Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression.

As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor α (LXRα) agonist), or peroxisome proliferator-activated receptor gamma (PPARγ) siRNA. Western blotting for PPARγ, LXRα, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRα-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.

Nonsurgical resolution of gallbladder mucocele in two dogs.

CASE DESCRIPTION: A gallbladder mucocele was diagnosed in 2 dogs. In both dogs, the mucocele resolved with medical treatment but without the need for surgical intervention. CLINICAL FINDINGS: A 12-year-old spayed female Miniature Schnauzer had a history of signs of gastrointestinal tract disease and high serum liver enzyme activities. Gallbladder mucocele and hypothyroidism were diagnosed. A 6-year-old neutered mixed-breed dog had chronic intermittent diarrhea and recurrent otitis; gallbladder mucocele and hypothyroidism were diagnosed. TREATMENT AND OUTCOME: The first dog was treated with S-adenosyl-methionine, omega-3 fatty acids, famotidine, ursodiol, and levothyroxine. Substantial improvement in the gastrointestinal tract condition and complete resolution of the gallbladder mucocele within 3 months were evident, but the dog was not available for further follow-up monitoring. The second dog was treated with fenbendazole, ursodiol, and levothyroxine and fed a hypoallergenic diet. One month after evaluation, abdominal ultrasonography revealed that the gallbladder mucocele was resolving, and treatment was continued. Ultrasonographic evaluation 2 and 4 months later revealed complete resolution of the mucocele. CLINICAL RELEVANCE: Review of the clinical course of 2 dogs in which there was nonsurgical resolution of gallbladder mucocele revealed that surgery is not necessary in all dogs with gallbladder mucocele. Hypothyroidism may have resulted in delayed gallbladder emptying, and its role in the pathogenesis of gallbladder mucocele merits investigation. Despite this information, until further prospective trials with a control group and standardized treatments and follow-up monitoring can be performed, the authors recommend surgical intervention for treatment of dogs with gallbladder mucocele.

Sincalide in patients with parenteral nutrition-associated gallbladder disease.

OBJECTIVE: To review the role of sincalide in treating and preventing parenteral nutrition (PN)-associated gallbladder disease. DATA SOURCES: A MEDLINE (1996-March 2004) search was performed using the key terms cholecystokinin, sincalide, parenteral nutrition, cholelithiasis, cholestasis, and sludge. DATA SYNTHESIS: Five human studies investigated the safety and efficacy of sincalide in patients with PN-associated gallbladder disease. Sincalide at intravenous doses of 0.04 microg/kg 3 times daily increased bile flow and improved serum bilirubin levels. However, patients with advanced liver disease did not respond to sincalide therapy. Long-term follow-up data on sincalide effects on liver disease progression are not yet available. CONCLUSIONS: Sincalide improved the signs of cholestasis. However, its long-term effects in preventing and treating PN-associated gallbladder disease remain unknown and its routine use for this indication cannot be recommended at this time.

Experimental studies on the pharmacokinetics and therapeutic effect of cefbuperazone in biliary infection.

A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.

[Antibiotic management of bacterial bile-duct and gallbladder infections].

The sensitivity to antibiotics of the various bacterium strains has been studied in the bile samples of 373 patients with gallbladder and/or biliary duct infection and the clinical effect of antibiotic therapy applied to 325 instances was recorded. The antibiograms suggested an increased resistance mainly of the intestinal bacteria isolated from the bile samples. An increase in the ratio of polyresistant strains was observed. Gentamycin, neomycin, polymixin and kanamycin were the most potent in vitro. Parenterally administered chloramphenicol and oxytetracycline acted favourable in most cases of biliary infection. This therapy was successful even against pathogens resistant in vitro to chloramphenicol and oxytetracycline. The higher efficacy of aimed antibiotic therapy compared to randomly applied treatment is stressed and confirmed by numerical data.