High rising flames: a sign of complex extraperitoneal bladder rupture.

Extraperitoneal bladder rupture is the most common type of bladder injury following pelvic trauma and is seen in 80-90% of cases. Generally, the contrast extravasation seen on computed tomography (CT) cystography is confined to the perivesical space, giving a characteristic flame-shaped appearance. Occasionally contrast extravasation can extend to the scrotum, thigh or anterior abdominal wall, depending on the extent of injury. Here we report an unusual CT cystogram finding of complex extraperitoneal bladder rupture with associated pelvic fracture urethral distraction defect, showing large-volume contrast extravasation extending beyond the perivesical space to the left perinephric region resembling high rising flames.

High rising flames: a sign of complex extraperitoneal bladder rupture.

Extraperitoneal bladder rupture is the most common type of bladder injury following pelvic trauma and is seen in 80-90% of cases. Generally, the contrast extravasation seen on computed tomography (CT) cystography is confined to the perivesical space, giving a characteristic flame-shaped appearance. Occasionally contrast extravasation can extend to the scrotum, thigh or anterior abdominal wall, depending on the extent of injury. Here we report an unusual CT cystogram finding of complex extraperitoneal bladder rupture with associated pelvic fracture urethral distraction defect, showing large-volume contrast extravasation extending beyond the perivesical space to the left perinephric region resembling high rising flames.

Chronic ethanol consumption increases myocardial mitochondrial DNA mutations: a potential contribution by mitochondrial topoisomerases.

AIMS: Alcoholic cardiomyopathy (ACM) presents as decreased myocardial contractility, arrhythmias and secondary non-ischemic dilated cardiomyopathy leading to heart failure. Mitochondrial dysfunction is known to have a significant role in the development and complications of ACM. This study investigated if chronic ethanol feeding promoted myocardial mitochondrial topoisomerase dysfunction as one underlying cause of mitochondrial DNA (mtDNA) damage and mitochondrial dysfunction in ACM. METHODS: The impact of chronic ethanol exposure on the myocardial mitochondria was examined in both neonatal cardiomyocytes using 50 mM ethanol for 6 days and in rats assigned to control or ethanol feeding groups for 4 months. RESULTS: Chronic ethanol feeding led to significant (P < 0.05) decreases in M-mode Fractional Shortening, ejection fraction, and the cardiac output index as well as increases in Tau. Ethanol feeding promoted mitochondrial dysfunction as evidenced by significantly decreased left ventricle cytochrome oxidase activity and decreases in mitochondrial protein content. Both in rats and in cultured cardiomyocytes, chronic ethanol presentation significantly increased mtDNA damage. Using isolated myocardial mitochondria, both mitochondrial topoisomerase-dependent DNA cleavage and DNA relaxation were significantly altered by ethanol feeding. CONCLUSION: Chronic ethanol feeding compromised cardiovascular and mitochondrial function as a result of a decline in mtDNA integrity that was in part the consequence of mitochondrial topoisomerase dysfunction. Understanding the regulation of the mitochondrial topoisomerases is critical for protection of mtDNA, not only for the management of alcoholic cardiomyopathy, but also for the many other clinical treatments that targets the topoisomerases in the alcoholic patient.

Type II diabetes increases mitochondrial DNA mutations in the left ventricle of the Goto-Kakizaki diabetic rat.

Mitochondrial dysfunction has a significant role in the development of diabetic cardiomyopathy. Mitochondrial oxidant stress has been accepted as the singular cause of mitochondrial DNA (mtDNA) damage as an underlying cause of mitochondrial dysfunction. However, separate from a direct effect on mtDNA integrity, diabetic-induced increases in oxidant stress alter mitochondrial topoisomerase function to propagate mtDNA mutations as a contributor to mitochondrial dysfunction. Both glucose-challenged neonatal cardiomyocytes and the diabetic Goto-Kakizaki (GK) rat were studied. In both the GK left ventricle (LV) and in cardiomyocytes, chronically elevated glucose presentation induced a significant increase in mtDNA damage that was accompanied by decreased mitochondrial function. TTGE analysis revealed a number of base pair substitutions in the 3' end of COX3 from GK LV mtDNA that significantly altered the protein sequence. Mitochondrial topoisomerase DNA cleavage activity in isolated mitochondria was significantly increased in the GK LV compared with Wistar controls. Both hydroxycamptothecin, a topoisomerase type 1 inhibitor, and doxorubicin, a topoisomerase type 2 inhibitor, significantly exacerbated the DNA cleavage activity of isolated mitochondrial extracts indicating the presence of multiple functional topoisomerases in the mitochondria. Mitochondrial topoisomerase function was significantly altered in the presence of H2O2 suggesting that separate from a direct effect on mtDNA, oxidant stress mediated type II diabetes-induced alterations of mitochondrial topoisomerase function. These findings are significant in that the activation/inhibition state of the mitochondrial topoisomerases will have important consequences for mtDNA integrity and the well being of the diabetic myocardium.