The interaction between neuropeptides and cytokines and its role in cutaneous wound healing is becoming evident. The goal of the present study is to investigate the impact of diabetes on peripheral cytokine and neuropeptide expression and their role in diabetic wound healing. To achieve this goal, the effect of diabetes on wound healing along with the role of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8) secreted in the wound microenvironment and neuropeptides, such as substance P (SP) and neuropeptide Y (NPY), secreted from peripheral nerves is monitored in non-diabetic and diabetic rabbits. Rabbits in the diabetic group received alloxan monohydrate (100mg/kg i.v.). Ten days after diabetic induction, four full thickness circular wounds were created in both ears using a 6mm punch biopsy. Wound healing was monitored over ten days and gene expression of cytokines and neuropeptides was assessed in the wounds. Compared to the non-diabetic rabbits, wounds of diabetic rabbits heal significantly slower. Diabetic rabbits show significantly increased baseline gene expression of IL-6 and IL-8, their receptors, CXCR1, CXCR2, GP-130 and a decrease of pre-pro Tachykinin-A (PP-TA), the precursor of SP whereas the expression of prepro-NPY (PP-NPY), the precursor of NPY is not different. Similarly, baseline protein expression of CXCR1 is higher in diabetic rabbit skin. Post-injury, the increase over baseline gene expression of IL-6, IL-8, CXCR1, CXCR2 and GP-130 is significantly less in diabetic wounds compared to non-diabetic wounds. Whereas, there is no difference in PP-TA gene expression between non-diabetic and diabetic rabbits post-injury, the gene expression of PP-NPY is reduced in diabetic rabbits. In conclusion, diabetes causes dysregulation in the neuropeptide expression in the skin along with a suppressed focused inflammatory response to injury. This suggests that the chronic inflammation in the skin of diabetic rabbits inhibits the acute inflammation much needed for wound healing.

Intimal hyperplasia (IH) limits the patency of all cardiovascular vein bypass grafts. We previously found the myristoylated alanine-rich C kinase substrate (MARCKS), a key protein kinase C (PKC) substrate, to be up-regulated in canine models of IH. Here, we further characterize the role of MARCKS in IH and examine the phenotypic consequences of MARCKS silencing by small interfering RNA (siRNA) transfection in human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) in vitro and use a rapid 10-min nonviral siRNA transfection technique to determine the effects of MARCKS silencing in human saphenous vein cultured ex vivo. We demonstrate MARCKS silencing attenuates VSMC migration and arrests VSMC proliferation in part through the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1). Conversely, MARCKS silencing had little or no effect on EC migration or proliferation. These phenotypic changes culminated in reduced neointimal formation in cultured human saphenous vein. These data identify MARCKS as a pathogenic contributor to IH and indicate therapeutic MARCKS silencing could selectively suppress the "atherogenic," proliferative phenotype of VSMCs without collateral harm to the endothelium. This approach could be readily translated to the clinic to silence MARCKS in vein bypass grafts prior to implantation.

Objectives We sought to elucidate the risks for access site-related complications (ASC) following percutaneous lower extremity revascularization and to evaluate benefit of routine ultrasound-guided access (RUS) in decreasing ASC. Methods We reviewed all consecutive percutaneous revascularizations (PTA or stent) performed for lower extremity atherosclerosis at our institution from 2002–2012. RUS began September 2007. Primary outcome was any ASC (bleeding, groin or retroperitoneal [RP] hematoma, vessel rupture, or thrombosis). Multivariable logistic regression was used to determine predictors of ASC. Results A total of 1,371 punctures were performed on 877 patients (43% women, median age 69 [IQR 60–78] yrs for claudication (29%), critical limb ischemia (59%), or bypass graft stenosis (12%) using 4–8Fr sheaths. There were 72 ASCs (5%): 52 instances of bleeding or groin hematoma, 9 pseudoaneurysms, 8 retroperitoneal hematomas, 2 artery lacerations, and 1 thrombosis. ASC were less frequent when RUS was used (4% vs. 7%, P=.02). Multivariable predictors of ASC were age >75 years (OR 2.0, 95% CI 1.1–3.7, P=.03), CHF (OR 1.9, 95% CI 1.1–1.3, P=.02), preoperative warfarin use (OR 2.0, 95% CI 1.1–3.5, P=.02), & RUS (OR 0.4, 95% CI 0.2–0.7, P<.01). Vascular closure devices (VCDs) were not associated with lower rates of ASCs (OR 1.1, 95% CI 0.2–0.7, P<.01). RUS lowered ASCs in those >75 years (5% vs. 12%, P<.01) but not those on warfarin preoperatively (10% vs. 13%, P=.47). RUS did not decrease VCD failure (6% vs. 4%, P=.79). Conclusions We were able to decrease the rate of ASCs during lower extremity revascularization with the implementation of RUS. VCDs did not impact ASCs. Particular care should be taken on patients >75 years old, those with CHF, and those on warfarin.

A 56-year-old woman with a total gastrectomy and an esophagojejunal anastomosis developed a severe stricture of the surgical anastomosis (l " Fig. 1). The stricture was radiologically dilated, resulting in perforation during the dilation maneuvers. The perforation was resolved nonsurgically. The stricture recurred, so we placed a covered metal stent that was removed after 2 months, but the stricture recurred again afterwards. In this situation, we decided to place the SX-Ella-BD (Ella-CS, s. r. o., Hradec KrµlovØ, Czech Republic)-a new polydioxanone