The purpose of this study was to determine whether regular exercise (treadmill running, 10 wk) alters the susceptibility of rat isolated heart mitochondria to Ca(2+)-induced permeability transition pore (PTP) opening and whether this could be associated with changes in the modulation of PTP opening by selected physiological effectors. Basal leak-driven and ADP-stimulated respiration in the presence of substrates for complex I, II, and IV were not affected by training. Fluorimetric studies revealed that in the control and exercise-trained groups, the amount of Ca(2+) required to trigger PTP opening was greater in the presence of complex II vs. I substrates (230 +/- 12 vs. 134 +/- 7 nmol Ca(2+)/mg protein, P < 0.01; pooled average of control and trained groups). In addition, with a substrate feeding the complex II, training increased by 45% (P < 0.01) the amount of Ca(2+) required to trigger PTP opening both in the presence and absence of the PTP inhibitor cyclosporin A. However, membrane potential, reactive oxygen species production, NAD(P)H ratio, and Ca(2+) uptake kinetics were not different in mitochondria from both groups. Together, these results suggest the existence of a substrate-specific regulation of the PTP in heart mitochondria and suggest that regular exercise results in a reduced sensitivity to Ca(2+)-induced PTP opening in presence of complex II substrates.
Opening of the mitochondrial permeability transition pore (PTP) is known to occur during reperfusion of the ischemic heart and to cause dysfunction and injury. The purpose of the present study was to determine whether short-term training (treadmill dunning for 5 days, 30 m.min(-1), 0%) in male Sprague Dawley rats reduces the occurrence of PTP opening in the ischemic-reperfused heart. Hearts from control (C) and trained (T) rats perfused in the Langendorff mode were submitted to ischemia-reperfusion (I-R: 30 and 40 min respectively). In situ PTP opening was quantified using the mitochondrial 2-deoxy [(3)H]glucose ([(3)H]DOG) entrapment method. Following I-R, the recovery of intact mitochondria upon isolation was significantly greater in T vs C hearts (11.7 +/- 0.5 vs 9.1 +/- 0.4 mU citrate synthase.g(-1) wet ventricles, p < or = 0.01). Training also reduced the entrapment of mitochondrial [(3)H]DOG normalized for the loss of intact mitochondria (14.4 +/- 1.4 vs 9.6 +/- 0.8 [(3)H]DOG ratio units, p < or = 0.01). However, under the experimental conditions used the recovery of contractile function, coronary flow and release of LDH in the coronary effluent were similar in both experimental groups. Taken together, these results suggest that short-term training can confer mitochondrial protection and reduce PTP opening.
Background
Diabetic foot infections are frequent and associated with substantial morbidity and substantial cost to the healthcare system. Up to 34% of diabetic patients will develop an ulcer potentially leading to osteomyelitis. Imaging plays a crucial role in the diagnostic process. Imaging modalities to investigate the diabetic foot infection are many and imaging prescription habits remain heterogeneous across physicians. We aimed to improve the appropriateness of imaging examination requested, and performed, for diabetic foot osteomyelitis and we aimed to reduce the overall imaging-related cost.
Methods
Local committee was created to develop an algorithm for suspected diabetic foot osteomyelitis. Best practices were defined by the local algorithm. The algorithm was shared with our physicians. Pre- and post-intervention analysis was conducted retrospectively. All adult diabetic patients with suspected foot osteomyelitis were included. Adherence to best practices was measured. Statistical analysis with Chi-Square and two tailed unpaired t-test was performed.
Results
Pre-intervention cohort had 223 patients (mean age: 63; 168 men). Adherence to best practice was 43%. Scintigraphy (48%) preferred over MRI (44%) and performed simultaneously in 15 patients. Post-intervention cohort had 73 patients (mean age: 66; 62 men). Adherence to best practice was 78%, improved by 35% (p < 0.001). MRI (51%) preferred over scintigraphy (23%) and performed simultaneously in three patients. Scintigraphy examinations decreased by 25% (p < 0.001). MRI examinations increased by 7% (p = 0.32). Hospital imaging related fees decreased by 22% per patient (p = 0.002).
Conclusion
Interval improvement in adequate adherence while reducing unnecessary examinations for patients and decreasing costs for the healthcare system was observed.
The PREE-Fr should be considered in French speaking populations for patients with elbow pathology, whether it is for research or evaluation purposes as it is valid, reliable and responsive to change.
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