The Journal of surgical research最新文献

{"title":"Interleukin-10 regulates the fetal hyaluronan-rich extracellular matrix via a STAT3-dependent mechanism.","authors":"Alice King,&nbsp;Swathi Balaji,&nbsp;Emily Marsh,&nbsp;Louis D Le,&nbsp;Aimen F Shaaban,&nbsp;Timothy M Crombleholme,&nbsp;Sundeep G Keswani","doi":"10.1016/j.jss.2013.04.009","DOIUrl":"https://doi.org/10.1016/j.jss.2013.04.009","url":null,"abstract":"<p><strong>Background: </strong>The midgestational fetus is capable of regenerative healing. We have recently demonstrated a novel role for the anti-inflammatory cytokine interleukin 10 (IL-10) as a regulator of hyaluronan (HA) in the extracellular matrix. The signaling pathway of IL-10 has been studied in monocytes but is unknown in dermal fibroblasts. We hypothesized IL-10 signals through its primary receptor, IL-10R1, to activate STAT3, resulting in HA synthesis.</p><p><strong>Methods: </strong>Murine midgestational (E14.5) fetal fibroblasts were evaluated in vitro. Pericellular matrix was quantified using a particle exclusion assay. STAT3 levels and cellular localization were evaluated by Western blot/band densitometry and immunocytochemistry/confocal microscopy. HA levels were quantified by enzyme-linked immunosorbent assay. The effects of IL-10R1 signal blockade by a neutralizing antibody and STAT3 inhibition were evaluated. An ex vivo midgestation fetal forearm culture incisional wound model in control and transgenic IL-10-/- mice was used to evaluate the role of STAT3 on the extracellular matrix.</p><p><strong>Results: </strong>Fetal fibroblasts produce a robust hyaluronan-rich pericellular matrix that is IL-10R1 and STAT3 dependent. Inhibition of IL-10R1 signaling results in decreased phosphorylated STAT3 levels and inhibition of nuclear localization. Inhibition of STAT3 results in decreased HA production. At day 3, midgestation fetal wounds have efficient re-epithelialization, which is significantly slowed in IL-10-/- wounds at the same gestation and with inhibition of STAT3.</p><p><strong>Conclusions: </strong>Our data demonstrate that IL-10 regulates HA synthesis through its primary receptor IL-10R1 and STAT3 activation. This supports a novel nonimmunoregulatory mechanism of IL-10 in its role in fetal regenerative wound healing.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"671-7"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.04.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31439387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near-infrared imaging of face transplants: are both pedicles necessary?","authors":"John T Nguyen,&nbsp;Yoshitomo Ashitate,&nbsp;Vivek Venugopal,&nbsp;Florin Neacsu,&nbsp;Frank Kettenring,&nbsp;John V Frangioni,&nbsp;Sylvain Gioux,&nbsp;Bernard T Lee","doi":"10.1016/j.jss.2013.04.039","DOIUrl":"https://doi.org/10.1016/j.jss.2013.04.039","url":null,"abstract":"<p><strong>Background: </strong>Facial transplantation is a complex procedure that corrects severe facial defects due to traumas, burns, and congenital disorders. Although face transplantation has been successfully performed clinically, potential risks include tissue ischemia and necrosis. The vascular supply is typically based on the bilateral neck vessels. As it remains unclear whether perfusion can be based off a single pedicle, this study was designed to assess perfusion patterns of facial transplant allografts using near-infrared (NIR) fluorescence imaging.</p><p><strong>Methods: </strong>Upper facial composite tissue allotransplants were created using both carotid artery and external jugular vein pedicles in Yorkshire pigs. A flap validation model was created in n = 2 pigs and a clamp occlusion model was performed in n = 3 pigs. In the clamp occlusion models, sequential clamping of the vessels was performed to assess perfusion. Animals were injected with indocyanine green and imaged with NIR fluorescence. Quantitative metrics were assessed based on fluorescence intensity.</p><p><strong>Results: </strong>With NIR imaging, arterial perforators emitted fluorescence indicating perfusion along the surface of the skin. Isolated clamping of one vascular pedicle showed successful perfusion across the midline based on NIR fluorescence imaging. This perfusion extended into the facial allograft within 60 s and perfused the entire contralateral side within 5 min.</p><p><strong>Conclusions: </strong>Determination of vascular perfusion is important in microsurgical constructs as complications can lead to flap loss. It is still unclear if facial transplants require both pedicles. This initial pilot study using intraoperative NIR fluorescence imaging suggests that facial flap models can be adequately perfused from a single pedicle.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"714-21"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.04.039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31456484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in aortic arch radius of curvature, neck size, and taper in patients with traumatic and aortic disease.","authors":"Hillary B Alberta,&nbsp;Jessica L Secor,&nbsp;Taylor C Smits,&nbsp;Mark A Farber,&nbsp;William D Jordan,&nbsp;Jon S Matsumura","doi":"10.1016/j.jss.2013.05.098","DOIUrl":"https://doi.org/10.1016/j.jss.2013.05.098","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to determine the differences in aortic morphology that would potentially affect the management of thoracic endovascular aneurysm/aortic repair between trauma and aneurysm patients.</p><p><strong>Materials and methods: </strong>This was a prospective analysis of the pretreatment digital imaging of 98 traumatic injury patients and 63 aneurysm patients enrolled in multicenter regulatory studies of the Conformable GORE TAG Thoracic Device (CTAG Device) (manufactured by W.L. Gore and Associates, Flagstaff, AZ). A standardized protocol was used to perform an independent assessment of the images and measurements of the radius of curvature and proximal and distal neck diameters. The radius of curvature was measured using axial images and the proximal and distal intimal neck diameter measurements were completed using the orthogonal \"centerline\" view. Taper was measured over the entire treated aorta and was calculated by subtracting the distal neck diameter measurement from the proximal neck diameter. The results were analyzed with independent t-tests.</p><p><strong>Results: </strong>The trauma patients had a significantly smaller radius of curvature than aneurysm patients. There was a significant difference in the aortic neck size, with trauma patients having smaller proximal and distal intimal neck diameters. Taper was noted in trauma patients but not in aneurysm patients.</p><p><strong>Conclusions: </strong>The aortic anatomy varies between treated aortic pathologies. Aneurysm patients have a wider arch and larger aortas when compared with trauma patients. Aneurysm patients have less taper than trauma patients. Despite these differences, both of these cohorts of patients are treatable under the broader oversizing ranges of the CTAG Device.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"613-8"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.05.098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31560055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxycycline impacts hernia repair outcomes.","authors":"Job C Tharappel,&nbsp;Sandeep K Ramineni,&nbsp;Drew Reynolds,&nbsp;David A Puleo,&nbsp;J Scott Roth","doi":"10.1016/j.jss.2013.05.101","DOIUrl":"https://doi.org/10.1016/j.jss.2013.05.101","url":null,"abstract":"<p><strong>Background: </strong>Incisional hernias occur commonly in up to 20% of all abdominal operations. Incisional hernia formation has been associated with increased levels of matrix metalloproteinases (MMPs), reduced collagen 1, and increased collagen 3 expression. Doxycycline, a nonspecific inhibitor of MMPs, has been shown to beneficially reduce MMP levels in both cancer and aneurysm models. This study evaluates the impact of doxycycline upon MMP expression, collagen subtypes, and hernia repair distraction forces in an animal model of incisional hernia repair.</p><p><strong>Materials and methods: </strong>Twenty-four Sprague Dawley rats underwent incisional hernia creation and subsequent repair with polypropylene mesh. Animals were administered doxycycline or saline daily beginning 1 d prior to hernia repair and survived for 1, 2, or 4 wk. Serum and tissue were evaluated for MMP content and collagen subtyping utilizing enzyme-linked immunosorbent assay and Western blot. Tensiometric properties of the native abdominal wall after hernia repair were measured with an Instron Corp. (Canton, MA) mechanical testing system.</p><p><strong>Results: </strong>There were no differences in control and experimental groups 1 and 2 wk following hernia repair; 4 wk following hernia repair, doxycycline treated animals demonstrated reduced serum MMP-2 and MMP-9 levels, reduced tissue levels of MMP-2, MMP-3, and MMP-9, and increased collagen 1 to 3 ratios. Distraction forces required to disrupt the hernia repair were increased in the doxycycline treated group compared with controls.</p><p><strong>Conclusions: </strong>Doxycycline administration is associated with improved hernia repair strength with concomitant reduction of MMP levels with increased collagen 1 deposition. Longer term studies are required to better understand the impact of this treatment.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"699-704"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.05.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31560054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative pressure wound therapy in infants and children: a single-institution experience.","authors":"Rebecca M Rentea,&nbsp;Kimberly K Somers,&nbsp;Laura Cassidy,&nbsp;Jessica Enters,&nbsp;Marjorie J Arca","doi":"10.1016/j.jss.2013.05.056","DOIUrl":"https://doi.org/10.1016/j.jss.2013.05.056","url":null,"abstract":"<p><strong>Background: </strong>Information regarding the use of negative pressure wound therapy (NPWT) in the pediatric population is limited. Because of adverse outcomes in adult patients, the Food and Drug Administration issued a warning in 2011 about the use of NPWT in infants and children.</p><p><strong>Methods: </strong>We performed an institutional review board-approved, single-institution, retrospective review of pediatric patients who had undergone NPWT from 2007-2011. We collected the types of wounds for which NPWT was initiated, the NPWT outcomes, and the complications encountered.</p><p><strong>Results: </strong>The data from 290 consecutive patients were reviewed. Their average age was 9.3 y (range 12 d to 18 y), and their average weight was 46.5 kg (range 1.1-177). Of the wounds, 66% were classified as acute, 10% as chronic, and 24% as traumatic. The two most common indications were surgical wound dehiscence (n = 47) and skin grafting (n = 41). NPWT was used in 15 wounds containing surgical hardware, with 2 devices requiring eventual removal. NPWT was used for a median of 9 d per patient (two dressing changes). Complications occurred in 5 patients (1.7%). Documentation problems were noted in 44 patients. After NPWT, about one-third of the patients (n = 95 patients) were able to undergo delayed primary closure.</p><p><strong>Conclusions: </strong>NPWT is an effective adjunct in wound healing and closure in the pediatric population, with no mortality ascribed to NPWT. Also, the complication rates were low.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"658-64"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.05.056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31600299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgens regulate MMPs and the cellular processes of intimal hyperplasia.","authors":"Deidra J H Mountain,&nbsp;Brian M Freeman,&nbsp;Stacy S Kirkpatrick,&nbsp;John W Beddies,&nbsp;Joshua D Arnold,&nbsp;Michael B Freeman,&nbsp;Mitchell H Goldman,&nbsp;Scott L Stevens,&nbsp;Frederick A Klein,&nbsp;Oscar H Grandas","doi":"10.1016/j.jss.2013.05.070","DOIUrl":"https://doi.org/10.1016/j.jss.2013.05.070","url":null,"abstract":"<p><strong>Background: </strong>Testosterone deficiency has been associated with an increased risk of vascular disease. Matrix metalloproteinases (MMPs) have been implicated in vascular remodeling. Our group has demonstrated an association between female hormones and MMP-modulated intimal hyperplasia. In the present study, we investigated testosterone in the modulation of MMPs and the cellular processes of intimal hyperplasia.</p><p><strong>Materials and methods: </strong>Male vascular smooth muscle cells (VSMCs) were treated with a range of testosterone or dihydrotestosterone (DHT) concentrations (0.3-3000 nM). MMPs were assayed using quantitative polymerase chain reaction, Western blot analysis, and zymography. VSMC migration and proliferation were assayed using Boyden chamber and MTT assays.</p><p><strong>Results: </strong>MT1-MMP gene expression was not affected by low DHT exposure but was downregulated at high levels (3000 nM = 85% ± 3%). TIMP-2 gene expression was downregulated at low DHT exposure (0.3 nM = 82% ± 4%, 3.0 nM = 82% ± 1%) but was not affected at high levels. MMP-2 enzymatic activity was increased at low DHT exposure (3.0 nM = 110% ± 4%) and decreased below basal levels at high doses (300 nM = 91% ± 7%, 3000 nM = 77% ± 8%). High concentrations of DHT decreased VSMC migration (3.0 nM = 72% ± 9%, 30 nM = 50% ± 6%, 300 nM = 47% ± 5%, 3000 nM = 53% ± 6%). Testosterone also decreased migration but had less effect. The highest tested concentration of DHT and testosterone decreased the basal VSMC proliferation (3000 nM = 87% ± 3% and 87% ± 4% respectively).</p><p><strong>Conclusions: </strong>The DHT levels differentially affected the expression of regulatory isoforms responsible for the activation and inhibition of MMP-2, leading to an inverse relationship among the DHT levels, MMP-2 activity, and VSMC migration. In vivo studies will be used to examine testosterone deficiency and supplementation in MMP-modulated intimal hyperplasia in animal models of vascular disease. These studies are needed as a prerequisite to determining whether testosterone replacement in testosterone-deficient men should be evaluated for attenuation of atherosclerosis.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"619-27"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.05.070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31604605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus fails to regulate collagen expression in dermal fibroblasts.","authors":"Victor W Wong,&nbsp;Fanglei You,&nbsp;Michael Januszyk,&nbsp;Anna A Kuang","doi":"10.1016/j.jss.2013.04.006","DOIUrl":"https://doi.org/10.1016/j.jss.2013.04.006","url":null,"abstract":"<p><strong>Background: </strong>The purpose of this study was to investigate the effects of tacrolimus on human fibroblasts derived from unwounded skin, hypertrophic scars (HTS), and keloids. We hypothesized that tacrolimus, a potent anti-inflammatory and immunosuppressant drug known to attenuate solid organ transplant fibrosis, would block collagen expression in human dermal fibroblasts.</p><p><strong>Methods: </strong>We performed genomewide microarray analysis on human dermal fibroblasts treated with tacrolimus in vitro. We used principal component analysis and hierarchical clustering to identify targets regulated by tacrolimus. We performed quantitative polymerase chain reaction to validate the effect of tacrolimus on collagen 1 and 3 expression.</p><p><strong>Results: </strong>We identified 62, 136, and 185 gene probes on microarray analysis that were significantly regulated (P < 0.05) by tacrolimus in normal, HTS, and keloid fibroblasts, respectively. Collagen pathways were not blocked after tacrolimus exposure in any of the fibroblast groups; we validated these findings using quantitative polymerase chain reaction for collagen 1 and 3. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 were significantly downregulated (P < 0.05) by tacrolimus in both HTS and keloid fibroblast populations but not normal fibroblasts.</p><p><strong>Conclusions: </strong>Tacrolimus does not modulate the expression of collagen 1 or 3 in human dermal fibroblasts in vitro. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 are blocked by tacrolimus in pathologic fibroblasts but not normal fibroblasts, and may represent novel genes underlying HTS and keloid pathogenesis. Tacrolimus-based anti-fibrotics might prove more effective if non-fibroblast populations such as inflammatory cells and keratinocytes are targeted.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"678-90"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.04.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31410995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking the P2X7 receptor improves outcomes after axonal fusion.","authors":"Charles L Rodriguez-Feo,&nbsp;Kevin W Sexton,&nbsp;Richard B Boyer,&nbsp;Alonda C Pollins,&nbsp;Nancy L Cardwell,&nbsp;Lillian B Nanney,&nbsp;R Bruce Shack,&nbsp;Michelle A Mikesh,&nbsp;Christopher H McGill,&nbsp;Christopher W Driscoll,&nbsp;George D Bittner,&nbsp;Wesley P Thayer","doi":"10.1016/j.jss.2013.04.082","DOIUrl":"https://doi.org/10.1016/j.jss.2013.04.082","url":null,"abstract":"<p><strong>Background: </strong>Activation of the P2X7 receptor on peripheral neurons causes the formation of pannexin pores, which allows the influx of calcium across the cell membrane. Polyethylene glycol (PEG) and methylene blue have previously been shown to delay Wallerian degeneration if applied during microsuture repair of the severed nerve. Our hypothesis is that by modulating calcium influx via the P2X7 receptor pathway, we could improve PEG-based axonal repair. The P2X7 receptor can be stimulated or inhibited using bz adenosine triphosphate (bzATP) or brilliant blue (FCF), respectively.</p><p><strong>Methods: </strong>A single incision rat sciatic nerve injury model was used. The defect was repaired using a previously described PEG methylene blue fusion protocol. Experimental animals were treated with 100 μL of 100 μM FCF solution (n = 8) or 100 μL of a 30 μM bzATP solution (n = 6). Control animals received no FCF, bzATP, or PEG. Compound action potentials were recorded prior to transection (baseline), immediately after repair, and 21 d postoperatively. Animals underwent behavioral testing 3, 7, 14, and 21 d postoperatively. After sacrifice, nerves were fixed, sectioned, and immunostained to allow for counting of total axons.</p><p><strong>Results: </strong>Rats treated with FCF showed an improvement compared with control at all time points (n = 8) (P = 0.047, 0.044, 0.014, and 0.0059, respectively). A statistical difference was also shown between FCF and bzATP at d 7 (P < 0.05), but not shown with d 3, 14, and 21 (P > 0.05).</p><p><strong>Conclusions: </strong>Blocking the P2X7 receptor improves functional outcomes after PEG-mediated axonal fusion.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"705-13"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.04.082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31476671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased levels of CD34+ cells are associated in patients with abdominal aortic aneurysms compared with patients with peripheral vascular disease.","authors":"Elyse N Van Spyk,&nbsp;Kevin C Chun,&nbsp;Kiana M Samadzadeh,&nbsp;John H Peters,&nbsp;Eugene S Lee","doi":"10.1016/j.jss.2013.03.070","DOIUrl":"https://doi.org/10.1016/j.jss.2013.03.070","url":null,"abstract":"<p><strong>Background: </strong>Circulating progenitor cells are integral to vascular health and effectively predict vascular reactivity. CD34 is a known marker of circulating progenitor cells. Few studies have examined the role of CD34+ cells in abdominal aortic aneurysm (AAA) disease and peripheral vascular disease (PVD). The aim of this study was to compare the percentage of CD34+ cells between patients with AAA versus PVD.</p><p><strong>Materials and methods: </strong>We collected peripheral whole blood from AAA or PVD patients. The blood was stained with fluorescently labeled antibodies against CD34 or isotype controls. We collected data using a flow cytometer and analyzed them. We also recorded risk factors such as hypertension, diabetes, total cholesterol, serum white blood cells, serum creatinine, body mass index, blood pressure, statin use, current smoking status, coronary artery disease, cerebral vascular accident, and chronic obstructive pulmonary disease.</p><p><strong>Results: </strong>We enrolled 24 patients in this study (AAA, n = 12; PVD, n = 12). The AAA patients had a greater percentage of CD34+ cells compared with PVD patients. (r = 0.84; P = 0.016). There were no significant risk factors differences between AAA and PVD patients.</p><p><strong>Conclusions: </strong>Based on CD34+ cell counts, AAA is a less severe vascular disease than PVD. Whether CD34+ cells can serve as a biomarker for risk stratification or a potential therapy warrants further study.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"638-43"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.03.070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31437447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination chemotherapy of nafamostat mesylate with gemcitabine for gallbladder cancer targeting nuclear factor-κB activation.","authors":"Ryota Iwase,&nbsp;Koichiro Haruki,&nbsp;Yuki Fujiwara,&nbsp;Kenei Furukawa,&nbsp;Hiroaki Shiba,&nbsp;Tadashi Uwagawa,&nbsp;Takeyuki Misawa,&nbsp;Toya Ohashi,&nbsp;Katsuhiko Yanaga","doi":"10.1016/j.jss.2013.06.003","DOIUrl":"https://doi.org/10.1016/j.jss.2013.06.003","url":null,"abstract":"<p><strong>Background: </strong>Gemcitabine is an effective chemotherapeutic agent for advanced gallbladder cancer. However, chemoresistance attributable to gemcitabine-induced nuclear factor-κB (NF-κB) activation has been reported. We previously reported that nafamostat mesylate inhibited NF-κB activation and induced apoptosis in pancreatic cancer. Therefore, we hypothesized that nafamostat mesylate inhibits gemcitabine-induced NF-κB activation and enhances apoptosis induced by gemcitabine in gallbladder cancer.</p><p><strong>Materials and methods: </strong>In vitro, we assessed NF-κB activation of a gallbladder cancer cell line (NOZ) treated with nafamostat mesylate, gemcitabine, or a combination of both. In vivo, we established a xenograft gallbladder cancer model in mice by subcutaneous injection of NOZ cells. Five weeks after implantation, the animals were treated with nafamostat mesylate three times a week in the nafamostat mesylate group, with gemcitabine once a week in the gemcitabine group, or with a combination of nafamostat mesylate three times a week and gemcitabine once a week in the combination group, respectively. In the control group, only the vehicle of gemcitabine and nafamostat mesylate was injected at the same time course.</p><p><strong>Results: </strong>In the combination group, NF-κB activation was inhibited and apoptosis was enhanced compared with gemcitabine alone in vitro and vivo. Tumor growth in the combination group was significantly slower than that in the gemcitabine group (P < 0.001). At the end of the study, the tumor weight and volume in the combination group were significantly lower than those in the gemcitabine group (P = 0.039 and 0.028, respectively).</p><p><strong>Conclusions: </strong>Combination chemotherapy of gemcitabine with nafamostat mesylate enhances the anti-tumor effect against xenograft gallbladder cancer model in mice.</p>","PeriodicalId":191568,"journal":{"name":"The Journal of surgical research","volume":" ","pages":"605-12"},"PeriodicalIF":2.2,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.jss.2013.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31560057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}