Plasma levels of vitamin E and carotenoids are decreased in patients with Nonalcoholic Steatohepatitis (NASH).

OBJECTIVES: Oxidative stress is suggested to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The present study was aimed to compare plasma levels of antioxidants in patients suffering from NASH and healthy controls. METHODS: Plasma levels of the antioxidants α-tocopherol, γ-tocopherol, lutein, zeaxanthin, ß-cryptoxanthin, lycopene, α-carotene ß-carotene were determined in 57 patients with biopsy-proven NASH and 40 healthy controls. RESULTS: Levels of α-tocopherol (22.4 vs. 26.8 nmol/ ml; p<0.01), lutein (0.19 vs. 0.33 nmol/ml; p<0.0001), zeaxanthin (0.04 vs. 0.08 nmol/ml; p<0.0001), lyco?pene (0.15 vs. 0.42 nmol/ml; p<0.0001), α-carotene (0.03 vs. 0.06 nmol/ml; p<0.005) and ß-carotene (0.25 vs. 0.39 nmol/ml; p<0.01) were significantly decreased in NASH patients compared to controls. Age, aminotransferase status (ALT, AST) and BMI were not correlated with the levels of tocopherols or caro?tenoids. CONCLUSIONS: Given the decreased levels supplementation of lipophilic antioxidants might be a rational treatment option for patients with NASH.

Bile acids for non-alcoholic fatty liver disease and/or steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease is a condition characterised by fatty deposition in the hepatocytes of patients in patients with minimal or no alcohol intake. Some patients develop non-alcoholic steatohepatitis. Bile acids may potentially protect cellular structures and may be of benefit in patients with non-alcoholic fatty liver or steatohepatitis. OBJECTIVES: To systematically evaluate the beneficial and harmful effects of bile acids versus no intervention, placebo, or other interventions for patients with non-alcoholic fatty liver or steatohepatitis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2005), MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005), and The Chinese Biomedical Database (1978 to July 2005). No language restrictions were applied. SELECTION CRITERIA: Randomised clinical trials evaluating any bile acids versus no intervention, placebo, or other interventions in patients with NAFLD. DATA COLLECTION AND ANALYSIS: We extracted data from the identified trials as well as contacted authors. We evaluated the methodological quality of the randomised trials by assessing the generation of allocation sequence, allocation concealment, blinding, and follow-up. We made our analyses following the intention-to-treat method by imputing missing data. MAIN RESULTS: We identified four randomised clinical trials randomising 279 patients. Only one of the trials was considered a low-bias risk trial. One of the trials reported a non-liver-related death in the bile acid group. No significant differences were found regarding mortality or improvement in liver function tests observed after treatment with ursodeoxycholic acid. Data on the radiological and histological responses were too scant to draw any definite conclusions. Adverse events were non-specific and considered of no major clinical relevance. AUTHORS' CONCLUSIONS: Presently, there are insufficient data to support or refute the use of ursodeoxycholic acid for patients with non-alcoholic fatty liver or steatohepatitis. It may be advisable to carry out large randomised clinical trials on this topic.

Probiotics for non-alcoholic fatty liver disease and/or steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease comprises a spectrum of diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, and cirrhosis. Probiotics have been proposed as a treatment option because of their modulating effect on the gut flora that could influence the gut-liver axis. OBJECTIVES: To evaluate the beneficial and harmful effects of probiotics for non-alcoholic fatty liver disease and/or steatohepatitis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2006), MEDLINE (1966 to May 2006), and EMBASE (1980 to May 2006). No language restrictions were applied. SELECTION CRITERIA: Randomised clinical trials evaluating probiotic treatment in any dose, duration, and route of administration versus no intervention, placebo, or other interventions in patients with non-alcoholic fatty liver disease. The diagnosis was made by history of minimal or no alcohol intake, imaging techniques showing hepatic steatosis and/or histological evidence of hepatic damage, and by exclusion of other causes of hepatic steatosis. DATA COLLECTION AND ANALYSIS: We had planned to extract data in duplicate and analyse results by intention-to-treat. MAIN RESULTS: No randomised clinical trials were identified. Preliminary data from two pilot non-randomised studies suggest that probiotics may be well tolerated, may improve conventional liver function tests, and may decrease markers of lipid peroxidation. AUTHORS' CONCLUSIONS: The lack of randomised clinical trials makes it impossible to support or refute probiotics for patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterised by fatty deposition in the hepatocytes of patients with minimal or no alcohol intake and without other known cause. NAFLD includes a wide spectrum of histologic abnormalities ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), or even cirrhosis. Antioxidant supplements, therefore, could potentially protect cellular structures against oxidative stress and the resulting lipid peroxidation. OBJECTIVES: To systematically evaluate the beneficial and harmful effects of antioxidant supplements versus no intervention, placebo, or other interventions for patients with NAFLD or NASH. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2006), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), and the Chinese Biomedical Database (1978 to June 2006). No language restrictions were applied. SELECTION CRITERIA: Randomised clinical trials evaluating any antioxidant supplements versus no intervention, placebo, or other interventions in patients with NAFLD or NASH. Our inclusion criteria for NAFLD or NASH were based on history of minimal or no alcohol intake, imaging techniques showing hepatic steatosis, and/or histological evidence of hepatic damage (including simple steatosis, fatty infiltration plus nonspecific inflammation, steatohepatitis, fibrosis, and cirrhosis), and by exclusion of other causes of hepatic steatosis. DATA COLLECTION AND ANALYSIS: We extracted data from the identified trials and contacted authors. We used a random-effects model and fixed-effect model with the significant level set at P = 0.05. We evaluated the methodological quality of the randomised trials by looking at how the generation of allocation sequence, allocation concealment, blinding, and follow-up were performed. We made our analyses following the intention-to-treat method by imputing missing data. MAIN RESULTS: We identified six trials: two were regarded of high methodological quality and four of low methodological quality. None of the trials reported any deaths. Treatment with antioxidant supplements showed a significant, though not clinically relevant, amelioration of aspartate aminotransferase levels, but not of alanine aminotransferase levels, as compared to placebo or other interventions. Gamma-glutamyl-transpeptidase was decreased, albeit not significantly, in the treatment arm. Radiological and histological data were too limited to draw any definite conclusions on the effectiveness of these agents. Adverse events were non-specific and of no major clinical relevance. AUTHORS' CONCLUSIONS: There is insufficient data to either support or refute the use of antioxidant supplements for patients with NAFLD. It may be advisable to carry out large prospective randomised clinical trials on this topic.

Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. It is suspected in persons with elevated aminotransferase levels and features of insulin resistance (or metabolic) syndrome. The pathogenesis of NAFLD is not clear and there is no universal treatment. OBJECTIVES: To assess beneficial and harmful effects of drugs improving insulin resistance for NAFLD and/or NASH. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Chinese Biomedical Database until February 2006. SELECTION CRITERIA: We included randomised clinical trials assessing the effects of drugs improving insulin resistance for patients with NAFLD or NASH. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Only three randomised clinical trials could be included. Two of the trials had unclear allocation concealment. None was blinded regarding outcome assessment. In two trials, metformin was associated with significantly higher normalization of serum alanine aminotransferase (OR fixed 2.83, 95% CI 1.27 to 6.31 versus diet and OR fixed 7.75, 95% CI 2.37 to 25.35 versus vitamin E) and improvement of liver echographic response (OR fixed 5.25, 95% CI 1.09 to 25.21). An improvement of fatty infiltration was observed in a limited number of patients undergoing liver biopsy. In the single pioglitazone trial, a statistically significant improvement of NASH histology was demonstrated. AUTHORS' CONCLUSIONS: At present, there is insufficient data to either support or refute the use of drugs improving insulin resistance for patients with NAFLD, although current limited information suggests a favourable role of drugs improving insulin resistance. It is advisable to carry out large randomised trials on this topic employing clinically relevant outcome measures and adequate methodology, including blinded outcome assessment.

Development of mantle cell lymphoma in a patient with adrenocortical carcinoma and an 18-year survival after complete removal of the primary cancer and resection of local recurrences.

The case of a patient with a non-functional and poorly-differentiated adrenocortical carcinoma, who had an unexpected long-term survival after a right adrenalectomy and subsequent removal of 2 local recurrences, is reported. However, fifteen years after the complete resection of the primary neoplasm, the patient first developed an autoimmune thrombocytopenic purpura and later a mantle cell lymphoma located in the mediastinal lymph nodes. This case confirms the possible growth of a second tumour in patients with adrenocortical carcinomas, especially if presenting a long survival after resection of the primary malignancy, and emphasises the need for the close follow-up of these patients.

Hepatitis C virus infection in a resident elderly population: a 10-year follow-up study.

BACKGROUND: The natural history of hepatitis C virus infection in the elderly is poorly known. OBJECTIVE: To assess the mortality rate, the progression of liver disease, the hepatitis C virus carrier state and the co-morbidity in a cohort of 35 out of 1,063 anti-hepatitis C virus positive elderly people prospectively followed-up from 1992 to 2002. METHODS: Liver function tests, hepatitis C virus-RNA analysis, hepatitis C virus genotyping and abdominal ultrasonography were assessed at the beginning of the study, and then, liver function tests and ultrasonography were performed annually during the first 5 years of the follow-up. At the end of the 10-year period, causes of death were recorded, while surviving patients underwent again medical examination, liver function tests and abdominal ultrasonography. RESULTS: Out of 35 patients with a 10-year follow-up, 12 patients died: only 2 (5.7%) from liver-related disease (hepatocellular carcinoma and liver failure), whilst 10 (28.5%) from extrahepatic causes. Out of the two patients dying from liver-related causes, one was hepatitis C virus-RNA positive and one hepatitis C virus-RNA negative. Among the 23 living patients, 13 were hepatitis C virus-RNA positive (56.5%), the majority being infected with genotype 2 (69%); of them, 6 (46.1%) had persistently normal alanine aminotransferase levels. None of the hepatitis C virus-RNA positive individuals had excessive alcohol intake. CONCLUSION: Despite the presumably long duration of infection in our cohort, the liver-related mortality was five-fold lower than that from extrahepatic causes (five-fold higher). Lack of hepatic co-morbidity factors, such as alcohol consumption, seems to be relevant for the limited severity of liver disease.

Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease.

BACKGROUND/AIMS: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. METHODS AND RESULTS: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. CONCLUSIONS: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

Congenital anomalies of the spleen mimicking hematological disorders and solid tumors: a single-center experience of 2650 consecutive diagnostic laparoscopies.

Congenital anomalies of the spleen range from splenic lobulation, to accessory spleen to polysplenia. Though most of these anatomical variants have no clinical significance, an accessory spleen may simulate a tumor in the adrenal gland, pancreas, stomach or intestine. Alternatively, a missed accessory spleen may be the site of the relapse of a hematological disorder. We, therefore, assessed retrospectively: (i) the frequency of congenital anomalies of the spleen observed during 2650 consecutive laparoscopies and (ii) looked for possible misdiagnoses of the accessory spleen as hematological disorders or solid tumors located in the left upper quadrant of the abdomen. Congenital anomalies of the spleen were detected in 55 cases, accounting for 2.07%. Accessory spleens were observed in 44 patients (1.6%) and spleen lobulation in 11 (0.47%). An accessory spleen was the most common of the splenic anomalies. Among the 44 patients in whom an accessory spleen was discovered laparoscopically, the recognition of this anomaly prevented a relapse of a hematological disease in one case and avoided a useless exploratory laparotomy in the second, where the radiologist had interpreted this malformation as a space-occupying lesion. In the third case, the accessory spleen was initially misdiagnosed as a solid tumor of the pancreas, but was eventually recognized as a congenital anomaly by a second laparoscopy.

The effect of drugs on bile flow and composition. An overview.

Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.

The monoethylglycinexylidide test for grading of liver cirrhosis.

BACKGROUND: Monoethylglycinexylidide (MEGX) formation following lignocaine injection has recently been proposed as a simple dynamic liver function test based on a single measurement of its serum concentration. AIM: To determine the optimal sampling time for MEGX determination. METHODS: A modelling analysis of lignocaine and MEGX kinetics was performed in seven normals and in four patients with compensated liver cirrhosis; a similar study was performed in 74 cirrhotic patients, divided into two groups according to disease severity (Pugh score). RESULTS: Only the MEGX fractional formation rate (kf) and formation delay (tau) were significantly altered in cirrhotic patients compared to normals: kf = 0.15 +/- 0.03 vs. 0.32 +/- 0.10 min-1 (mean +/- s.d.); tau = 7.7 +/- 2.0 vs. 3.9 +/- 2.9 min-1. A good correlation was found between kf and late (r = 0.82) but not early (r = 0.63) serum MEGX formation, suggesting that late measurements for the clinical MEGX test are preferred. In the second part of our investigation, by discriminant analysis of MEGX test data for 74 cirrhotic patients, the late MEGX concentrations gave the best discrimination between the two classes. In particular, the 60 min MEGX concentration showed the best diagnostic accuracy (81%), sensitivity (75%) and specificity (84%). The association of this with other MEGX parameters, either singly or derived from the whole curve measurements, did not improve the performance of the method. CONCLUSION: The MEGX test, based on a single determination 60 min after lignocaine injection, may be regarded as a simple and sensitive quantitative liver function test.

Influence of rifamycin SV on bile acid metabolism in rats.

Sodium cholate was infused with or without Rifamycin SV in rats in order to determine the site of interference of the drug on hepatic bile salt metabolism. Both compounds were administered at rates such as to saturate their respective maximal excretory capacities. When Rifamycin SV was given, bile acid uptake and excretion significantly decreased, with a significant reduction of the percent of conjugated bile salts in bile. Rifamycin SV neither modified bile flow nor affected the correlation between bile flow and bile salt excretion. These data suggest that the antibiotic interferes with the three main steps of hepatic bile acid metabolism. The cholestatic effect and the modification of biliary bile salt output produced by Ryfamycin SV in rats, could be of clinical relevance.

Gallstone disease in an elderly population: the Silea study.

BACKGROUND: Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS: Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS: Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS: In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.

Bladder injury during diagnostic laparoscopy. A case report.

We report the case of a bladder injury that was incurred during diagnostic laparoscopy in a 19-year-old man with hepatomegaly, neuropsychiatric disturbances, and urinary retention whose final diagnosis was Wilson's disease. In order to define the nature of his hepatomegaly, the patient underwent laparoscopy. However, the lack of recognition of urinary retention by the operator and the absence of cooperation by the patient caused bladder injury during the insertion of the Veress needle, resulting in the leakage of a yellow fluid consistent with urine. Since the injury was small, it was managed with antibiotics and bladder drainage, alone and deemed not to require surgical repair. We also discuss potential risk factors and describe some approaches that can help to avoid this laparoscopic complication.

Agenesis of the gallbladder associated with Gilbert's syndrome.

A case of gallbladder agenesis associated with Gilbert's syndrome in a 52-year-old man with a striking family history of cholelithiasis is reported. The diagnosis of Gilbert's syndrome was made 30 years earlier, whereas the anomaly of the gallbladder was manifested when the patient, at the age of 34 years, started complaining of abdominal symptoms suggestive of biliary tract disease. Diagnostic confirmation was accomplished by magnetic resonance cholangiography, thus avoiding laparotomy, whereas conventional hepatobiliary imaging studies and laparoscopy could not achieve a definite diagnosis. No other malformations were detected. To our knowledge, this is the first report of an association between gallbladder agenesis and Gilbert's syndrome. Such association may be incidental or could represent the occurrence of a concomitant metabolic error in adults with isolated agenesis of the gallbladder.

Are liver cirrhosis and portal hypertension associated with an increased risk of bleeding during laparoscopy? A retrospective analysis of 1,000 consecutive cases.

Laparoscopy is a relatively safe invasive procedure. However, the rate of bleeding complications during this procedure is still debatable. Moreover, it is not clear whether portal hypertension may increase the risk of this event. The authors analyzed retrospectively the records of 1,000 consecutive patients with chronic liver disease undergoing laparoscopy and guided direct-vision hepatic biopsy, and they examined the rate of bleeding complications from the trocar site after insertion of the Veress needle or after liver biopsy. A total of 400 of 1,000 patients had liver cirrhosis. Of these, 22.7% had splenomegaly, 13.0% had laparoscopic signs of portal hypertension, and 8.2% had esophageal varices. Bleeding occurred in 0.9% of patients from the trocar site, in 0.2% from the biopsy site, and in 0% from the Veress needle site. These figures were independent of the presence of advanced liver disease, with or without portal hypertension. Bleeding complications occur rarely during laparoscopy with guided liver biopsy and do not seem to be related per se to the presence of liver cirrhosis and portal hypertension. If anything, bleeding complications represent an unpredictable event in most cases.

Hormones and polyamines in intestinal and pancreatic adaptation.

The evidence for and against an enteropancreatic trophic axis is reviewed. Luminal nutrition is essential for the maintenance of normal intestinal mucosal, and exocrine pancreatic, structure and function. Exclusion of luminal nutrition leads to mucosal hypoplasia and hypofunction with similar changes in the pancreas. The trophic effect of luminal nutrition may be mediated through the release of regulatory peptides with endocrine or paracrine effects. Enteroglucagon is the strongest candidate for the role of 'enterotrophin' while cholecystokinin (CCK) markedly influences pancreatic growth. Thus, CCK not only stimulates exocrine pancreatic secretion but makes acinar cells divide and the pancreas grow. The cellular mechanisms whereby trophic peptides influence normal and adaptive growth are also discussed with emphasis on polyamines (putrescine, spermidine and spermine) and the key enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO). When polyamine synthesis is blocked with the ODC inhibitor, difluoromethyl ornithine (DFMO), the adaptive intestinal hyperplasia of pancreatico-biliary diversion is either inhibited or completely prevented. A proposed sequence of events might be as follows: luminal nutrients, particularly long-chain fats, reach the ileum and colon and stimulate increased enteroglucagon release. Enteroglucagon binds to cell receptors and triggers an intracellular cascade involving ODC and the polyamines, which, in turn, stimulate RNA polymerase, DNA, RNA and protein synthesis, cell division, and adaptive tissue growth.

SAR150640, a selective beta3-adrenoceptor agonist, prevents human myometrial remodelling and activation of matrix metalloproteinase in an in vitro model of chorioamnionitis.

BACKGROUND AND PURPOSE: The uterine pathophysiology underlying inflammatory conditions such as chorioamnionitis remains largely unclear. As we have shown that beta(3)-adrenoceptors act as regulators of myometrial inflammation, we wanted to investigate the potential role of beta(3)-adrenoceptors in preventing uterine remodelling induced by inflammation. EXPERIMENTAL APPROACH: The consequences of human chorioamnionitis on myometrial remodelling were characterized by Sirius Red staining and metalloproteinase (MMP) expression, and compared with the effects of incubating human myometrial samples with Escherichia coli lipopolysaccharide (LPS) in vitro. We also assessed the effect of SAR150640, a selective beta(3)-adrenoceptor agonist, on the production and activity of MMPs. KEY RESULTS: Chorioamnionitis was associated with a 46% decrease in total collagen, as well as over-expression of MMP2 (+61%) and MMP9 (+84%); both effects were reproduced by incubation with LPS (10 microg x mL(-1), 48 h). LPS-induced over-expression of MMP2 and MMP9 in normal human myometrium was paralleled by an overactivity of the proteins. Both over-expression and overactivity were prevented by the beta(3)-adrenoceptor agonist SAR150640 in a concentration-dependent manner. SAR150640, by itself, did not exhibit any effect on MMP production in control tissues. CONCLUSIONS AND IMPLICATIONS: This study shows that inflammation was associated with an intense remodelling of human myometrium, a process likely to be explained by MMP activation. Our study emphasizes the potential therapeutic relevance of beta(3)-adrenoceptor agonists to the treatment of preterm labour and other uterine inflammatory conditions.