International multicenter trial on clinical natural orifice surgery--NOTES IMTN study: preliminary results of 362 patients.

Objectives: Natural orifice translumenal endoscopic surgery (NOTES) is evolving as a promising alternative for abdominal surgery. IMTN Registry was designed to prospectively document early results of natural orifice surgery among a large group of clinical cases.

Methods: Sixteen centers from 9 countries were approved to participate in the study, based on study protocol requirements and local institutional review board approval.

New hybrid approach for NOTES transvaginal cholecystectomy: preliminary clinical experience.

Objectives: Natural orifice translumenal endoscopic surgery (NOTES) represents the first step toward scar-less surgery. The objective of this study is to evaluate early clinical results of transvaginal cholecystectomy using a new technique.

Methods: Institutional review board approval was obtained and transvaginal NOTES cholecystectomy was performed in 12 women for cholelithiasis.

The Combination of S-adenosylmethionine and Dilinoleoylphosphatidylcholine Attenuates Non-alcoholic Steatohepatitis Produced in Rats by a High-Fat Diet.

In the pathogenesis of non-alcoholic steatohepatitis (NASH), oxidative stress resulting from free radicals generated by cytochrome P4502E1 (CYP2E1) plays a major role suggesting the importance of antioxidants. The objective of this study was to assess in a high-fat diet (HF) rat model the effects of the combination of s-adenosylmethionine (SAMe) plus dilinoleoylphosphatidylcholine (DLPC) in the treatment of NASH. To test the hypothesis that these two antioxidants are beneficial in NASH, male Sprague-Dawley rats were fed five different diets for six weeks: control, HF diet and HF plus SAMe and DLPC or their combination.

Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function.

Chronic alcohol consumption affects the gene expression of a NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator1alpha (PGC-1alpha). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days.

Natural orifice translumenal endoscopic surgery (NOTES) transvaginal cholecystectomy in a morbidly obese patient.

Transvaginal natural orifice translumenal endoscopic surgery (NOTES) is a new diagnostic and potentially therapeutic method of surgical endoscopy. The first case of NOTES transvaginal cholecystectomy in a morbid obese patient in the literature is described. IRB approval was obtained at the institution for transvaginal NOTES clinical trials.

Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats.

The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator1alpha (PGC-1alpha) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1alpha mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1alpha, while the transcription factor PPAR-gamma remained unchanged.

Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH.

Background/aims: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH.

Methods: We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT.

Role of medium-chain triglycerides in the alcohol-mediated cytochrome P450 2E1 induction of mitochondria.

Background: Chronic alcohol consumption is known to induce cytochrome P450 2E1 (CYP2E1) leading to lipid peroxidation, mitochondrial dysfunction and hepatotoxicity. We showed that replacement of dietary long-chain triglycerides (LCT) by medium-chain triglycerides (MCT) could be protective. We now wondered whether the induction of mitochondrial CYP2E1 plays a role and whether liver injury could be avoided through mitochondrial intervention.

Model of nonalcoholic steatohepatitis.

Background: Obesity and diabetes are frequently associated with nonalcoholic steatohepatitis (NASH), but studies have been hampered by the absence of a suitable experimental model.

Objective: Our objective was to create a rat model of NASH.

Design: Sprague-Dawley rats were fed a high-fat, liquid diet (71% of energy from fat, 11% from carbohydrates, 18% from protein) or the standard Lieber-DeCarli diet (35% of energy from fat, 47% from carbohydrates, 18% from protein).

Acarbose attenuates experimental non-alcoholic steatohepatitis.

The alpha-glucosidase inhibitor acarbose is beneficial in the prevention of type 2 diabetes. To determine whether it attenuates the commonly associated non-alcoholic steatohepatitis (NASH), we used an experimental NASH model. Rats were fed ad libitum a nutritionally adequate high fat diet (71% of calories as fat) with or without acarbose (200 mg/1000 calories) for 3 weeks.

Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons.

Unlabelled: GOAL/BACKGROUND: Hepatoprotective effects of silymarin in patients with alcoholic liver disease are controversial. For strict control, this was assessed in non-human primates. STUDY Twelve baboons were fed alcohol with or without silymarin for 3 years with a nutritionally adequate diet.

Models of alcoholic liver disease in rodents: a critical evaluation.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were J. Christian Bode and Hiroshi Fukui.

Inducibility of cytochromes P-4502E1 and P-4501A1 in the rat pancreas.

Cytochrome P-450 (CYP) isoenzymes have been incriminated in the toxicity and carcinogenicity of various xenobiotics in different tissues, but prior measurements of their activity in pancreatic microsomes have been disappointing. We now applied new isolation methods and a highly sensitive procedure to assay for the metabolism of p-nitrophenol and 7-ethoxyresorufin, specific substrates for CYP2E1 (2E1) and CYP1A1 (1A1), respectively. 2E1 and 1A1 content was estimated with high-resolution chemiluminescent Western blots using recombinant 2E1 and 1A1 as standards.

Polyenylphosphatidylcholine decreases alcohol-induced oxidative stress in the baboon.

Diets supplemented with polyunsaturated fatty acids or triglycerides exacerbate alcohol-induced liver injury in rats, whereas, in baboons, polyenylphosphatidylcholine (PPC) protects against alcohol-induced fibrosis and cirrhosis. Because the aggravation in rats was attributed to enhanced lipid peroxidation, the present study was undertaken to assess parameters of oxidative stress in percutaneous liver biopsies of baboons fed alcohol, with or without PPC (2.8 g per 1000 calories).

Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon.

Background/aims: Polyunsaturated soybean lecithin (55%-60% phosphatidylcholine [PC]) protects against fibrosis in alcohol-fed baboons. The present study was undertaken to determine whether PC is the active agent.

Methods: Virtually pure PC (equivalent to that contained in the lecithin) was administered for up to 6.

Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin.

Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate.

S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon.

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs.

Experimental methods of ethanol administration.

Techniques are reviewed for the experimental feeding of alcohol, including a liquid diet procedure invented 25 years ago. This technique results in much higher ethanol intake than with other approaches. As a consequence, various complications observed in alcoholics can be reproduced in animal models.

Effects of mineral and vitamin supplementation on the alcohol-induced fatty liver and microsomal induction.

In rats fed ethanol (36% of total energy) for 1 month as part of a standard liquid diet, significant increases in hepatic lipids, microsomal cytochrome P-450, and in the activity of the microsomal ethanol oxidizing system were observed. Similar effects were noted in another group of animals treated with the same ethanol-containing diet, except that the content of minerals and vitamins was increased by 50%. Body weight gains were also comparable in these groups.

Liquid diet technique of ethanol administration: 1989 update.

A technique of feeding alcohol as part of a liquid diet is reviewed that achieves an alcohol consumption of clinical relevance, while maintaining dietary control and providing adequate nutrition. With this procedure, blood alcohol levels are obtained which mimic clinical conditions and allow experimental duplications of many pathological complications caused by alcohol. In the rat, the liquid diet technique provides a model for the alcoholic fatty liver, various alcohol-induced metabolic, endocrine and central nervous system abnormalities (including tolerance and dependence) and the interaction of ethanol with industrial solvents, many commonly used drugs, analgesics, carcinogens and nutrients.

Role of acetone, dietary fat and total energy intake in induction of hepatic microsomal ethanol oxidizing system.

Chronic ethanol consumption results in the induction of a specific hepatic cytochrome P-450 (P450IIE1). However, since compounds other than ethanol (i.e.