Nejvíce citovaný článek - PubMed ID 10597755
Gallbladder atrophy (GBA) is characterised by a reduction in the size and volume of the gallbladder. In human medicine, it is well-established that GBA frequently occurs together with pathologies affecting the gallbladder and pancreas. However, to the best of our knowledge, there is currently a dearth of reported cases of GBA in dogs within the veterinary field. In this study, we present a case report of GBA in a 7-year-old Yorkshire Terrier. The diagnosis of GBA was confirmed using abdominal ultrasonography and advanced imaging techniques, including computed tomography, which were performed over a 4-year period. The patient initially presented with predominantly gastrointestinal symptoms, which were subsequently diagnosed and treated as pancreatitis. Concurrently, a gallbladder nodule and an anomalous structure suspected to be cholelithiasis were identified. However, during the 4-year follow-up, the gallbladder structure regressed, leaving only the presence of the gallbladder nodule. Notably, cholecystectomy was not performed, and apart from pancreatitis-related symptoms, the patient did not show any gallbladder-related problems throughout the spontaneous atrophic process. Based on these findings, we propose that the observed GBA was likely induced by cholecystitis associated with pancreatitis. This case underscores the significance of considering GBA as a potential diagnosis in canine patients presenting with pancreatitis and gastrointestinal symptoms. Furthermore, it highlights the value of comprehensive diagnostic imaging in accurately determining the underlying cause of these symptoms.
- Klíčová slova
- cholecystitis, cholelithiasis, computed tomography, gastroinetstinal symptom, nodule,
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs' properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.
- Klíčová slova
- ASBT, IBABP, MDR, MRP, NTCP, OATP, bile acid, bile salt, drug delivery, enterohepatic circulation, transport protein,
- MeSH
- enterohepatická cirkulace * MeSH
- játra metabolismus MeSH
- transportní proteiny metabolismus MeSH
- žlučové cesty MeSH
- žlučové kyseliny a soli * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- transportní proteiny MeSH
- žlučové kyseliny a soli * MeSH
BACKGROUND AND AIMS: Automated chyme reinfusion (CR) in patients with intestinal failure (IF) and a temporary double enterostomy (TDE) restores intestinal function and protects against liver injury, but the mechanisms are incompletely understood. The aim was to investigate whether the beneficial effects of CR relate to functional recovery of enterohepatic signaling through the bile salt-FGF19 axis. APPROACH AND RESULTS: Blood samples were collected from 12 patients, 3 days before, at start, and 1, 3, 5, and 7 weeks after CR initiation. Plasma FGF19, total bile salts (TBS), 7-α-hydroxy-4-cholesten-3-one (C4; a marker of bile salt synthesis), citrulline (CIT), bile salt composition, liver tests, and nutritional risk indices were determined. Paired small bowel biopsies prior to CR and after 21 days were taken, and genes related to bile salt homeostasis and enterocyte function were assessed. CR induced an increase in plasma FGF19 and decreased C4 levels, indicating restored regulation of bile salt synthesis through endocrine FGF19 action. TBS remained unaltered during CR. Intestinal farnesoid X receptor was up-regulated after 21 days of CR. Secondary and deconjugated bile salt fractions were increased after CR, reflecting restored microbial metabolism of host bile salts. Furthermore, CIT and albumin levels gradually rose after CR, while abnormal serum liver tests normalized after CR, indicating restored intestinal function, improved nutritional status, and amelioration of liver injury. CR increased gene transcripts related to enterocyte number, carbohydrate handling, and bile salt homeostasis. Finally, the reciprocal FGF19/C4 response after 7 days predicted the plasma CIT time course. CONCLUSIONS: CR in patients with IF-TDE restored bile salt-FGF19 signaling and improved gut-liver function. Beneficial effects of CR are partly mediated by recovery of the bile salt-FGF19 axis and subsequent homeostatic regulation of bile salt synthesis.
- MeSH
- anastomóza chirurgická škodlivé účinky MeSH
- enterální výživa metody MeSH
- enterostomie škodlivé účinky MeSH
- fibroblastové růstové faktory krev metabolismus MeSH
- gastrointestinální obsah * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nutriční stav MeSH
- prospektivní studie MeSH
- selhání střeva krev etiologie metabolismus terapie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- žlučové kyseliny a soli krev metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
- Názvy látek
- FGF19 protein, human MeSH Prohlížeč
- fibroblastové růstové faktory MeSH
- žlučové kyseliny a soli MeSH
Moving from macroscale preparative systems in proteomics to micro- and nanotechnologies offers researchers the ability to deeply profile smaller numbers of cells that are more likely to be encountered in clinical settings. Herein a recently developed microscale proteomic method, microdroplet processing in one pot for trace samples (microPOTS), was employed to identify proteomic changes in ∼200 Barrett's esophageal cells following physiologic and radiation stress exposure. From this small population of cells, microPOTS confidently identified >1500 protein groups, and achieved a high reproducibility with a Pearson's correlation coefficient value of R > 0.9 and over 50% protein overlap from replicates. A Barrett's cell line model treated with either lithocholic acid (LCA) or X-ray had 21 (e.g., ASNS, RALY, FAM120A, UBE2M, IDH1, ESD) and 32 (e.g., GLUL, CALU, SH3BGRL3, S100A9, FKBP3, AGR2) overexpressed proteins, respectively, compared to the untreated set. These results demonstrate the ability of microPOTS to routinely identify and quantify differentially expressed proteins from limited numbers of cells.
- Klíčová slova
- Barrett’s esophagus, X-ray, lithocholic acid, microPOTS, proteomics,
- MeSH
- Barrettův syndrom * genetika MeSH
- buněčné linie MeSH
- heterogenní jaderné ribonukleoproteiny skupiny C MeSH
- lidé MeSH
- mukoproteiny MeSH
- nádory jícnu * MeSH
- onkogenní proteiny MeSH
- proteiny vázající takrolimus MeSH
- proteomika MeSH
- reprodukovatelnost výsledků MeSH
- ubikvitin konjugující enzymy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AGR2 protein, human MeSH Prohlížeč
- FKBP3 protein, human MeSH Prohlížeč
- heterogenní jaderné ribonukleoproteiny skupiny C MeSH
- mukoproteiny MeSH
- onkogenní proteiny MeSH
- proteiny vázající takrolimus MeSH
- RALY protein, human MeSH Prohlížeč
- UBE2M protein, human MeSH Prohlížeč
- ubikvitin konjugující enzymy MeSH
BACKGROUND: Bile salts likely contribute to liver injury in patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Fibroblast growth factor 19 (FGF19) is a bile salt-induced enterokine with hepatoprotective potential as it suppresses de novo bile salt synthesis. Here, we evaluated the bile salt receptor FXR/FGF19 gut-liver axis in PSC and PBC patients. METHODS: Fasted patients with PSC (n = 12) and PBC (n = 10), and healthy controls (HC; n = 10) were orally challenged with the natural FXR agonist chenodeoxycholic acid (CDCA 15 mg/kg). Blood was sampled hourly until 8 h afterwards. Serum FGF19 and bile salt excursions were determined. Serum levels of 7α-hydroxy-4-cholesten-3-one (C4), reflecting bile salt synthesis, were measured as a biomarker of FGF19 response. RESULTS: Baseline serum FGF19 levels were comparable between groups, while fasted bile salt levels in PSC patients were elevated. Upon CDCA challenge, HC and PBC patients showed a serum FGF19 peak after 4 h followed by a decline. PSC patients showed a prolonged and elevated serum FGF19 response up to 8 h, combined with a sustained serum elevation of CDCA and other bile salts. In general, C4 levels declined following FGF19 elevation. In PSC patients with less favorable prognosis, baseline C4 levels were drastically suppressed and did not further decline. CONCLUSION: Following an oral CDCA challenge, PSC patients showed an impaired clearance of CDCA and a prolonged serum FGF19 response. FXR agonist therapy in PSC could cause prolonged exposure to elevated levels of FGF19, and we propose careful monitoring for detrimental side effects in patient studies.
- Klíčová slova
- Chenodeoxycholic acid, Farnesoid X receptor, Fibroblast growth factor 19, Primary sclerosing cholangitis,
- MeSH
- aplikace orální MeSH
- cholestenony krev MeSH
- dospělí MeSH
- fibroblastové růstové faktory krev metabolismus MeSH
- játra metabolismus MeSH
- klinické protokoly MeSH
- kyselina chenodeoxycholová aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- purgativa aplikace a dávkování MeSH
- senioři MeSH
- sklerozující cholangitida krev farmakoterapie metabolismus MeSH
- střevní sliznice metabolismus MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 7 alpha-hydroxy-4-cholesten-3-one MeSH Prohlížeč
- cholestenony MeSH
- FGF19 protein, human MeSH Prohlížeč
- fibroblastové růstové faktory MeSH
- kyselina chenodeoxycholová MeSH
- purgativa MeSH
