We determined the sensitivity of computed tomography and color duplex ultrasonography in the detection and characterization of vascular complications in acute pancreatitis. The relationship of these complications with the etiology and activity of the disease was assessed. In a prospective study, 189 patients with acute pancreatitis seen in the Department of Gastroenterology. Charité Hospital in Berlin over a period of 38 months underwent color duplex ultrasonography every second day for 3 weeks and thereafter at least once a week for 2 months. Dynamic computed tomography was performed within 72 hours after admission, and follow-up computed tomography scans were obtained. In 45 patients (23%), at least temporary thromboses of portal venous vessels were demonstrated by color duplex ultrasonography. The incidence of venous thromboses was 30% in severe acute pancreatitis with fluid collections without necroses and 57% in necrotizing pancreatitis. In 27 of those 45 patients, a formation of collaterals was documented. In 13 patients, arterial pseudoaneurysms were demonstrated. Vascular complications were significantly more frequent in alcohol-induced than in gallstone-induced pancreatitis. Only 62% of all sonographically diagnosed thromboses and only 32% of all collaterals were demonstrated by computed tomography. The prevalence of vascular complications in acute pancreatitis was much higher as suspected. The risk of gastrointestinal bleeding was lower than previously reported. Color duplex sonography is the method of choice for the detection of vascular complications in acute pancreatitis.

Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice.

Doxorubicin-induced nephropathy in mice is a model for studying experimental nephrotic syndrome. It corresponds to puromycin aminonucleoside nephrosis in rats. In this model, susceptible 129 S1/SvImJ mice are administered a rapid intravenous injection that can be accomplished via either the lateral tail vein or the retrobulbar sinus. Because doxorubicin is a highly toxic substance, extravasation must be avoided during the administration of the intravenous injection to prevent the development of large necrotizing lesions and exacerbation of the animals’ stress. In the present study, we compared the safety and stress of these two injection routes by using histopathological analyses of the animals’ orbital cavities or tails, respectively. The injection of 14.5 µg/g body weight doxorubicin into the mice’s lateral tail veins ( n = 9) or retrobulbar sinuses ( n = 19) caused no clinically detectable stress or impairment. Histopathologies of the specimens five days after doxorubicin injection revealed inflammatory lesions at the injection sites in both groups. In the orbital sinus specimens from the retrobulbar-injected group, fibrosis was evident 25 days after injection. Moreover, while all of the retrobulbar-injected mice (100%) developed nephrotic syndrome, tail vein-injected mice had a significantly lower response rate (66%, p = 0.047, Fisher’s exact test) and exhibited only attenuated features of nephrotic syndrome. It was therefore concluded that doxorubicin administration via either lateral tail vein or retrobulbar sinus injections led to a similar induction of histopathological changes with no effects on the clinical well-being of the mice. However, retrobulbar sinus injections were more efficient for inducing experimental nephrotic syndrome.

Susceptibility to doxorubicin-induced nephropathy (DIN), a toxic model for the induction of proteinurie in mice, is related to the single nucleotide polymorphism (SNP) C6418T of the prkdc gene encoding for the DNA repair enzyme DNA-PKcs. In addition, plasminogen (plg) has been reported to play a role in glomerular damage. Here, we investigated the interdependence of both factors for the development of DIN. Genotyping confirmed the SNP of the prkdc gene in C57BL/6 (prkdcC6418/C6418) and 129S1/SvImJ (prkdcT6418/T6418) mice. Intercross of heterozygous 129SB6F1 mice led to 129SB6F2 hybrids with Mendelian inheritance of the SNP. After doxorubicin injection, only homozygous F2 mice with prkdcT6418/T6418 developed proteinuria. Genetic deficiency of plg (plg−/-) in otherwise susceptible 129S1/SvImJ mice led to resistance to DIN. Immunohistochemistry revealed glomerular binding of plg in plg+/+ mice after doxorubicin injection involving histone H2B as plg receptor. In doxorubicin resistant C57BL/6 mice, plg binding was absent. In conclusion, susceptibility to DIN in 129S1/SvImJ mice is determined by a hierarchical two hit process requiring the C6418T SNP in the prdkc gene and subsequent glomerular binding of plasminogen.