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1.
J Cardiovasc Surg (Torino) ; 61(1): 67-72, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29616520

RESUMO

BACKGROUND: Due to recent advances in endograft design and percutaneous access, technical success could be increased during endovascular aneurysm repair (EVAR). Beside EVAR, endovascular aneurysm sealing (EVAS) provides an alternative procedure to treat aneurysms. To compare the two methods, additional benchmark criteria should be evaluated: Screening time, dose area product (DAP), procedure time and contrast use. In this study these technical variables are analyzed for EVAS vs. EVAR in comparable patient cohorts. METHODS: It is a retrospective, single-center study. Only elective cases of infrarenal aortic aneurysms were included, all treated by the same surgeon (D.B.). Procedures were performed within the instructions for use without additional procedures. All operations were undertaken in a hybrid operating theatre. For EVAR, only the Medtronic Endurant® and the Gore C3 Excluder® were included. For EVAS the Nellix® from Endologix was used. RESULTS: Between 2012 and 2016, 67 patients were treated with EVAS and 40 with EVAR; of these 20 and 16 could be introduced into the study respectively. Median age was 73 and 72 years respectively (only men). The two groups were comparable in terms of BMI, GFR and ASA-status. Screening time was reduced for EVAS (10.6 vs. 14.5 min., P<0.01), while the DAP was not significantly different. Procedural time and contrast use were increased for EVAS (120 vs. 96 min., 120 vs. 79 mL, P<0.01). CONCLUSIONS: Especially the younger EVAS-procedure requires ongoing review in order to further reduce contrast agent. Reduced screening time for EVAS does not have a significant impact on radiation dose.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Aortografia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Meios de Contraste/administração & dosagem , Procedimentos Endovasculares/instrumentação , Doses de Radiação , Exposição à Radiação , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Meios de Contraste/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Biochem Biophys Res Commun ; 511(2): 343-349, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30782482

RESUMO

Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease with life-threatening complications. Increasing evidence suggests that smooth muscle cell (SMC) dysfunction and cell death contribute to dilatation and rupture of the aorta by inducing an inflammatory response. The exact mechanism of this response however, is incompletely understood. We here investigated in vitro the capacity of autologous necrotic cell debris (CD) to induce inflammasome components and inflammatory mediators in aortic SMC (AAA-SMC) isolated from patients with AAA undergoing surgical repair. AAA-SMCs were additionally primed with Interferon- γ (IFN-γ) before treatment with CD in order to mimic the proinflammatory status caused by higher IFN-γ concentrations that have been demonstrated in the wall of AAAs. Real-time RT-PCR revealed that CD significantly increased NLRP3 and IL1B mRNA expression in different SMC cultures within 6 h of exposure. Priming of the AAA-SMC with IFN-γ significantly increased expression of NLRP3, AIM2, IFI16 and CASP1 mRNAs, whereas IL1B mRNA was reduced. Additional exposure of IFN-γ-primed AAA-SMC to CD for 6-24 h, further augmented expression of AIM2, NLRP3, and Caspase-1 protein levels. Analysis of the SMC supernatants by ELISA revealed CD-induced release of the senescence-associated cytokines IL-6 and MCP-1 in native and IFN-γ-primed SMC, whereas no secretion of Interleukin-(IL) 1α and IL-1ß secretion were observed. Our results implicate a role of necrotic cell debris derived from dead neighboring cells in SMC dysfunction and in inflammatory response of AAA tissue.


Assuntos
Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/patologia , Inflamassomos/imunologia , Miócitos de Músculo Liso/patologia , NF-kappa B/imunologia , Aorta Abdominal/citologia , Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/imunologia , Células Cultivadas , Humanos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/imunologia , Necrose/complicações , Necrose/imunologia , Necrose/patologia
3.
Eur Surg Res ; 60(1-2): 13-23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30726831

RESUMO

BACKGROUND/PURPOSE: To establish a high-quality vascular biomaterial bank to serve vascular research teams and act as a basis for translational medicine. The aim was to collect and store material so that investigation into the pathogenesis of vascular disease would be possible employing methods based on histopathology and/or molecular biology. METHODS: The Vascular Biomaterialbank Heidelberg (VBBH) evolved as part of an established, partly accredited biobank complex at the University of Heidelberg (BioMaterialBank Heidelberg - BMBH). The BMBH provided infrastructure regarding legal and quality issues as well as safety, protocols for specimen collection, data management, and publication of results. Protocols were modified where necessary to accommodate specific needs of vascular tissue research. Correct identification of vascular biomaterial is controlled by certified vascular surgeons and pathologists at biobank entry and exit. Pseudonymized clinical data are attached to every specimen. RESULTS: The VBBH provides standardized operating procedures (SOP) regulating the request, processing, and delivery of material to researchers, as well as project tracking. Tissue samples for a research project are requested by filling out an online application form. Within 3-5 working days, a scientific board, including a member of the VBBH and a member of the BMBH, decide upon acceptance or rejection of the research project. Criteria determining acceptance include whether enough samples are available for the particular investigation and whether planned methods are judged adequate to successfully complete the research project. Through tracking of all ongoing studies involving specimens from the VBBH, methods for tissue conservation are continually being optimized. The VBBH platform has supported numerous high-ranking publications involving diverse medical departments and reflects a gain in translational medicine. CONCLUSIONS: SOPs and controls by certified specialists ensure the high quality of specimens obtained through the VBBH. Research performed by vascular surgeons can be facilitated by using the VBBH.


Assuntos
Materiais Biocompatíveis , Bancos de Espécimes Biológicos , Pesquisa Médica Translacional , Procedimentos Cirúrgicos Vasculares , Bancos de Espécimes Biológicos/legislação & jurisprudência , Bancos de Espécimes Biológicos/normas , Gerenciamento de Dados , Humanos , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Doenças Vasculares/etiologia
4.
Vasa ; 48(2): 186-192, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30421661

RESUMO

BACKGROUND: The enzyme glyoxalase1 (GLO1) is the main opponent in the degradation of the reactive metabolite methylglyoxal (MG), which by glycation of macromolecules is involved in atherogenesis. Reduced GLO1-activity in atherosclerotic tissue is known to be associated with diabetes. It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells. The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes. PATIENTS AND METHODS: Patients with type 2 diabetes and carotid artery disease were included into the study prospectively. Type of diabetes-medication was documented upon admission along with demographic and clinical history. Using shock frozen endarterectomy-derived carotid artery plaques, GLO1-activity as well as protein expression was measured by a spectophotometric assay and western-blotting respectively. RESULTS: 33 patients (76 % male, mean age 71 years) were included into the study and were divided according to treatment with metformin or not (15 vs. 18 patients). GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056). Normalisation of GLO1-activity onto GLO1-expression level lead to a significant increase by more than twofold (8.48 vs. 3.85, p = 0.044) while GLO1-protein levels did not differ significantly. GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment. CONCLUSIONS: Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions. Regarding the macro- and microvascular complications in these patients further studies are needed to gain more insight into the effect of metformin on the GLO/MG system.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Metformina/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Lactoilglutationa Liase , Masculino , Respeito
5.
Semin Vasc Surg ; 29(3): 106-113, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27989315

RESUMO

Endovascular repair of abdominal aortic aneurysms (EVAR) is now an established treatment modality for suitable patients presenting with aneurysm rupture. EVAR for ruptured aneurysms reduces transfusion, mechanical ventilation, intensive care. and hospital stay when compared with open surgery. In the emergency setting, however, EVAR is limited by low applicability due to adverse clinical or anatomical characteristics and increased need for reintervention. In addition, ongoing bleeding from aortic side branches post-EVAR can cause hemodynamic instability, larger hematomas, and abdominal compartment syndrome. Endovascular aneurysm sealing, based on polymer filling of the aneurysm, has the potential to overcome some of the limitations of EVAR for ruptured aneurysms and to improve outcomes. Recent literature suggests that endovascular aneurysm sealing can be performed with early mortality similar to that of EVAR for ruptured aortic aneurysms, but experience is limited to a few centers and a small number of patients. The addition of chimney grafts can increase the applicability of endovascular aneurysm sealing in order to treat short-neck and juxtarenal aneurysms as an alternative to fenestrated endografts. Further evaluation of the technique, with larger longitudinal studies, is necessary before advocating wider implementation of endovascular aneurysm sealing in the emergency setting.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Angiografia por Tomografia Computadorizada , Emergências , Endoleak/etiologia , Endoleak/prevenção & controle , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Humanos , Desenho de Prótese , Fatores de Risco , Resultado do Tratamento
6.
J Vasc Surg ; 64(4): 990-4, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27478003

RESUMO

OBJECTIVE: Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level. METHODS: HbA1c level was determined in venous blood of patients with carotid artery disease. Protein level of GLO1 was measured in endarterectomy-derived carotid artery plaques by Western blotting. Activity was measured by spectrophotometric assay in the plaques as well as in the erythrocytes; GLO1 activity in erythrocytes was compared with that in a cohort of healthy individuals (n = 15; 33% men; average age, 60 years). RESULTS: There were 36 patients with carotid artery disease (69% men; average age, 69 years) included in this study and divided into two equal groups: group I, HbA1c < 5.7% (<39 mmol/mol); and group II, 5.7% ≤ HbA1c < 6.5% (39 mmol/mol ≤ HbA1c < 48 mmol/mol). GLO1 activity in carotid plaques was reduced by 29% in group II compared with group I (P = .048), whereas protein expression was unchanged (P = .25). Analysis of GLO1 activity in erythrocytes revealed no difference between the groups (P = .36) or in comparison to healthy controls (P = .15). Examination of clinical parameters showed an increased amount of patients with concomitant peripheral arterial disease in group II (44% vs 10%; P = .020). CONCLUSIONS: Reduction of GLO1 activity in atherosclerotic lesions of nondiabetic patients with increased HbA1c is associated with a functional involvement of this protective enzyme in atherogenesis. Systemic GLO1 activity seems to be independent of both HbA1c and localized atherosclerosis as it was unchanged between group I and group II as well as compared with healthy controls, respectively.


Assuntos
Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/enzimologia , Hemoglobina A Glicada/análise , Lactoilglutationa Liase/análise , Placa Aterosclerótica , Idoso , Biomarcadores/sangue , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/cirurgia , Estudos de Casos e Controles , Regulação para Baixo , Endarterectomia das Carótidas , Eritrócitos/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Cima
7.
Langenbecks Arch Surg ; 401(3): 289-98, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27055854

RESUMO

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) represents one of the most challenging emergencies in surgery. Open repair (OR) is associated with relevant morbidity and mortality and has not been reduced significantly over the last decade. The introduction of endovascular aneurysm repair (EVAR) and its meanwhile common use in the treatment of rAAA has raised the demand for randomised controlled trials (RCTs) in order to resolve a potential superiority of either OR or EVAR. PURPOSE: This review discusses the current treatment strategies in rAAA repair including diagnostics, peri-operative management and results of OR and EVAR, focussing on RCTs comparing both modalities. RESULTS: Thirty-day mortality after OR and EVAR shows no significant difference in published RCTs. In particular with respect to OR, 30-day mortality was much lower than anticipated throughout all RCTs ranging from 18 to 37 %. EVAR for rAAA resulted in reduced in-hospital stay. Limitations of all except one RCT are low patient recruitment and exclusion of haemodynamically unstable patients. CONCLUSIONS: OR and EVAR need to be provided for rAAA. Despite lacking evidence, EVAR is the first choice treatment in experienced high-volume vascular centres. Low mortality rates in all RCTs raise the question if aortic surgery should be centralised.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Resultado do Tratamento
8.
Vascular ; 24(6): 621-627, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27059764

RESUMO

PURPOSE: Infections are a major setback of vascular reconstruction and associated with considerable morbidity and mortality. We evaluated retrospectively our results with self-made bovine pericardial grafts in infected vessel revascularization versus standard graft material. BASIC METHODS: Retrospective analysis of 9 patients with bovine reconstruction and 10 patients with miscellaneous grafts (vein, homograft) for vascular infections. PRINCIPAL FINDINGS: Infection-free rate of the pericardial group was 100% in 17 months. For patients after reconstructions with miscellaneous grafts, the infection-free rate was 82% in 45 months. Overall in-hospital mortality was 10.5%. There were no in-hospital deaths in the pericardial group. Graft patency of the whole cohort was 100%. The median follow up was 11.74 months. CONCLUSION: Self-made bovine pericardial tube grafts can be crafted to almost any size and adjusted to complex anatomic requirements. The use was feasible in various situations and was associated with good preliminary results concerning patency and reinfection.


Assuntos
Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular/efeitos adversos , Pericárdio/transplante , Infecções Relacionadas à Prótese/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Animais , Implante de Prótese Vascular/mortalidade , Bovinos , Intervalo Livre de Doença , Feminino , Xenoenxertos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Infecções Relacionadas à Prótese/fisiopatologia , Recidiva , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Veias/transplante
9.
J Diabetes Res ; 2016: 2981639, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26788517

RESUMO

Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage. Yet, the role of Glo1 in atherosclerosis remains unclear. In this study, the effect of Glo1 on mouse metabolism and atherosclerosis is evaluated. Methods. Glo1 knockdown mice were fed a high fat or a standard diet for 10 weeks. Body weight and composition were investigated by Echo MRI. The PhenoMaster system was used to measure the energy expenditure. To evaluate the impact of Glo1 on atherosclerosis, Glo1(KD) mice were crossed with ApoE-knockout mice and fed a high fat diet for 14 weeks. Results. Glo1 activity was significantly reduced in heart, liver, and kidney lysates derived from Glo1(KD) mice. Yet, there was no increase in methylglyoxal-derived AGEs in all organs analyzed. The Glo1 knockdown did not affect body weight or body composition. Metabolic studies via indirect calorimetry did not show significant effects on energy expenditure. Glo1(KD) mice crossed to ApoE(-/-) mice did not show enhanced formation of atherosclerosis. Conclusion. A Glo1 knockdown does not have major short term effects on the energy expenditure or the formation of atherosclerotic plaques.


Assuntos
Doenças da Aorta/enzimologia , Aterosclerose/enzimologia , Metabolismo Energético , Lactoilglutationa Liase/deficiência , Animais , Doenças da Aorta/genética , Doenças da Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/patologia , Calorimetria Indireta , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo Energético/genética , Predisposição Genética para Doença , Rim/enzimologia , Lactoilglutationa Liase/genética , Fígado/enzimologia , Imagem por Ressonância Magnética , Masculino , Camundongos Knockout , Miocárdio/enzimologia , Fenótipo , Placa Aterosclerótica , Aldeído Pirúvico/metabolismo
10.
Ann Vasc Surg ; 29(5): 1019.e7-1019.e10, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25765639

RESUMO

BACKGROUND: The aim of this study was to report the occurrence of a type IIIb endoleak after endovascular repair of a thoracic aortic aneurysm caused by endoanchor dislocation. CASE REPORT: An 84-year-old female patient underwent thoracic endovascular repair for aneurysmal disease of her thoracic aorta. The procedure included primary left subclavian artery revascularization and the placement of endoanchors to enhance fixation of the endograft within the aortic arch. Dislocation of one of the endoanchors resulted in a graft defect leading to a type IIIb endoleak and aortic diameter expansion. CONCLUSIONS: Endoanchors represent a promising adjunct in endovascular repair settings. However, their use requires careful procedure planning and special attention during follow-up.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Migração de Corpo Estranho/complicações , Âncoras de Sutura , Técnicas de Sutura/efeitos adversos , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico , Aortografia , Prótese Vascular , Endoleak/diagnóstico , Endoleak/cirurgia , Feminino , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/cirurgia , Humanos , Imageamento Tridimensional , Falha de Prótese , Reoperação , Técnicas de Sutura/instrumentação , Tomografia Computadorizada por Raios X
11.
Med Sci Monit Basic Res ; 21: 262-70, 2015 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-26718893

RESUMO

BACKGROUND The aim of this study was to analyze device conformability in TEVAR of acute and chronic (a/c) type B aortic dissections (TBAD) using the Gore Conformable Thoracic Aortic Stent-graft (CTAG). MATERIAL AND METHODS From January 1997 to February 2014, a total of 90 out of 405 patients in our center received TEVAR for TBAD. Since November 2009, 23 patients (16 men; median age: 62 years) were treated with the CTAG. Indications were complicated aTBAD in 15 (65%) and expanding cTBAD in 8 (35%) patients. Primary endpoints were the assessment of device conformability by measuring the distance (D) from the radiopaque gold band marker (GM) at the proximal CTAG end to the inner curvature (IC) of the arch on parasagittal multiplanar reformations of CT angiography, as well as the evaluation of aortic diameter changes following TEVAR. Median follow-up was 13.3 months (range: 2 days to 35 months). RESULTS Primary and secondary success rates were 91.3% (21/23) and 95.6% (22/23), respectively. There was 1 type Ia endoleak, retrograde dissection or primary conversion was not observed. Median GM-IC-D was 0 mm (range: 0 mm to 10 mm). GM-IC-D was associated with zone 2 placement compared to zone 3 (P=0.036). There was no association between GM-IC-D formation and arch type. In aTBAD cases the true lumen significantly increased after TEVAR (P=0.017) and the false lumen underwent shrinkage (P=0.025). In cTBAD patients the false lumen decreased after TEVAR (P=0.036). CONCLUSIONS The CTAG shows favorable conformability and wall apposition in challenging arch pathologies such as TBAD.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Procedimentos Endovasculares/métodos , Stents , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
J Vasc Surg ; 62(2): 471-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24767709

RESUMO

OBJECTIVE: Age and gender are two factors that determine the risk of atherosclerosis. The latter effect is only partly understood. Dicarbonyls, in particular methylglyoxal, participate in the development of atherosclerosis, and their major detoxification route is the enzyme glyoxalase 1 (GLO1), which is known to decrease during aging. METHODS: GLO1 expression and activity were studied in atherosclerotic carotid artery lesions of 71 patients with respect to demographic and clinical characteristics. RESULTS: GLO1 activity was nonsignificantly reduced by >50% in individuals with carotid artery disease compared with control individuals. There was no significant difference in GLO1 expression between the groups; however, the GLO1 activity-to-protein ratio showed a significant reduction for the carotid artery disease patients compared with the controls. The reduction in the GLO1 activity-to-protein ratio was more pronounced in men and was associated with increased inflammation shown by a significant elevation in the expression-level of interleukin-1ß. CONCLUSIONS: These data suggest that GLO1 is regulated on the post-translational level by factors such as gender as well as factors that affect the overall burden of atherosclerosis.


Assuntos
Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/metabolismo , Lactoilglutationa Liase/biossíntese , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interleucina-1beta/biossíntese , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
13.
Arch Dermatol Res ; 307(2): 191-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25348252

RESUMO

Many tissues are constantly exposed to mechanical stress, e.g. shear stress in vascular endothelium, compression forces in cartilage or tensile strain in the skin. Dermal fibroblasts can differentiate into contractile myofibroblasts in a process requiring the presence of TGFß1 in addition to mechanical load. We aimed at investigating the effect of cyclic mechanical strain on dermal fibroblasts grown in a three-dimensional environment. Therefore, murine dermal fibroblasts were cultured in collagen gels and subjected to cyclic tension at a frequency of 0.1 Hz (6 cycles/min) with a maximal increase in surface area of 10 % for 24 h. This treatment resulted in a significant increase in active TGFß1 levels, leaving the amount of total TGFß1 unaffected. TGFß1 activation led to pSMAD2-mediated transcriptional elevation of downstream mediators, such as CTGF, and an auto-induction of TGFß1, respectively.


Assuntos
Fibroblastos/metabolismo , Transdução de Sinais/fisiologia , Pele/citologia , Estresse Mecânico , Fator de Crescimento Transformador beta1/metabolismo , Animais , Western Blotting , Células Cultivadas , Colágeno , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Meios de Cultura , Fibroblastos/patologia , Técnica Indireta de Fluorescência para Anticorpo , Camundongos , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/genética
14.
Rev Sci Instrum ; 85(2): 02A951, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24593530

RESUMO

The clinical operation at the Heidelberg Ion Beam Therapy Center (HIT) started in November 2009; since then more than 1600 patients have been treated. In a 24/7 operation scheme two 14.5 GHz electron cyclotron resonance ion sources are routinely used to produce protons and carbon ions. The modification of the low energy beam transport line and the integration of a third ion source into the therapy facility will be shown. In the last year we implemented a new extraction system at all three sources to enhance the lifetime of extraction parts and reduce preventive and corrective maintenance. The new four-electrode-design provides electron suppression as well as lower beam emittance. Unwanted beam sputtering effects which typically lead to contamination of the insulator ceramics and subsequent high-voltage break-downs are minimized by the beam guidance of the new extraction system. By this measure the service interval can be increased significantly. As a side effect, the beam emittance can be reduced allowing a less challenging working point for the ion sources without reducing the effective beam performance. This paper gives also an outlook to further enhancements at the HIT ion source testbench.


Assuntos
Ciclotrons/instrumentação , Radioterapia/instrumentação , Manutenção , Fatores de Tempo
15.
Biochem Soc Trans ; 42(2): 528-33, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24646273

RESUMO

Glo1 (glyxoalase I) is a cytosolic protein expressed in all mammalian cells. Its physiological function is the detoxification of MG (methylglyoxal), which is a potent precursor of AGEs (advanced glycation end-products). Although the impact of AGEs on different forms of vascular diseases has been intensively investigated, the evidence for the involvement of Glo1 and MG is still scarce. Recently, several studies have provided significant evidence for Glo1 having a protective effect on microvascular complications in diabetic patients, such as retinopathy and nephropathy. Regarding macrovascular complications, especially atherosclerotic lesions, the impact of Glo1 is even less clear. In the present article, we review the latest findings regarding the role of Glo1 and MG in vascular biology and the pathophysiology of micro- and macro-vascular disease.


Assuntos
Aterosclerose/enzimologia , Lactoilglutationa Liase/metabolismo , Doenças Vasculares/enzimologia , Animais , Aterosclerose/metabolismo , Humanos , Doenças Vasculares/metabolismo
16.
J Vasc Surg ; 59(3): 794-803, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23790454

RESUMO

BACKGROUND: Absent in melanoma (AIM2) was recently identified to act as a cytosolic DNA sensor in innate immunity. Considering the role of chronic inflammation in atherosclerosis, we hypothesized that AIM2 may act as a damage signal that is activated in response to cellular stress likewise in vascular cells of larger arteries. We thus addressed AIM2 expression in healthy arterial wall and in different vascular lesions. In addition, AIM2 expression was characterized in cultured human aortic endothelial cells (HAoECs), smooth muscle cells (HAoSMCs), and T/G-HA-vascular smooth muscle cells (VSMCs) in response to different stimuli. METHODS: Carotid and aortic lesions from patients who underwent surgery and normal arterial specimens were analyzed by immunohistochemistry for AIM2 expression. Cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs were stimulated in vitro with proinflammatory cytokines (tumor necrosis factor-α, interferon-γ) or poly(dA:dT) and analyzed for AIM2 transcript and protein expression. RESULTS: AIM2 was detected in ECs of the intima and vasa vasorum of normal carotid artery and aorta. Moreover, AIM2 was moderately expressed in VSMCs of normal media and intima layers, as well as in VSMCs of atherosclerotic lesions. Increased AIM2 expression was detected around the necrotic core of atherosclerotic carotid lesions and in the vasa vasorum neovasculature of aortic aneurysms. Subsequent in vitro analysis identified an endogenous AIM2 expression in cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs that was markedly increased upon treatment of the cells with tumor necrosis factor-α, interferon-γ, or cytosolic DNA. CONCLUSIONS: ECs and VSMC are able to respond to inflammatory signals by upregulation of AIM2 expression, indicating a role of AIM2 in vascular pathogenesis.


Assuntos
Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Doenças das Artérias Carótidas/metabolismo , Células Endoteliais/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteínas Nucleares/metabolismo , Doenças da Aorta/genética , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/patologia , Estudos de Casos e Controles , Linhagem Celular , Proteínas de Ligação a DNA , Células Endoteliais/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Músculo Liso Vascular/imunologia , Miócitos de Músculo Liso/imunologia , Necrose , Proteínas Nucleares/genética , Placa Aterosclerótica , Poli dA-dT/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Tempo , Transcrição Genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
17.
J Behav Ther Exp Psychiatry ; 45(1): 39-45, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23978628

RESUMO

BACKGROUND AND OBJECTIVES: Social phobia is characterized by avoidance of feared social situations. Although avoidance is a central feature of social anxiety, few studies have examined avoidance learning. METHODS: We used a probabilistic instrumental learning paradigm where participants had to learn by trial and error which response led to the disappearance of a neutral or angry face. 20 high socially anxious and 20 non-socially anxious individuals with an average level of social anxiety learned to avoid an angry or a neutral face by choosing one of two cues. Each of the cues led to the disappearance of the face either with high or low reinforcement probability. RESULTS: Groups learned to choose the more effective cue across trials and did not differ with regard to self-report valence, arousal for the faces or the a posteriori estimated reinforcement probability for both cues. High socially anxious individuals as compared to the controls chose the high probability cue significantly more often and were slower particularly when the neutral face could be avoided. Notably, HSA engaged in more avoidance responding to the neutral as compared to the angry face early on during the experiment. LIMITATIONS: Due to the experimental design, the observed avoidance behavior most likely reflects the motivation for avoidance rather than contingency learning per se. CONCLUSIONS: In social anxiety, neutral faces might be processed as ambiguous social cues and strongly motivate avoidance behavior.


Assuntos
Aprendizagem da Esquiva/fisiologia , Reação de Fuga/fisiologia , Transtornos Fóbicos/fisiopatologia , Aprendizagem por Probabilidade , Adulto , Análise de Variância , Nível de Alerta/fisiologia , Sinais (Psicologia) , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Inquéritos e Questionários , Adulto Jovem
18.
Exp Dermatol ; 21(10): 765-70, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23078398

RESUMO

Mechanical forces are highly variable ranging from the ubiquitous gravity force to compression, fluid shear, torsion, tension and other forms. Mechanical forces act on cells and modulate their biological responses by regulating gene transcription, enzyme and growth factor activity. In soft connective tissues, formation of myofibroblasts strictly requires a mechanically loaded environment in addition to local transforming growth factor (TGF)-ß activity, which itself can be modulated by the mechanical status of the environment. The aim of this study was to monitor the adaptive responses of primary dermal fibroblasts towards cyclic mechanical stress under conditions of high force to better understand the regulation of gene expression in normal skin and mechanisms of gene regulation in mechanically altered fibrotic skin. Primary murine dermal fibroblasts were exposed to equi-biaxial tensile strain. Cyclic mechanical tension was applied at a frequency of 0.1 Hz (6× /min) for 24 h with a maximal increase in surface area of 15%. This treatment resulted in downregulation of alpha smooth muscle actin (αSMA) and connective tissue growth factor (CTGF) but not of TGFß1 expression. Cyclic strain also strongly reduced endothelin-1 (ET-1) expression and supplementing strained cultures with exogenous ET-1 rescued αSMA and CTGF levels. Of note, no biologically significant levels of TGFß1 activity were detected in strained cultures. We provide evidence for a novel, TGFß1-independent mechanism regulating ET-1 expression in dermal fibroblasts by biomechanical forces. Modulation of ET-1-dependent activities regulates downstream fibrotic marker genes; this pathway might therefore provide an approach to attenuate myofibroblast differentiation.


Assuntos
Endotelina-1/genética , Endotelina-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismo , Adaptação Fisiológica , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Regulação para Baixo , Endotelina-1/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Estresse Mecânico , Fator de Crescimento Transformador beta1/genética
19.
J Cell Sci ; 123(Pt 22): 3872-83, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20980390

RESUMO

Wound healing crucially relies on the mechanical activity of fibroblasts responding to TGFß1 and to forces transmitted across focal adhesions. Integrin-linked kinase (ILK) is a central adapter recruited to integrin ß1 tails in focal adhesions mediating the communication between cells and extracellular matrix. Here, we show that fibroblast-restricted inactivation of ILK in mice leads to impaired healing due to a severe reduction in the number of myofibroblasts, whereas inflammatory infiltrate and vascularization of the granulation tissue are unaffected. Primary ILK-deficient fibroblasts exhibit severely reduced levels of extracellular TGFß1, α-smooth muscle actin (αSMA) production and myofibroblast conversion, which are rescued by exogenous TGFß1. They are further characterized by elevated RhoA and low Rac1 activities, resulting in abnormal shape and reduced directional migration. Interference with RhoA-ROCK signaling largely restores morphology, migration and TGFß1 levels. We conclude that, in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGFß1 production, which is essential for dermal repair following injury.


Assuntos
Fibroblastos/metabolismo , Miofibroblastos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/biossíntese , Animais , Movimento Celular/fisiologia , Fibroblastos/citologia , Fibroblastos/enzimologia , Tecido de Granulação/enzimologia , Tecido de Granulação/metabolismo , Tecido de Granulação/patologia , Camundongos , Miofibroblastos/citologia , Miofibroblastos/enzimologia , Proteínas Serina-Treonina Quinases/deficiência , Transdução de Sinais , Pele/citologia , Pele/enzimologia , Pele/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Cicatrização/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
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