With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy’s beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally.

Background: Acute cholecystitis is one of the most common acute diseases of the biliary system and a frequent reason for emergency hospital admission and surgical treatment. More severe forms are associated with a higher need for intensive care, more frequent use of open surgery, and less favourable outcomes. Age and chronic comorbidity burden may play an important role in determining disease severity. The age-adjusted Charlson Comorbidity Index (CCI-Age) is a simple and widely used tool for integrated assessment of age and comorbidity burden, but its role in acute cholecystitis is not sufficiently defined. Methods: Data for this study were collected by retrospective analysis of hospital records from the hospital information system of the University Hospital Centre Zagreb. Patients treated conservatively were excluded. The association of age and CCI-Age with the severity of the clinical presentation of acute cholecystitis was analysed using dichotomised clinical variables and comparative statistical methods. Results: The results showed that age and the presence of chronic diseases were strongly associated with the severity of the clinical presentation of acute cholecystitis. Older patients and those with a greater burden of chronic comorbidities significantly more often developed more severe forms of the disease. Among chronic diseases, peripheral vascular disease, diabetes mellitus, and chronic renal disease showed the strongest association with more severe clinical presentation. Conclusions: Age and CCI-Age were strongly associated with the severity of the clinical presentation of acute cholecystitis. CCI-Age may represent a useful tool for early clinical risk stratification and support therapeutic decision making in everyday surgical practice.

Cytoprotection provides a conceptual framework for the preservation and restoration of tissue integrity under conditions of noxious injury. In liver disease, however, effective protection may require more than direct limitation of hepatocellular damage, encompassing endothelial function, microcirculation, vascular homeostasis, oxidative stress, inflammation, fibrosis, and portal hemodynamics. This review examines possibilities for cytoprotective liver therapy, with particular emphasis on stable gastric pentadecapeptide BPC 157 and comparison with established or experimentally investigated agents, including N-acetylcysteine, ursodeoxycholic acid, corticosteroids, resveratrol, L-arginine, curcumin, sildenafil, VEGF-related approaches, stem cell therapies, melatonin, simvastatin, prostacyclin analogues, and coenzyme Q10. Evidence is considered across representative experimental models of acetaminophen and carbon tetrachloride hepatotoxicity, bile duct ligation, and alcohol-induced liver injury. The diversity of effective agents indicates that liver injury involves multiple interconnected pathological mechanisms and that preservation of hepatocellular integrity may be achieved through different pharmacological pathways. BPC 157 is distinguished by evidence of beneficial effects across these major models and additional vascular and occlusion/occlusion-like syndromes. In particular, reported findings indicate prevention and reversal of experimentally induced portal hypertension, including prehepatic, intrahepatic, and posthepatic disturbances, together with attenuation of hepatic congestion, thrombosis, oxidative injury, and associated multiorgan dysfunction. These findings support the concept that cytoprotection may extend from hepatoprotection to restoration of vascular and tissue homeostasis. Collectively, the available preclinical evidence supports further investigation of integrated cytoprotective strategies for liver injury. Nevertheless, experimental evidence, however extensive, does not establish clinical efficacy, and appropriately designed clinical studies remain necessary to determine therapeutic applicability in human liver disease.