Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries.

OBJECTIVE: This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA). METHODS: Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography. RESULTS: High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619. CONCLUSION: These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.

Skin sensory alteration and kneeling ability following cruciate retaining total knee arthroplasty are not affected by the incision position: A randomised controlled trial of simultaneous bilateral surgery.

PURPOSE: The purpose of this randomised controlled trial was to assess the impact of skin incision location on the patients' ability to kneel. METHODS: A total of 29 patients undergoing bilateral total knee arthroplasty (58 knees) were randomised to receive a lateral or midline incision, with the contralateral limb receiving the alternative option. Cruciate retaining implants were used in all cases by three experienced arthroplasty surgeons. The primary outcome measures assessed functional ability to kneel using an innovative five-point kneeling scale, preferred knee to kneel on and the area of cutaneous sensory loss around the incision at 6 weeks, 6 months and 12 months. Secondary outcome measures were the OKS, KOOS JR, FJS and EQ5D patient reported outcome measures (PROMS), length of surgical scar, overall knee preference and range of motion (ROM). RESULTS: There were no significant differences between the two groups for any primary or secondary outcome measures. Flexion range however, had a significant positive correlation with kneeling score (r = 0.335, p = 0.010). The kneeling score increased at each time point after surgery and was significantly greater at 12 months than preoperatively (2.7 v 3.5, p = 0.015). The area of sensory loss lateral to the incision was significantly less at 6 and 12 months than at 6 weeks (43.6cm2 and 40.1cm2 v 84.1cm2, p < 0.0001). CONCLUSION: The ability to kneel following cruciate retaining total knee arthroplasty is not affected by the incision position but by time and flexion range. TKA improves the ability to kneel by 12 months post-surgery. Sensory loss lateral to the incision reduces with time. LEVEL OF EVIDENCE: Therapeutic Level 2.

Image-derived instrumentation vs. conventional instrumentation with 3D planning for glenoid component placement in reverse total shoulder replacements: a randomized controlled trial.

Hypothesis: Glenoid baseplate positioning for reverse total shoulder arthroplasty (rTSA) is important for stability and longevity, with techniques such as image-derived instrumentation (IDI) developed for improving implant placement accuracy. We performed a single-blinded randomized controlled trial comparing glenoid baseplate insertion accuracy with 3D preoperative planning and IDI jigs vs. 3D preoperative planning and conventional instrumentation. Methods: All patients had a preoperative 3D computed tomography to create an IDI; then underwent rTSA according to their randomized method. Repeat computed tomography scans performed at six weeks postoperatively were compared to the preoperative plan to assess for accuracy of implantation. Patient-reported outcome measures and plain radiographs were collected with 2-year follow-up. Results: Forty-seven rTSA patients were included (IDI n = 24, conventional instrumentation n = 23). The IDI group was more likely to have a guidewire placement within 2mm of the preoperative plan in the superior/inferior plane (P = .01); and exhibited a smaller degree of error when the native glenoid retroversion was >10° (P = .047). There was no difference in patient-reported outcome measures or other radiographic parameters between the two groups. Conclusion: IDI is an accurate method for glenoid guidewire and component placement in rTSA, particularly in the superior/inferior plane and in glenoids with native retroversion >10°, when compared to conventional instrumentation.