bluuebunny/crossref_metadata_2025 huggingface dataset:
PEPTIC ULCER: PATHOGENESIS, HEALING AND ANTI‐ULCER DRUGS
Authors: GYÖMBER E. , VATTAY P. , SZABO S. , RAINSFORD KD
Published: March 2008

Abstract  Studies were performed in three models of acute gastric mucosal damage (induced by oral ethanol, aspirin and indomethacin) and a model of chronic gastritis (induced by 7 day treatment with iodoacetamide) in rats to establish the role of leukotrienes (LTs) in the pathogenesis of these lesions. The protective effects of highly selective 5‐lipoxygenase (5‐LO) inhibitors and leukotriene antagonists were thus examined in rats given these ulcerogens. Ethanol (1 mL, p.o.)‐induced haemorrhagic lesions were significantly reduced by prior oral administration of the 5‐LO inhibitor L‐656 224 (50 mg/kg), whereas lower doses of this drug were ineffective. Prior treatment with oral doses (5 and 10 mg/kg) of the 5‐LO inhibitor L‐655 224 or the LT antagonists L‐649 923 or L‐660 711, failed to affect lesions induced by aspirin (100 mg/kg, p.o.) and indomethacin (400 mg/kg, s.c), whereas higher doses of all three drugs (50 mg/kg) showed protective effects. Repeated prior dosing up to 5 h with the novel five lipoxygenase activating protein (FLAP) inhibitor, MK886 (50 and 100 mg/kg), reduced the lesions developed by indomethacin (30 mg/kg, s.c). Twice daily dosing with the 5‐LO inhibitor L‐656 224 (5 mg/kg) or the LT antagonist L‐649 923 (2 or 5 mg/kg) for 7 days significantly reduced the development of iodoacetamide‐induced gastritis during the period of induction of this condition, but higher doses of these inhibitors were not protective. We conclude that 5‐LO products partially mediate the production of gastric mucosal lesions induced by damaging agents, which varies according to the ulcer model employed; the limited protective effects of the respective 5‐LO inhibitors and LT antagonists depend on their individual pharmacokinetics and their time of dosing.
Treatment with a novel lipid A analogue, FS‐112, and partial hepatectomy causes submassive liver necrosis and impaired liver regeneration in mice
Authors: MAEDA T , OHNISHI H , HAYASHI T , ISHIKI Y , MORIWAKI H , MUTO Y
Published: March 2008

A novel experimental model of submassive liver necrosis with impaired regeneration has been established. A novel lipid A analogue, FS‐112, was injected intravenously into male BALB/c mice, followed 2 days later by a 70% partial hepatectomy. Over the next 9 days, mice became severely jaundiced, with a peak total bilirubin (TBil) concentration of (mean±s.d.) 12.9±2.1 mg/dL 7 days postoperatively. In contrast, the TBil concentration in vehicle‐treated mice remained less than 2 mg/dL. Significant elevations of L‐alanine:2‐oxoglutarate aminotransferase (ALT) were also observed 3–7 days after the operation in mice pretreated with FS‐112, compared with mice pretreated with the vehicle. Submassive liver necrosis was observed with extensive mononuclear cell infiltration in mice treated with FS‐112 and subjected to partial hepatectomy. Furthermore, both the BrdU and the proliferating cell nuclear antigen (PCNA) labelling index (LI) 1 day following partial hepatectomy in mice pretreated with FS‐112 (8.6±4.3 and 7.9±4.2%, respectively) were significantly lower than levels in vehicletreated mice (25.8±3.8 and 26.5±10.5%, respectively). The time course of changes in the BrdU LI in liver specimens from mice treated with both FS‐112 and partial hepatectomy did not increase, even 3, 5, and 7 days postoperatively. Excellent liver regeneration with a PCNA LI 10‐fold higher than the resting level was observed in mice treated with D‐galactosamine hydrochloride. These results strongly suggest that this animal model of submassive liver necrosis may be suitable for clarifying the mechanisms of impaired liver cell regeneration often seen in fulminant hepatitis.
Serum procarboxypeptidase B, amylase and lipase in chronic renal failure
Authors: CHEN CHUN‐CHIA , WANG SUN‐SANG , CHEN TZEN‐WEN , JAP TJIN‐SHING , CHEN SHEN‐JYH , JENG FONG‐SHYA , LEE SHOU‐DONG
Published: March 2008

Procarboxypeptidase B (human pancreas‐specific protein) has been reported to be a good serum marker for the diagnosis of acute pancreatitis. The current study was conducted in order to evaluate the frequency and degree of elevated serum levels of procarboxypeptidase B in chronic renal failure and their correlations with serum levels of amylase, lipase and renal function tests. Blood samples were taken from 84 asymptomatic patients with chronic renal failure, including 34 patients with periodical haemodialysis and 50 patients without haemodialysis. Serum levels of procarboxypeptidase B, amylase, lipase, creatinine and blood urea nitrogen were measured. Serum levels of procarboxypeptidase B in 84 patients were 63.4±5.5 μg/L significantly greater than the figure of 29.6±1.6 μg/L in healthy adults in our previous report (P< 0.0001). There was a significant difference in serum levels of PCPB between patients with and without haemodialysis (78.0±9.4 vs 53.6±6.3 μg/L; P< 0.01). The frequencies of elevated serum levels of procarboxypeptidase B, amylase and lipase greater than upper normal limits were 27.4, 35.7 and 26.2%, respectively. The frequencies of elevated PCPB in patients with and without haemodialysis were 38.2 and 20%, respectively. Only one patient had a serum procarboxypeptidase B level greater than three‐fold the upper normal limit. A significant correlation was found between procarboxypeptidase B and lipase (r = 0.785; P< 0.0001). No significant correlation was noted between procarboxypeptidase B vs amylase or renal function tests. In conclusion, in patients with chronic renal failure, the elevation of serum procarboxypeptidase B is as common as the elevations of other pancreatic enzymes.
Review: Treatment of primary biliary cirrhosis
Authors: HEATHCOTE JENNY
Published: March 2008

Primary biliary cirrhosis (PBC) is a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. One‐third of patients are asymptomatic and one‐third of these develop symptoms within 5 years. Therapeutic regimens should be directed at the control of symptoms, prevention of complications and specific therapy aimed at controlling progression of the disease. Symptoms may be secondary to cholestasis or due to other associated diseases. The cause of pruritus secondary to cholestasis remains unknown; the anion exchange resin cholestyramine generally brings relief. In patients resistant or intolerant to this therapy, rifampin may be helpful, as well as ultraviolet light without sunblock. Liver transplantation may rarely be the only option for uncontrollable pruritus. Clinical manifestations of keratoconjunctivitis sicca and xerostomia need constant attention to prevent corneal ulcers and dental caries. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary and the administration of the fat soluble vitamins A, D and K once hyperbilirubinaemia is present. Osteoporosis is a complication of all cholestatic liver disease. There is no satisfactory preventative therapy. It may be appropriate to give hormone replacement therapy to all post‐menopausal women with PBC to reduce osteoporosis. Liver transplantation is the best option for those with fractures. Oesophageal varices may develop early in the course of PBC, non‐selective beta‐blocker therapy should be used as prophylaxis against variceal haemorrhage. The only specific therapy shown to cause both a biochemical and survival benefit in patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays progression, but does not result in a cure of this disease. Currently, liver transplantation is the only definitive treatment available for end‐stage disease.
Plasma interleukin‐8 levels in patients with post‐hepatitic cirrhosis: Relationship to severity of liver disease, portal hypertension and hyperdynamic circulation
Authors: LI CHUNG‐PIN , LEE FA‐YAUH , TSAI YANG‐TE , LIN HAN‐CHIEH , LU REI‐HWA , HOU MING‐CHIH , WANG TEH‐FANG , CHEN LING‐SHENG , WANG SUN‐SANG , LEE SHOU‐DONG
Published: March 2008

The present study investigated plasma levels of interleukin‐8 (IL‐8) in patients with post‐hepatitic cirrhosis and correlated it with the severity of liver diseases and haemodynamic parameters. Plasma IL‐8 levels were significantly higher in 57 post‐hepatitic cirrhotic patients (7.5 ± 1.8 pg/mL; P< 0.005) than those in 41 healthy subjects (2.0 ± 0.2 pg/mL). Elevated (> 5 pg/mL) plasma IL‐8 levels were found in up to 30% of cirrhotic patients. In cirrhotic patients, plasma IL‐8 levels progressively increased in relation to the severity of liver dysfunction (4.5 ± 1.0, 4.9 ± 1.4 and 20.5 ± 8.3 pg/mL for Pugh's class A, B and C, respectively; P<0.005). A significant correlation was observed between plasma IL‐8 levels and serum bilirubin levels (r = 0.72; P<0.001). There were no differences in the hepatic venous pressure gradient (15.4 ± 1.1 vs 15.1 ± 0.9 mmHg; P>0.05) and systemic vascular resistance (1119 ± 118 vs 1199 ± 54 dyn.s/cm5; P>0.05) between cirrhotic patients with and without elevated plasma IL‐8 levels. In addition, plasma IL‐8 levels did not correlate with hepatic venous pressure gradient (r = 0.26; P>0.05) and systemic vascular resistance (r=‐0.24; P>0.05). These results demonstrate that plasma IL‐8 levels are increased in patients with post‐hepatitic cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of enhanced IL‐8 levels. IL‐8 does not play a role in the hyperdynamic circulation observed in patients with post‐hepatitic cirrhosis.
High acid secretion may protect the gastric mucosa from injury caused by ammonia produced by Helicobacter pylori in duodenal ulcer patients
Authors: SHIBATA TOMOYUKI , IMOTO ICHIRO , TAGUCHI YUKIKO , TAKAJI SATOSHI , IKEMURA NORIHISA , NAKAO KAZUYUKI , KOSHIYAMA MASUMI , SHIMA TERUO
Published: March 2008

The aim of the present study was to investigate the mechanism by which gastric atrophy does not tend to occur in patients with duodenal ulcer despite frequent Helicobacter pylori infection. This investigation was performed in 60 patients with duodenal ulcer and 63 age‐matched gastritis patients. Endoscopic findings in the antrum and corpus were classified as normal, atrophic and superficial changes. Biopsy specimens were taken from the antrum and corpus. Ninety per cent of patients with duodenal ulcer and 63.5% of patients with gastritis had H. pylori infection (P<0.01). The incidence of normal findings in duodenal patients was 30% in antral regions and 50% in the corpus (P<0.05). Atrophic change was observed in 21.7% of patients in the antrum and 3.3% of patients in the corpus (P<0.01). The grade of inflammation in duodenal ulcer specimens was significantly higher in the antrum than in the corpus (P<0.01). >H. pylori density was significantly higher in the antrum than in the corpus in ulcer patients (P<0.01). No significant difference in endoscopic findings, >H. pylori density or the grade of inflammation was found between the antrum and corpus in patients with gastritis. The mean intragastric ammonia concentration was 10.3 mg/dL in duodenal ulcer patients and 6.2 mg/dL in gastritis patients (P<0.01). The mean pH was 3.5 and 4.6 in ulcer and gastritis specimens, respectively (P<0.01). Our data suggest that gastric mucosa injury is less frequently associated with duodenal ulcers than with gastritis due to the low >H. pylori density in the corpus and to the higher acid output that neutralizes the ammonia produced by H. pylori.
Epithelial cell proliferation during colonic chemical carcinogenesis in the rat
Authors: OKADA HIROYUKI , MIZUNO MOTOWO , IKEDA NOBUMASA , TOMODA JUN , TSUJI TAKAO
Published: March 2008

To define the significance of alterations in epithelial cell proliferation as a marker of high risk mucosa for colorectal cancer, we examined cell proliferative events in the colonic mucosa during chemical carcinogenesis using in vitro bromodeoxyuridine labelling and by analysing serial colonoscopic biopsy specimens from dimethylhydrazine (DMH)‐treated rats. In both the rectum and flexure of the colon, an increased labelling index of colonic epithelial cells, an upward extension of the proliferating zone and an upward shift of the major area of DNA synthesis of epithelial cells were observed during DMH‐induced colonic carcinogenesis in rats. These changes preceded the development of the colonic tumour and were observed in endoscopically normal rectal mucosa where the tumour was absent. We confirmed the altered cell proliferative events preceding the development of the tumour by examining serial colonoscopic biopsies. The results suggest that these alterations are features that identify premalignant colonic mucosa in DMH‐treated rats.
Lymphocyte proliferative responses to recombinant hepatitis C virus antigens in patients with chronic hepatitis C
Authors: MORI HIROMITSU , YABU KOJI , YOSHIZAWA KANAME , TANAKA EIJI , KIYOSAWA KENDO
Published: March 2008

The purpose of the present study was to analyse lymphocyte proliferative responses to recombinant hepatitis C virus (HCV) antigens in chronic hepatitis C. Four recombinant peptides derived from the NS3, core, E1 and E2/NS1 regions of the HCV genome were used as antigens in lymphocyte proliferative responses. Forty‐two patients, classified into various sub‐groups, and 17 healthy control subjects were tested and the specific response was expressed as a stimulation index. Responses were analysed with alanine aminotransferase (ALT) level and histological diagnosis. NS3‐ and core‐antigen specific responses in all patient groups were significantly higher than in the healthy control group. E1‐ and E2/NS1‐antigen‐specific responses in the patient group with ALT levels exceeding 100 IU/L were significantly higher than those in other patient groups. Histological diagnosis was not correlated to the intensity of the core‐ and NS3‐specific responses. E1‐ and E2/NS1‐antigens induced significantly elevated responses in patients with chronic active hepatitis and liver cirrhosis compared with results in the healthy control group and in patients with chronic persistent hepatitis. In conclusion, the significantly elevated responses to core‐ and NS3‐antigens may be related to HCV infection and such responses to E1‐ and E2/NS1‐antigens could be related to the severity and activity of the disease.
Case Report: Intrahepatic cholangiocarcinoma with rhabdoid transformation
Authors: HONDA MASANAO , ENJOJI MUNECHIKA , SAKAI HIRONORI , YAMAMOTO ICHIRO , TSUNEYOSHI† MASAZUMI , NAWATA HAJIME
Published: March 2008

Sarcomatous transformation is found in approximately 5% of patients with intrahepatic cholangiocarcinoma. According to previous reports, sarcomatous cholangiocarcinomas are composed of spindle‐shaped cells and/or multinucleated giant cells. Usually, vimentin is expressed by these sarcomatoid cells. We report a case of intrahepatic cholangiocarcinoma with an element of rhabdoid cells that occurred in a 61‐year‐old woman admitted for back pain. Various imaging techniques demonstrated multiple liver masses. Histologically, these tumours formed in both sarcomatous and ordinary tubular adenocarcinomatous areas. The sarcomatoid areas were occupied mainly by loosely arranged, eosinophilic rhabdoid cells, which expressed both keratin and vimentin. These findings suggest that rhabdoid cells may occur in an undifferentiated stage of cholangiocarcinoma and possess a strong tendency to metastasize.
DNA flow‐cytometric analysis in colorectal cancer: A comparison of metastasizing and non‐metastasizing tumours
Authors: YANG JIA‐LIN , CROWE PHILIP J , OW KIM T , HAM JOHN M , CROUCH ROGER L , RUSSELL PAMELA J
Published: March 2008

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non‐metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin‐embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non‐malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi‐squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.
Regeneration of nerve fibres across a colonic anastomosis in the guinea‐pig
Authors: BROOKES SJH , LAM TCF , LUBOWSKI DZ , COSTA M. , KING† DW
Published: March 2008

Resection and re‐anastomosis of the bowel interrupts enteric neuronal pathways. The re‐establishment of neuronal connections across a colonic anastomosis was studied using immunohistochemical, retrograde tracing and physiological techniques. In control guinea‐pig proximal colon, retrograde labelling with 1,1′‐didodecyl‐3,3,3,3′‐tetramethylindocarbocyanine perchlorate (DiI) revealed that enteric neurons with anally‐directed projections are more numerous and have longer axons than orally‐projecting neurons. In resected bowel, up to 26 weeks after re‐anastomosis, descending neuronal pathways were substantially interrupted. Immunohistochemical labelling of nerve fibres revealed that some enteric nerve fibres did regenerate across narrow regions of the anastomosis, growing preferentially in the oral to anal direction. However, nerve fibres immunoreactive for neurofilament protein triplet were substantially depleted in myenteric ganglia anal to the anastomosis, even after the longest recovery periods, demonstrating that axonal regrowth was limited. This was confirmed in retrograde tracing studies, as no nerve cell bodies oral to an anastomosis were labelled when DiI was placed on myenteric ganglia just anal to the anastomosis. Physiological studies confirmed that regrowth of nerve fibres across the anastomosis occurred and that it was asymmetric, as electrical stimulation led to aboral conduction across the anastomosis more reliably than oral conduction, as measured by circular muscle contraction. After resection and re‐anastomosis of the colon, the disruption of neuronal pathways in the enteric nervous system was observed, with limited and preferential re‐establishment of aborally‐directed long connections.
Response to interferon in chronic hepatitis C due to mixed genotype infection
Authors: HORIIKE NORIO , MASUMOTO TOSHIKAZU , MICHITAKA KOJIRO , KUROSE KIYOTAKA , AKBAR SM FAZLE , ONJI MORIKAZU
Published: March 2008

We examined the response to interferon (IFN) in patients with chronic hepatitis C (CHC) due to two different genotypes of hepatitis C virus (HCV) infection. Among 64 CHC patients studied, one (2%) had HCV‐RNA genotype I, 36 (56%) had genotype II, 19 (30%) had genotype III, 2 (3%) had genotype IV and 6 (9%) had both genotypes II and III. There was no significant difference in age, sex, history of blood transfusion and liver histology among patients with genotypes II, III and II + III. The HCV‐RNA titre of genotype II patients was significantly higher than that of genotype III patients (P < 0.05). However, there was no significant difference in the HCV‐RNA titre between genotype II + III and the other groups. The complete response rate achieved with IFN therapy was significantly higher in genotype III patients (74%) than in genotype II patients (17%; P < 0.01). Of the six patients with genotype II + III, a complete response to IFN was only achieved by two patients (33%), both of whom had a low HCV‐RNA titre (≦ 104,5 copies/mL) and HCV serotype 2. The remaining four patients had HCV serotype 1 and three of the patients had a high HCV‐RNA titre (≧ 105 copies/mL). The HCV genotype III was lost in two patients after IFN therapy. These data suggest that HCV‐RNA titre and HCV serotype are important factors for predicting the efficacy of IFN therapy in patients with mixed genotype infection and show direct evidence of higher susceptibility towards CHC of patients with genotype III than genotype II.
Increase of sulfated ursodeoxycholic acid in the serum and urine of patients with chronic liver disease after ursodeoxycholic acid therapy
Authors: NAKAMURA KIMIHIDE , YONEDA MASASHI , KIMURA ATSUSHI , TAMORI KEISUKE , YOKOHAMA SHIRO , SATO YOICHI , KATO TAKAFUMI , HASEGAWA TAKENAO , SAITO HIDEAKI , AOSHIMA MASARU , FUJITA MASANORI , MAKINO ISAO
Published: March 2008

The present study was undertaken in order to investigate the influence of ursodeoxycholic acid (UDCA) on the composition of sulfate‐conjugated bile acids in the serum and urine of patients with chronic active hepatitis and compensated liver cirrhosis. After a 12 week UDCA treatment (600 mg/day), total serum bile acid concentration increased two‐fold in patients with compensated liver cirrhosis and increased slightly in patients with chronic active hepatitis. The percentage of sulfated bile acids significantly increased in patients with both compensated liver cirrhosis and chronic active hepatitis. UDCA made up 63% of the total serum bile acids in compensated liver cirrhosis and 61% in chronic active hepatitis after UDCA treatment. Of the serum bile acids after UDCA treatment, 35.2 and 53.9% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. Urinary excretion of total bile acid and UDCA after UDCA treatment in compensated liver cirrhosis were higher than in chronic active hepatitis. UDCA made up 68% of the total urinary bile acids in compensated liver cirrhosis and 64% in chronic active hepatitis after UDCA treatment. Of the urinary bile acids after UDCA treatment, 51.8 and 54.8% of UDCA was sulfate conjugated in compensated liver cirrhosis and chronic active hepatitis, respectively. UDCA treatment for compensated liver cirrhosis was less effective than for chronic active hepatitis. We found that sulfate conjugation is one of the major metabolic pathways for UDCA after UDCA treatment in chronic liver diseases.
A distinctive aphthous ileitis linked to Ancylostoma caninum
Authors: CROESE JOHN , FAIRLEY STEPHEN , LOUKAS ALEX , HACK JOHN , STRONACH PAM
Published: March 2008

Ileal ulceration is diagnosed commonly at colonoscopy in northeastern Australia. This observation has occurred contemporaneously with the description of a painful enteritis caused through supposedly rare infections by Ancylostoma caninum, the cosmopolitan dog hookworm. In this study, we describe the morphology and prevalence of ileal ulcers and investigate their cause. There were 182 patients with a distinctive aphthous ileitis highlighted by haemorrhage into the tips of surrounding villi. The annual rate reached 4.7% of ileal examinations. Eosinophilic enteritis was the characteristic, but inconsistent, histological appearance. Ulceration was linked to infection by A. caninum through serological testing and, in three patients, by the retrieval of single hookworms. Affected patients were also more likely to own a dog (53%) than the total colonoscopic population (43%; P< 0.02). The monthly rates of diagnosis were related to climate with fewest recordings during winter. Pain was the chief indication for colonoscopy (49%), proportionally higher than in controls (28%; P< 0.0001). Patients with ulcers had increased blood eosinophil, immunoglobulin E and serological values. These results were higher still in the subset with pain compared with the rest. Most patients, however, had colonoscopy performed for unrelated reasons, such as bowel cancer surveillance, and were identified as having subclinical ulceration (rate 3.2%). The findings establish a distinctive aphthous ileitis characterized by tissue eosinophilia. The cause has been tentatively linked to canine hookworms. It is proposed that infection in this geographic region is common and only rarely does a painful enteritis develop as a consequence of hypersensitization.
Point mutation in precore region of hepatitis B virus: Sequential changes from ‘wild’ to ‘mutant'
Authors: EHATA TOSHIKI , YOKOSUKA OSAMU , IMAZEKI FUMIO , OMATA MASAO
Published: March 2008

One point mutation to make a stop codon in the precore (pre‐C) region of the hepatitis B virus DNA in anti‐HBe‐positive patients has been reported recently. This mutation disturbs the formation of the pre‐C protein that is processed to make HBeAg. The relationship between the point mutation and HBe antigen antibody status was investigated in B‐viral liver diseases. The pre‐C region was amplified by a polymerase chain reaction (PCR) method and the nucleotide sequences were determined by a direct sequencing method. In seven cases who were persistently HBeAg‐positive, the wild type (no mutation in pre‐C region) was detected in all. In 20 cases who were anti‐HBeAg‐positive at diagnosis, the mutant type (point mutation at nucleotide 1896 in pre‐C region, which makes a stop codon) was detected in 16 cases and the wild type in two cases. In HBe seroconversion (SC) cases, the types of virus were investigated in serial blood samples. No mutant type was detected in initial sera during the HBeAg‐positive period. In two ‘natural’ SC cases, the mutant type appeared before anti‐HBe formation. However, in three anti‐viral ‘drug‐induced’ SC cases, the mutant type appeared after the formation of anti‐HBe. In two ‘reversed’ seroconversion cases only the wild type was detected throughout the follow‐up period. These data suggest that the appearance of a pre‐C mutant may help to predict seroconversion from HBeAg to anti‐HBe and may help distinguish ‘natural’ and ‘drug‐induced’ seroconversion of HBeAg.
Gastric Secretion
Authors: THOMSON ABR , MAHACHAI V. , BAILEY RJ , KIRDEIKIS P. , ZUK L. , MARRIAGE B. , SIMPSON I. , JAMALI F.
Published: March 2008

Abstract  The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00–08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00–22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2vs N1) or ranitidine (R2vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2‐receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2‐receptor antagonists; doubling the dose of the H2‐receptor antagonist (R2vs R1 and N2vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six‐fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.
Clinical assessment of the bacterial load of Helicobacter pylori on gastric mucosa by a new multi‐scaled rapid urease test
Authors: CHOU CHANG‐HUA , SHEU BOR‐SHYANG , YANG HSIAO‐BAI , CHENG PIN‐NAN , SHIN JENG‐SHIANN , CHEN CHIUNG‐YU , LIN XI‐ZHANG
Published: March 2008

The present study tests the efficacy of the multi‐scaled urease test (MUT) in detecting Helicobacter pylori infection and determines whether the MUT can predict the bacterial density on histology. A total of 111 sets of gastric specimens were obtained from patients with dyspepsia but without recent bleeding. Two biopsies were taken as closely as possible in each set. One sample was used for the MUT (Hp fast; GI Supply, Camp Hill, PA, USA), while the other was used to determine the histological density of H. pylori by modified Giemsa stain (grade 0–5). The results of MUT were interpreted as negative if the colour was yellow or bright green (reaction score 0) and positive if the colour was green, light blue, or blue (reaction score 1, 2 and 3, respectively). The reaction scores of MUT were recorded sequentially at 15 and 30 min and 1, 4 and 24 h. On the basis of histological confirmation, MUT had a sensitivity of 89.6%, a specificity of 88.2%, a positive predictive value of 94.5% and a negative predictive value of 78.9%. Focusing on specimens with the presence of bacteria under histology, 77 specimens were divided into five subgroups by grades of density of H. pylori (HPD1–5). The reaction scores had become sequentially elevated from 30 min through to 24 h in each subgroup. For subgroups HPD4 and 5, the positive rates of MUT were 70.6 and 66.6%, respectively, as early as 30 min and progressed to 100% within 4 h. In contrast, the positive rate for the HPD1 subgroup was 16.6% at 4 h and increased to only 62.5% at 24 h. In subgroups HPD 2 and 3, the positive rates were less than 30% at 30 min, but became more than 66.6% at 4 h and were 100% at 24 h. The early (i.e. mean value of reaction scores before 4 h) and late (24 h) mean reaction scores disclosed two elevated trends as the density of H. pylori increased (early: 0.2, 0.7, 0.8, 1.5, 1.2; late: 1.4, 2.3, 2.6, 3.0, 3.0; P < 0.05). In conclusion, MUT is a reliable method for the diagnosis of H. pylori infection. It can also indirectly predict the density of H. pylori on histology.
Can misoprostol and omeprazole reduce nicotine and ethanol induced gastric mucosal injury? A quantitative macroscopic and microscopic analysis in rats
Authors: HUI WM , HO J , CHEN BW , CHO C‐H , BRANICKI FJ , LAM SK
Published: March 2008

We compared the effects of misoprostol, omeprazole and methylcellulose (control) on gastric mucosal injury induced by nicotine and/or ethanol. The results demonstrate that misoprostol and omeprazole each significantly reduce macroscopic injury and deep injury at a microscopic level (P < 0.05) induced by nicotine alone, ethanol alone or a combination of ethanol and nicotine. Misoprostol and omeprazole each reduced the leakage of fluorescein isothiocyanate‐albumin into the interstitium in the gastric mucosa. Misoprostol and omeprazole are each effective in preventing injury induced by nicotine and ethanol and vascular factors are involved.
Antibody response to E2/NS1 hepatitis C virus protein in patients with acute hepatitis C
Authors: KOBAYASHI MASAKAZU , TANAKA EIJI , MATSUMOTO AKIHIRO , ICHIJO TETSUYA , KIYOSAWA KENDO
Published: March 2008

Antibody response to the E2/NS1 protein of the hepatitis C virus (HCV) was studied in 26 patients with post‐transfusion acute hepatitis C. Second‐generation HCV (HCV‐2) antibody, E2/NS1 antibody and HCV‐RNA were measured in serial serum samples taken within 1 month and 3, 6 and 12 months after the onset of acute hepatitis C. The HCV genotype was also tested to study its clinical significance. Of 26 patients, eight showed normalization of alanine aminotransferase (ALT) and clearance of HCV‐RNA (resolved group). In the remaining 18 patients, HCV viraemia and ALT abnormality (except one patient) continued for more than 3 years (unresolved group). Both HCV‐2 and E2/NS1 antibodies were positive at least once in all patients. The prevalence of E2/NS1 antibody was significantly (P < 0.05) higher in the resolved group (88%) than in the unresolved group (39%) in the period within 1 month of onset; the prevalence was similar between the two groups thereafter. The prevalence of HCV‐2 antibody did not differ between the two groups at any point. The HCV genotype was not related to the chronicity of acute hepatitis C. In conclusion, the E2/NS1 antibody appeared in all patients with acute hepatitis C and was associated with the clearance of HCV.
Effect of cholestasis induced by organic anion on the lipid composition of hepatic membrane subfractions and bile in rats
Authors: MIURA HIROYUKI , TAZUMA SUSUMU , YAMASHITA GUNJI , HATSUSHIKA SUMIE , KAJIYAMA GORO
Published: March 2008

Several organic anions inhibit the secretion of cholesterol and phospholipid into bile without affecting total bile acid secretion (uncoupling). The uncoupling induced by sulphobromophthalein (BSP) alters the fatty acid composition of biliary lecithin. The purpose of this study was to investigate the relationship between the lipid composition of bile and of liver subcellular membrane fractions during BSP‐induced uncoupling. After depletion of the bile salt pool, rats fitted with a bile duct cannulus were infused with sodium taurocholate given either alone or with BSP. Bile was collected and liver microsomes and canalicular membranes were isolated for analysis of lipid composition. In bile, uncoupling increased the cholesterol/phospholipid ratio (C/P ratio) and the saturated/unsaturated fatty acid ratio (S/U ratio) in phosphatidylcholine. The C/P ratio was increased in the canalicular membrane, but the membrane phosphatidylcholine S/U ratio decreased during uncoupling. In microsomes, the S/U ratio of membrane phosphatidylcholine was slightly increased, but the C/P ratio was unaffected during uncoupling. These results support the hypothesis that an increased secretion of hydrophobic phosphatidylcholine species from the canalicular membrane into bile reduces the proportion of hydrophobic phosphatidylcholine species in the canalicular membrane during uncoupling. The decreased contribution of hydrophobic phosphatidylcholine species may ameliorate the decrease in membrane fluidity resulting from the accumulation of cholesterol in the canalicular membrane and stimulate the synthesis of hydrophobic phosphatidylcholine species in the microsomes.
Decreasing hepatitis D virus infection in Taiwan: An analysis of contributory factors
Authors: HUO TEH‐IA , WU JAW‐CHING , LIN RUEY‐YI , SHENG WEN‐YUNG , CHANG FULL‐YOUNG , LEE SHOU‐DONG
Published: March 2008

Superinfection of hepatitis D virus (HDV) among hepatitis B virus (HBV) carriers is mainly through heterosexual contact in Taiwan. This study investigated the change of HDV endemicity and its associated contributory factors. Seventy‐seven patients with acute HDV superinfection among 527 consecutive exacerbating hepatitis B surface antigen (HBsAg) carriers were identified over the past 12 years. The prevalence decreased significantly by each 3‐year period from June 1983 to May 1995 (23.7, 15.5, 13.1 and 4.2%, respectively, P < 0.001). This trend was more significant in the hepatitis B e antigen (HBeAg)‐negative group (P < 0.001) than in the HBeAg‐positive group (P=0.073). Subjects with a history of paid sex and prostitutes were also recruited for analysis both in 1989 and 1996. Although not statistically significant, there was a trend showing a decrease in the prevalence of serum antibody against HDV (anti‐HDV) in each risk group: it was lower in 1996 among HBsAg‐positive brothel‐goers (10.3 vs 6.9%), licensed prostitutes (54.5 vs 50%) and unlicensed prostitutes (36.1 vs 30.8%). Accumulation of anti‐HDV‐positive subjects in risk groups may mask the actual decrease of new HDV‐infected cases. The prevalence of the HBsAg carrier rate among all prostitutes has significantly decreased (18.3 vs 12.2%, P=0.015). The efficacy of each preventive strategy was examined and mapped with the trend. It was concluded that active preventive measures directed against promiscuity and sexually transmitted disease and the promotion of disposable needles may have contributed to the decrease in HDV endemicity.
Clinical significance of hepatitis G virus infection in patients on long‐term haemodialysis
Authors: IDEURA TADASHI , TANAKA EIJI , NAKATSUJI YOSHIYUKI , KOBAYASHI MAMORU , KANNO YUTAKA , OGUCHI HISAO , HORA KAZUHIKO
Published: March 2008

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long‐term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non‐structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)‐RNA and 16 (9.8%) were positive for HGV‐RNA. Five of the 16 patients with HGV‐RNA were also positive for HCV‐RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.
Characterization of isolated duodenal epithelial cells along a cryptvillus axis in rats fed diets with different iron content
Authors: OATES PHILLIP S , THOMAS CARLA , MORGAN EVAN H
Published: March 2008

The intestinal mucosa is characterized by cell proliferation, commitment, differentiation, digestion and absorption. These processes occur at specified locations along the crypt to villus axis. A technique is reported for the isolation of cells along this axis which allows the study of any one of these processes in an enriched population of cells. As an example, the uptake of transferrin‐bound iron by enterocytes was studied. Rats were fed diets normal, high (3% carbonyl iron) or low in iron for 12 days. Cells from either the duodenum or ileum were isolated by incubating in a Ca2+‐, Mg2+‐free, cation chelating solution for varying periods. The incorporation of thymidine into DNA was measured in these cells as a marker of the crypt region, while alkaline phosphatase and sucrase activities marked mature enterocytes. The in vivo uptake of transferrin‐bound 59Fe was measured in cells isolated either 2 or 4 h after intravenous injection. This procedure resulted in the isolation of 10 fractions of viable cells. Earlier fractions were enriched at least 10‐fold in villus cells and the last fractions in crypt cells. Cells in intermediate fractions were at various stages of development. Uptake of transferrin‐bound iron into enterocytes was highest with feeding an iron‐loaded diet compared with control or iron‐deficient diets. However, with all diets uptake was highest in crypt cells and this fell at the crypt‐villus junction to be only 25%, as high at the villus tip as the crypt. A technique for the reproducible isolation of viable enterocytes along a crypt‐villus axis is described. Transferrin receptor activity changes with maturation of the enterocyte.
Antibodies to P450IID6, SLA, PDH‐E2 and BCKD‐E2 in Japanese patients with chronic hepatitis
Authors: NISHIOKA MIKIO , MORSHED SYED AHMED , PARVEEN SALINA , KONO KAZUO , MATSUOKA HIROSHI , MANNS MICHEAL P
Published: March 2008

Auto‐antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched‐chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti‐LKM1 was also measured by indirect immunofluorescent test. Anti‐P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH‐C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non‐B non‐C (NBNC) and AIH were seronegative for anti‐LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH‐B. Anti‐BCKD‐E2 but not anti‐PDH‐E2 was found in four patients (2.5%), one with AIH, two with CH‐C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti‐SLA and anti‐BCKD‐E2. Antibodies to P450IID6, SLA, PDH‐E2 and BCKD‐E2 are uncommon in adult CH‐C, CH‐B, CH‐NBNC and AIH patients in Japan. Some of these patients positive for auto‐antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto‐antibodies.
Determination of hepatic acyl‐coenzyme A‐cholesterol acyltransferase activity in LPN hamsters: A model for cholesterol gallstone formation
Authors: SMITH JEFFERY L , LUTTON CLAUDE
Published: March 2008

Acyl‐coenzyme A‐cholesterol acyltransferase (ACAT) catalyses the esterification of cholesterol with long‐chain fatty acyl‐coenzyme A derivatives and has been implicated in the development of cholesterol gallstones. In this study we have examined several key components of the hepatic ACAT assay in order to develop a reliable and sensitive ACAT assay for LPN hamsters, a breed of golden Syrian hamster which has been characterized recently by this laboratory as a particularly good model for studying the pathogenesis of cholesterol gallstones. The newly developed ACAT assays were subsequently used to examine whether hepatic ACAT activity is altered in this animal model. Important new methodological findings were: (i) ACAT activity displayed two pH optima, one at 7.0 when assayed using endogenous cholesterol as substrate, and the other at about pH 8.5–9.0 when assayed in the presence of exogenous cholesterol; (ii) ACAT activity increased markedly when exogenous cholesterol was delivered to ACAT in Tween 80 (125‐fold) or hydroxypropyl‐β‐cyclodextrin (200‐fold) in contrast to the use of cholesterol/phosphatidylcholine liposomes (9‐fold); (iii) the addition of dithiothreitol, but not reduced glutathione, to the assay mixture resulted in a marked decrease in ACAT activity. Using the optimal assay conditions (exogenous cholesterol added), hepatic ACAT activity was shown to be significantly reduced in hamsters fed a high sucrose lithogenic diet compared with controls (587 ± 42 vs 737 ± 44 pmol/min per mg; P= 0.025). In contrast, ACAT activity measured using endogenous cholesterol as a substrate was greater in sucrose‐fed hamsters compared with controls (22.3 ± 2.5 vs 13.2 ± 2.9 pmol/min per mg; P= 0.030). These results highlight the importance of using an ACAT activity assay which has been well characterized and supports the hypothesis that the pathogenesis of cholesterol gallstones in LPN hamsters is related to an altered hepatic cholesterol metabolism.
Characterization of a novel cell damage model induced by acid and pepsin using rat gastric epithelial cells: Protective effect of sucralfate
Authors: FURUKAWA O , NAKAMURA E , OKABE S
Published: March 2008

We have established a new model for rat gastric epithelial cell (RGM1) damage caused by both acid and pepsin. Exposure of RGM1 to an acidified medium (pH 3.5–5.0) for 10‐50 min decreased cell viability in a time‐ and pH‐dependent manner. Pepsin (0.5–1.0 mg/mL) at pH 4.5 potentiated cell damage in a concentration‐dependent manner. Based on these results, two types of cell damage models caused by incubation of cells at pH 4.0 and with pepsin (0.75 mg/mL) at pH 4.5 for 30 min, respectively, were established. The intracellular pH (pH) gradually decreased with a decrease in medium pH and an increase in exposure time. At pH ≤ 4.0, pHi reached approximately pH 6.3. Pepsin at pH 4.5 caused a further reduction in pHi compared with the acidified medium alone. Pepsin pre‐incubated with pepstatin did not induce any cell damage. Pretreatment with sucralfate (0.1 ‐3 mg/mL) for 2 h significantly prevented cell damage caused at both pH 4.0 and with pepsin at pH 4.5 in a concentration‐dependent manner. Sucralfate (3 mg/mL) significantly prevented the reduction in pHi at pH 4.0 or with pepsin at pH 4.5. 16,16‐Dimethyl prostaglandin E2 (30 μg/mL) had no effect on either cell damage or pHi. These cell damage models involving RGM1 are useful for studying the mechanism underlying cell damage and for the screening of cytoprotective drugs.
REVIEW: Peyer's patches
Authors: HEEL KATHRYN A , McCAULEY ROSALIE D , PAPADIMITRIOU JOHN M , HALL JOHN C
Published: March 2008

The function of Peyer's patches as antigenic sampling sites involves the complex interplay of a variety of mechanisms that aim to recognize luminal antigens, induce an immunological response and decrease the incidence of antigen translocation across the mucosal epithelium. This is achieved by M cells, which facilitate the uptake of luminal antigens, a vascular architecture that promotes the retention of absorbed antigens within the patch interstitium (allowing for maximal antigenic activation of lymphocytes) and the presence of lymphoid follicles that contain antigen‐presenting cells and lymphocytes. Lymphocytes encountering antigen in the Peyer's patches proliferate, differentiate into fully mature antigen‐specific effector cells and migrate to the mesenteric lymph nodes where they undergo final maturation. The mature lymphocytes then enter the systemic circulation and migrate throughout the other mucosa‐associated lymphoid tissues of the body and ‘home’ into the gut via high endothelial venules and gut‐associated lymphoid tissue‐specific adhesion molecules, providing antigen‐specific lymphocytes at sites likely to re‐encounter the antigen.
REVIEW: Pharmacotherapeutic agents in the treatment of portal hypertension
Authors: LEBREC DIDIER
Published: March 2008

Certain vasoactive substances reduce portal pressure in patients or animals with portal hypertension by either inducing splanchnic vasoconstriction or reducing hepatic vascular resistance. Studies have shown that propranolol or nadolol significantly reduce the risk of a first episode of gastrointestinal (GI) bleeding and increase the survival rate in patients with cirrhosis and oesophageal varices. Isosorbide‐5‐mononitrate is also effective in the prevention of bleeding. The combination of betablockers and nitrates may be more effective than one drug alone. These results show that β‐adrenoceptor antagonists must be used to prevent the first episode of GI bleeding. Beta‐blocker administration also significantly reduces the risk of recurrent GI bleeding and increases the survival rate in patients with cirrhosis. Studies have shown that propranolol is as effective as endoscopic sclerotherapy. The combination of a beta‐blocker with endoscopic sclerotherapy may be more effective than pharmacological or endoscopic treatment alone for the prevention of rebleeding. Finally, new experimental and clinical studies are needed to improve the pharmacological treatment of portal hypertension.