Metformin and thiazolidinediones (TZDs) are believed to exert their antidiabetic effects via different mechanisms. As evidence suggests that both impair cell respiration in vitro, this study compared their effects on mitochondrial functions. The activity of complex I of the respiratory chain, which is known to be affected by metformin, was measured in tissue homogenates that contained disrupted mitochondria. In homogenates of skeletal muscle, metformin and TZDs reduced the activity of complex I (30 mmol/l metformin, ؊15 ؎ 2%; 100 mol/l rosiglitazone, ؊54 ؎ 7; and 100 mol/l pioglitazone, ؊12 ؎ 4; P < 0.05 each). Inhibition of complex I was confirmed by reduced state 3 respiration of isolated mitochondria consuming glutamate ؉ malate as substrates for complex I (30 mmol/l metformin, ؊77 ؎ 1%; 100 mol/l rosiglitazone, ؊24 ؎ 4; and 100 mol/l pioglitazone, ؊18 ؎ 5; P < 0.05 each), whereas respiration with succinate feeding into complex II was unaffected. In line with inhibition of complex I, 24-h exposure of isolated rat soleus muscle to metformin or TZDs reduced cell respiration and increased anaerobic glycolysis (glucose oxidation: 270 mol/l metformin, ؊30 ؎ 9%; 9 mol/l rosiglitazone, ؊25 ؎ 8; and 9 mol/l pioglitazone, ؊45 ؎ 3; lactate release: 270 mol/l metformin, ؉84 ؎ 12; 9 mol/l rosiglitazone, ؉38 ؎ 6; and 9 mol/l pioglitazone, ؉64 ؎ 11; P < 0.05 each). As both metformin and TZDs inhibit complex I activity and cell respiration in vitro, similar mitochondrial actions could contribute to their antidiabetic effects. Diabetes

From a biomechanical point of view, the femoral neck system is a valid alternative to treat unstable femoral neck fractures, representing the advantages of a minimally invasive implant with comparable stability to the 2 DHS systems and superior to cannulated screws.

BackgroundScrew fixation of pelvic ring fractures is a common, but demanding procedure and navigation techniques were introduced to increase the precision of screw placement. The purpose of this case series was the evaluation of screw misplacement rate and functional outcome of percutaneous screw fixation of pelvic ring disruptions using a 2D navigation system.MethodsBetween August 2004 and December 2007, 44 of 442 patients with pelvic injuries were included for closed reduction and percutaneous screw fixation of disrupted pelvic ring lesions using an optoelectronic 2D-fluoroscopic based navigation system. Operating and fluoroscopy time were measured, as well as peri- and postoperative complications documented. Screw position was assessed by postoperative CT scans. Quality of live was evaluated by SF 36-questionnaire in 40 of 44 patients at mean follow up 15.5 ± 1.2 month.Results56 iliosacral- and 29 ramus pubic-screws were inserted (mean operation time per screw 62 ± 4 minutes, mean fluoroscopy time per screw 123 ± 12 seconds). In post-operative CT-scans the screw position was assessed and graded as follows: I. secure positioning, completely in the cancellous bone (80%); II. secure positioning, but contacting cortical bone structures (14%); III. malplaced positioning, penetrating the cortical bone (6%). The malplacements predominantly occurred in bilateral overlapping screw fixation. No wound infection or iatrogenic neurovascular damage were observed. Four re-operations were performed, two of them due to implant-misplacement and two of them due to implant-failure.Conclusion2D-fluoroscopic navigation is a safe tool providing high accuracy of percutaneous screw placement for pelvic ring fractures, but in cases of a bilateral iliosacral screw fixation an increased risk for screw misplacement was observed. If additional ramus pubic screw fixations are performed, the retrograde inserted screws have to pass the iliopubic eminence to prevent an axial screw loosening.

Thiazolidinediones (TZDs) are believed to induce insulin sensitization by modulating gene expression via agonistic stimulation of the nuclear peroxisome proliferator-activated receptor-␥ (PPAR-␥). We have shown earlier that the TZD troglitazone inhibits mitochondrial fuel oxidation in isolated rat skeletal muscle. In the present study, rat soleus muscle strips were exposed to TZDs to examine whether the inhibition of fuel oxidation is mediated by PPAR-␥ activation. Our findings consistently indicated direct, acute, and PPAR-␥؊inde-pendent TZD action on skeletal muscle fuel metabolism.

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