{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:55:56Z","timestamp":1787496956384,"version":"build-2736575974"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Across Southeast Asia and China, more than 17000 Asian bears are kept under suboptimal conditions and farmed for their bile to meet the consumer demand for traditional medicine products. Years of unsterile and repetitive bile extraction contribute to the development of chronic sterile or bacterial cholecystitis, a pathology commonly diagnosed in formerly bile-farmed bears. In both human and veterinary medicine, the diagnostic value of the macroscopic bile examination for assessing gallbladder disease is unclear. The objective of this study is to identify the role of gallbladder bile color, viscosity, and turbidity, while comparing them with established markers of cholecystitis. Moreover, it aims to define the optimal duration of oral antibiotic treatment for chronic bacterial cholecystitis in bears associated with bile farming. Thirty-nine adult, formerly bile-farmed Asiatic black bears (\n                    <jats:italic>Ursus thibetanus<\/jats:italic>\n                    ) were examined under anesthesia and underwent percutaneous ultrasound guided cholecystocentesis. A total of 59 bile samples were collected with 20 animals sampled twice to evaluate the therapeutic success. All bile aspirates were assessed macroscopically and microscopically followed by submission for bacterial culture and antimicrobial sensitivity. In the majority of bears, samples with cytological evidence of bactibilia lacked inflammatory cells and did not always correlate with positive bacterial cultures. The most common bacterial isolates were\n                    <jats:italic>Enterococcus spp<\/jats:italic>\n                    ,\n                    <jats:italic>Streptococcus spp and Escherichia coli<\/jats:italic>\n                    . Based on our findings, the optimal duration of antibiotic treatment for chronic bacterial cholecystitis is 30 days. Moreover, unlike Gamma-glutamyl Transferase (GGT) and gallbladder wall thickness, the organoleptic properties of bile were found to be reliable markers of chronic gallbladder inflammation with color and turbidity indicating cholestasis. The current study highlights the importance of cholecystocentesis for the management of gallbladder disease and provides initial results on the possible diagnostic value of macroscopic bile examination.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0264391","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T13:57:00Z","timestamp":1646315820000},"page":"e0264391","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic cholecystitis: Diagnostic and therapeutic insights from formerly bile-farmed Asiatic black bears (Ursus thibetanus)"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3689-6369","authenticated-orcid":true,"given":"Szilvia K.","family":"Kalogeropoulu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Rauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Redtenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"H\u00e4fner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwan A.","family":"Burgener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Painer-Gigler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"pone.0264391.ref001","first-page":"161","article-title":"The Asian trade in bears and bear parts: impacts and conservation recommendations","volume":"9","author":"J Mills","year":"1994","journal-title":"bears: their biology and management"},{"issue":"1","key":"pone.0264391.ref002","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1746-4269-5-2","article-title":"Bear bile: dilemma of traditional medicinal use and animal protection","volume":"5","author":"Y Feng","year":"2009","journal-title":"J Ethnobiol Ethnomed"},{"key":"pone.0264391.ref003","doi-asserted-by":"crossref","unstructured":"Garshelis, D., Steinmetz, R. Ursus thibetanus (errata version published in 2017). The IUCN Red List of Threatened Species 2016. https:\/\/dx.doi.org\/10.2305\/IUCN.UK.2020-3.RLTS.T22824A166528664.en.","DOI":"10.2305\/IUCN.UK.2020-3.RLTS.T22824A166528664.en"},{"key":"pone.0264391.ref004","unstructured":"Haikui H, Zhi L. Bear Farming and Bear Conservation in China. In: Williamson DF. Proceedings of the Fourth International Symposium on the Trade in Bear Parts: Nagano, Japan October 4th, 2006. TRAFFIC East Asia-Japan; 2007:37\u201349."},{"key":"pone.0264391.ref005","doi-asserted-by":"crossref","DOI":"10.1186\/s13002-019-0292-5","article-title":"Community attitudes towards bears, bear bile use, and bear conservation in Luang Prabang, Lao PDR","volume":"15","author":"D Sukanan","year":"2019","journal-title":"J Ethnobiol Ethnomed"},{"key":"pone.0264391.ref006","unstructured":"Ending Bear Farming. Wildlife Crime Bulletin 2020. https:\/\/env4wildlife.org\/category\/wildlife-crime-bulletins\/."},{"key":"pone.0264391.ref007","unstructured":"Foley KE, Stengel CJ, Shepherd CR. Pills, powders, vials and flakes: the bear bile trade in Asia. TRAFFIC Southeast Asia, Petaling Jaya, Selangor, Malaysia. 2011."},{"key":"pone.0264391.ref008","unstructured":"Dang NX. Bear parts trade in Vietnam and measures for its control. In: Williamson DF. Proceedings of the fourth International Symposium on the Trade in Bear Parts: Nagano, Japan October 4th, 2006. Tokyo: TRAFFIC East Asia-Japan; 2007:61\u201366."},{"issue":"1","key":"pone.0264391.ref009","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1748-1090.2009.00097.x","article-title":"Veterinary issues related to bears (Ursidae): review: veterinary issues related to bears","volume":"44","author":"DC Bourne","year":"2010","journal-title":"Int Zoo Yearb"},{"key":"pone.0264391.ref010","doi-asserted-by":"crossref","unstructured":"Cianci P, Tartaglia N, Fersini A, Capuzzolo S, Giambavicchio LL, Ambrosi A, et al. Acute Cholecystitis: Diagnostic Pitfall and Timing of Treatment. In: Abdeldayem HM, editor. Updates in Gallbladder Diseases [Internet]. InTech; 2017. http:\/\/www.intechopen.com\/books\/updates-in-gallbladder-diseases\/acute-cholecystitis-diagnostic-pitfall-and-timing-of-treatment.","DOI":"10.5772\/67549"},{"issue":"4","key":"pone.0264391.ref011","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.femsre.2004.09.003","article-title":"The interaction between bacteria and bile","volume":"29","author":"M Begley","year":"2005","journal-title":"FEMS Microbiol Rev"},{"issue":"2","key":"pone.0264391.ref012","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3748\/wjg.v7.i2.203","article-title":"Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones","volume":"7","author":"D J\u00fcngst","year":"2001","journal-title":"World J Gastroenterol"},{"key":"pone.0264391.ref013","volume-title":"StatPearls","author":"NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health","year":"2020"},{"issue":"9","key":"pone.0264391.ref014","doi-asserted-by":"crossref","first-page":"534","DOI":"10.12968\/coan.2017.22.9.534","article-title":"Treatment of gallbladder disease in dogs and cats","volume":"22","author":"S Kilpatrick","year":"2017","journal-title":"Companion Anim"},{"issue":"5","key":"pone.0264391.ref015","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/gut.9.5.536","article-title":"Biliary excretion of antibiotics in man","volume":"9","author":"G Acocella","year":"1968","journal-title":"Gut"},{"issue":"4","key":"pone.0264391.ref016","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000213828","article-title":"Relation of gallbladder motility to viscosity and composition of gallbladder bile in patients with cholesterol gallstones","volume":"79","author":"D Gr\u00fcndel","year":"2009","journal-title":"Digestion"},{"issue":"3","key":"pone.0264391.ref017","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/0016-5085(86)91123-6","article-title":"Nature and composition of biliary sludge","volume":"90","author":"SP Lee","year":"1986","journal-title":"Gastroenterology"},{"key":"pone.0264391.ref018","unstructured":"Aguirre A. Diseases of the gallbladder and extrahepatic biliary system. In: Ettinger SJ, Feldman EC, C\u00f4t\u00e9, editors. Textbook of veterinary internal medicine: diseases of the dog and the cat.2010: p.4080."},{"issue":"6","key":"pone.0264391.ref019","first-page":"60","article-title":"Tokyo Guidelines 2013: antimicrobial therapy for acute cholangitis and cholecystitis","volume":"20","author":"H Gomi","year":"2013","journal-title":"J Hepatobiliary Pancreat Sci"},{"issue":"1","key":"pone.0264391.ref020","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jhbp.518","article-title":"Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis","volume":"25","author":"H Gomi","year":"2018","journal-title":"J Hepatobiliary Pancreat Sci"},{"issue":"3","key":"pone.0264391.ref021","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1148\/radiology.178.3.1994414","article-title":"Diagnostic fine-needle puncture of the gallbladder with US guidance","volume":"178","author":"W Swobodnik","year":"1991","journal-title":"Radiology"},{"issue":"4","key":"pone.0264391.ref022","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1556\/avet.50.2002.4.2","article-title":"Percutaneous ultrasound-guided cholecystocentesis in dogs","volume":"50","author":"K V\u00f6r\u00f6s","year":"2002","journal-title":"Acta Vet Hung"},{"key":"pone.0264391.ref023","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1939-1676.2003.tb02451.x","article-title":"Percutaneous Ultrasound\u2010Guided Cholecystocentesis in Healthy Cats","volume":"17","author":"KCM Savary-Bataille","year":"2003","journal-title":"J Vet Intern Med"},{"issue":"3","key":"pone.0264391.ref024","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1111\/jvim.13943","article-title":"Percutaneous Ultrasound\u2010guided Cholecystocentesis and Bile Analysis for the Detection of Platynosomum spp.\u2010Induced Cholangitis in Cats","volume":"30","author":"L K\u00f6ster","year":"2016","journal-title":"J Vet Intern Med"},{"key":"pone.0264391.ref025","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1097\/00000658-196303000-00019","article-title":"Sedimentation of bile constituents","volume":"157","author":"H. Tera","year":"1963","journal-title":"Ann Surg"},{"key":"pone.0264391.ref026","first-page":"5436961","article-title":"Optimizing the method of cell separation from bile of patients with cholangiocarcinoma for flow cytometry","author":"Y Xia","year":"2019","journal-title":"Gastroenterol Res Pract"},{"key":"pone.0264391.ref027","unstructured":"Performance Standards for Antimicrobial Susceptibility Testing. 12th informational supplement M100-S12. Wayne, PA:NCCLS;2002; Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria isolated from Animals. Approved standard M31-A2, Wayne, PA:NCCLS;2002)."},{"key":"pone.0264391.ref028","unstructured":"Cocker S, Richter K. Diagnostic evaluation of the liver. In: Ettinger SJ, Feldman EC, C\u00f4t\u00e9, editors. Textbook of veterinary internal medicine: diseases of the dog and the cat.2010: p.3942."},{"key":"pone.0264391.ref029","unstructured":"Albert Z. Further studies on the activity of gamma-glutamyl transpeptidase in man and certain other mammals. Enzyme Histochemistry. Simposio Antonio Baselli, Milan. 1967."},{"key":"pone.0264391.ref030","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF02214900","article-title":"Gamma glutamyl transferase in domestic animals","volume":"6","author":"JP Braun","year":"1983","journal-title":"Vet Res Commun"},{"issue":"2","key":"pone.0264391.ref031","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0195-5616(95)50026-9","article-title":"Clinicopathological evaluation of the liver","volume":"25","author":"SM Dial","year":"1995","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"3","key":"pone.0264391.ref032","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1939-1676.1992.tb00335.x","article-title":"A Review of disorders of the gallbladder and extrahepatic biliary tract in the dog and dat","volume":"6","author":"TM Neer","year":"1992","journal-title":"J Vet Intern Med"},{"issue":"2","key":"pone.0264391.ref033","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.cvsm.2006.11.009","article-title":"Interpretation of liver enzymes","volume":"37","author":"SA Center","year":"2007","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"pone.0264391.ref034","unstructured":"Teare JA, ed:2013, \u201cUrsus thibetanus\u201d. No selection by gender. All ages combined. Standard International Units 2013 CD.html. in ISIS Physiological Reference Intervals for Captive Wildlife: A CD-ROM Resource., International Species Information System."},{"issue":"2","key":"pone.0264391.ref035","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1740-8261.2001.tb00918.x","article-title":"Ultrasonographic evaluation of gallbladder wall thickness in cats","volume":"42","author":"KM Hittmair","year":"2001","journal-title":"Veterinary Radiol Ultrasound"},{"issue":"1","key":"pone.0264391.ref036","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00534-012-0568-9","article-title":"TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos)","volume":"20","author":"M Yokoe","year":"2013","journal-title":"J Hepatobiliary Pancreat Sci"},{"issue":"3","key":"pone.0264391.ref037","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.cvsm.2009.01.004","article-title":"Diseases of the gallbladder and biliary tree","volume":"39","author":"SA Center","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"3","key":"pone.0264391.ref038","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2460\/javma.234.3.359","article-title":"Clinical, ultrasonographic, and laboratory findings associated with gallbladder disease and rupture in dogs: 45 cases (1997\u20132007)","volume":"234","author":"LJ Crews","year":"2009","journal-title":"J Am Vet Med Assoc"},{"issue":"5","key":"pone.0264391.ref039","doi-asserted-by":"crossref","first-page":"254","DOI":"10.12968\/coan.2017.22.5.254","article-title":"Diagnostic approach to gallbladder disease in dogs and cats","volume":"22","author":"Y Uetsu","year":"2017","journal-title":"Companion Anim"},{"issue":"1","key":"pone.0264391.ref040","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/jvim.13645","article-title":"Cytological findings of 140 bile samples from dogs and cats and associated clinical pathological data","volume":"30","author":"LM Peters","year":"2016","journal-title":"J Vet Intern Med"},{"issue":"3","key":"pone.0264391.ref041","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5326\/15473317-33-3-207","article-title":"Acalculous cholecystitis in four canine cases: ultrasonographic findings and use of ultrasonographic-guided, percutaneous cholecystocentesis in diagnosis","volume":"33","author":"BJ Rivers","year":"1997","journal-title":"J Am Anim Hosp Assoc"},{"issue":"6","key":"pone.0264391.ref042","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/j.1748-5827.2006.00012.x","article-title":"Bacterial cholangitis\/cholangiohepatitis with or without concurrent cholecystitis in four dogs","volume":"47","author":"EJ O\u2019Neill","year":"2006","journal-title":"J Small Anim Pract"},{"key":"pone.0264391.ref043","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1939-1676.2007.tb02984.x","article-title":"Bacterial culture results from liver, gallbladder, or bile in 248 dogs and cats evaluated for hepatobiliary disease: 1998\u20132003","volume":"21","author":"KA Wagner","year":"2007","journal-title":"J Vet Intern Med"},{"issue":"5","key":"pone.0264391.ref044","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1111\/jvim.14792","article-title":"Association between gallbladder ultrasound findings and bacterial culture of bile in 70 cats and 202 dogs","volume":"31","author":"RP Smith","year":"2017","journal-title":"J Vet Intern Med"},{"issue":"1","key":"pone.0264391.ref045","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1638\/2014-0076R2.1","article-title":"Obstructive cholelithiasis and cholecystitis in a kinkajou (Potos flavus)","volume":"46","author":"R Potier","year":"2015","journal-title":"J Zoo Wildl Med"},{"issue":"9","key":"pone.0264391.ref046","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/jsap.12230","article-title":"Gallbladder rupture associated with cholecystitis in a domestic ferret (Mustela putorius)","volume":"55","author":"M Huynh","year":"2014","journal-title":"J Small Anim Pract"},{"key":"pone.0264391.ref047","article-title":"Compromised health and welfare of bears farmed for bile in China","volume":"11","author":"IK Loeffler","year":"2009","journal-title":"Anim Welf"},{"issue":"3","key":"pone.0264391.ref048","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1172\/JCI115961","article-title":"Disorders of bile acid metabolism in cholesterol gallstone disease","volume":"90","author":"F Berr","year":"1992","journal-title":"J Clin Ivest"},{"issue":"3","key":"pone.0264391.ref049","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1194\/jlr.S091199","article-title":"Gallbladder bile supersaturated with cholesterol in gallstone patients preferentially develops from shortage of bile acids","volume":"60","author":"M Rudling","year":"2019","journal-title":"J Lipid Res"},{"key":"pone.0264391.ref050","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1186\/1471-2458-13-1158","article-title":"Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam","volume":"13","author":"KV Nguyen","year":"2013","journal-title":"BMC Public Health"},{"key":"pone.0264391.ref051","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1093\/jac\/dkx260","article-title":"A current perspective on antimicrobial resistance in Southeast Asia","volume":"72","author":"RM Zellweger","year":"2017","journal-title":"J Antimicrob Chemother"},{"issue":"10","key":"pone.0264391.ref052","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1046\/j.1365-3156.2000.00630.x","article-title":"Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community","volume":"5","author":"M Larsson","year":"2000","journal-title":"Trop Med Int Health"},{"key":"pone.0264391.ref053","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s10393-016-1130-z","article-title":"Antimicrobial consumption in medicated feeds in Vietnamese pig and poultry production","volume":"13","author":"VC Nguyen","year":"2016","journal-title":"Ecohealth"},{"key":"pone.0264391.ref054","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/zph.12165","article-title":"Antimicrobial usage in chicken production in the Mekong Delta of Vietnam","volume":"62","author":"JJ Carrique-Mas","year":"2015","journal-title":"Zoonoses Public Health"},{"key":"pone.0264391.ref055","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1093\/jac\/dkv053","article-title":"Prevalence and risk factors for carriage of antimicrobial-resistant Escherichia coli on household and small-scale chicken farms in the Mekong Delta of Vietnam","volume":"70","author":"VT Nguyen","year":"2015","journal-title":"J Antimicrob Chemother"},{"issue":"5","key":"pone.0264391.ref056","first-page":"247","article-title":"First survey on the use of antibiotics in pig and poultry production in the red river delta region of Vietnam","volume":"3","author":"DP Kim","year":"2013","journal-title":"Food Public Health"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T05:47:03Z","timestamp":1700286423000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264391"}},"subtitle":[],"editor":[{"given":"Mariya Y","family":"Pakharukova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,3]]},"references-count":56,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264391","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,3]]}}}