at 4 weeks than in the Hp group (P < 0.05).

Conclusions
: Ethanol intake preceding H. pylori inoculation could promote the progression of gastric mucosal inflammation in Mongolian gerbils.

© 1999 Blackwell Science Asia Pty Ltd
Effects of end‐to‐side portacaval shunt and distal splenorenal shunt on systemic and pulmonary haemodynamics in patients with cirrhosis
Authors: Luca Angelo , García‐Pagán Juan C , De Lacy Antonio M , Escorsell Angels , Feu Fausto , Visa Josep , Bosch Jaime
Published: March 2003

Background
: Patients with cirrhosis exhibit splanchnic, peripheral and pulmonary vasodilation, which are thought to play a role in increasing portal pressure, promoting sodium retention and determining arterial hypoxaemia. The present study investigated whether these abnormalities are influenced by portal hypertension or by portal systemic shunting.

Methods
: Sixty‐one patients with cirrhosis who had haemodynamic measurements before and after end‐to‐side portacaval shunt (n = 30) or distal splenorenal shunt (n = 31) were evaluated.

Results
: End‐to‐side portacaval shunts were more effective than distal splenorenal shunts in decompressing the portal system (portocaval pressure gradient 3.2 ± 2.5 vs splenocaval gradient 6.5 ± 3.2 mmHg, P < 0.0001), because of a greater shunt blood flow (33 ± 12 vs 21 ± 12 mL/min per kg, P < 0.005). Azygos blood flow and hepatic blood flow decreased significantly after both surgical shunts. However, end‐to‐side portacaval shunts caused a greater decrease in peripheral resistance than distal splenorenal shunts (–23 ± 18 vs–11 ± 27%, P < 0.05). Mean arterial pressure and pulmonary vascular resistance were significantly reduced after an end‐to‐side portacaval shunt (–7 ± 10%, P < 0.001 and –14 ± 33%, P < 0.004, respectively), but not after splenorenal shunt.

Conclusions
: These results show that end‐to‐side portacaval shunts, despite normalizing portal pressure, worsen the peripheral and pulmonary vasodilatation. The splenorenal shunt that maintained a higher portal pressure, caused less peripheral vasodilatation and did not enhance pulmonary vasodilatation. These findings suggest that portal systemic shunting is more important than increased portal pressure in determining peripheral vasodilatation in cirrhosis.

© 1999 Blackwell Science Asia Pty Ltd
CASE REPORT: Acute encephalitis immediately prior to acute onset of hepatitis C virus infection
Authors: Fujita Hiroshi , Chuganji Yoshimichi , Yaginuma Masakimi , Momoi Masaru , Tanaka Takehiko
Published: March 2003

A 34‐year‐old male presented with acute viral encephalitis of unknown aetiology with subsequent acute onset of hepatitis C virus (HCV) infection. Although the neurological syndrome improved after administration of acyclovir, jaundice appeared. Neurological complications of HCV infections have rarely been described. In this case report, we discuss the close relationship between neurological syndromes and HCV infection. In the future, we hope that further discussion of clinical cases will determine whether or not the HCV produces neurological manifestations.

© 1999 Blackwell Science Asia Pty Ltd
Role of energy metabolism in drug‐induced acute gastric mucosal injuries in humans
Authors: Sasahara Katsuyuki , Uchida Yoshihito , Matsuda Kazuya , Kawabata Hidehiro , Nishioka Mikio
Published: March 2003

Background
: In various drug‐induced gastric mucosal injuries, it has been speculated that changes in gastric mucosal energy metabolism differ according to the cause of injury. This study was conducted to investigate the role of energy metabolism in two drug‐induced gastric mucosal injuries in humans.

Methods
: The subjects were patients with acute gastric mucosal injury due to non‐steroidal anti‐inflammatory drugs (NSAID) or steroids, and normal controls. Two sets of tissue specimens from the antrum and corpus of the stomach were obtained. One specimen from each area was used for histological analysis and the other was stored in liquid nitrogen. The stored tissues were homogenized. Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were measured by the luciferin–luciferase method.

Results and Conclusions
: In the NSAID group, the ATP levels and the total adenine nucleotide (TAN) levels in both the antrum and corpus were significantly lower than in the control group. In the steroid group, no significant differences were observed in either the ATP or TAN levels. The NSAID decreased energy metabolism in the entire stomach while the steroid had a negligible effect on energy metabolism.
Mast cell stabilization prevents ethanol‐induced rat gastric mucosal injury: Mechanisms of protection
Authors: Kalia N , Bardhan Kd , Reed Mwr , Jacob S , Brown Nj
Published: March 2003

Introduction
: We previously demonstrated that 60% ethanol increased macromolecular leakage and induced lesion formation in areas of permanent flow stasis within gastric mucosal vessels. Mast cells and their mediators have been implicated in acute mucosal injury. Fluorescent in vivo microscopy was used to assess the effects of ketotifen, a mast cell stabilizer, and pyrilamine, a histamine (H1)‐receptor antagonist, on ethanol‐induced rat gastric mucosal injury.

Methods
: Experiments were carried out on anaesthetized rats pretreated orally with ketotifen (1 mg/kg) or pyrilamine (30 mg/kg). Fluorescein isothiocyanate–bovine serum albumin (FITC‐BSA; 0.2 mL/100 g), a marker for quantitating macromolecular leakage was administered intra‐arterially. Ethanol (60%) or distilled water was applied topically to the gastric mucosa. Macromolecular leakage of FITC‐BSA, vessel diameters and leucocyte activity were quantified using image analysis.

Results
: Pretreatment with ketotifen or pyrilamine, followed by ethanol, caused no change in macromolecular leakage compared with controls. Both compounds prevented blood flow stasis in all areas and no lesion formation was observed. However, increased leucocyte activity and increases in vessel diameter were observed following pretreatment with ketotifen and pyrilamine, respectively.

Conclusions
: The data suggest that vasoactive substances released from mast cells may be involved in the aetiology of ethanol‐induced gastric mucosal damage. The prevention of these normal physiological responses to injury may lead to the employment of other microcirculatory mechanisms of defence.
Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone
Authors: Suga T , Kawa S , Horiuchi A , Nakamura N , Mukawa K , Akamatsu T , Kiyosawa K
Published: March 2003

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.
Evaluation of gut motility in type II diabetes by the radiopaque marker method
Authors: Iida Motoyuki , Ikeda Masahiko , Kishimoto Michihiko , Tsujino Takafumi , Kaneto Hideaki , Matsuhisa Munehide , Kajimoto Yoshitaka , Watarai Takao , Yamasaki Yoshimitsu , Hori Masatsugu
Published: March 2003

Background
: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms.

Methods
: After administration of a Sitzmark capsule®, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan’s methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R‐R intervals on the electrocardiograms (CVR‐R) was measured to evaluate parasympathetic autonomic function.

Results
: In the diabetics, the average (± SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 ± 8.3 vs 9.9 ± 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 ± 20.9 and 57.9 ± 22.3 h, respectively) compared with control subjects (23.3 ± 8.5 and 33.2 ± 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CVR‐R.

Conclusions
: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts.
Effect of nucleoside analogue therapy on duck hepatitis B viral replication in hepatocytes and bile duct epithelial cells in vivo
Authors: Nicoll Amanda , Locarnini Stephen , Chou Sheung To , Smallwood Richard , Angus Peter
Published: March 2003

Background
: Recent studies have implicated bile duct epithelial cells (BDEC) as a reservoir of hepatitis B virus (HBV) infection that may be particularly important in the development of post‐liver transplant recurrence of hepatitis B. The aim of this study was to compare the effects of antiviral therapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia.

Methods
: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post‐liver transplant HBV recurrence, half the animals underwent bile duct ligation. Duck HBV‐DNA in serum was measured at day 1, and serum and liver DHBV‐DNA were determined when the animals were killed on day 17. Intrahepatic expression of viral preS1 antigen and DHBV‐DNA was measured by immunohistochemistry and in situ hybridization, respectively.

Results
: Viraemia became undetectable in the penciclovir‐treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV‐DNA. Penciclovir greatly reduced the intrahepatic viral burden, but there was no antiviral effect on viral markers within BDEC. Despite the increased number of BDEC after bile duct ligation, the same proportion of BDEC was seen to be infected, and this was unaffected by antiviral therapy.

Conclusions
: In the duck model with and without biliary hyperplasia, penciclovir controls DHBV replication and reduces viral burden in hepatocytes, but not in BDEC. The BDEC appear to be an important reservoir of virus that is relatively unaffected by antiviral treatment, and may play an important role in disease persistence and relapse following cessation of therapy.

© 2000 Blackwell Science Asia Pty Ltd
Case selection for interferon treatment of hepatitis C
Authors: Zeniya Mikio , Toda Gotaro
Published: March 2003

To establish a case selection algorithm for the treatment of hepatitis C, predictive factors were studied and reported articles were reviewed and analysed. Because of the relatively poor efficacy of interferon (IFN) monotherapy, which is ineffective in 60–70% of patients, case selection at present is determined by the likelihood of attaining a sustained response (SR; defined by normalizing serum ALT and eliminating serum HCV RNA after treatment) to therapy. According to the present study, viral load and genotype, and IL‐10 and IL‐1ra serum levels, are the most predictive of achieving SR after IFN monotherapy given in a comparatively high dose regimen for 6 months. In addition, reported studies with logistic analyses were carefully reviewed and analysed for the most effective predictive factors of case selection. The results again indicated that viral load and HCV‐genotype (serotype) were closely related to SR. Age, gender, and histological changes at treatment were also considered for case selection. These results, however, relate solely to IFN‐monotherapy. Future development of more effective strategies for treating hepatitis C could alter the exclusion criteria for IFN treatment and will negate the need for the case selection algorithm discussed here.
Hepatitis C: Retreatment and treatment of patients with renal failure
Authors: Chow Wan‐Cheng
Published: March 2003

This paper addresses two difficult issues in the treatment of hepatitis C: patients who fail to achieve a sustained response after the first course of treatment, and those who simultaneously suffer from chronic renal failure. With the recent improvements in firstline treatment, retreatment is mainly applicable to those who have previously received 6‐month of interferon monotherapy at 3 MU thrice weekly. For those who had an end‐of‐treatment response but relapsed, there is a choice between interferon monotherapy at increased dose and/or duration of treatment, or a 6‐month course of combination therapy. Retreatment of non‐responders is generally unsuccessful, but some patients may respond to interferon‐alpha 3 MU and ribavirin 1.0–1.2 g/day. For patients with chronic renal failure and hepatitis C, combination treatment is not possible because ribavirin is contraindicated. Interferon given at a dose of 1.5 MU thrice weekly was reported to be fairly well tolerated by patients who were on dialysis and resulted in end‐of‐treatment and sustained biochemical and virological response in some cases. Interferon given in the usual doses may be associated with severe adverse effects in patients with renal failure, and can precipitate allograft rejection in patients who have undergone renal transplantation.
Natural history of chronic hepatitis C
Authors: Yatsuhashi Hiroshi , Yano Michitami
Published: March 2003

The natural history of chronic hepatitis C is one of a slow progression from early stage chronic hepatitis without fibrosis to cirrhosis or hepatocellular carcinoma (HCC). The disease progresses to advanced stage chronic hepatitis C over 10–30 years. Data from Japan indicate that mortality associated with chronic hepatitis C results mainly from the development of HCC. We studied 186 patients referred between 1968 and 1994. The mean follow‐up interval was 8.6 (2–23) years. HCC developed in 34 patients (18%). The cumulative probability of HCC development was 4% at 5 years, 18% at 10 years and 45% at 15 years. Univariable analysis indicated that age at entry, fibrosis stage, inflammation activity and the status of IFN treatment (treated vs untreated) were predictive risk factors for developing HCC in patients with chronic hepatitis C. Multivariable analysis of these risk factors indicated that age at entry (> 50 vs < 50; Risk Ratio = 3.2, P < 0.005) and fibrosis stage (F3 vs F0; Risk Ratio = 5.6, P < 0.005) are independent risk factors for HCC. From these results it was concluded that (1) 20% of patients referred to liver clinics with chronic hepatitis C in Japan can be expected to develop HCC over a 10 year period; (2) the risk of HCC increases with progression of liver fibrosis (F3, F4) and age (greater than 50 years old) at the time of diagnosis and (3) the degree of liver fibrosis is a critical predictive factor for the occurrence of HCC.
Water extract of Helicobacter pylori stimulates interleukin‐8 secretion by a human gastric epithelial cell line (JR‐St) through protein tyrosine phosphorylation
Authors: Yakabi Koji , Ro Shoki , Okazaki Ryo , Shiojima Junko , Tsuda Katsuhiko , Mimura Harumi , Tomono Hiroki , Nakamura Takashi
Published: March 2003

Background
: Infection by Helicobacter pylori induces cytokine production in gastric mucosal cells. Production of interleukin‐8 (IL‐8) is known to be markedly increased and is believed to play an important role in gastric mucosal inflammation. The aim of this study was to elucidate the effects of soluble factors of H. pylori on IL‐8 production in a gastric epithelial cell line, JR‐St.

Methods
: JR‐St cells were cocultured with a H. pylori water extract, live H. pylori or culture medium supernatant for 24 h, then the IL‐8 secreted into the culture medium was assayed. The effects of three different inhibitors; (i) an inhibitor of protein kinase C (PKC); (ii) an inhibitor of PKC and protein kinase A (PKA); and (iii) an inhibitor of protein tyrosine kinase (PTK) were also compared. Specific induction of IL‐8 mRNA was also examined.

Results
: Water extract of H. pylori increased IL‐8 secretion 7.72‐fold, more than the control. The increase was concentration dependent. Live bacteria, supernatant and water extract significantly stimulated IL‐8 secretion. Addition of live bacteria increased IL‐8 secretion most strongly, while the effect of water extract was small (22% that of live bacteria). Secretion was not inhibited by the PKC inhibitor staurosporine or the inhibitors of PKA and PKC H7. However, secretion was significantly reduced by the PTK inhibitor herbimycin in a dose‐dependent manner. Furthermore, 24 h exposure to water extract increased IL‐8 mRNA expression, suggesting water extract increased production of IL‐8.

Conclusions
: Some soluble factors of H. pylori can stimulate IL‐8 production by JR‐St cells. Stimulation was not dependent on PKA or PKC but was, at least partially, dependent on protein tyrosine phosphorylation. This suggests that soluble factors of H. pylori can play an important role in mediating the inflammatory response of H. pylori gastritis.

© 2000 Blackwell Science Asia Pty Ltd
Sho‐saiko‐to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma
Authors: Shimizu Ichiro
Published: March 2003

Herbal medicines, which have been used in China for thousands of years, are now being manufactured in Japan, in standardized form in terms of quality and quantities of ingredients. The Chinese herbal medicine Sho‐saiko‐to is a mixture of seven herbal preparations, which is widely administered in Japan to patients with chronic hepatitis and cirrhosis. In a prospective study, this herbal medicine was found to play a chemopreventive role in the development of hepatocellular carcinoma in cirrhotic patients. However, little is known about the mechanism by which Sho‐saiko‐to protects against hepatic fibrosis and carcinoma. Several laboratories, including ours, have clearly demonstrated the preventive and therapeutic effects of Sho‐saiko‐to on experimental hepatic fibrosis, as well as its inhibitory effect on the activation of hepatic stellate cells, which are the major types of collagen‐producing cells. We provided evidence that Sho‐saiko‐to functions as a potent anti‐fibrosuppressant via the inhibition of oxidative stress in hepatocytes and hepatic stellate cells and that its active components are baicalin and baicalein. In addition, Sho‐saiko‐to has anti‐carcinogenic properties in that it inhibits chemical hepatocarcinogenesis in animals, acts as a biological response modifier and suppresses the proliferation of hepatoma cells by inducing apoptosis and arrests the cell cycle. Among the active components of Sho‐saiko‐to, baicalin, baicalein and saikosaponin‐a have the ability to inhibit cell proliferation. It should be noted that baicalin and baicalein are flavonoids with chemical structures very similar to silybinin, which shows anti‐fibrogenic activities. This may provide valuable information on the search for novel anti‐fibrogenic agents.
Hepatic resection for benign tumours of the liver
Authors: Chen Miin‐Fu
Published: March 2003

The most frequent benign tumours of the liver include haemangioma, liver cell adenoma and focal nodular hyperplasia. Patients may undergo hepatic resection because of a preoperative diagnosis of malignancy or uncertainty in diagnosis despite an extensive work‐up.
Plaunotol suppresses interleukin‐8 secretion induced by Helicobacter pylori: Therapeutic effect of plaunotol on H. pylori infection
Authors: Takagi Atsushi , Koga Yasuhiro , Aiba Yuji , Kabir Abu Ma , Watanabe Sumio , Ohta‐Tada Uki , Osaki Takako , Kamiya Shigeru , Miwa Takeshi
Published: March 2003

Background
: It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin‐8 (IL‐8).

Methods
: We studied the effect of plaunotol, a drug extracted from the Plau‐noi tree of Thailand, and reported it to be effective in the treatment of ulcers, of IL‐8 secretion induced by H. pylori and of the inhibitory adhesion activity of the bacterium to gastric epithelial cells. Moreover, the therapeutic effect of plaunotol on H. pylori infection was assessed by using the gnotobiotic murine model.

Results
: Plaunotol inhibited the growth of H. pylori (1.5 × 10
4 c.f.u./mL) at high doses (24–48 μg/mL), but not at low doses (3–6 μg/mL). Interleukin‐8 secretion induced by H. pylori was inhibited by coculture with plaunotol in a dose‐dependent manner. The adhesion of H. pylori to MKN45 cells was also suppressed by coculture with plaunotol in a dose‐dependent manner. An in vivo study showed that plaunotol improved histological gastritis and decreased the H. pylori antibody titre.

Conclusions:
These findings suggest that plaunotol has a therapeutic effect on gastritis induced by H. pylori.
Influence of RNA titre and amino acid changes in the NS5A region of GB virus C/hepatitis G virus on the effectiveness of interferon therapy
Authors: Fujisawa Tomoki , Horiike Norio , Michitaka Kojiro , Onji Morikazu
Published: March 2003

Background
: A relationship between the pretreatment RNA titre of GB virus C/hepatitis G virus (GBV‐C/HGV) and the effectiveness of interferon (IFN) therapy has been reported previously. However, the influence of changes in the amino acid sequence of the NS5A region of GBV‐C/HGV on the effectiveness of IFN therapy has not been examined, although this influence has been explored in patients with chronic hepatitis caused by hepatitis C virus. We examined the relationship between changes in the amino‐acid sequence of the NS5A region and the effectiveness of IFN therapy.

Methods
: The subjects were 10 patients with chronic hepatitis C coinfected with GBV‐C/HGV and treated with IFN. The pretreatment level of GBV‐C/HGV‐RNA (copies/mL) in their sera was measured by real‐time detection polymerase chain reaction (PCR) assay. At 6 months after cessation of therapy, four of 10 patients had become negative for GBV‐C/HGV‐RNA (CR, complete response) and six patients were still positive for GBV‐C/HGV‐RNA (NR, non‐response). We determined the nucleotide sequence of the NS5A region (amino acid residues 1865–2279; NS5A1865–2279) of pretreatment GBV‐C/HGV‐RNA by direct sequencing.

Results
: The pretreatment GBV‐C/HGV‐RNA level of CR patients (7.8 × 104–6.2 × 105, mean 3.30 × 105) was significantly lower than that of NR patients (6.3 × 107–7.2 × 108, mean 3.55 × 108; P < 0.01). The number of amino acid substitutions in NS5A1865–2279 was five to seven (mean 5.8 ± 1.0) in CR patients, and four to eight (mean 6.8 ± 1.6) in NR patients, a difference that is not significant. Moreover, there were no amino acid substitutions or sites of substitution in NS5A1865–2279 that were specific to either group.

Conclusions
: The effectiveness of IFN therapy for GBV‐C/HGV is strongly related to the pretreatment GBV‐C/HGV‐RNA level, but is not related to changes in NS5A1865–2279.
Telomerase activity in peripheral blood for diagnosis of hepatoma
Authors: Tatsuma Toshiro , Goto Shigeru , Kitano Seigo , Lin Yu‐Chun , Lee Chuan‐Mo , Chen Chao‐Long
Published: March 2003

Background
: Telomerase activity may be used as a molecular marker for the detection of circulating hepatoma cells in blood of patients with hepatoma.

Methods
: Telomerase activity in peripheral blood from hepatocellular carcinoma (HCC) patients was assessed by using a highly sensitive and non‐radioisotope telomerase polymerase chain reaction (PCR) ELISA. Initially, tissue telomerase activity was measured in the hepatoma and non‐tumour portions by using PCR ELISA within the same specimen, to compare its sensitivity with the conventional telomeric repeat amplification protocol (TRAP) method. Second, telomerase activity was measured in the peripheral blood obtained from patients with HCC, patients with chronic liver disease and in healthy controls.

Results
: Of the 17 HCC patients, telomerase activity was found to be positive in 14 (82%) by using TRAP and 15 (88%) by using PCR ELISA, indicating that PCR ELISA is a reliable tool for the measurement of telomerase activity. By using the Telomerase PCR ELISA assay, telomerase activities in the peripheral blood of 20 HCC patients was 1.65 ± 0.78 units. This was significantly greater than the results obtained for 20 chronic liver disease patients (0.43 ± 0.36 units) and 20 healthy controls (0.39 ± 0.14 units; P < 0.0001). When the arbitrary cut‐off level was set at 0.7 units (maximum value of healthy controls + 0.1), the positive frequency of telomerase activity was 25% for chronic liver disease and 80% for HCC patients (sensitivity 80%, specificity 75%). Among the HCC patients, high telomerase activity in the peripheral blood was shown at stage III HCC with vascular invasion (2.10 ± 0.62 units, n = 9). This was significantly higher than patients at stage II of HCC (1.28 ± 0.72 units, n = 11, without vascular invasion; P = 0.012).

Conclusion
: These results suggest that peripheral blood telomerase activity, which may reflect haematogenous micrometastasis, is potentially a practical diagnostic/predictive marker of HCC.
L‐Arginine protects and exacerbates ethanol‐induced rat gastric mucosal injury
Authors: Kalia Nalia , Bardhan Karna Dev , Reed Malcolm Wr , Jacob Samuel , Brown Nicola Jane
Published: March 2003

Background and Aims
: We have previously demonstrated that 60% ethanol (EtOH) increases macromolecular leakage and induces focal lesion formation in areas of permanent flow stasis within gastric mucosal vessels. Nitric oxide (NO) may prevent lesion formation by inhibiting leakage. This study used fluorescent in vivo microscopy to investigate (i) whether
L‐arginine (NO precursor) prevented EtOH induced injury and (ii) the mechanisms of protection.

Methods
: Experiments were carried out on anaesthetized rats (hypnorm/diazepam) receiving either intra‐arterial fluorescein isothiocyanate–bovine serum albumin (0.2 mL/100 g), a marker for quantitating leakage, or Acridine red (0.1 mL/100 g) which labels leukocytes. Animals then received 100, 300 or 500 mg/kg
L‐arginine (i.a.) followed by 60% EtOH or distilled water, topically applied to the gastric mucosa (n = 6 for each group). Vessel diameter, macromolecular leakage of labelled albumin from post capillary venules (PCV) and capillaries and leukocyte activity were quantitated using image analysis.

Results
:
L‐Arginine (100 mg/kg) did not increase vessel diameter or prevent EtOH‐induced lesion formation and leakage. Both 300 mg/kg and 500 mg/kg alone induced significant and sustained increases in PCV diameter after 15 (P < 0.01) and 5 min (P < 0.001), respectively. Lesion formation was only prevented by 300 mg/kg
L‐arginine, whereas 500 mg/kg exacerbated haemorrhagic lesion formation over the entire exposed mucosa. Neither 300 mg/kg nor 500 mg/kg
L‐arginine prevented leakage following EtOH. No leukocyte activity was observed following EtOH with or without
L‐arginine pretreatment.

Conclusion
:
L‐Arginine (300 mg/kg) prevented lesion formation. The mechanism of protection probably involved the increased blood flow in the dilated PCV and not the inhibition of leakage. The combined effects of EtOH and the possible high NO levels exacerbate gastric mucosal damage despite the increases observed in vessel diameter.
Acute and chronic effects of isosorbide‐5‐mononitrate administration on effective renal plasma flow and the renin‐aldosterone system in cirrhotic patients
Authors: Chen Shy‐Den , Hsieh Jih‐Fang , Tsai Shih‐Chuan , Lin Wan‐Yu
Published: March 2003

Background and Aims
: Isosorbide‐5‐mononitrate (ISMO) has been shown to be effective in reducing the risk of variceal bleeding in patients with cirrhosis. However, recent studies have suggested that this drug compromises renal function. The present study was conducted to assess the acute and chronic effects of ISMO on effective renal plasma flow (ERPF) and the renin‐aldosterone profile in cirrhotic patients.

Methods
: Fifteen cirrhotic patients were included in the present study. The mean arterial pressure (MAP), heart rate (HR), serum renin concentration (SR), ERPF and plasma aldosterone concentration (PA) were checked before ISMO treatment (baseline study), after a single oral dose of 20 mg ISMO (acute effect study) and after 3 weeks of ISMO treatment (chronic effect study).

Results
: Our data showed that the oral administration of a single dose (20 mg) of ISMO to cirrhotic patients was associated with significant decreases in ERPF (from 405.18 to 369.06 mL/min) and MAP (from 93.26 to 86.40 mmHg), and increases in HR (from 65.53 to 70.06 beats/min), SR (from 24.15 to 54.41 pg/mL), and PA (from 105.1 to 148.7 pg/mL). However, no significant changes were observed in HR, MAP, PA, SR, or ERPF after 3 weeks of ISMO treatment when compared with the baseline study.

Conclusions
: The administration of ISMO causes a decrease in ERPF in cirrhotic patients and its use in patients with renal impairment should be considered cautiously.
Apoptosis and liver diseases: Recent concepts of mechanism and significance1
Authors: Ockner Robert K
Published: March 2003

Abstract Apoptosis, or programmed cell death, is a highly conserved mechanism that plays an essential role in numerous normal developmental and regulatory processes and disease states. It is mediated by a variable interaction among several components of the cell, including cell surface death receptors, the caspase cascade, mitochondrial metabolism and energetics, and the cytoskeleton. Even in those instances in which cell surface death receptors play a role, mitochondria are often central to the process, not only in mediating the death program, but in initiating it as well. In regard to mitochondrial involvement, a key role is hypothesized for an interaction among AMP‐activated protein kinase, cytoskeletal intermediate filaments, and mitochondrial oxidation of fatty acids. This proposed interaction may be a critical element in the pathogenesis of intramitochondrial oxidative stress, diminished inner membrane potential (ΔΨm), and other mitochondrial changes that contribute to cell death. Apoptosis may participate in a wide variety of disease processes, ranging from chemical and physical injury to viral infection and cancer, but its mechanistic and functional relationship to these conditions remains incompletely understood. Despite this, an understanding of the mechanisms involved and of the identity of potential pharmacologic targets is increasing, and warrants an optimistic view of their potential for clinical application.
Diazoxide, a KATPopener, accelerates restitution of ethanol or indomethacin‐induced gastric ulceration in rats independent of polyamines
Authors: Rahgozar M , Pazokitoroudi H , Bakhtiarian A , Djahanguiri B
Published: March 2003

Background and Aims:Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5′‐triphosphate (ATP)‐dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATPchannel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide‐induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied.

Methods:Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations.

Results:Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide‐induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU.

Conclusion:The KATPchannels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU.
Effect of mouth washing on the [13C]‐urea breath test
Authors: Lee Tzong‐Hsi , Yang Jyh‐Chin , Lee Shui‐Cheng , Farn Shiou‐Shiow , Wang Teh‐Hong
Published: March 2003

Background: Mouth washing is often mentioned as a possible method to eliminate the interference of urease activity in the oral cavity before the [13C]‐urea breath test (UBT). However, the effectiveness of mouth washing prior to testing has not been demonstrated clearly in the literature. Thus, the present study was designed to examine the consistency of the [13C]‐UBT and the effects of mouth washing on it.

Methods: A total of 101 healthy volunteers underwent the [13C]‐UBT three times. The first and second tests used a standard protocol and collected samples at 5, 10, 15 and 30 min. In the third test, the procedure was the same except that mouth washing was omitted.

Results: We used 5 permil (‰) as the cut‐off value and there were 21 (20.8%) positive cases. The κ values for the samples collected at 5, 10, 15 and 30 min between the first and second tests were 0.68, 0.97, 1 and 1, respectively, and all showed good consistency, except for the sample collected at 5 min. Judging from the mean value of the [13C] enrichment of the first and second tests (with mouth washing) and the third test (without mouth washing), 50 (63.3%), 15 (18.8%), 0 and 0 cases at 5, 10, 15 and 30 min, respectively, changed from negative to positive. There were 14 (17.5%) and six (7.5%) cases at 15 and 30 min, respectively, whose [13C] enrichment changed from less than 3 (negative) to between 3 and 5 (border zone).

Conclusions: These results indicate that mouth washing had an important effect on samples obtained at 5 and 10 min, while this influence decreased at 15 min and was lowest at 30 min.
Reactive oxygen species activity, mucosal lipoperoxidation and glutathione in Helicobacter pylori‐infected gastric mucosa
Authors: Jung Hye Kyung , Lee Kyung Eun , Chu Sang Hui , Yi Sun Young
Published: March 2003

Background and Aim: Helicobacter pylori is considered as the major pathogen in Helicobacter pylori‐associated gastroduodenal disease, but the mechanism of its action has not been fully explained. This study was performed to assess the reactive oxygen species activity and the damage in Helicobacter pylori‐infected gastric mucosa.

Methods: Gastric biopsy specimens were obtained from 308 patients undergoing endoscopy. Gastric mucosal damage was assessed by using luminol enhanced chemiluminescence, thiobarbituric acid‐reactive substance, and mucosal glutathione.

Results: The chemiluminescence and thiobarbituric acid‐reactive substance‐equivalent levels in the mucosa of patients with Helicobacter pylori‐positive gastric mucosa (43.8 ± 134.9 c.p.m./μg tissue, 157.0 ± 96.2 nmol/g tissue, respectively) were significantly higher than in those with Helicobacter pylori‐negative mucosa (6.8 ± 20.3 c.p.m./μg tissue, 110.0 ± 51.6 nmol/g tissue, respectively; P = 0.000, P = 0.016, respectively). The glutathione levels in the mucosa of patients with Helicobacter pylori‐positive gastric mucosa (159.3 ± 76.6 nmol/μg tissue) were significantly lower than in those with Helicobacter pylori‐negative gastric mucosa (212.3 ± 134.3 nmol/μg tissue; P = 0.008). After the data were divided according to the presence of Helicobacter pylori, there were no significant differences in chemiluminescence, thiobarbituric acid‐reactive substance, and glutathione among the different macroscopic findings within Helicobacter pylori‐positive and ‐negative gastric mucosa.

Conclusions: Helicobacter pylori infection plays a pathological role in many gastrointestinal diseases through excessive mucosal‐reactive oxygen species production, pronounced membrane damage, and the depletion of gastric anti‐oxidants.
Overlap of idiopathic portal hypertension and scleroderma: Report of two autopsy cases and a review of literature
Authors: TSUNEYAMA KOICHI , HARADA KENICHI , KATAYANAGI KAZUYOSHI , WATANABE KISHICHIRO , KURUMAYA HIROSHI , MINATO HIROSHI , NAKANUMA YASUNI
Published: March 2003

Abstract Idiopathic portal hypertension (IPH) is characterized by dense fibrosis of portal tracts and portal venous obliteration. Little is known about the etiopathogenesis of IPH. Association of various autoimmune diseases such as systemic lupus erythematosus in IPH suggests that IPH may share immunological disturbances with such autoimmune diseases. We recently experienced two autopsy cases presenting with both diffuse scleroderma and IPH. Dense fibrosis was found in both the dermis and intrahepatic portal tract of these cases. In addition, small vascular damages were commonly observed to various degrees in these fibrotic areas of both organs. The activation of fibroblasts and vascular damages mediated by various growth factors and cytokines reportedly involved in the dermis in scleroderma might have also been operative in portal tracts in these two cases of IPH. A review of literature disclosed eight overlapping cases of IPH and scleroderma (middle‐ to old‐aged females), and scleroderma was diagnosed earlier than IPH. These findings suggest that similar pathogenetic processes are operative in the dermis as well as in the portal tracts of the liver in these cases.
Changing role of endoscopy in the new millennium. Bushell Lecture, Asia–Pacific Digestive Week 2001
Authors: Sung Joseph Jy
Published: March 2003

Abstract  Endoscopy has confronted many challenges, including serology tests for Helicobacter pylori, virtual colonoscopy and magnetic resonance cholangiopancreatography. These new modalities might eventually replace endoscopy in diagnosing digestive tract diseases. New advancements such as capsule endoscopy, infrared spectroscopy, optical coherent tomography, and various therapeutic procedures have opened new horizons in the field. Endoscopists should keep their mind open and be prepared for the changing role of endoscopy in the new millennium.

© 2002 Blackwell Publishing Asia Pty Ltd
Chinese tea consumption and lower risk of Helicobacter infection
Authors: YEE YUK‐KEI , Koo MARCEL WING‐LEUNG , SZETO MING‐LEUNG
Published: March 2003

Abstract

Background:
Our first study had shown that Chinese tea has anti‐Helicobacter activity. The present study investigated the relationship between patients’Helicobacter status and the history of Chinese tea consumption.

Methods:
Chinese patients who had their first upper endoscopy were recruited. Before the procedure, patients completed questionnaires about their current Chinese tea consumption habits and those when they were around 10–25 years old. This information was used to calculate the tea consumption indices (TCI). Gastric biopsies (two from the antrum and two from the corpus) were taken for histological examination for Helicobacter.

Results:
Eighty patients were recruited. Eight patients were rejected because of either an incomplete questionnaire, absence of gastric biopsy or a suspected history of treatment for Helicobacter infection. Of the 72 patients, 42 (58.3%) were Helicobacter positive. The age, sex ratio and indications for endoscopy were similar in both Helicobacter‐positive and ‐negative groups. Classifying patients using either current, past or total TCI, patients with high tea consumption had significantly lower Helicobacter infection rate than those with low tea consumption (45% compared to 74%, 42% compared to 67% and 40% compared to 83%, respectively). Helicobacter‐negative patients had higher overall TCI than Helicobacter‐positive patients (28.2:17.3). When current and previous histories were analyzed separately, Helicobacter‐negative patients also had a trend towards higher TCI currently (16.6:11.0) and in their 20s (11.6:6.1).

Conclusions:
There is a significant inverse relationship between Chinese tea consumption and Helicobacter infection. Chinese tea consumption may decrease the chance of Helicobacter infection.

© 2002 Blackwell Publishing Asia Pty Ltd
Oval cell‐mediated liver regeneration: Role of cytokines and growth factors
Authors: LOWES KYM N , CROAGER EMMA J , OLYNYK JOHN K , ABRAHAM LAWRENCE J , YEOH GEORGE C T
Published: March 2003

Abstract   In experimental models, which induce liver damage and simultaneously block hepatocyte proliferation, the recruitment of a hepatic progenitor cell population comprised of oval cells is invariably observed. There is a substantial body of evidence to suggest that oval cells are involved in liver regeneration, as they differentiate into hepatocytes and biliary cells. Recently, bone marrow cells were shown to be a source of a stem cells with the capacity to repopulate the liver. Presently, the relationship between bone marrow cells and oval cells is unclear. Investigations will be greatly assisted by the availability of in vitro models based on a knowledge of cytokines that affect oval cells. While the cytokines, which regulate the different hematopoietic lineages, are well characterized, there is relatively little information regarding those that influence oval cells. This review outlines recent developments in the field of oval cell research and focuses on cytokines and growth factors that have been implicated in regulating oval cell proliferation and differentiation.

© 2003 Blackwell Publishing Asia Pty Ltd