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The pathogenic mechanism of nicotine, a major product of smoking, on vascular endothelial cells is not well defined yet. The purpose of this study was to determine whether chronic exposure to nicotine alters angiogenic activity in human umbilical vein endothelial cells and to identify a potential role for endothelial nitric oxide synthase (eNOS) expression. Our study demonstrated that acute nicotine treatment enhanced nitric oxide release, eNOS activation, and proangiogenic activity. However, chronic nicotine exposure impaired proangiogenic function (decreased cell migration and tubular structure formation) in human umbilical vein endothelial cells compared with acute exposure, but sustained the antiapoptotic effect. These findings seem to be related to eNOS gene expression and nitric oxide production, which may be involved in the pathophysiology of chronic nicotine addicts.

OBJECTIVE We evaluated whether LD can detect alterations in skin microcirculatory flow in type II diabetic neuropathy patients and determined which parameters were most predictive. METHODS A prospective analysis was performed for three groups with presumed varying degrees of microvascular dysfunction: diabetics with neuropathy (DMN, n = 20), diabetics without microangiopathic complications (DM, n = 20), and healthy controls (n = 16). LD was performed under strictly controlled protocols with provocation, consisting of vasoconstrictive (valsalva, postural) and vasodilative tests (PORH, LTH). RESULTS There was an overall decrease in LD values in response to both vasoconstrictive and vasodilative provocations in DMN patients compared to DM and control groups. Statistically significant parameters were as follows: valsalva, PORH and LTH between DMN and control; valsalva only between DMN and DM; and PORH and LTH between DM and control. ROC curve analysis showed that Valsalva was the most accurate parameter in DMN patients. CONCLUSIONS LD could consistently detect differences in microcirculatory flow between the three study groups consisting of gradually more severe microvascular dysfunction. The Valsalva parameter was the most accurate in detecting established microvascular dysfunction, whereas PORH and LTH may have a possible role for detection of early microvascular impairment.

The cystoscopic removal of ureteral stents causes discomfort and pain, especially in young male patients. We aimed to evaluate the usefulness of ureteral stent removal by flexible cystoscopy on pain and satisfaction in young males. In total, 104 patients undergoing ureteroscopic removal of stones with indwelling of ureteral stent (May 2013–July 2015) were randomised to receive a ureteral stent removal by either rigid cystoscopy (group 1) or flexible cystoscopy (group 2). Visual analogue scale (VAS) pain score and satisfaction scale score were assessed immediately after stent removal. All patients were males and the mean age was 22.72 ± 2.49 years. Group 2 showed significantly lower VAS pain score (p < 0.001) and higher satisfaction scale score (p < 0.001) than group 1. Ureteral stent removal by flexible cystoscopy may offer advantages on pain and satisfaction to young male patients.

Femoral-anterior tibial artery bypasses with autogenous grafts are difficult to perform when sufficiently long saphenous veins are not available. We performed 12 bypasses on patients with Buerger disease during a 20-year period using a new intermuscular tunneling technique. The graft is passed from the thigh between the muscle compartments without penetrating the muscle fibers, providing an anatomically superior and shorter path. The primary patency rates were 75% at 5 years and 65% at 10 years. We believe that our tunneling technique is safe and durable and might be a viable alternative for proximal femoral-anterior tibial artery bypass in selected patients.

Purpose To examine the fate of muscle-derived stem cells (MDSC) after injection into different host conditions and provide an insight for their mechanism of action. Materials and methods MDSCs differentiated in vitro towards the endothelial lineage and transfected with lentivirus tagged with green fluorescent protein (GFP) were injected into two animal models mimicking vascular diseases: hindlimb ischemia and carotid injury models. Injected cells were tracked at the site of injection and in remote organs by harvesting the respective tissues at different time intervals and performing immunofluorescent histological analyses. Stem cell survival was quantified at the site of injection for up to 4 weeks. Results MDSCs were successfully tagged with fluorescent material GFP and showed successful implantation into the respective injection sites. These cells showed a higher affinity to implant in blood vessel walls as shown by double fluorescent co-stain with CD31. Quantification of stem cell survival showed a timede pendent decrease from day 3 to 4 weeks (survival rate normalized against day 3 was 72.0% at 1 week, 26.8% at 2 weeks and 2.4% at 4 weeks). Stem cells were also found in distant organs, especially the kidneys and liver, which survived up to 4 weeks. Conclusion MDSCs were successfully tracked in different vascular disease models, and their fate was assessed in terms of cell survival and distribution. Better understanding of the donor cell properties, including their interaction with the host conditions and their mechanism of action, are needed to enhance cell survival and achieve improved outcomes.

To determine the role of endothelial progenitor cells (EPCs) in the pathogenesis of thromboangiitis obliterans (TAO), EPC numbers and colony-forming units, migratory function and tubular structure formation in vitro were compared between 13 young male TAO patients and two age-matched healthy control groups: 11 smokers and 12 non-smokers. TAO patients had significantly lower numbers of EPCs and EPC colonies compared to both non-smokers [190 (97.0–229) vs 528 (380–556), p < 0.001 for EPCs and 0.80 (0.53–1.00) vs 2.80 (2.08–4.00) per mm2, p = 0.001 for EPC colonies] and smokers [190 (97.0–229) vs 272 (229–326), p = 0.012 for EPCs and 0.80 (0.53–1.00) vs 2.80 (1.80–3.93) per mm2, p = 0.001 for EPC colonies]. However, there were no significant differences in migratory function or tube formation between the three groups. These results suggest that TAO patients have an intrinsic decrease in EPCs not entirely associated with smoking, which may be the cause of endothelial dysfunction seen in TAO patients leading to the development of this disease at early ages.

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.

Purpose: Varicose veins are a major problem worldwide and improvement in quality of life (QoL) is the ultimate goal after treatment of this benign disease. However QoL is highly dependent on personal and social factors. This study compares high ligation and stripping (HS) and radiofrequency ablation (RFA) in terms of QoL and recurrence in Korea. Methods: A retrospective analysis of prospectively collected data between August 2006 and October 2008 was performed for patients undergoing HS and RFA at a single institution. QoL was assessed with a questionnaire preoperatively, at 3 months postoperatively and annually thereafter. Recurrence was assessed by Duplex ultrasound annually after surgery. Results: A total of 272 patients completed the questionnaire at 3 months. Among these patients, 155 patients returned for their annual follow-up. There were no significant differences between HS and RFA in global QoL scores, although RFA showed less pain. However, paresthesia rates were also higher after RFA. Recurrence rates were similar between the two modalities, although technical failures were more common after RFA. Conclusion: Overall QoL and recurrence rates were similar between the two modalities. The benefits of RFA do not seem to be enough to overcome the higher costs of HS in Korea.

Purpose: The main treatment modality of peripheral arterial occlusive disease (PAOD) of the lower extremities has shifted from traditional bypass surgery (BS) to a less invasive endovascular intervention (EI), but there is still conflicting data about the differences in long-term patency between the two modalities The purpose of this study was to analyze restenosis rates of femoral EI and to compare both anatomical and functional results between EI and femorodistal BS. Methods: Between July 2003 and June 2009, 88 limbs (61 patients) and 47 limbs (43 patients) with femoral artery PAOD were treated with EI and BS, respectively. A retrospective analysis of prospectively collected data was performed by reviewing medical records, radiologic images and noninvasive vascular studies. Patient demographics and risk factors were analyzed. Technical outcomes such as restenosis rates, patency rates and functional outcomes using modified questionnaires were evaluated. Results: The restenosis rates for EI at 6 months, 1 year, 2 years and 3 years were 10.4%, 20.1%, 41.1% and 52.7%, respectively, and the mean restenosis duration was 36.5±3.24 months. Comparison of patency rates between EI and BS showed no significant difference (P=0.204) in TASC C and D lesions. Functional outcome analysis showed that both EI and BS improved functional status after treatment, and comparison between the two groups showed that BS had a better functional improvement than EI (P=0.010). Conclusion: EI could provide equivalent patency rates compared with BS, but for TASC C and D lesions, BS is still a preferred treatment modality based on better functional outcomes. (J Korean Surg Soc 2010;79:215-222)