BackgroundAberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice.ResultsWe show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II–III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria.ConclusionsWe conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12858-015-0051-8) contains supplementary material, which is available to authorized users.
Objectives:To evaluate the efficacy of transanal irrigation (TAI) in pediatric patients with neurogenic bowel dysfunction (NBD) who were treatment naïve to catheter-based TAI using Peristeen device (Coloplast).Methods:Prospective recruitment of patients with NBD who were unsatisfied with their bowel regimen or had no bowel regimen in place, were assessed using the neurogenic bowel dysfunction score (NBDS) before initiating treatment (Time 0) with Peristeen. NBDS scores were reassessed twice: within the first 6 months (Time 1) of initiation of Peristeen and again after greater than 6 months of usage with Peristeen (Time 2).Results:Over a 26-month period, 104 patients with NBD were enrolled. Mean age was 10.6 years ± 4.7 (range 3–18 years). The NBDS at Time 1 had an average reduction of 14 points from the original score. A similar trajectory was seen at Time 2, with an average reduction of 13 points from original score. There was a statistically significant decrease of 14 points, P < 0.001 at Time 1 and this response was sustained at Time 2 with a statistically significant decrease in scores from initiation by 13 points, P < 0.001. Improved patient satisfaction and quality of life with Peristeen was seen at Time 1 and Time 2.Conclusion:Our results suggest that Peristeen can improve quality of life in pediatric patients with NBD. Significant improvement in NBDS occurred in our pediatric patients with NBD when initiated on Peristeen. Lower scores were seen at both Time 1 and Time 2, which indicated an improvement in their overall NBD.
A 16-year-old African American girl presented after a presyncopal event. Initial evaluation revealed anemia (hemoglobin 5.2 mmol/L) and positive stool hemoccult. Esophagogastroduodenoscopy revealed an ulcerated, bleeding, submucosal mass (Fig. 1). Bleeding was controlled with argon plasma coagulation. Abdominal computed tomography showed a heterogenous 6.8 cm mass at the serosal surface of the lesser curvature. Neck and thorax computed tomography did not show metastases. Endoscopic ultrasound with fine needle biopsy (Fig. 2) revealed histology consistent with a gastrointestinal stromal tumor (GIST). Laparotomy was performed with complete resection of the mass. Pediatric GISTs are rare and they account for about 1% of all GISTs (1). When suspected, endoscopic biopsy, either core needle or forceps biopsy, is the preferred method to prevent tumor spillage which is highly associated with GIST recurrence (2). Pediatric GISTs usually lack KIT or PDGFRA gene mutations, making them wild-type GISTs (3). In this case, genetic testing revealed associations with hereditary paraganglioma-pheochromocytoma syndromes (4). Prognosis is based on the mitotic rate, tumor size, and tumor site; gastric site being the most favorable (5). MRI after surgery showed no residual tumor. The patient will continue close monitoring via annual MRI, which is the preferred modality for surveillance (6).
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