bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol protects against arsenic trioxide‐induced cardiotoxicity in vitro and in vivo
Authors: Zhao X‐Y , Li G‐Y , Liu Y , Chai L‐M , Chen J‐X , Zhang Y , Du Z‐M , Lu Y‐J , Yang B‐F
Published: March 2008

Background and purpose: The clinical use of arsenic trioxide (As2O3), a potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT interval prolongation and apoptosis have been implicated in the cardiotoxicity of As2O3. The present study was designed to evaluate the effects of resveratrol on As2O3‐induced apoptosis and cardiac injury.

Experimental approach: In a mouse model of As2O3‐induced cardiomyopathy in vivo, QT intervals and plasma enzyme activities were measured; cardiac tissues were examined histologically and apoptosis assessed. In H9c2 cardiomyocyte cells, viability, apoptosis, generation of reactive oxygen species (ROS) and cellular calcium levels were measured.

Key results: In the mouse model, resveratrol reduced As2O3‐induced QT interval prolongation and cardiomyocyte injury (apoptosis, myofibrillar loss and vacuolization). In addition, increased lactate dehydrogenase activity and decreased activities of glutathione peroxidase, catalase and superoxide dismutase were observed in the plasma of As2O3‐treated mice; these changes were prevented by pretreatment with resveratrol. In As2O3‐treated H9c2 cardiomyocytes, resveratrol significantly increased cardiomyocyte viability and attenuated cell apoptosis as measured by acridine orange/ethidium bromide staining, TdT‐mediated dUTP nick end labelling assay and caspase‐3 activity. As2O3‐induced generation of ROS and intracellular calcium mobilization in H9c2 cells was also suppressed by pretreatment with resveratrol.

Conclusions and implications: Our results showed that resveratrol significantly attenuated As2O3‐induced QT prolongation, structural abnormalities and oxidative damage in the heart. In H9c2 cardiomyocytes, resveratrol also decreased apoptosis, production of ROS and intracellular calcium mobilization induced by treatment with As2O3. These observations suggested that resveratrol has the potential to protect against cardiotoxicity in As2O3‐exposed patients.
Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon
Authors: Bassil A K , Borman R A , Jarvie E M , McArthur‐Wilson R J , Thangiah R , Sung E Z H , Lee K , Sanger G J
Published: March 2008

Background and purpose: Lubiprostone (Amitiza), a possible ClC‐2 channel opener derived from prostaglandin E1 and indicated for the treatment of constipation, increases chloride ion transport and fluid secretion into the intestinal lumen. As lubiprostone may also directly modulate gastrointestinal motility, we investigated its actions and the possible involvement of prostaglandin EP receptor activation on rat and human isolated gastrointestinal preparations.

Experimental approach: Rat and human isolated preparations were mounted in tissue baths for isometric recording. The effects of lubiprostone on muscle tension and on electrically stimulated, neuronal contractions were investigated in the absence and presence of EP receptor antagonists.

Key results: In rat and human stomach longitudinal muscle, lubiprostone induced a contraction (pEC50 of 7.0±0.0, n=4 and 6.4±0.2, n=3, respectively), which was inhibited by pretreatment with the EP1 receptor antagonist, EP1A 300 nM (pEC50 reduced to 6.2±0.2, n=6), but not by the EP3 or EP4 receptor antagonists (L‐798106 and GW627368X, respectively, 1 μM, P>0.05). Lubiprostone also reduced electrically stimulated, neuronal contractions in rat and human colon circular muscle preparations (pIC50 of 8.9±0.4, n=7 and 8.7±0.9, n=6, respectively), an effect mediated pre‐junctionally. This effect was reduced by the EP4 receptor antagonist (pIC50 of 6.7±1.1, n=7 and 7.7±0.4, n=6, respectively) but not by EP1 or EP3 receptor antagonists.

Conclusions and implications: In rats and humans, lubiprostone contracts stomach longitudinal muscle and inhibits neuronally mediated contractions of colon circular muscle. Experiments are now needed to determine if this additional activity of lubiprostone contributes to its clinical efficacy and/or side‐effect profile.
KATP channel expression and pharmacological in vivo and in vitro studies of the KATP channel blocker PNU‐37883A in rat middle meningeal arteries
Authors: Ploug K B , Boni L J , Baun M , Hay‐Schmidt A , Olesen J , Jansen‐Olesen I
Published: March 2008

Background and purpose: Dilatation of cerebral and dural arteries causes a throbbing, migraine‐like pain, indicating that these structures are involved in migraine.

Clinical trials suggest that adenosine 5′‐triphosphate‐sensitive K+ (KATP) channel opening may cause migraine by dilatating intracranial arteries, including the middle meningeal artery (MMA). We studied the KATP channel expression profile in rat MMA and examined the potential inhibitory effects of the KATP channel blocker PNU‐37883A on KATP channel opener‐induced relaxation of the rat MMA, using the three KATP channel openers levcromakalim, pinacidil and P‐1075.

Experimental approach: mRNA and protein expression of KATP channel subunits in the rat MMA were studied by quantitative real‐time PCR and western blotting, respectively. The in vivo and in vitro effects of the KATP channel drugs on rat MMA were studied in the genuine closed cranial window model and in myograph baths, respectively.

Key results: Expression studies indicate that inwardly rectifying K+ (Kir)6.1/sulphonylurea receptor (SUR)2B is the major KATP channel complex in rat MMA. PNU‐37883A (0.5 mg kg−1) significantly inhibited the in vivo dilatory effect of levcromakalim (0.025 mg kg−1), pinacidil (0.38 mg kg−1) and P‐1075 (0.016 mg kg−1) in rat MMA. In vitro PNU‐37883A significantly inhibited the dilatory responses of the three KATP channel openers in rat MMA at 10−7 and 3 × 10−7 M.

Conclusions and implications: We suggest that Kir6.1/SUR2B is the major functional KATP channel complex in the rat MMA. Furthermore, we demonstrate the potent in vivo and in vitro blocking potentials of PNU‐37883A on KATP channel opener‐induced relaxation of the rat MMA.
Hypersomatostatinaemia in duodenal ulcer
Authors: LAM SHIU‐KUM , WONG HELEN , NG MATTHEW M. T.
Published: March 2008

Abstract A sensitive and specific radioimmunoassay of serum somatostatin has been developed that overcomes the problems encountered in earlier assays of peptide disintegration and the need for prior plasma extraction, which is known to result in artifactual loss of somatostatin. In 37 normal controls, a significant positive correlation between fasting serum gastrin and somatostatin concentrations, and a significant negative correlation between pentagastrin‐stimulated maximal acid output and fasting serum somatostatin levels were observed. In the majority of 134 patients with active duodenal ulcer in whom the fasting serum somatostatin levels were normal, these relationships were absent. In the remaining 25% in whom the fasting serum somatostatin levels were abnormally raised, these relationships were retained. Following a mixed meal, circulating somatostatin levels remained unchanged in controls and patients as a group. These results suggest that: (i) in the normal state, fasting levels of circulating gastrin and somatostatin are closely related, and that acid secretion may paradoxically exert an inhibitory effect on fasting somatostatin levels; (ii) hypersomatostatinaemia identifies a subgroup of patients with duodenal ulcer in whom these relationships are retained; and (iii) somatostatin may not have a significant hormonal role in the postprandial state in man.
Obliterative portal venopathy: A comparative study of 184 cases of extrahepatic portal obstruction and 469 cases of idiopathic portal hypertension
Authors: KAMEDA HARUO , YAMAZAKI KAZUNOBU , IMAI FUKASHI , SUGIURA MITSUO , NAKASHIMA TOSHIRO , OKUDA KUNIO ,   THE JAPANESE MINISTRY OF HEALTH WELFARE RESEARCH COMMITTEE ON IDIOPATHIC PORTAL HYPERTENSION
Published: March 2008

Abstract A total of 184 cases of extrahepatic portal obstruction (EHPO), mostly demonstrated by intraoperative portography and studied at 17 institutes during the period 1957–1983, were compared with 469 cases of idiopathic portal hypertension (IPH) similarly studied. Of the cases of EHPO, there were 101 males and 83 females; 93 were under 20 years of age and the average age was 25.9 years (i.e. much younger than that of IPH cases). There were two age peaks, one before age 19 years and the other at age 40–49 years. One out of three adult cases had a history of abdominal surgery, but otherwise the aetiologic factor was difficult to elicit. Bleeding was the initial symptom in the majority, and splenectomy and haematological findings of hypersplenism were less pronounced compared with IPH. Liver function tests were almost always normal. The liver appeared normal macroscopically in 69% and histologically in 35%. The changes seen in the remainder were similar to those in IPH; they were less frequent in young patients than in cases above age 20 years. Compared with IPH, the wedged hepatic venous pressure in patients with EHPO was lower and the gradient from the portal venous pressure was greater. It is concluded that extrahepatic portal obstruction is less common compared with IPH in Japan, and that there are cases particularly among adults that present clinicopathological features very similar to those of IPH. It is unclear at present whether these two disorders represent two different disease entities, or whether they represent one disorder with differences in the site of involvement along the portal vein system.
Sero‐epidemiological survey of hepatitis virus infection in Taiwan: A study in 6863 subjects from the general population
Authors: OKUDA H. , CHIOU S. S. , OBATA H. , TAKASAKI T. , KOBAYASHI S. , SATO K. , DEMURA H. , YUAN C. Y. , WEI T. C.
Published: March 2008

Abstract A sero‐epidemiological study was made of 6863 apparently healthy randomly selected volunteers from various parts of Taiwan. It revealed an 18% incidence of hepatitis B surface antigen (HBsAg) carriers amongst the general population, the prevalence being significantly higher in males than females (21.7% vs 14.1%). The Takasago natives showed the highest HBsAg carrier rate (27.0%). Those who are primarily derived from Ming Nan had a significantly higher prevalence (19.0%) than those from Hakka (14.7%) and recent immigrants from Mainland China (14.6%). About one‐third of female carriers of child‐bearing age in southern Taiwan were positive for e antigen (HBeAg) in a limited study; they may be an important source of HB virus (HBV) infection. The positivity rate for HBeAg was significantly higher in subjects below 40 years of age (36.7%) than those above 40 years (7.5%). There was a significant association between HBsAg positivity and elevated serum transaminase levels, especially in males; 20.3% of carriers had elevated transaminase in comparison with 11.1% of female carriers. Among HBsAg seronegative individuals, the frequency of abnormal transaminase increased with age with an overall abnormality rate of 10.6% in males and 5.0% in females, suggesting that factors other than HBV may also contribute to liver disease in Taiwan. Altogether, 9.3% had elevated transaminase. Out of 82 randomly selected HBsAg carriers who were evenly distributed in geography, serum antidelta antibody was positive in only five men (6.1%), of whom four had a mild elevation of transaminase levels (< 100 KU). The overall positivity rate for anti‐hepatitis A (HA) antibody was 93.0% in southern Taiwan, indicating poor sanitation. These findings indicate that HB and HA virus infections are highly endemic in Taiwan and that delta infection is infrequent despite a high prevalence of HB virus infection.
Azodisalicylate (Olsalazine) in the treatment of active ulcerative colitis. A placebo controlled clinical trial and assessment of drug disposition
Authors: HETZEL D. J. , SHEARMAN D. J. C. , BOCHNER F. , IMHOFF D. M. , GIBSON G. E. , FITCH R. J. , HECKER R. , LABROOY J. , ROWLAND R.
Published: March 2008

Abstract The efficacy, safety and disposition of azodisalicylate, (ADS, Olsalazine) was assessed in patients with left‐sided ulcerative colitis (UC) or proctitis in a double‐blind placebo controlled trial. Thirty patients with a mild‐to‐moderate attack of UC were randomly allocated to ADS capsules 1 g (b.d.) or placebo for 6 weeks; other therapy was ceased. Patients were reviewed weekly and plasma, urine and faecal concentrations of ADS and its metabolites were determined by high performance liquid chromatography (HPLC). Sigmoidoscopy and biopsy were repeated at 6 weeks.

Four patients receiving placebo and two receiving ADS were withdrawn because of diarrhoea. Five patients known to be allergic to sulphasalazine had no adverse reactions to ADS. Good clinical response was found in six patients receiving ADS and in two receiving placebo (P= 0.11). Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more frequently in ADS‐treated patients. Plasma concentrations of ADS were significantly higher in patients who improved. Faecal ADS, 5‐ASA and acetyl‐5‐ASA varied widely and showed no correlation with response. ADS showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine‐sensitive patients but appeared to cause watery diarrhoea in two patients.
Serum procollagen‐III‐peptide in chronic hepatitis and schistosomiasis
Authors: ROBERTS F. D. , HALLIDAY J. W. , COOKSLEY W. G. E. , SANDFORD N. , KARAWI M. , SHAHED M. , MOHAMED A. , POWELL L. W.
Published: March 2008

Abstract Recent reports have suggested that the serum concentration of procollagen‐III‐peptide (PPCP III) reliably reflects the degree of hepatic fibrosis but the topic remains controversial. Serum PPCP III levels have been measured in 40 patients with chronic hepatitis or schistosomiasis. In five patients both diseases were present. The relationship between serum PPCP III levels, hepatic fibrosis and disease activity have been studied histologically and biochemically. The mean serum concentration of PPCP III in patients with chronic hepatitis and in those with active liver disease was significantly higher than that in patients with inactive liver disease. In patients with chronic hepatitis only, serum PPCP III levels correlated with fibrosis, inflammation, and necrosis and also with the combined histological scores. When patients with schistosomiasis as well as hepatitis were included, significant correlations were still observed. In patients with schistosomiasis only, the serum PPCP III levels varied widely and did not correlate with disease activity or with the degree of inflammation, necrosis and fibrosis, either separately or combined. Serum PPCP III concentrations only correlated with serum aspartate amino transferase levels when the patient groups were combined. Serial measurements in 21 patients showed that PPCP III levels varied widely over a short period of time, and that these fluctuations did not significantly correlate with the respective changes in serum AST levels.

In conclusion, serum PPCP III concentrations do not reliably reflect hepatic fibrosis, they are influenced by inflammation and activity of the disease, and they probably reflect the end result of the metabolic state of collagen in the liver, that is the combined effect of synthesis and degradation.
Ultrasonographic features of amoebic abscess: Study in 59 patients
Authors: HADI SUJONO
Published: March 2008

Sonographic examination was carried out in 59 patients with a clinical diagnosis of amoebic liver abscess during the previous 4 years (January 1982 to December 1985). The amoebic liver abscess was located in the right lobe in 45 patients, in the left lobe in eight patients, and in both lobes in six patients. The ultrasonic diagnosis was confirmed in the majority of patients by the indirect haemaglutination test (titres 1:512 or greater) coupled with excellent response to metronidazole, or by ultrasonic‐guided percutaneous aspiration producing anchovy sauce pus.

The sonographic patterns of the abscess were evaluated. All patients had well‐defined hypoechoic lesions near the surface, which demonstrated fine homogeneous low‐level echoes throughout at a normal and a high‐gain setting, without a peripheral echo‐free halo. The configuration of the abscess was round, oval or lobulated. The walls were irregular in 53 patients, and showed a slight distal sonic enhancement. This ultrasonic feature is suggestive of amoebic liver abscess. The specific ultrasonographic features of amoebic liver abscess, combined with a feature of pleural effusion, pericardial effusion, or an abdominal abscess, were suggestive of the complications of liver abscess found in 19 patients.

It is concluded that ultrasonography is a valuable aid in the diagnosis of amoebic liver abscess. It is of value not only for detection, but also for determination of the site, depth, size, and location of the complicating rupture of the abscess.
Small mass lesions in cirrhosis: Transition from benign adenomatous hyperplasia to hepatocellular carcinoma?
Authors: ARAKAWA MASAHIRO , SUGIHARA SHIGETAKA , KENMOCHI KUNIHIKO , KAGE MASAYOSHI , NAKASHIMA TOSHIRO , NAKAYAMA TOSHIMICHI , TASHIRO SEIKI , HIRAOKA TAKEHISA , SUENAGA MASAHIRO , OKUDA KUNIO
Published: March 2008

Abstract Ten patients with cirrhosis, in whom small mass lesions were detected by imaging techniques and histological diagnosis of the resected specimens was difficult, are described. There were 17 grossly discrete lesions measuring 10 × 8 mm to 27 × 22 mm. Four were compatible with so‐called adenomatous hyperplasia showing no histological features of malignancy, and eight were equivocal as to whether they were benign or malignant. The other five lesions (in four patients) were hepatocellular carcinoma, co‐existing with apparently benign lesions. The eight equivocal lesions were eventually judged to be highly differentiated hepatocellular carcinomas. These benign‐appearing lesions, found by advanced imaging in patients with cirrhosis, create a serious problem in regions where primary liver cancer is endemic among cirrhotics, and hepatic resection is the preferred treatment.

It is possible that these lesions represent a transition from adenomatous hyperplasia occurring in cirrhotic livers to hepatocellular carcinoma through a histologically equivocal state and that the current morphological methods are inadequate for differentiating malignant from benign lesions.
The effects of ethanol on collagen synthesis by rat hepatocytes in primary culture
Authors: DAVIS CRAIG K. C. , IRVING MICHAEL G.
Published: March 2008

Abstract The effect of ethanol upon protein metabolism was investigated using rat hepatocytes purified by centrifugal elutriation and maintained in culture. Hepatocytes maintained in capped culture flasks allowed long‐term studies of the effects of ethanol without cytotoxic damage to cultured cells and the phenotypic integrity of cultured cells was maintained. Ethanol (25–100 mmol/1) markedly inhibited hepatocyte protein synthesis. This inhibition of protein synthesis was not due to defective uptake of amino acids but to alterations to the intracellular redox state. Extracellular redox systems did not regulate hepatocyte protein synthesis. Protein degradation was not affected by ethanol. Glycosaminoglycans secreted into the the medium and extra and intracellular hepatocyte collagen synthesis were markedly stimulated by ethanol; collagen synthesis representing 6–8% of total protein synthesis at high ethanol concentrations. These studies indicate that ethanol exerts selective effects on protein synthesis by hepatocytes in primary culture and suggest that hepatocytes may contribute significantly to perisinusoidal fibrosis in alcohol‐induced liver disease.
Delta infection in Japan: Immunohistological and immuno‐electron microscopic study of delta antigen in liver tissue
Authors: MORI JUNKO , ITO YOSHIMI , OMATA MASAO , YOKOSUKA OSAMU , OKUDA KUNIO
Published: March 2008

Abstract Although the vast majority of hepatitis B surface antigen (HBsAg) carriers of the world inhabit South‐east Asia, very little is known about delta infection in this area. Therefore, a serological and immunohistological study was made in the Tokyo‐Chiba area. One of 58 (1.7%) HBsAg carriers had anti‐delta antibody in a high titre in serum. Delta antigen was immuno‐histologically localized in the liver in two of 146 (1.4%) HBsAg carriers studied. The antigen was strongly stained in the nuclei, and positive cells were diffusely scattered throughout the liver in both cases. Neither subject was an illicit drug user: one had travelled to Italy 10 years earlier and the other had a blood transfusion during a 5‐year residence in Bangkok in the past.

Thus, there is delta infection among non‐intravenous drug users in Japan. Delta infection has been linked to severe liver damage, occasionally fatal. Once introduced, it could become epidemic in a country where hepatitis B virus infection is endemic, and might spread among non‐drug users.
Lactose tolerance despite hypolactasia in adult coeliac disease
Authors: KERLIN PAUL , WONG LAWRENCE
Published: March 2008

Although symptoms of milk intolerance are common in primary (genetically determined) hypolactasia it is a clinical impression that such symptoms are infrequent in adult patients with hypolactasia secondary to damage of the mucosa of the small intestine. This study was designed to determine whether a lactose (50 g) challenge is better tolerated by patients with coeliac disease and secondary hypolactasia than patients with primary hypolactasia. Based on intestinal histology and disaccharidase levels, three groups of adults were studied: controls (n= 20), patients with primary hypolactasia (n= 20) and patients with hypolactasia secondary to newly diagnosed coeliac disease (n= 15). The response to a challenge with 50 g lactose was assessed by a score of five symptoms and breath hydrogen production. Despite an equivalent level of hypolactasia, symptoms affected fewer patients with coeliac disease (33%) than subjects with primary hypolactasia (90%). Further, a positive lactose breath hydrogen test was noted in all (100%) patients with primary hypolactasia but in only six (40%) of those patients with newly diagnosed coeliac disease. These results suggest the presence of a considerable absorptive reserve for lactose in the distal small bowel of many patients with coeliac disease.
Studies on duck hepatitis B virus: Identification and epidemiological survey in Taiwan
Authors: CHANG ALLAN CHING‐HWA , SHIEN YONG‐SHOU , HUANG GUAN‐TARN , CHEN DING‐SHINN , LEE SHENG‐CHUNG , SUNG JUEI‐LOW
Published: March 2008

The presence of duck hepatitis B virus (DHBV) in domestic ducks in Taiwan was confirmed by DNA polymerase assay, Southern blot analysis and electron microscopy. To investigate the epidemiology of this virus, a total of 1274 serum samples were collected from 30 duck farms from different areas of Taiwan and studied by spot hybridization and/or DNA polymerase assay. The positive rates varied among different strains of ducks: 16% in 243 Pekin ducks, 12% in 392 Chinese common domestic ducks, 4% in 196 Muscovy, 25% in 292 Taiwan Kaiyas and 13% in 151 mule ducks. The positive rate was much higher in the younger ducks; it was highest (30.7%) in ducklings under 1 month of age, followed by ducks aged 1–12 months (11.8%), and lowest in those ducks older than 1 year (7.7%). It was concluded that the prevalence of DHBV infection in domestic ducks in Taiwan is generally high, and that the infected ducks may serve as an animal model for human hepatitis B virus infection which is also prevalent in Taiwan.
Pattern of upper gastrointestinal haemorrhage in northern India—An endoscopic study of 316 patients
Authors: DILAWARI J. B. , KAUR UPJEET , NARAYANAN V. A. , AUGUSTINE PHILLIP , DAS JAYARAM , ALI HASSAN , BAMBERY P.
Published: March 2008

Three hundred and sixteen patients with acute upper gastrointestinal haemorrhage were studied prospectively and consecutively. The most frequent cause was variceal bleeding due to portal hypertension (36%), followed by peptic ulceration (24%) and gastric erosions (19%). Variceal haemorrhage tended to be severe and had a high individual mortality rate. Associated acute mucosal lesions with portal hypertension were strikingly less frequent when compared with the experience from the West. Seven per cent of patients died of bleeding alone and an equal number of an associated systemic disorder or complication. Splenomegaly was present in all patients with a variceal haemorrhage due to non‐cirrhotic portal hypertension. However, in patients with portal hypertension due to cirrhosis splenomegaly was present in 63%. Endoscopy altered the clinical diagnosis in 13.2% of patients. Based on previous experience oesophago‐gastro‐duodenal endoscopy has been a useful tool in the management of acute upper gastrointestinal haemorrhage.
Expression of urokinase‐type plasminogen activator in the mucosal lesions of inflammatory bowel disease
Authors: ELLIOTT ROBERT , STEPHENS ROSS W. , DOE WILLIAM F.
Published: March 2008

The expression of plasminogen activators was analysed in mucosal homogenates from inflammatory bowel disease patients to determine whether the urokinase‐type (u‐PA) is implicated in the pathogenesis of mucosal tissue injury. Homogenates of mucosal biopsy tissue from ulcerative colitis, Crohn's disease, infectious colitis and normal control patients were subjected to polyacrylamide gel electrophoresis. The types of plasminogen activator present were detected by zones of lysis in a fibrin‐agarose gel overlay. All the tissues studied displayed tissue plasminogen activator activity (t‐PA). In ulcerative colitis, 18 of the 19 diseased colon biopsies, but none of six biopsies from uninvolved areas of the same colon, showed u‐PA activity. Similar results were found in 12 Crohn's disease patients. Biopsies from the infectious colitis group and from radiation colitis patients also showed both u‐PA and t‐PA activity. The age, sex, duration of disease, and presence and type of treatment did not affect u‐PA expression in the inflamed mucosa. The results suggest that u‐PA may be implicated in the mediation of tissue injury in the inflamed intestinal mucosa.
The relationship between portal pressure and plasma albumin in the development of cirrhotic ascites
Authors: WOOD L. J. , COLMAN J. , DUDLEY F. J.
Published: March 2008

Ascites develops as a result of avid renal sodium retention together with an imbalance of Starling's equilibrium at the level of the hepatic sinusoid and mesenteric capillary. This study aimed to examine the effect of the imbalance between portal pressure, measured as corrected wedged hepatic vein pressure (cWHVP) and plasma oncotic pressure, measured as plasma albumin on the development of cirrhotic ascites. Fifty‐two patients with biopsy‐proven alcoholic cirrhosis were studied on 72 separate occasions. The absence of ascites was determined by the combination of lack of signs of free intraperitoneal fluid and normal prothrombin time in patients not receiving diuretics. If signs of free intraperitoneal fluid were found, the presence of ascites was confirmed by ultrasonography or diagnostic paracentesis and graded clinically as mild, moderate or severe.

Ascites tended to occur with a cWHVP > 15 mmHg and plasma albumin < 35 g/l, but there was a large overlap in values between patients with and without ascites. When plasma albumin was plotted against cWHVP a clear line of separation between the presence or absence of ascites could be obtained. The equation of the line was: Plasma albumin (g/l) ‐ 16 = 1.23 cWHVP (mmHg). Ascites was present in all patients with [Plasma albumin ‐ 16]/cWHVP < 1.23. There was no significant difference in plasma albumin, cWHVP or [Plasma albumin ‐ 16]/cWHVP between patients with mild, moderate or severe ascites. If [Plasma albumin ‐ 16]/cWHVP was > 1.23, ascites was not clinically detectable and these patients no longer required diuretics.

The clinical applicability of this ratio was assessed in 16 patients who had no detectable ascites but who were still receiving diuretics. In all 10 patients with a ratio > 1.23 diuretics were ceased without reaccumulation of ascites. Thus this ratio may be used to predict when patients no longer require diuretic therapy.
Role of cholic acid in the dietary induction of cholesterol gall‐bladder stones in mice
Authors: WATTS M. J. WHITING AND J. MCK.
Published: March 2008

The diet of male Swiss mice was supplemented with cholesterol and different bile acids, or the plant sterol diosgenin, to determine the effect on cholesterol metabolism and gallstone formation. Cholic acid enhanced intestinal cholesterol absorption and markedly increased cholesterol levels in serum, liver and bile. In contrast, chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid inhibited the increase in cholesterol absorption and liver cholesterol content produced by a cholesterol‐supplemented diet. Biliary cholesterol reached saturated levels in mice fed cholesterol and cholic acid or diosgenin, but gallstones were observed only in association with the cholic acid‐containing diet. This diet also induced marked gall‐bladder enlargement with mucus glycoprotein hypersecretion. These results indicate that both supersaturated bile and gall‐bladder mucus production may be necessary for the development of gallstones in mice.
Percutaneous transhepatic catheterization of the portal venous system
Authors: BURCHARTH FLEMMING , JOYCE FREDERIC
Published: March 2008

During recent years, percutaneous transhepatic catheterization of the portal venous system has become the most accurate procedure for investigation of the portal system. The procedure can be performed under local analgesia, is relatively simple, and complications are rare. The success rate is high, approximately 90%, especially when the liver hilum is localized by ultrasonography prior to catheterization. The free portal pressure can be measured. Selective catheterization of all portal tributaries can be performed. The indications are: portography in patients with cirrhosis of the liver and portal hypertension for delineation of collateral vein systems including gastro‐oesophageal varices; visualization of veins that may be used for portosystemic shunt operations; postoperative control of shunt patency; diagnosis of portal and hepatic vein thrombosis; localization of stenosis in the portal vein system; pre‐operative evaluation of patients with tumours in the biliary tract and pancreas; obliteration of bleeding oesophageal varices; and verification and localization of endocrine pancreatic tumours making curative resection possible. Further, transhepatic catheterization of the portal system may be used in research on the development of portal hypertension, collateral veins, variceal bleeding, and for haemodynamic, metabolic and pharmacologic studies in the gastrointestinal tract.
Increased expression of urokinase‐type plasminogen activator in colorectal carcinoma and in adenomatous polyps
Authors: ELLIOTT ROBERT , STEPHENS ROSS W. , SIM PHENG‐SIEW , DOE WILLIAM F.
Published: March 2008

Human plasminogen activators (HPA) comprise the tissue type produced mainly by endothelial cells of 66 000 molecular weight (MW) which is principally involved in fibrinolysis (HPA66) and the urokinase type of 52 000 MW (HPA52) which is implicated in the invasion process of malignancy. The purpose of this study was to elucidate the pattern of HPA expression in histologically normal colonic mucosa, sporadic polyps, polyposis coli polyps, and in colon cancer tissue, to determine whether the expression of HPA52 is a correlate of neoplastic transformation of colonic epithelial cells. Homogenates of colonoscopic biopsies and resected colon tissue were subjected to polyacrylamide gel electrophoresis and the HPA activity was detected by a fibrin overlay gel. In histologically normal mucosal biopsies from non‐cancer‐bearing colons and in uninvolved mucosa from cancer‐bearing colons, only HPA66 was detected. By contrast, all 19 colon cancer specimens expressed HPA52 and 16 of these also showed HPA66 activity. Two of three colon cancer cell lines showed HPA52 activity, but none expressed HPA66. HPA52 activity was observed in 17 of 20 adenomatous polyps, all of which displayed HPA66 activity. No correlation was found between polyp size, degree of epithelial dysplasia or the type of polyp architecture, and the semiquantitative estimates of HPA52 activity as judged by the areas of fibrinolysis generated.

This study of HPA52 in the colon epithelial neoplasms comprising adenomatous polyps, colon cancer tissue and colon cancer cell lines suggests that the transformation of the colon epithelial cell correlates with increased expression of HPA52, an enzyme that has been implicated in the invasive process of malignancy.
Effect of cholestasis produced by temporary bile‐duct occlusion on hepatic glutathione and γ‐glutamyl transferase levels in the pig
Authors: SHI E. C. P. , ROSE M. A. , HAM J. M.
Published: March 2008

Important factors in drug metabolite‐induced hepatocellular injury are the production of toxic intermediaries by biotransformation processes and the protective capacity of hepatic detoxification systems. In the present study, the hepatic total glutathione (reduced glutathione plus oxidized glutathione), and γ‐glutamyl transferase (γGT) levels, which are important components of a hepatic detoxification system, were measured in pigs before, during, and after bile‐duct occlusion (BDO). The hepatic reduced glutathione (GSH) level fell significantly in the group with BDO compared with a sham operated control group. However, there were no significant changes in the hepatic oxidized glutathione (GSSG) and γGT levels in the two groups. It was also demonstrated that the hepatic GSH level returned to normal 1 week after the BDO was relieved.
The effects of antiviral agents on serum hepatitis B e antigen levels in chronic type B hepatitis
Authors: KURAI KIYOHIKO , IINO SHIRO , KOIKE KAZUHIKO , MITAMURA KEIJI , ENDO YASUO , OKA HIROSHI
Published: March 2008

In the present study, aiming at the evaluation of the effects of antiviral therapy on hepatitis B e antigen (HBeAg) levels, serum HBeAg concentration was determined serially by a quantitative assay in 44 patients with chronic hepatitis B who received a total of 73 courses of antiviral treatment. The posttreatment HBeAg levels were significantly lower than pretreatment baseline in all treated groups, not only at the end of treatment but also 6 months after the completion of therapy. The proportional decrease in treated patients was significantly greater than in 15 untreated controls. Six months after the completion of treatment, serum HBeAg became negative in seven out of 25 treatments with interferon, seven out of 28 with adenine arabinoside, and five out of 20 with adenine arabinoside 5'‐monophosphate. All patients who became negative for HBeAg had normalization of alanine aminotransferase as well. A progressive decrease in HBeAg in patients treated with multiple courses of drug was observed, and the frequency of negative tests increased, paralleling the number of courses of treatment.

These results suggest that antiviral therapy may alleviate inflammatory changes in the liver by promoting clearance of HBeAg from the serum, and may eventually shorten the natural course of hepatitis associated with chronic hepatitis B virus infection.
Measurement of carboxy terminal peptide of type I procollagen in sera of patients with viral hepatitis and liver cirrhosis
Authors: NIITSU YOSHIRO , KODA KYUHEI , ITO NOBUYUKI , OWADA MINORU , MORITA KOETSU , WATANABE NAOKI , KOHGO YUTAKA , SEIFTER SAM , URUSHIZAKI ICHIRO
Published: March 2008

In the present investigation, a radioimmunoassay for carboxy terminal peptide of human type I procollagen (type 1 C‐peptide) was developed. Its clinical implication for serodiagnosis of hepatic fibrosis in 85 patients with viral hepatitis, 45 patients with post‐hepatitic liver cirrhosis and 37 patients with alcoholic liver diseases was evaluated in comparison with that of the previously established amino terminal peptide (type III N‐peptide) assay. Anti‐sera against type I procollagen was obtained by immunization of rabbit with purified type I procollagen from culture medium of IMR‐90.

The serum level of type I C‐peptide in normal subjects was found to be 42 ng/ml (s.d. = 19). Type I C‐peptide levels in patients with acute hepatitis were within normal range, while in chronic hepatitis, the mean type I C‐peptide level increased as the grade of fibrosis advanced from grade I to III. However, there was no statistically significant difference between the mean type I C‐peptide level of grade III and that of liver cirrhosis. Increments of type I C‐peptide levels were also observed in alcoholic liver fibrosis (fatty liver with fibrosis and liver cirrhosis).

On the other hand, type III N‐peptide assay appeared to reflect not only the degree of hepatic fibrosis, but also the degree of hepatic inflammation, giving the high levels in acute viral hepatitis.

Collectively, the results indicate the usefulness of type I C‐peptide assay for monitoring hepatic fibrosis in viral hepatitis as well as in alcoholic liver disease.
Immunological aspects of chronic hepatitis
Authors: BÜSCHENFELDE KARL‐HERMANN MEYER ZUM , MANNS MICHAEL , GERKEN GUIDO
Published: March 2008

Chronic active hepatitis (CAH) is a clinically and histologically defined syndrome which is aetiologically heterogeneous. Immune reactions are involved in almost all types of chronic inflammatory liver diseases. The host's immune system is thought to contribute significantly to the degree of liver cell destruction in chronic hepatitis B—HBcAg is regarded as a major target antigen. Auto‐immune type CAH is a syndrome of unknown aetiology, a loss of tolerance against self antigens is thought to be a principal pathogenetic mechanism. At least three different subgroups of auto‐immune type CAH can be distinguished by circulating auto‐antibodies: antinuclear antibodies (ANA), smooth muscle antibodies (SMA), liver membrane auto‐antibodies (LMA); liver‐kidney‐microsomal antibodies (LKM); and antibodies to a soluble liver antigen (SLA). The identification of auto‐immune type CAH has clinical relevance since only auto‐immune type CAH seems to profit from immunosuppressive therapy. A suppressor T cell defect was demonstrated in chronic hepatitis B and auto‐immune type CAH. However, this defect could only be reversed by the addition of prednisone in vitro in auto‐immune type CAH. Present research concentrates on the evaluation of the precise cellular mechanisms leading to liver cell destruction. In vitro cytotoxicity assays including autologous target cell systems have several drawbacks due to the use of peripheral blood lymphocytes and the questionable viability of the hepatocytes isolated from liver biopsies. Immunohistological studies using monoclonal antibodies revealed that T8 positive T lymphocytes account for the majority of the inflammatory cell infiltrate. In addition, T cell clones derived from liver biopsies are mainly T8 positive and show cytotoxic function in vitro. At present, little is known about the antigen specificity of these liver‐derived T cell clones.
Nucleotide sequence of a hepatitis B virus genome of subtype adw isolated from a Philippine: Comparison with the reported three genomes of the same subtype
Authors: ESTACIO RHODORA C. , CHAVEZ CARLITA C. , OKAMOTO HIROAKI , LINGAO AUGUSTO L. , REYES MARITA T. , DOMINGO ERNESTO , MAYUMI MAKOTO
Published: March 2008

The complete nucleotide sequence was determined for a hepatitis B virus genome of subtype adw (pFDW294) isolated and cloned from the plasma sample of a Philippino. The genome was 3221 base‐pair long with a point mutation at the 1376th nucleotide that affected the coding capacity of the P and X genes. There was a wide range of sequence divergence among pFDW294 and the reported three genomes of the same subtype (1.1–9.9%), occurring more often in the pre‐S region and the S gene than in the pre‐C region and the C gene.
Failure of enteric‐coated peppermint oil in the irritable bowel syndrome: A randomized, double‐blind crossover study
Authors: LAWSON M. J. , KNIGHT R. E. , TRAN K. , WALKER G. , ROBERTS‐THOMSON I. C.
Published: March 2008

Enteric‐coated capsules containing peppermint oil were compared with placebo in a double‐blind crossover trial involving 25 patients with the irritable bowel syndrome, carefully selected for the predominance of colonic symptoms. Patients were randomly allocated to receive active drug or placebo, three capsules per day, for 4 weeks and then changed to the alternative medication for a further 4 weeks. Symptom scores were assessed by the patient using visual analogue scales. While on peppermint oil, there was a small but statistically significant increase in stool frequency but no significant change in scores for global severity or scores for the specific symptoms of pain, bloating, urgent defecation and the sensation of incomplete evacuation. Seven patients failed to complete the study, three because of perianal burning associated with peppermint oil. Enteric‐coated capsules containing peppermint oil are unhelpful in patients with the irritable bowel syndrome and prominent colonic symptoms.
Regulatory mechanism of bombesin on gastrin release
Authors: AZUMA TAKESHI , INOKUCHI HIDETO , KAWAI KEIICHI
Published: March 2008

Bombesin has been demonstrated to stimulate gastrin release by an atropine‐resistant mechanism. In the present study, the effects of truncal vagotomy and chemical sympathectomy on the gastrin release by exogenous and endogenous bombesin using rat antral mucosa in tissue culture were studied. Exogenous bombesin 10‐8 mol/l significantly stimulated gastrin release. The stimulation of gastrin release by bombesin was abolished by truncal vagotomy, but not altered by chemical sympathectomy. Bombesin antiserum inhibited gastrin release by blocking the effect of endogenous bombesin. The inhibition of gastrin release by bombesin antiserum was abolished by truncal vagotomy, but not altered by chemical sympathectomy. In addition, the concentrations of bombesin‐like immunoreactivity in antral mucosa were not altered by truncal vagotomy. These results suggest that the mechanism of gastrin release by bombesin is influenced by non‐cholinergic local nerves under vagal control.
Hydatid disease: A global health problem still to be solved*
Authors: GEMMELL M. A.
Published: March 2008

An assessment has been made of the significance to human health of cystic (CHD) and alveolar (AHD) hydatid disease caused by Echinococcus granulosus and E. multilocularis. In the case of CHD, it is concluded that: morbidity is usually grossly underestimated; infection can usually be treated successfully by surgery, but not yet by drug therapy; and control in animals is generally feasible, but justification for its implementation requires an effective assessment of ill health in humans. For AHD it is concluded that: despite surgical intervention the infection is almost invariably fatal in the short rather than the long term, but drug treatment should improve the quality and duration of life; and methods and feasibility of control in animals have yet to be researched.
Choledochal cyst: Anomalous arrangement of the pancreaticobiliary ductal system and biliary malignancy
Authors: KOMI NOBUHIKO , TAKEHARA HIROO , KUNITOMO KAZUFUMI
Published: March 2008

Congenital biliary dilatation (CBD) or choledochal cyst has previously been considered a rarity; however, the number of cases reported in the literature has been increasing. It is generally accepted that there is a predominance in Japanese, as more than one‐third of the cases are from Japanese literature.
Parietal cells in duodenal ulcer disease: A histochemical study of the effects of omeprazole and ranitidine on mitochondrial activities
Authors: HUI WAI‐MO , LIU HIN‐CHING , LAM SHIU‐KUM
Published: March 2008

H2‐Receptor antagonists and omeprazole, a H‐K ATPase inhibitor, inhibit acid secretion from the parietal cells. The ultrastructural changes of the parietal cells after treatment have been described, but the changes in the mitochondrial activity which reflect the energetic metabolism were not well defined. To study the effect of omeprazole and H2‐receptor antagonists on the mitochondrial activity of the parietal cells, endoscopic biopsies were taken from nine patients with duodenal ulcer before and after treatment with either 10 mg or 20 mg omeprazole each morning, or 150 mg ranitidine twice daily for 2 weeks, given in a double‐blind randomized manner. Three patients with healed duodenal ulcer who were on maintainence treatment with 150 mg ranitidine nightly for 1 year had an endoscopy performed after 4 and 12 months and two non‐ulcer dyspeptic patients were recruited as controls. Three biopsies were taken during each endoscopy from the body of the stomach. The mitochondrial activity was assessed by the reaction of succinic dehydrogenase with nitroblue tetrazolium and of cytochrome oxidase with naphthoic acid mixed with N‐phenyl‐p‐phenylenediamine, according to the intensity of the staining reaction. After treatment with omeprazole or ranitidine, the mitochondrial activity decreased appreciably and returned to the pretreatment level on cessation of treatment. Patients on maintainence ranitidine showed decreased mitochondrial activities after 4 months, which, however, returned to pretreatment levels in two patients. It is concluded that short‐term treatment with omeprazole or ranitidine resulted in reversible suppression of mitochondrial activity while long‐term treatment with ranitidine resulted in an initial suppression followed by a tendency to return to pretreatment level despite continued treatment.
Lymphangioma of the pancreas
Authors: NG IRENE O. L. , FAN S. T. , NICHOLLS J.
Published: March 2008

Abstract Lymphangiomas of the pancreas are rare. Only six cases have been reported. An additional case of lymphangioma of the pancreas in a 20 year old male which was demonstrated by computerized tomography and treated with complete surgical excision is reported.
Comparison of two plasma‐derived hepatitis B vaccines: Long‐term report of a prospective, randomized trial
Authors: LAU J. Y. N. , LAI C. L. , WU P. C. , LIN H. J.
Published: March 2008

Abstract Subjects at high risks for hepatitis B virus (HBV) infection were allocated randomly (n = 591) to receive one of the two plasma‐derived hepatitis B vaccines produced by the Institut Pasteur Production, Paris (HEVAC B) or the Green Cross Corporation, Osaka (GCC VAC). There are differences in the production of these two vaccines, with an added step of heat inactivation and longer formaldehyde treatment for the GCC VAC. Three doses of vaccines were given at 0, 1, and 5 months for both vaccines. Antibody to hepatitis B surface antigen (anti‐HBs) titres were tested at 1, 3, 6, 9, 12, 18, 24 months. Antibody to hepatitis B core antigen (anti‐HBc) was tested at 6 and 24 months. A fourth dose was given after 12 months to subjects who did not develop an anti‐HBs titre of 10 miu/mL at month 6. Two hundred and seventy‐four subjects received HEVAC B. Excluding nine subjects (3.4%) who became positive for anti‐HBc, the immunogenicity was 87.2%. For the 317 subjects receiving GCC VAC, excluding 17 subjects (5.4%) who became positive for anti‐HBc, the immunogenicity was 83.7% (the difference was not statistically significant). The anti‐HBs titres were significantly higher in those who received HEVAC B in the 3, 6, 9, 12 and 18 months but the anti‐HBs levels for GCC VAC recipients were still well above the ‘protective’ level of 10 miu/mL. Most hypo/non‐responders did not respond to the fourth dose of vaccine. The side‐effects were transient and mild, and occurred in 1.5% of subjects for both vaccines. Anti‐HBs response decreased significantly with increasing age of the recipents.

It is concluded that both HEVAC B and GCC VAC had comparable immunogenicity and safety, although GCC VAC gave a significantly lower but still ‘protective’ anti‐HBs level at 3–18 months. This might be related to the added steps of inactivation in its production.