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OBJECTIVES: Dialysis fistula aneurysms are common complications which in selective cases require surgical revision. It is recommended to detect and treat outflow stenosis concurrent with a dialysis fistula aneurysm, but usually, the treatment is divided into two stages - the open and endovascular stages are performed separately. We describe the results of hybrid procedures composed of aneurysm resection and endovascular correction for outflow veins performed for a dialysis fistula aneurysm treatment. METHODS: From March 2012, we performed hybrid procedures in 28 patients to correct dialysis fistula aneurysms. Patients, dialysis access, operative data, and the results obtained during a median follow-up of 28.5 months were analyzed. RESULTS: For dialysis fistula aneurysm correction, we performed 27 bypasses and 1 aneurysmorraphy. For outflow vein stenosis correction, we performed standard balloon angioplasty, no stents or stentgraft were used. The average increase in minimal diameter after angioplasty was 135.5% (range 57-275%). The 12- and 24-month primary patency rates of corrected fistulas in the observed group were 92.3% and 80%, respectively. A significant difference in the one-year patency rates between the urgent and planned procedures was observed (81.2% vs. 100%, respectively). No early complications related to endovascular or open procedures were observed. Late complications were observed in seven patients (25%) - mainly thrombosis caused by the recurrence of outflow vein stenosis (six patients, 21.5%), infection, lymphocele, and hematoma (one case of each complication). CONCLUSIONS: A hybrid procedure for the surgical correction of dialysis fistula aneurysms with the simultaneous correction of outflow pathologies enables effective long-term treatment. The obtained data showed the efficiency and good results of this procedure. Procedures performed for urgent indications significantly increase the risk for later complications, especially fistula thrombosis and loss of dialysis access.
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Aneurisma/terapia , Angioplastia de Balón , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular , Diálisis Renal , Venas/cirugía , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/etiología , Aneurisma/fisiopatología , Angioplastia de Balón/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/fisiopatologíaRESUMEN
BACKGROUND: Achieving well-functioning dialysis fistulas is a common problem in dialyzed patients, and it is mainly caused by the pathologies of vessels used for fistula creation. Hybrid therapies, combining surgical and endovascular procedures, potentially enable the creation of functional dialysis fistulas in patients with vessels that are otherwise unsuitable for vascular access. METHODS: Between January 1, 2014 and June 30, 2018, we created dialysis fistulas simultaneously with endovascular correction of outflow pathologies in 15 patients. The included patients had a long history of dialysis (median 10.5 years, range 3-22) and many previous dialysis access procedures (mean 5.3 procedures, range 2-9). In 13 patients (86.7%), the fistula was created on the upper arm; in 5 patients (33.3%), it was arteriovenous graft done with polytetrafluoroethylene (PTFE) prosthesis (in an additional 3 patients, a PTFE prosthesis was used to extend the vein), and 7 patients had native vessel fistulas (46.7%). Endovascular procedures, in some cases performed on more than 1 vein, were applied for correction of the subclavian vein (8 patients, 53.3%); brachiocephalic vein (6 patients, 40.0%); cephalic, basilic, and axillary veins (2 patients each, 13.3%); and superior cava vein (1 patient, 6.7%). Access for the endovascular procedure was achieved through a dissected vein used for arteriovenous anastomosis. The fistula function was monitored, and all complications of dialysis access were noted. The median follow-up in the observed group was 18 months. We compared the patency of dialysis fistula creation combined with endovascular correction of outflow vein pathology to our results of standard dialysis fistula operations: radiocephalic dialysis fistula creation (RCAVF group, 65 patients) and dialysis fistula stenosis angioplasty (PTA group, 30 patients). RESULTS: The 12- and 24-month primary patency rates of dialysis fistulas created in hybrid procedures with simultaneous outflow vein pathology correction were 72.7% and 63.6%, respectively. No early complications related to endovascular or open procedures were observed. CONCLUSIONS: A hybrid procedure for the creation of a dialysis fistula with the simultaneous correction of outflow pathologies enables a properly functioning dialysis fistula to be obtained. This procedure can be performed in patients with complicated vascular situations, enabling the creation of dialysis fistulas. Our results of hybrid procedures, involving simultaneous endovascular correction of the outflow vein with dialysis fistula creation, showed the efficiency and good results.
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Angioplastia , Derivación Arteriovenosa Quirúrgica , Implantación de Prótesis Vascular , Diálisis Renal , Extremidad Superior/irrigación sanguínea , Enfermedades Vasculares/terapia , Venas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia/efectos adversos , Angioplastia/instrumentación , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/instrumentación , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/terapia , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Grado de Desobstrucción Vascular , Venas/diagnóstico por imagen , Venas/fisiopatologíaRESUMEN
Red Cell Distribution Width (RDW) is associated with increased morbidity and mortality in subjects with clinically manifested vascular diseases as well as predicts cardiovascular incidents and different types of cancer in a healthy population. AIM: The aim of the study was to evaluate relationship between clinical outcomes in patients after carotid thromboendarterectomy and initial RDW values. MATERIALS AND METHODS: Data from 115 subsequent patients who underwent carotid thromboendartherectomy (TEA) were retrospectively analyzed. All patients had complete blood count measured including RDW and were observed for 18 months post-operatively. On each visit doppler ultrasound of carotid arteries was performed to evaluate the development of restenosis and progression of atherosclerosis. RESULTS: Primary endpoint defined as cardiovascular death, new cerebrovascular incidents (stroke or TIA), any new revascularization procedure (carotid, coronary or peripheral) and restenosis of the operated artery occurred in 28 patients. They differed from subjects with uneventful course with increased prevalence of previous cerebrovascular incidents (75.0% and 42.5%, respectively; p=0.0028) and higher RDW values (14,37±1.55% and 13.77±0.96%, p=0.0155). CONCLUSIONS: In patients with high risk for cerebrovascular incidents, RDW identifies population at increasingly high probability of vascular complications which should be subjected to intensive therapeutic regimen.
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Enfermedades de las Arterias Carótidas , Índices de Eritrocitos , Arterias Carótidas , Humanos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Radial artery is now the most frequent access for coronary angiography and intervention. Despite the common opinion that it is safer than femoral access, it has the potential for serious complications. One of them is upper limb ischemia caused by radial artery thrombosis. CASE REPORT: We are presenting a case of critical hand ischemia after coronary angiography performed through radial access despite existing risk factors, which may be considered as relative contraindications. CONCLUSIONS: In the presented case, decision was made to use radial access despite several risk factors of upper limb ischemia - diabetes, end-stage renal failure, hyperparathyroidism, or even symptoms of left upper limb ischemia. Furthermore, for diagnostic coronary angiography 5F instead of 4F introducer was used.
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Anemia is a feature of CKD and a complication of renal transplantation, often caused by impaired production of erythropoietin. The kidney is a target organ for human cytomegalovirus (hCMV) in such patients, but it is not known whether hCMV effects erythropoietin production. We found that kidneys from patients with CKD were positive for hCMV protein and that blood levels of hCMV IgG inversely correlated with red blood cell count. In mice, systemic murine cytomegalovirus infection decreased serum erythropoietin levels. In human erythropoietin-producing cells, hCMV inhibited hypoxia-induced expression of erythropoietin mRNA and protein. hCMV early gene expression was responsible, as ultraviolet-inactivated virus had no effect and valganciclovir treatment showed that late gene expression was nonessential. Hypoxia-induced gene transcription is controlled by the transcription factors hypoxia-inducible transcription factor (HIF)-1α and HIF2α, which are constitutively produced but stable only under low oxygen conditions. We found that hCMV inhibited constitutive production of HIF2α mRNA. HIF2α is thought to be the master regulator of erythropoietin transcription. Single-cell analysis revealed that nuclear accumulation of HIF2α was inhibited in hCMV-infected cells, and the extent of inhibition correlated with hCMV protein expression. Our findings suggest that renal hCMV infection could induce or exacerbate anemia in patients.
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Citomegalovirus/fisiología , Eritropoyetina/metabolismo , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/virología , Animales , Anticuerpos Antivirales/sangre , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Técnicas de Cultivo de Célula , Hipoxia de la Célula , Recuento de Eritrocitos , Eritropoyetina/genética , Hemoglobinas/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inmunoglobulina G/metabolismo , Ratones , ARN Mensajero/metabolismo , Insuficiencia Renal Crónica/patologíaRESUMEN
OBJECTIVE: Intimal hyperplasia is considered to be a healing response and is a major cause of vessel narrowing after injury, where migration of vascular progenitor cells contributes to pathological events, including transplant arteriosclerosis. APPROACH AND RESULTS: In this study, we used a rat aortic-allograft model to identify the predominant cell types associated with transplant arteriosclerosis and to identify factors important in their recruitment into the graft. Transplantation of labeled adventitial tissues allowed us to identify the adventitia as a major source of cells migrating to the intima. RNA microarrays revealed a potential role for monocyte chemoattractant protein 1 (MCP-1), stromal cell-derived factor 1, regulated on activation, normal T cell expressed and secreted, and interferon-inducible protein 10 in the induced vasculopathy. MCP-1 induced migration of adventitial fibroblast cells. CCR2, the receptor for MCP-1, was coexpressed with CD90, CD44, NG2, or sca-1 on mesenchymal stem cells. In vivo experiments using MCP-1-deficient and CCR2-deficient mice confirmed an important role of MCP-1 in the formation of intimal hyperplasia in a mouse model of vascular injury. CONCLUSIONS: The adventitia is a potentially important cellular source that contributes to intimal hyperplasia, and MCP-1 is a potent chemokine for the recruitment of adventitial vascular progenitor cells to intimal lesions.
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Quimiocina CCL2/metabolismo , Células Madre Mesenquimatosas/citología , Neointima/patología , Túnica Íntima/patología , Animales , Movimiento Celular , Quimiocina CCL2/genética , Hiperplasia/genética , Hiperplasia/patología , Células Madre Mesenquimatosas/metabolismo , Ratones , Modelos Animales , Miocitos del Músculo Liso/metabolismo , Neointima/metabolismo , Ratas , Sensibilidad y Especificidad , Transducción de Señal , Células Madre/citología , Células Madre/metabolismo , Trasplante Homólogo , Túnica Íntima/metabolismo , Lesiones del Sistema Vascular/patología , Lesiones del Sistema Vascular/fisiopatologíaRESUMEN
Endovascular procedures are commonly used for treatment of vascular pathologies. These interventions are routinely performed under angiographic control. Angioplasty is increasingly more often used for correction of dialysis fistula - especially dilatation of stenosis. We describe the technique of dialysis fistula angioplasty under ultrasound control. Benefits of this procedure include lack of nephrotoxic contrast, what is especially important in chronic kidney disease patients in pre-dialysis period. Advantages of ultrasound guidance during dialysis fistula angioplasty lead to cause more and more frequent employment of this technique.
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The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.
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Aterosclerosis , Índices de Eritrocitos , Animales , Aterosclerosis/patología , Células Sanguíneas , Arterias Carótidas/patología , Eritrocitos/patología , Humanos , Ratones , Pronóstico , Factores de RiesgoRESUMEN
INTRODUCTION: Dialysis fistula aneurysms are common complications, which require surgical revision in selective cases. The results of aneurysm excision with arteriovenous anastomosis proximalization for the treatment of dialysis fistula aneurysms have been described below. METHODS: Patients qualified for the reconstruction of a dialysis fistula aneurysm underwent a duplex ultrasound examination. The diameter, length of the aneurysm, relations with the artery, thrombus presence and blood flow were determined. In the case of favorable anatomical conditions, we performed aneurysm excision with arteriovenous anastomosis proximalization as the procedure of choice. Patients, dialysis access, operative data and the results obtained during a median follow-up of 41 months were then analyzed. FINDINGS: Since 2012, we have performed 20 aneurysm excision combined with primary anastomosis as dialysis fistula aneurysm treatment. In 18 patients, aneurysm excision was combined with simple re-anastomosis in the more proximal arterial segment. In 2 autogenous radio-cephalic forearm direct fistulas the aneurysm excision was combined with switching anastomosis type from side-to-end to end-to-end. The 12- and 24-month primary patency rates of corrected fistulas in the observed group were 94.7% and 82.4%, respectively. No early complications were noted. In 7 patients (35%) we observed late complications, which required reintervention or led to access failure. Dialysis fistula thrombosis as an indication for treatment was a significant risk factor for late re-occlusion. DISCUSSION: A simple primary reconstruction by arteriovenous anastomosis proximalization and aneurysm excision for the surgical correction of dialysis fistula aneurysms has potential benefits compared to established methods-aneurysmorraphy and aneurysm excision with a vascular prosthesis bypass. The obtained data showed the efficiency, safety and excellent long-term results of this procedure.
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Aneurisma/cirugía , Derivación Arteriovenosa Quirúrgica/efectos adversos , Enfermedades Renales/terapia , Procedimientos de Cirugía Plástica , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma/diagnóstico por imagen , Aneurisma/etiología , Aneurisma/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Procedimientos de Cirugía Plástica/efectos adversos , Reoperación , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: The management of patent dialysis fistulas in patients after kidney transplantation (KTx) is controversial-the options that are usually considered are the fistula's closure or observation. Many complications of dialysis fistulas occur in patients after KTx, and immunosuppression increases the risk of fistula aneurysms and hyperkinetic flow. This study aimed to evaluate the results of dialysis fistula aneurysm treatment in patients after KTx and to compare them to procedures performed in an end-stage renal disease (ESRD) dialyzed population. METHODS: We enrolled 83 renal transplant recipients and 123 ESRD patients with dialysis fistula aneurysms qualified for surgical revision to this single-center, prospective study. The results of the surgical treatment of dialysis fistula aneurysms were analyzed, and the primary, assisted primary and secondary patency rate, percentage and type of complications were also assessed. RESULTS: For the treatment of dialysis fistula aneurysms in transplant patients, we performed dialysis fistula excisions with fistula closure in 50 patients (60.2%), excision with primary fistula reconstruction (n = 10, 12.0%) or excision with PTFE bypasses (n = 23, 27.7%). Postoperative complications occurred in 11 patients (13.3%) during a follow-up (median follow-up, 36 months), mostly in distant periods (median time after correction procedure, 11.7 months). The most common complication was outflow stenosis, followed by hematoma, dialysis fistula thrombosis and the formation of a new aneurysm and postoperative bleeding, infection and lymphocele. The 12-month primary, primary assisted and secondary patency rates of fistulas corrected by aneurysm excision and primary reconstruction in the KTx group were all 100%; in the control ESRD group, the 12-month primary rate was 70%, and the primary assisted and secondary patency rates were 100%. The 12-month primary, primarily assisted and secondary patency rates after dialysis fistula aneurysm excision combined with PTFE bypass were better in the KTx group than in the control ESRD group (85% vs. 71.8%, 90% vs. 84.5% and 95% vs. 91.7%, respectively). Kaplan-Meier analysis showed a significant difference in primary patency (p = 0.018) and assisted primary (p = 0.018) rates and a strong tendency in secondary patency rates (p = 0.053) between the KTx and ESRD groups after dialysis fistula excisions combined with PTFE bypass. No statistically significant differences in patency rates between fistulas treated by primary reconstruction and reconstructed with PTFE bypass were observed in KTx patients. CONCLUSIONS: Reconstructions of dialysis fistula aneurysms give good long-term results, with a low risk of complications. The reconstruction of dialysis fistulas can be an effective treatment method. Thus, this is an attractive option in addition to fistula ligation or observation in patients after KTx. Reconstructions of dialysis fistula aneurysms enable the preservation of the dialysis fistula while reducing various complications.
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BACKGROUND: Hemodialysis used as renal replacement therapy requires a well-functioning vascular access. Arterio-venous fistula (AVF) created on the forearm is the best vascular access, but it also reveals numerous complications such as: lack of fistula maturation and hemodynamically significant stenoses. Many risk factors of fistula dysfunction are still not identified. MATERIAL/METHODS: Radial artery and cephalic vein diameter and patency were ultrasonographically examined before forearm AVF creation. Intima-media complex width, blood flow and peak systolic velocity in distal part of radial artery were measured. Presence of thrombosis and post-inflammatory changes in cephalic vein were also checked. Forearm AVF was created in 66 patients. Fistula US examination was performed 3 and 12 months after operation with measurement of vessel diameter and blood flow. Fistula patency was observed in 24 months after creation. Comparison of pre- and postoperative US examinations between groups with well functioning and thrombosed fistulas was performed. RESULTS: Primary patency of forearm AVF after 12 and 24 months was 65.2% and 53.0%, respectively. Patients with well functioning forearm AVF have significantly bigger cephalic vein diameter and peak systolic velocity in radial artery. We did not observe significant influence of radial artery intima-media complex width and radial artery diameter on AVF function. In postoperative examination, fistula diameter and flow significantly influenced the risk of AVF thrombosis. CONCLUSIONS: US examination of radial artery and cephalic vein performed before forearm AVF creation enables identification of patients with greater risk of fistula dysfunction. Cephalic vein diameter and peak systolic velocity are prognostic factors of fistula function. Control postoperative US examination of forearm fistula enables detection of AVF at risk of thrombosis.
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INTRODUCTION: Percutaneous endovascular angioplasty has become the treatment of choice for dialysis fistula stenosis. The ultrasound-guided endovascular procedure is used in patients with severe renal impairment and advanced renal transplant failure, when the need for nephrotoxic contrast administration in standard angioplasty may worsen renal function. AIM: To evaluate endovascular angioplasty guided by ultrasound for dialysis fistula stenosis in renal transplant patients with severe graft insufficiency. MATERIAL AND METHODS: We compared ultrasound (US)-guided angioplasty, performed in patients after renal transplantation, with standard contrast angioplasty performed in dialysis patients. We treated 10 kidney allograft recipients (9 kidneys and 1 kidney-pancreas) with significantly compromised renal transplant function and significant stenosis in dialysis fistulas, as detected during US examination. Patients were qualified for percutaneous angioplasty under US guidance. The mean period from transplantation was 32.7 months (5-100 months). Results of their treatment were compared to the control group of 20 end-stage renal disease patients with dialysis fistula stenosis treated by angioplasty under standard contrast visualization. RESULTS: The immediate effectiveness of the angioplasty was 100% in both groups. No early complications of angioplasty or problems with the guidewire crossing the stenosis were observed. Twelve months of primary patency was observed in 80% and 45% in the US-guided and control groups, respectively. CONCLUSIONS: The US-guided endovascular procedure is an effective and safe method of treating dialysis fistula stenosis in patients with impaired renal transplant function.
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Pseudoaneurysm formation is a rare but dangerous complication of carotid artery dissection. It can result from trauma, spontaneous artery dissection, or iatrogenic causes. Presence of symptoms and ineffective medical therapy are one of the indications for invasive treatment. We present the case of 3 symptomatic patients with dissecting pseudoaneurysms-2 traumatic and 1 spontaneous. They were treated with 3 different endovascular procedures: the use of covered stentgraft, trans-stent coil embolization, and carotid stenting. After invasive and dual antiplatelet therapy, complete resolution of symptoms was achieved in all patients.
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Aneurisma Falso/etiología , Disección de la Arteria Carótida Interna/etiología , Lesiones del Sistema Vascular/etiología , Accidentes de Tránsito , Adulto , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/fisiopatología , Aneurisma Falso/cirugía , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Disección de la Arteria Carótida Interna/diagnóstico por imagen , Disección de la Arteria Carótida Interna/fisiopatología , Disección de la Arteria Carótida Interna/cirugía , Angiografía por Tomografía Computarizada , Embolización Terapéutica/instrumentación , Procedimientos Endovasculares/instrumentación , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Stents , Resultado del Tratamiento , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/fisiopatología , Lesiones del Sistema Vascular/cirugía , Adulto JovenRESUMEN
The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wide range of disturbances in cell cycle and DNA damage response in FAD fibroblasts. This was manifested by significantly increased content of BRCA1 phosphorylated on Ser1524 and abnormal ubiquitination and subcellular distribution of presenilin 1 (PS1). Accordingly, the iPSC-derived FAD neurons showed increased content of BRCA1(Ser1524) colocalized with degraded PS1, accompanied by an enhanced immunostaining pattern of amyloid-ß. Finally, overactivation of BRCA1 was followed by an increased content of Cdc25C phosphorylated on Ser216, likely triggering cell cycle re-entry in FAD neurons. This study suggests that overactivated BRCA1 could both influence PS1 turnover leading to amyloid-ß pathology and promote cell cycle re-entry-driven cell death of postmitotic neurons in AD.
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Enfermedad de Alzheimer/metabolismo , Proteína BRCA1/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Degeneración Nerviosa/metabolismo , Neuronas/metabolismo , Presenilina-1/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Células Cultivadas , Técnicas de Reprogramación Celular , Biología Computacional , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica , Humanos , Degeneración Nerviosa/genética , Degeneración Nerviosa/patología , Neuronas/patología , Fosforilación , Presenilina-1/genética , Presenilina-2/genética , Presenilina-2/metabolismo , Transducción de Señal , Transcriptoma , Fosfatasas cdc25/metabolismoRESUMEN
OBJECTIVE: Smooth muscle cells (SMCs) involved in intimal hyperplasia during transplant vasculopathy are derived both from the graft and the host. Here, the role of an allogenic immune response in the accumulation of host-derived SMCs in the neointima was explored. METHODS: Infrarenal aorta was transplanted from female F344 to male Lewis rats with or without immunosuppression by cyclosporine A (CsA). Accumulation of host-derived SMCs and inflammatory cells in the grafts, SMC proliferation, and apoptosis were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR) for the SRY gene. Finally, SMCs were seeded in an allogenic or isogenic manner after balloon injury to carotid arteries and SMC survival was estimated. RESULTS: Proliferating graft SMCs and infiltrating leukocytes were observed in the intima early after transplantation. In parallel, inflammatory cells and immunoglobulins infiltrated the media and apoptosis of medial SMCs occurred, leading to destruction of this layer. CsA decreased the number of SRY+ SMCs in the lesions, restricted medial destruction, and improved survival of allogenic SMCs after seeding in injured arteries. CONCLUSIONS: Development of intimal thickenings during transplant vasculopathy involves an allogenic immune response, which promotes accumulation of host-derived SMCs and apoptosis of resident graft SMCs.
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Aorta/trasplante , Arteriosclerosis/patología , Músculo Liso/patología , Túnica Íntima/patología , Animales , Aorta/inmunología , Apoptosis , Arteriosclerosis/inmunología , Femenino , Reacción Huésped-Injerto , Inmunohistoquímica/métodos , Etiquetado Corte-Fin in Situ , Masculino , Músculo Liso/inmunología , Neovascularización Patológica , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Trasplante Homólogo , Trasplante Isogénico , Túnica Íntima/inmunologíaRESUMEN
The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment.
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Fístula Arteriovenosa/patología , Modelos Animales de Enfermedad , Vena Femoral/patología , Pierna/fisiopatología , Síndrome de Sturge-Weber/patología , Várices/patología , Animales , Presión Sanguínea , Humanos , Masculino , Ratas , Ratas WistarRESUMEN
This study indicates that circulating progenitors of bone marrow origin give rise to cells with smooth muscle-like properties during formation of neointimal thickenings in the arterial wall after allotransplantation and after balloon injury. A segment of abdominal aorta was transplanted from female F344 to male LEW rats, and the grafts were analyzed for male cells by using the gene as a marker. Immunostaining demonstrated that CD45-positive leukocytes made up 35-45% of the neointimal cells during the 8-week period examined. Concurrently, up to 70% of the neointimal cells were of host origin, as shown by real-time polymerase chain reaction for the gene (Y chromosome). This suggests that the neointima contained host cells also of noninflammatory character. Accordingly, many cells positive for smooth-muscle alpha-actin were detected in this layer. To explore the possible bone marrow origin of allograft cells, female LEW rats were irradiated and substituted with bone marrow from male LEW rats. Subsequently, the animals received an aortic transplant from female F344 rats or were exposed to a balloon injury of the carotid artery. Immunostaining and real-time polymerase chain reaction confirmed the above findings, but the fractions of leukocytes and -positive cells were lower in the carotids than in the allografts. Combined primed in situ labeling and immunostaining verified that not only inflammatory but also smooth muscle-like cells of male origin appeared in the vessel wall in both situations. These observations suggest that the smooth-muscle cells that participate in the development of neointimal lesions during vascular disease may, in part, originate from circulating progenitors.
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Aorta Abdominal/trasplante , Células de la Médula Ósea/fisiología , Traumatismos de las Arterias Carótidas/patología , Miocitos del Músculo Liso/fisiología , Células Madre/fisiología , Túnica Íntima/patología , Animales , Femenino , Genes sry , Inmunohistoquímica , Masculino , Etiquetado in Situ Primed , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Coloración y Etiquetado , Trasplante HomólogoRESUMEN
UNLABELLED: Limb ischaemia caused by formation of dialysis fistula is rare but serious complication. The severity of symptoms may vary but rest pains and necrotic lesions are observed in most advance cases. In these patients different invasive procedures for treatment are performed - from simplest dialysis fistula ligation to complicated vascular reconstructions. The aim of the study was to evaluate treatment results of upper limb ischaemia triggered by dialysis fistula. MATERIAL AND METHODS: We have analysed methods and results of treatment of 14 patients with symptomatic upper limb ischaemia caused by dialysis fistula treated in our department between 1st January, 2006 and 30th June, 2013. Treatment was subject to anatomical situation and clinical symptoms. In three patients the ligation of dialysis fistula was performed, four patients underwent inflow reconstruction - in one case by ligation of ligation of vein branch, in three patients by cephalic transfer of arterial anastomosis. In 2 patients hyperkinetic fistula aneurysm was excised and replaced by PTFE bypass, in three patients fistula reconstruction with DRIL method (distal revascularization - interval ligation) was performed, in one patient surgical operation of brachial artery stenosis was conducted. One patient underwent brachial artery angioplasty. RESULTS: Rest pains occurred in all patients (100%), regressive changes in 10 patients (71.4%). Eight patients (57.2%) had concomitant diabetes, seven (50%) ischaemic heart disease, five (35.5%) chronic lower limb ischemia and hyperparathyroidism was observed in fivepatients (35.5%). The imaging studies in all patients revealed pathological steal syndrome (stealing blood to the fistula), in majority concurrent with other pathologies - obstruction stenosis of peripheral artery, defects in blood out flow from the limb. As a result of the surgical treatment, symptoms of limb ischaemia subsided in all patients. CONCLUSIONS: Critical limb ischaemia caused by dialysis fistula is a dangerous complication. In most cases there are several causes of ischaemia. Treatment methods should be selected individually for each patient and clinical situation. Clinical symptoms should subside as a result of optimal choice of treatment and, if possible, maintaining of dialysis access.
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Brazo/irrigación sanguínea , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Fístula/etiología , Isquemia/etiología , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fístula/cirugía , Humanos , Isquemia/cirugía , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
In hemodialysis patients, a native arteriovenous fistula (AVF) is the preferred form of permanent vascular access. Despite recent improvements, vascular access dysfunction remains an important cause of morbidity in these patients. In this prospective observational cohort study, we evaluated potential risk factors for native AVF dysfunction. We included 68 patients with chronic renal disease stage 5 eligible for AVF construction at the Department of General and Vascular Surgery, Central Clinical Hospital Ministry of Internal Affairs, Warsaw, Poland. Patient characteristics and biochemical parameters associated with increased risk for AVF failure were identified using Cox proportional hazards models. Vessel biopsies were analyzed for inflammatory cells and potential associations with biochemical parameters. In multivariable analysis, independent predictors of AVF dysfunction were the number of white blood cells (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.24 to 2.25; p<0.001), monocyte number (HR 0.02; 95% CI 0.00 to 0.21; pâ=â0.001), and red blood cell distribution width (RDW) (HR 1.44; 95% CI 1.17 to 1.78; p<0.001). RDW was the only significant factor in receiver operating characteristic curve analysis (area under the curve 0.644; CI 0.51 to 0.76; pâ=â0.046). RDW>16.2% was associated with a significantly reduced AVF patency frequency 24 months after surgery. Immunohistochemical analysis revealed CD45-positive cells in the artery/vein of 39% of patients and CD68-positive cells in 37%. Patients with CD68-positive cells in the vessels had significantly higher white blood cell count. We conclude that RDW, a readily available laboratory value, is a novel prognostic marker for AVF failure. Further studies are warranted to establish the mechanistic link between high RDW and AVF failure.