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BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease. METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease.
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Flavonoides , Extrato de Sementes de Uva , Qualidade de Vida , Insuficiência Venosa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Método Duplo-Cego , Resultado do Tratamento , Doença Crônica , Estudos Prospectivos , Insuficiência Venosa/tratamento farmacológico , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/diagnóstico por imagem , Flavonoides/administração & dosagem , Fatores de Tempo , Adulto , Extrato de Sementes de Uva/farmacologia , Extrato de Sementes de Uva/administração & dosagem , Vitis/química , Idoso , Inquéritos e Questionários , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , República da Coreia , SementesRESUMO
Despite significant advancements in three-dimensional (3D) cell culture technology and the acquisition of extensive data, there is an ongoing need for more effective and dependable data analysis methods. These concerns arise from the continued reliance on manual quantification techniques. In this study, we introduce a microphysiological system (MPS) that seamlessly integrates 3D cell culture to acquire large-scale imaging data and employs deep learning-based virtual staining for quantitative angiogenesis analysis. We utilize a standardized microfluidic device to obtain comprehensive angiogenesis data. Introducing Angio-Net, a novel solution that replaces conventional immunocytochemistry, we convert brightfield images into label-free virtual fluorescence images through the fusion of SegNet and cGAN. Moreover, we develop a tool capable of extracting morphological blood vessel features and automating their measurement, facilitating precise quantitative analysis. This integrated system proves to be invaluable for evaluating drug efficacy, including the assessment of anticancer drugs on targets such as the tumor microenvironment. Additionally, its unique ability to enable live cell imaging without the need for cell fixation promises to broaden the horizons of pharmaceutical and biological research. Our study pioneers a powerful approach to high-throughput angiogenesis analysis, marking a significant advancement in MPS.
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Angiogênese , Aprendizado Profundo , Técnicas de Cultura de CélulasRESUMO
BACKGROUND: To evaluate early outcomes of aortoiliac or isolated iliac artery aneurysm repair using the Zenith® Bifurcated Iliac Side (ZBIS) stent graft combined with the LifeStream™ Balloon Expandable Vascular Covered Stent as a bridging stentgraft. METHODS: Between August 2018 and February 2020, 38 patients (37 male, mean age 72.7 years) received 46 LifeStream stents in conjunction with 38 ZBIS stent grafts to bridge hypogastric arteries for aneurysm repair in six university hospitals in Korea. The primary outcomes were technical success rate and procedure-related complications. Secondary outcomes were bridging stent graft patency and re-intervention. RESULTS: All procedures were performed as elective standard endovascular aortic aneurysm repair (EVAR) and unilateral iliac branch device (IBD). Mean follow-up was 13.1 months, and patient overall survival rate was 96.7%. Technical success rate was 76.3% (n = 29). Causes of failure included seven total endoleaks; six type Ic and one type IIIc from the IBD junction, one unintentional IIA coverage, and one failure to deploy the IIA stent graft. Procedure-related complications occurred in two patients: one LifeStream migration and one ZBIS stent graft migration. Overall patency rates for the LifeStream and ZBIS stents were 97.4% and 97.2%, respectively. CONCLUSION: This multicenter preliminary experience with the LifeStream™ Balloon Expandable Vascular Covered Stent in IBD demonstrated good patency; however, an unexpectedly high rate of type Ic endoleaks was observed. Combined use of the LifeStream stent with the ZBIS stent graft is safe and feasible to preserve pelvic circulation with good patency and a low rate of device-related reintervention.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Masculino , Idoso , Endoleak/etiologia , Endoleak/prevenção & controle , Prótese Vascular/efeitos adversos , Desenho de Prótese , Resultado do Tratamento , Estudos Retrospectivos , Stents/efeitos adversos , República da Coreia , Aneurisma da Aorta Abdominal/cirurgia , Fatores de RiscoRESUMO
BACKGROUND: Capmatinib (CAP) is a drug that has been used to treat non-small cell lung cancer (NSCLC) in adults. Presently, its novel effects on skeletal muscle insulin signaling, inflammation, and lipogenesis in adipocytes have been uncovered with a perspective of drug repositioning. However, the impact of CAP on LPS-mediated interaction between human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes has yet to be investigated. METHODS: HUVECs and THP-1 monocytes were treated with LPS and CAP. The protein expression levels were determined using Western blotting. Target protein knockdown was conducted using small interfering (si) RNA transfection. Interactions between HUVECs and THP-1 cells were assayed using green fluorescent dye. RESULTS: This study found that CAP treatment ameliorated cell adhesion between THP-1 monocytes and HUVECs and the expression of adhesive molecules, such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Moreover, phosphorylation of inflammatory markers, such as NFκB and IκB as well as TNFα and monocyte chemoattractant protein-1 (MCP-1) released from HUVECs and THP-1 monocytes, was prevented by CAP treatment. Treatment with CAP augmented PPARδ and IL-10 expression. siRNA-associated suppression of PPARδ and IL-10 abolished the effects of CAP on cell interaction between HUVECs and THP-1 cells and inflammatory responses. Further, PPARδ siRNA mitigated CAP-mediated induction of IL-10 expression. CONCLUSION: These findings imply that CAP improves inflamed endothelial-monocyte adhesion via a PPARδ/IL-10-dependent pathway. The current study provides in vitro evidence for a therapeutic approach for treating atherosclerosis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , PPAR delta , Humanos , Monócitos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Interleucina-10 , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , PPAR delta/metabolismo , PPAR delta/farmacologia , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/farmacologiaRESUMO
OBJECTIVE: The treatment of varicose veins has shifted from conventional surgical stripping (SS) to minimally invasive endovenous modalities. Cyanoacrylate closure (CAC) with the VenaSeal system (Medtronic, Dublin, Ireland) has increased in popularity owing to its nonthermal and nontumescent technique. The purpose of the present study was to compare the clinical outcomes of CAC and SS for the treatment of incompetent great saphenous veins. METHODS: An open-label, multicenter, prospective, randomized controlled trial was conducted. The subjects were randomized to either the CAC or SS procedure. The primary endpoint of the present study was to evaluate complete closure of the target vein at 3 months. Target vein occlusion was assessed on the third day and 1, 3, 6, and 12 months postoperatively using duplex ultrasound. The pain and ecchymosis grades were also assessed. Additionally, the clinical outcomes, such as the venous clinical severity score and Aberdeen Varicose Vein Questionnaire score, were assessed. RESULTS: Three-month follow-up data were obtained for all 126 enrolled and randomized subjects (63 with CAC and 63 with SS). At 3 months, complete target vein closure was observed in both groups. The postoperative pain score was significantly better in the CAC group than in the SS group (0.3 ± 0.6 in the CAC group and 1.1 ± 1.5 in the SS group; P < .001). In addition, the mean ecchymosis grade was 0.3 ± 0.5 in the CAC group and 1.1 ± 1.1 in the SS group (P < .001). The venous clinical severity score and quality of life had improved equally in both groups. The adverse events after both procedures were mostly minor complications (9 events in CAC group and 20 events in SS group). Major complications occurred in one patient who had undergone the SS procedure. CONCLUSIONS: The CAC and SS procedures were both associated with complete occlusion of the target vein at 3 months. The postoperative pain and ecchymosis grades were significantly lower in the CAC group. Other differences between the two groups included the frequency and nature of the complications. The results showed that CAC has high success with few complications.
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Cianoacrilatos/administração & dosagem , Procedimentos Endovasculares , Veia Safena/cirurgia , Varizes/terapia , Procedimentos Cirúrgicos Vasculares , Insuficiência Venosa/terapia , Idoso , Cianoacrilatos/efeitos adversos , Equimose/etiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Qualidade de Vida , Veia Safena/diagnóstico por imagem , Veia Safena/fisiopatologia , Seul , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Varizes/diagnóstico por imagem , Varizes/fisiopatologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/fisiopatologiaRESUMO
OBJECTIVE: Spontaneous Isolated Coeliac Artery Dissection (SICAD) is a rare disease with few reports of management strategies. This study reports the mid- to long-term outcomes of conservative management and endovascular intervention of SICAD treatment. METHODS: Sixteen patients presenting with symptomatic SICAD from September 2006 to October 2018 were reviewed retrospectively. The clinical manifestations, initial radiological findings, methods of treatment, and serial follow up studies were analysed. RESULTS: The mean age of the patients was 51.2 ± 7.9 years, with a median follow up of 33.3 (range 1.0-118.9) months. Four patients received early intervention because of aneurysmal dilatation or distal hypoperfusion. Four patients who received conservative management showed progression of disease and were recommended for delayed intervention. Although collaterals prevented further hepatic ischaemia, one of these four patients failed in delayed intervention because of extensive thrombi completely occluding the hepatic artery. In the remaining eight patients who were managed conservatively, three (37.5%) showed regression of disease, one (12.5%) showed partial regression, and five (62.5%) showed no change in intimal flap or thrombosis, but all had symptomatic improvement. The median follow up duration for the seven patients who underwent successful intervention was 77.3 (range 34.3-118.9) months, and all stenting remained patent during the follow up period. CONCLUSION: Early intervention in symptomatic SICAD patients may be necessary in over 50% of patients, and endovascular stenting has durable long term outcomes.
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Dissecção Aórtica/terapia , Arteriopatias Oclusivas/prevenção & controle , Artéria Celíaca/cirurgia , Tratamento Conservador/métodos , Procedimentos Endovasculares/métodos , Adulto , Dissecção Aórtica/complicações , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/etiologia , Artéria Celíaca/patologia , Tratamento Conservador/efeitos adversos , Tratamento Conservador/normas , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/normas , Estudos de Viabilidade , Feminino , Seguimentos , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Stents , Fatores de Tempo , Tempo para o Tratamento , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Gastrointestinal bleeding after kidney transplantation is a complication that can occur from immunosuppressant use. We present a case of refractory small bowel bleeding treated successfully with thalidomide after multiple failed attempts of conventional treatment. A 65-year-old male patient with diabetic nephropathy underwent living donor kidney transplantation. The surgery was uneventful, however, he developed immunosuppressant-induced melena with unstable vital signs 11 days later. There were a total of 4 bleeding episodes until the 90th postoperative day, and he received a total of 290 units of red blood cell transfusion during this period. Endoscopic clipping, transarterial embolization, and 2 surgical interventions failed to stop the bleeding. A trial of thalidomide 100 mg per day finally stopped the bleeding and the patient was discharged on the 110th postoperative day with a functioning renal graft. This case shows that thalidomide can be a safe option to treat immunosuppressant-induced refractory gastrointestinal bleeding in the setting of kidney transplantation. Additionally, this is the first case that reports the survival of a renal graft after more than 3000 mL of transfusion.
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Inibidores da Angiogênese/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Humanos , Imunossupressores/efeitos adversos , Doadores Vivos , Masculino , Melena/imunologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Tacrolimo/efeitos adversosRESUMO
OBJECTIVE AND DESIGN: Inflammation plays a causative role in atherosclerosis development. Salsalate is an anti-inflammatory drug used to treat atherosclerosis, but the mechanisms by which it affects atherosclerotic progression remain unclear. METHODS: Human umbilical vascular endothelial cells (HUVECs) and THP-1 human monocytes were treated with salsalate. Heme oxygenase 1 (HO-1) and sirtuin 1 (SIRT1) small interfering RNAs (siRNAs) were used to suppress each gene expression. Protein analyses were performed for measuring the expression of HO-1, SIRT1, nuclear factor kappa B (NFκB), cell adhesion molecules, and endoplasmic reticulum (ER) stress markers. Furthermore, cell adhesion assay, caspase 3 activity assay, and ELISA were also performed. RESULTS: In this study, we show that salsalate increases the expression of HO-1 and SIRT1 in HUVEC and suppresses lipopolysaccharide (LPS)-induced atherosclerotic responses via HO-1- and SIRT1-mediated pathways. Salsalate treatment of HUVEC and THP-1 cells reduced LPS-induced phosphorylation of NFκB and secretion of the proinflammatory cytokines TNFα and MCP-1. Salsalate treatment of HUVEC reduced the expression of the adhesion molecules ICAM, VCAM, and E-selectin and the LPS-induced adhesion of THP-1 cells to HUVEC. Salsalate treatment also attenuated LPS-induced ER stress and cell apoptosis. These anti-atherosclerotic effects were reversed by treating cells with siRNA for HO-1 and SIRT1. CONCLUSIONS: Salsalate ameliorates LPS-induced atherosclerotic reactions via HO-1 and SIRT1-dependent reduction of inflammation and ER stress. Activation of these pathways by salsalate may provide therapeutic strategies for treating atherosclerosis.
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Aterosclerose/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Salicilatos/farmacologia , Sirtuína 1/metabolismo , Quimiocina CCL2/metabolismo , Heme Oxigenase-1/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Sirtuína 1/genética , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: To evaluate superiority of a night float (NF) system in comparison to a traditional night on-call (NO) system for surgical residents at a single institution in terms of efficacy, safety, and satisfaction. METHODS: A NF system was implemented from March to September 2017 and big data analysis from electronic medical records was performed for all patients admitted for surgery or contacted from the emergency room (ER). Parameters including vital signs, mortality, and morbidity rates, as well as promptness of response to ER calls, were compared against a comparable period (March to September 2016) during which a NO system was in effect. A survey was also performed for physicians and nurses who had experienced both systems. RESULTS: A total of 150,000 clinical data were analyzed. Under the NO and NF systems, a total of 3,900 and 3,726 patients were admitted for surgery. Mortality rates were similar but postoperative bleeding was significantly higher in the NO system (0.5% vs. 0.2%, P = 0.031). From the 1,462 and 1,354 patients under the NO and NF systems respectively, that required surgical consultation from the ER, the time to response was significantly shorter in the NF system (54.5 ± 70.7 minutes vs. 66.8 ± 83.8 minutes, P < 0.001). Both physicians (90.4%) and nurses (91.4%) agreed that the NF system was more beneficial. CONCLUSION: This is the first report of a NF system using big data analysis in Korea, and potential benefits of this new system were observed in both ward and ER patient management.
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Severe inflammation in the islets is observed in obese patients with type 2 diabetes. Inflammation in the islets is caused by obesity-induced serum free fatty acids. Asprosin is a fasting-induced adipokine, which contributes to hepatic glucose production. However, the effects of asprosin on inflammation and cellular dysfunction in pancreatic ß-cells remain to be elucidated. Here, we demonstrated that treatment of mouse insulinoma MIN6 cells and human primary islets containing ß-cells with palmitate increased asprosin expression and secretion. Treatment of MIN6 cells and human primary islets with palmitate increased phosphorylation of the inflammatory marker nuclear factor-kappa B (NFκB) and the release of pro-inflammatory cytokines including TNF and MCP-1 and decreased glucose-stimulated insulin secretion and cell viability. However, siRNA-mediated suppression of asprosin reversed these changes. Recombinant asprosin treatment of MIN6 cells and human primary islets augmented the inflammation response, cellular dysfunction, and apoptosis in a dose-dependent manner. Asprosin induced toll-like receptor (TLR) 4 expression and JNK phosphorylation. siRNA for TLR4 or JNK mitigated the effects of asprosin on inflammation and cellular dysfunction. These results suggest that palmitate-derived asprosin secretion from ß-cells results in their inflammation and dysfunction through a TLR4/JNK-mediated pathway. This report suggests asprosin as a novel therapeutic target for the treatment of type 2 diabetes through preservation of ß-cell function.
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Glucose/toxicidade , Inflamação/metabolismo , Inflamação/patologia , Secreção de Insulina , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Fragmentos de Peptídeos/metabolismo , Hormônios Peptídicos/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , AMP Cíclico/biossíntese , Fibrilina-1 , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Palmitatos/toxicidade , Fosforilação/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: The use of endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysms (r-AAA) is steadily increasing. We report early experiences of EVAR for r-AAA performed in two tertiary referral centers in Korea. METHODS: We retrospectively reviewed r-AAA patients treated by EVAR from May 2013 to December 2017. An EVAR-first strategy for r-AAA was adopted whenever feasible. The demographic information, anatomic characteristics, operative details, postoperative complications with special attention to abdominal compartment syndrome (ACS), and 30-day mortality were collected and analyzed. RESULTS: We identified 13 patients who underwent EVAR for r-AAA. Mean age was 74.2 years and mean AAA size was 74.2 mm. Two patients underwent cardiopulmonary resuscitation at initial presentation. Bifurcated stent grafts were used in 12 out of 13 cases and physician-modified endografts with fenestrated/chimney techniques were performed in 2 cases with short neck. Successful stent graft deployment was achieved in all cases. Three patients were suspected of having ACS and 2 of them underwent laparotomy for decompression. The 30-day mortality was 7.7% (1 of 13), the only mortality being a patient that refused decompressive laparotomy for suspected ACS. CONCLUSION: Despite the small numbers, the outcomes of EVAR for treatment of r-AAA were very promising, even in selected cases with unfavorable anatomy. These outcomes were achieved by a dedicated and well-trained team approach, and by use of high-end angiographic technology. Finally, ACS after EVAR is not uncommon, and requires a high index of suspicion as well as liberal use of decompressive surgery.
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PURPOSE: Isolated iliac artery aneurysm (IIAA) is uncommon. It is frequently treated by endovascular aneurysm repair (EVAR). This study was to evaluate treatment results of IIAA and survey aortic diameter after EVAR. METHODS: Patients treated for IIAA in Seoul St. Mary's Hospital and Bundang Seoul National University from 2005 to April 2016 were retrospectively enrolled. The inclusion criteria of IIAA was >30 mm of iliac artery aneurysm without abdominal aortic aneurysm, which was treated by open surgical repair (OSR) or EVAR. Patients' clinical characteristics, treatment results, and mortality were obtained from electronic medical records. Diameters of aorta and iliac arteries were measured periodically with scheduled interval based on CT scans. RESULTS: Forty-nine patients (40 males; mean age, 71.9 ± 11.1 years) were enrolled. Five ruptured IIAAs were treated with EVAR (n = 1) or hybrid methods (n = 4). The diameter of ruptured IIAAs was 65 ± 31.4 mm, which was not significantly different from that of elective (44.3 ± 17.0 mm). Forty-four elective IIAA underwent 9 OSR, 31 EVARs, and 3 hybrid treatments (15 bifurcated and 12 straight stent-grafts). Treatment success rate was 93.8% without hospital mortality. There were 4 type I endoleak, 1 type II endoleak, and 1 type III endoleak without aneurysm-related mortality during follow-up. However, the aortic diameter was increased over time though there was no change or decrease in common iliac artery's diameter. CONCLUSION: Treatment of IIAA included various endovascular modalities as well as open surgery. Regular surveillance is still needed due to aortic dilatation after its treatment.
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Chitinase 3-like protein 1 (CHI3L1) is a novel biomarker of systemic inflammation. However, the effects of CHI3L1 on the progression of atherosclerosis remain to be explored. In the current study, we found that CHI3L1 induces peroxisome proliferator-activated receptor delta (PPARδ) expression, leading to a dose-dependent increase in oxygen-regulated protein 150 (ORP150) expression. We demonstrated that CHI3L1 suppresses atherosclerotic reactions caused by LPS treatment via a PPARδ-dependent pathway. Treatment of HUVECs and THP-1 cells with CHI3L1 suppressed LPS-induced phosphorylation of nuclear factor kappa B (NFκB) and secretion of proinflammatory cytokines such as TNFα and MCP-1. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly reduced after CHI3L1 treatment. Furthermore, LPS-induced endoplasmic reticulum (ER) stress and cell apoptosis were significantly ameliorated after treatment of HUVECs with CHI3L1. Particularly, all of the pro-atherosclerotic effects were significantly mitigated by treatment with small interfering (si) RNA for PPARδ. In conclusion, CHI3L1 ameliorates LPS-induced atherosclerotic reactions via PPARδ-mediated suppression of inflammation and ER stress.
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Aterosclerose/metabolismo , Proteína 1 Semelhante à Quitinase-3/metabolismo , Estresse do Retículo Endoplasmático , PPAR delta/metabolismo , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Aterosclerose/patologia , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Proteína 1 Semelhante à Quitinase-3/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR delta/genética , Células THP-1 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 (TGFß1) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of TGFß1 reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of TGFß1 or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a TGFß1-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented TGFß1 mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.
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Adiponectina/metabolismo , Glicoproteínas/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Adiponectina/administração & dosagem , Adiponectina/genética , Animais , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular , Proliferação de Células/fisiologia , Glicoproteínas/administração & dosagem , Glicoproteínas/genética , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Proteínas Recombinantes/administração & dosagem , Fator de Crescimento Transformador beta1/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose TumoralRESUMO
PURPOSE: Intermittent claudication is the most common early symptom of peripheral arterial occlusive disease. Walking impairment questionnaire (WIQ) is a short, inexpensive, easy-to-complete questionnaire to assess intermittent claudication and can provide data of usual walking. The purpose of this study is to validate the new Korean version of WIQ. METHODS: Total 51 patients with claudication were enrolled. While 4 patients were dropped out, 47 patients with claudication into were divided groups based on the treatment received: surgery (n = 33) and medication (n = 14). The surgery group was subdivided into the bypass (n = 13) and intervention (n = 20) groups. WIQ score, ankle-brachial index (ABI), and treadmill test scores were assessed initially and after 12 weeks. RESULTS: The WIQ scores were significantly correlated with ABI and pain-free walking distance (PFWD) and maximum walking distance (MWD) in all groups (except for MWD in the intervention group). Speed and stair-climb scores (2 WIQ domains) were well correlated with ABI, PFWD, and MWD. Distance scores were mostly correlated with ABI, PFWD, and MWD in all groups except ABI in the bypass and intervention groups and MWD in the bypass group. Reproducibility was observed in all groups (intraclass correlation coefficient > 0.8). CONCLUSION: The Korean version of the WIQ is valid and reproducible, and can be effectively used to assess Korean patients with intermittent claudication.
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BACKGROUND: Relationship between the distance of the catheter tip from the saphenous femoral junction and the length of residual stump after radiofrequency ablation (RFA) has not been sufficiently examined. OBJECTIVE: The purpose of this study was to investigate the change of great saphenous vein (GSV) stump with clinical outcomes after RFA. MATERIAL AND METHODS: From January 2014 to September 2014, 67 patients (91 limbs) underwent GSV RFA and the collected data were analyzed prospectively. Change of GSV stump length and clinical symptoms was evaluated at 1-, 3-, and 6-month intervals. Ablations were performed between 2 to 2.5 cm distal to the saphenofemoral junction. RESULTS: The residual GSV stump decreased in length to 1.465 ± 0.504 cm at the first month follow-up. This length persisted throughout the 1-, 3-, and 6-month follow-ups. There were no statistically significant differences during the follow-up period. Both the Venous Clinical Severity Score and the Aberdeen Varicose Vein Symptom Severity Score was significantly improved at 1 month and improved even further at 3 months. One patient (1.1%) developed endovenous heat-induced thrombosis (EHIT) Class 3 at 1-month follow-up and was treated with anticoagulation. CONCLUSION: This study has shown that the adequate positioning of RFA catheter tip (2.0-2.5 cm) is recommended to decrease the incidence of EHIT.
Assuntos
Ablação por Cateter , Procedimentos Endovasculares , Veia Safena/cirurgia , Trombose/epidemiologia , Insuficiência Venosa/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Temperatura Alta/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Trombose/etiologiaRESUMO
BACKGROUND: Postoperative catheter-related bladder discomfort (CRBD) can be a distressing complication for patients in whom a urinary catheter was inserted during an operation. Our randomized, dual-center, clinical trial investigated the effects of butylscopolamine on the prevention of postoperative CRBD in patients undergoing various operations. METHODS: Adult male patients undergoing elective operations requiring intraoperative urinary catheterization under general anesthesia were enrolled. They were assigned randomly to 2 groups: The butylscopolamine group (n = 49) received 20 mg of butylscopolamine intravenously immediately before the end of the operation; no medication was given for prevention of CRBD in the control group (n = 50). The presence and severity of CRBD were assessed at 1, 2, and 6 hours postoperatively. Adverse effects of butylscopolamine were also examined. RESULTS: The overall incidence of CRBD was less in the butylscopolamine group than in the control group (31% vs 66%, respectively; P = .001). The incidence of CRBD at 1, 2, and 6 hours postoperatively was also less in the butylscopolamine group (P = .006, .04, and .048, respectively). In addition, the average severity of CRBD for 6 hours postoperatively was significantly less in the butylscopolamine group than in the control group (median, 0 [interquartile range, 0-17] vs 22 [interquartile range, 0-47], respectively; P = .002). Adverse effects were comparable between the 2 groups. CONCLUSION: Intravenous administration of butylscopolamine at the end of an operation decreases effectively the incidence and severity of early postoperative CRBD without adverse effects.