Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder.

Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by the amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of cystic fibrosis transmembrane conductance regulatory protein (CFTR) in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR were compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR were quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish a significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared with control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for CFTR were accompanied by decreases in mRNA for the Cl-/[Formula: see text] exchanger SLC26A3, K+ channels (KCNQ1, KCNN4), and vasoactive intestinal polypeptide receptor (VIPR1), which suggest a driving force for change in secretory function of gallbladder epithelial cells in the pathogenesis of mucocele formation. There were no significant differences in CFTR gene variant frequency, type, or predicted impact comparing low-risk, high-risk, and definitively diagnosed groups of dogs. This study describes a unique, naturally occurring muco-obstructive disease of the canine gallbladder, with uncanny similarity to cystic fibrosis, and driven by the underlying failure of CFTR function.NEW & NOTEWORTHY Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.

Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.

Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and consistent inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. CFTR was expressed apically in non-CF pig gallbladder epithelium but was absent in CF. CF pig gallbladders lacked cAMP-stimulated anion transport. Using a novel gallbladder epithelial organoid model, we found that Cl- or HCO3- was sufficient for non-CF organoid swelling. This response was absent for non-CF organoids in Cl-/HCO3--free conditions and in CF. Single-cell RNA-sequencing revealed a single epithelial cell type in non-CF gallbladders that coexpressed CFTR, MUC5AC, and MUC5B. Despite CF gallbladders having increased luminal MUC5AC and MUC5B accumulation, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. In conclusion, these data suggest that loss of CFTR-mediated anion transport and fluid secretion contribute to microgallbladder development and luminal mucus accumulation in CF.

Implications of gallbladder cholesterolosis and cholesterol polyps?

BACKGROUND: The clinical significance of cholesterolosis has not been well established but there are some provocative, if not robust, studies of the role it may play in the pathophysiology of pancreatitis and biliary dyskinesia, as well as hypercholesterolemia. Our aim was to take advantage of a very large cholecystectomy (CCY) database to support or refute these potentially important reported associations. MATERIALS AND METHODS: A retrospective review of 6868 patients who underwent CCY from 2001-2013 was performed. Comparisons were made using the student t-test for continuous and chi-square analysis for categorical, variables. RESULTS: Among patients for whom the CCY was the primary operation, 1053 (18%) had cholesterolosis and 4596 did not. Compared to those without cholesterolosis, those with cholesterolosis were no more likely to have elevated cholesterol levels (P = 0.64) nor low gallbladder ejection fraction (P = 0.2). To evaluate cholesterolosis as a cause of pancreatitis, all patients with gallstones were eliminated, leaving 639 patients. Among these, not only was cholesterolosis not associated with more pancreatitis, but rather there was not a single patient with or without cholesterolosis who had pancreatitis. CONCLUSIONS: Despite prior reports of associations between cholesterolosis and elevated serum cholesterol, depressed ejection fraction, and increased risk of pancreatitis, careful analysis of this current, larger data set does not support these associations. Any patient with stones or sludge, or with biliary dyskinesia, and appropriate symptoms, should be considered for CCY, with or without suspected cholesterolosis.

[Research of conjugated bile acids in gallbladder bile of patients with polypoid lesions of gallbladder].

OBJECTIVE: To investigate the difference in conjugated bile acids in the gallbladder bile between gallbladder cholesterol polyps and adenomatous polyps patients, and screen the differential diagnosis-markers for polypoid lesions of gallbladder (PLG). METHODS: From January to June 2013, the 20 cholesterol polyps patients, 10 adenomatous polyps patients and 10 patients without gallbladder diseases were enrolled. High performance liquid chromatography assay with ultraviolet detection was used to test 8 conjugated bile acids in gallbladder bile. RESULTS: The 8 conjugated bile acids were completely analyzed in 10 minutes, and the assay was liner in the range 8-500 µg/ml. The correlation coeffients for linear regression was from 0.9996-0.9999 and the detection limits ranged from 3.90-7.81 µg/ml. The level of taurocholic acid (TCA) in adenomatous polyps group ((75 ± 51) µg/ml) was significantly lower than that in the cholesterol polyps ((228 ± 206) µg/ml, q = 3.120, P = 0.014) and control groups ((104 ± 40) µg/ml, q = 2.950, P = 0.027). The level of taurochenodeoxycholic acid (TCDCA) in cholesterol polyps group ((604 ± 444) µg/ml) was significantly higher than that in the adenomatous polyps ((310 ± 182) µg/ml, q = 2.560, P = 0.048) and control groups ((308 ± 21) µg/ml, q = 2.970, P = 0.023). CONCLUSIONS: The levels of TCA and TCDCA in the gallbladder biles in cholesterol polyps patients were higher than those in adenomatous polyps patients, which may be the differential diagnosis-markers for PLG.

Advancements in metabolomics research in benign gallbladder diseases: A review.

The burgeoning field of metabolomics has piqued the interest of researchers in the context of benign gallbladder diseases, which include conditions such as gallbladder polyps, gallstones, and cholecystitis, which are common digestive system disorders. As metabolomics continues to advance, researchers have increasingly focused their attention on its applicability in the study of benign gallbladder diseases to provide new perspectives for diagnostic, therapeutic, and prognostic evaluation. This comprehensive review primarily describes the techniques of liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance and their respective applications in the study of benign gallbladder disease. Metabolomics has made remarkable progress in various aspects of these diseases, ranging from early diagnosis, etiological research, assessment of disease progression and prognosis, and optimization of therapeutic strategies. However, challenges remain in the field of metabolomics in the study of benign gallbladder diseases. These include issues related to data processing and analysis, biomarker discovery and validation, interdisciplinary research integration, and the advancement of personalized medicine. This article attempts to summarize research findings to date, highlight future research directions, and provide a reference point for metabolomics research in benign gallbladder disease.

Comparison of fibroblast growth factor 19 concentrations between dogs with and without gallbladder mucoceles.

BACKGROUND: Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal-related flux of GB bile decreases serum FGF19 concentrations. OBJECTIVE: Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. ANIMALS: Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty-two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. METHODS: Prospective cross-sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. RESULTS: Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8-67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5-285.1). CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Increased lipogenesis and lipidosis of gallbladder epithelium in dogs with gallbladder mucocele formation.

BACKGROUND: Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown. METHODS: A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium. RESULTS: Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism. CONCLUSION: Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.

Metabolic dysfunction-associated steatotic liver disease and gallbladder polyp development: an observational study.

The influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096-10.53) and 5.338 (1.054-27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047-3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm.

Elevation of pancreatic enzymes in gallbladder bile associated with heterotopic pancreas. A case report and review of the literature.

CONTEXT: This is the first report associating heterotopic pancreas in the gallbladder and elevated pancreatic enzymes in bile. CASE REPORT: A 60-year-old woman underwent abdominal ultrasonography at a medical check-up, revealing a nodular protrusion at the neck of the gallbladder. It seemed likely to be a lymph node, but we could not exclude the possibility of gallbladder cancer. In order to make a correct diagnosis, laparoscopic cholecystectomy was successfully performed. Pathological examination revealed heterotopic pancreatic tissue in the gallbladder wall. In addition, we detected elevated levels of amylase and lipase in gallbladder bile. CONCLUSIONS: Preoperative diagnosis of heterotopic pancreas in the gallbladder is difficult. However, an increase of pancreatic enzymes in gallbladder bile may potentially play an important role in the occurrence of acalculous cholecystitis and biliary cancer. We need more accumulation of cases to know the true significance of this anomaly.

Expression of ezrin, HGF and c-met and its clinicopathological significance in the benign and malignant lesions of the gallbladder.

BACKGROUND/AIMS: To investigate the expression of ezrin, HGF and c-met in the benign and malignant lesions of the gallbladder. METHODOLOGY: Ezrin, HGF and c-met expression was detected by immunohistochemistry. RESULTS: The positive ezrin, HGF and c-met expression was significantly higher in gallbladder adenocarcinoma than in benign lesions. The benign lesions with positive ezrin, HGF and/or c-met expression showed moderately- or severely-atypical hyperplastic epithelium. The positive expression of ezrin, HGF and c-met was significantly associated with differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that increased expression of ezrin, HGF and c-met was associated with decreased overall survival. Multivariate Cox regression analysis showed that increased expression of ezrin, HGF or c-met was an independent bad-prognostic predictor in gallbladder adenocarcinoma. CONCLUSIONS: The expression of ezrin, HGF and/or c-met might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma.

[Evaluation of clinical effectiveness of treatment of hepatobiliary disorders in the negative effects of environmental factors in children].

303 children with the diagnosis "Hepatobiliary disorders of cystic duct or gall bladder" and "Sphincter Oddu's spasm" have been examined. After a profound children's examination, the data of objective survey, and also laboratory, biochemical, immune, functional rates (such as ultrasound survey, cardiointervalography) and findings of chemical-analytical survey of the toxics rate (such as aroma carbons, phenol, aldehydes, aliphatic alcohols) in biospheres of children's organisms were a nalysed. The evaluation of the effectiveness of children's hepatobilliary disorders'treatment in conditions of the environmentae negative factors' influence.

[Expression of ephrin-A7 and metadherin and its clinicopathological significances in the benign and malignant lesions of gallbladder].

OBJECTIVE: To study the expression of ephrin-A7 (EphA7) and metadherin (MTDH) and their clinicopathological significances in the benign and malignant lesions of gallbladder. METHODS: EnVisiom immunohistochemical methods was used for determining the expressions of EphA7 and MTDH in routinely paraffin-embedded sections of surgically-resected specimens from 108 cases with gallbladder adenocarcinoma, 15 cases with adenomatous polyp and 35 cases with chronic cholecystitis treated from June 1996 to June 2006. And 46 cases of peritumoral tissues were also harvested as controls (n = 35). RESULTS: The positive expression rates of EphA7 and MTDH were significantly higher in gallbladder adenocarcinoma than those in peritumoral tissues (χ(2)(EphA7) = 12.65, χ(2)(MTDH) = 13.00; P < 0.01), adenomatous polyp (χ(2)(EphA7) = 8.21, χ(2)(MTDH) = 9.39; P < 0.01) and chronic cholecystitis (χ(2)(EphA7) = 21.21, χ(2)(MTDH) = 23.68; P < 0.01); Moderately-or severely-atypical hyperplasia of gallbladder epithelium was found in the benign lesions with positive expression of EphA7 and/or MTDH. The positive rates of EphA7 and MTDH were significantly lower in the cases of well-differentiated adenocarcinoma, maximal diameter of tumor < 2 cm, no-metastasis of lymph node, and tumor with no-invasiveness of regional tissues than those in the poorly-differentiated adenocarcinoma (χ(2)(EphA7) = 12.34, χ(2)(MTDH) = 12.80; P < 0.01), maximal diameter of tumor ≥ 2 cm (χ(2)(EphA7) = 5.22, χ(2)(MTDH) = 5.00; P < 0.05), cases with metastasis of lymph node (χ(2)(EphA7) = 5.15, χ(2)(MTDH) = 5.86; P < 0.05) and cases with invasiveness of regional tissues (χ(2)(EphA7) = 7.06, P < 0.01; χ(2)(MTDH) = 4.13; P < 0.05) in gallbladder adenocarcinoma (P < 0.05). The high consistency was found between the expressive levels of EphA7 and MTDH in gallbladder adenocarcinoma (χ(2) = 13.11, P < 0.01). The univariate Kaplan-Meier analysis showed that the increased expression of EphA7 (P = 0.023) and MTDH (P = 0.034) was negatively associated with the overall survival. The multivariate Cox regression analysis showed that increased expression of EphA7 and/or MTDH (P(EphA2) = 0.023, P(MTDH) = 0.034) was an independent poor-prognostic predictor for gallbladder adenocarcinoma. CONCLUSIONS: The expression of EphA7 and/or MTDH might be closely related to the carcinogenesis, progression, clinical biological behaviors and prognosis of gallbladder adenocarcinoma. The positive expression of EphA7 and/or MTDH may predict bad-prognosis in gallbladder adenocarcinoma.

[The substantiation of UDCA usage in functional disorders of biliary tract].

Ursodeoxycholic acid (UDCA) has been widely used in clinical practice, more frequently in liver diseases treatment. Studies have shown that UDCA has choleretic and cholecyst-kinetic effects. In this paper we give pathogenetic substantiation of UDCA use in the gall bladder dysfunction, hypotension, and identified in clinical usage of UDCA in hypokinesia of the gallbladder.

Cytokeratin expression as an aid to diagnosis in medical liver biopsies.

The study of cytokeratin expression has provided a valuable insight into the biliary microanatomy of the liver in health and disease. The canals of Hering are a putative site of origin for progenitor cells, which may repopulate the liver after cellular damage and loss. Normal bile ducts and the bile ductular reaction that occurs in many chronic liver diseases - especially chronic biliary tract disease - express cytokeratin (CK) 7 and CK19. Therefore, both ductopenia and the process of bile ductular reaction can be highlighted with immunohistochemistry for these cytokeratins. Furthermore, CK7 is usually expressed in an increasingly widespread manner by hepatocytes as chronic cholestatic liver disease progresses. For these reasons, CK immunohistochemistry is a very useful adjunct to morphological assessment and histochemical stains for copper retention when a diagnosis of chronic biliary disease is being considered. This review describes the anatomical theory behind the use of CK immunohistochemistry for the assessment of bile duct number and distribution in the liver and provides practical advice for the application of this technique in the diagnostic setting of common medical liver diseases.

Endoscopically obtained bile aspirate is an accurate adjunct in the diagnosis of symptomatic gallbladder disease.

OBJECTIVES: The experience of a single surgeon in a rural hospital over a 10-year period was analyzed with respect to the utilization of endoscopically obtained bile aspirates as an adjunct in the diagnosis of symptomatic gallbladder disease. METHODS: A retrospective study of the author's entire cholecystectomy experience over a 10-year period with 641 patients was conducted to evaluate the utility of the bile aspirate in the preoperative selection of operative candidates and with respect to the ultimate pathologic diagnostic accuracy of the test. RESULTS: Derivation of preoperative diagnosis via traditional standard means was possible in 479 patients. An endoscopically obtained positive bile aspirate was found in 162 additional patients who failed to have positive traditional diagnostic studies (acalculous gallbladder disease). Micro-pathology was determined to be present in 603 patients (94.07%). In 27 of the 38 negatives, there had been positive radiological studies (71%). In 11 of the 38, a positive preoperative bile aspirate had been obtained (28.9%). Of the 162 patients with a positive bile aspirate, 151 (93.21%) of the gallbladder specimens had confirmatory histologic analysis (92.1% confidence interval ± 3.95%). CONCLUSION: In patients with symptoms suggestive of clinical gallbladder disease and negative traditional diagnostic studies, the endoscopically obtained bile aspirate has been shown to be a highly reliable tool in establishing the diagnosis and is recommended as an aid in the appropriate selection of candidates who may benefit from cholecystectomy.

Physical Activity Modulating Lipid Metabolism in Gallbladder Diseases.

Physical activity encompasses a series of overall benefits on cardiovascular health and metabolic disorders. Research has recently focused on the hepatobiliary tract, as an additional target of the health-related outcomes of different types of physical exercise. Here, we focus on the global features of physical activity with respect to exercise modality and intensity, and on studies linking physical activity to lipid metabolism, gallbladder diseases (gallstones, symptoms, complications and health-related quality of life), gallbladder motor-function, enterohepatic circulation of bile acids, and systemic metabolic inflammation. Additional studies need to unravel the pathophysiological mechanisms involved in both beneficial and harmful effects of physical activity in populations with different metabolic conditions.

Non-neoplastic Polyps of the Gallbladder: A Clinicopathologic Analysis of 447 Cases.

There is no systematic histopathologic analysis of non-neoplastic polyps in the gallbladder. In this study, in addition to a computer search for cases designated as "polyp," a systematic review of 2533 consecutive routinely sampled archival and 203 totally submitted prospective cholecystectomies were analyzed for >2 mm polyps (cut-off was based on radiologic sensitivity). A total of 447 non-neoplastic polyps were identified. The frequency was 3% in archival cases and 5% in totally submitted cases. Only 21 (5%) were ≥1 cm. The average age was 52 years, and the female to male ratio was 3.1. Two distinct categories were delineated: (1) injury-related polyps (n=273): (a) Fibro(myo)glandular polyps (n=214) were small (mean=0.4 cm), broad-based, often multiple (45%), almost always (98%) gallstone-associated, and were composed of a mixture of (myo)fibroblastic tissue/lobular glandular units with chronic cholecystitis. Dysplasia seen in 9% seemed to be secondary involvement. (b) Metaplastic pyloric glands forming polypoid collections (n=42). (c) Inflammatory-type polyps associated with acute/subacute injury (11 granulation tissue, 3 xanthogranulomatous, 3 lymphoid). (2) Cholesterol polyps (n=174) occurred in uninjured gallbladders, revealing a very thin stalk, edematous cores devoid of glands but with cholesterol-laden macrophages in 85%, and cholesterolosis in the uninvolved mucosa in 60%. Focal low-grade dysplasia was seen in 3%, always confined to the polyp, unaccompanied by carcinoma. In conclusion, non-neoplastic polyps are seen in 3% of cholecystectomies and are often small. Injury-related fibromyoglandular polyps are the most common. Cholesterol polyps have distinctive cauliflower architecture, often in a background of uninjured gallbladders with cholesterolosis and may lack the cholesterol-laden macrophages in the polyp itself. Although dysplastic changes can involve non-neoplastic polyps, they do not seem to be the cause of invasive carcinoma by themselves.

Fragile histidine triad (FHIT) gene and its association with p53 protein expression in the progression of gall bladder cancer.

OBJECTIVE: Present study deals with LOH and MSI in FHIT gene and p53 expression in GBC, CC, XGC, and normal GB to elucidate the role of FHIT gene in gall bladder cancer. METHODS: Five microsatellite markers D3S1217, D3S1300, D3S1313, D3S1600, and D3S2757, were selected. RESULTS: Among GBC cases the frequency of MSI-H and LOH was 17.5% and 27.5%, respectively. Significant difference was found between GBC and normal GB (p = .02), and GBC and CC groups (p= .002) when LOH was compared. CONCLUSIONS: Our results suggested CC might act as a preinvasive stage in the pathogenesis of GBC.

Solid state (13)C NMR analysis of human gallstones from cancer and benign gall bladder diseases.

Natural abundance (13)C cross polarized (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) analysis of human gall bladder stones collected from patients suffering from malignant and benign gall bladder disease was carried out which revealed different polymorphs of cholesterol in these stones. All gall bladder stones in present study had cholesterol as their main constituent. (13)C CP-MAS NMR analysis revealed three forms of cholesterol molecules in these stones, which are anhydrous form, monohydrate crystalline with amorphous form and monohydrate crystalline form. Our study revealed that stones collected from patients associated with chronic cholecystitis (CC) disease have mostly different polymorph of cholesterol than stones collected from patients associated with gall bladder cancer (GBC). Such study will be helpful in understanding the mechanism of formation of gallstones which are associated with different gall bladder diseases. This is the first study by solid state NMR revealing different crystal polymorphism of cholesterol in human gallstones, extending the applicability of (13)C CP-MAS NMR technique for the routine study of gallstones.

[Efficiency of ursotherapy in cholesterol-associated pathology of the gallbladder].

AIM: To assess of lipid disorders nature in holesterin associated pathology of biliary tract and determine the hypercholesterolemia effect on the effectiveness of ursotherapy at biliary sludge of cholesterol genesis, cholesterol cholicyststoliteasis and polypous form of cholesterosis gallbladder. MATERIAL AND METHODS: We included 450 patients with pathology holesterinassociated pathology of biliary tract: 100 - with biliary sludge (BS), 200 - with cholicyststoliteasis (CL), 150 - with polypous form of cholesterosis gallbladder (CGB). All patients evaluated the levels of common cholesterol (CC), HDL cholesterol and LDL cholesterol in serum. 52 patients with BS, 128 patients with HL and 81 patients with CGB was identified dynamics of these indicators after 3-month course of Ursodeoxycholic acid (UDCA) treatment. To assess the influence of hypercholesterolemia on the effectiveness of litholytic therapy 180 patients with BS, CL, and HZHP were divided into 3 groups of 60 patients in each (30 with normocholesterolemia and 30 - with hypercholesterolemia). UDCA was administered at a dose of 10 mg/kg body weight once at night. Monitoring the clearance of RBCs, dissolution of gallstones and cholesterol polyps performed using ultrasound every 3 months. RESULTS: Hypercholesterolemia was detected in 57,5% of cases (in 259 out of 450 patients). After 3-month course of UDCA therapy marked positive trend: the reduction of total cholesterol to normal rates depending on the holesterinassociated type of pathology was found in 50.6 - 63.5%. This UDCA had the greatest effect at the level of cholesterol in the blood serum ranging from 5.3 to 6.6 mmol/I, where the decline in total cholesterol was back to normal in the majority of patients. Cholesterol is a factor that reduces the effectiveness of UDCA. Thus, the frequency of complete elimination of BS in normocholesterolemia was 96.7%, while for hypercholesterolemia it was 70% (p <0.05). A similar trend continued in other groups of patients with holesterinassociated pathology of biliary tract. CONCLUSION: In the absence of risk factors for cardiovascular disease in patients with holesterinassociated pathology of biliary tract, accompanied by expressed hypercholesterolemia, ursotherapy allows lipid corrective effect without the statins use.