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1.
Ann Vasc Surg ; 78: 239-246, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34416283

RESUMO

BACKGROUND: Long standing, recalcitrant venous ulcers fail to heal despite standard compression therapy and wound care. Stenting of central veins has been reported to assist in venous ulcer healing. This study reports outcomes of deep venous stenting for central venous obstruction in patients with recalcitrant venous ulcers at a single comprehensive wound care center. METHODS: A single center retrospective analysis was conducted of patients with CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) 6 disease that had undergone deep venous stenting in addition to wound care and compression therapy. Intra-operative details, wound healing, and stent patency rates were recorded. Stent patency and intra-operative details were compared between the healed and unhealed groups. RESULTS: Between 2010 and 2019, 15 patients met inclusion criteria (mean age: 63 years old, 12 males). Pre-operative mean wound area was 14.1 cm2 with mean wound duration of 30 months. 93% of patients healed the ulcers at mean healing time of 10.6 months. Wound recurrence rate was 57% with mean recurrence time of 14.8 months. Ten patients presented with an inferior vena cava (IVC) filter, 4 in the healed group and 6 in the unhealed group. The common iliac vein was stented in all patients. Extension into the IVC was required in 4, the common femoral vein in 11, and femoral vein in 2 patients. The average stent length was 190cm. During the follow-up period, primary patency rates in healed patients (mean follow-up time: 19.2 months) was 83% and 59% in the unhealed group (mean follow-up time: 36.6 months); secondary patency rates were 83% and 89%, respectively. CONCLUSIONS: In patients with recalcitrant venous ulcers with central venous obstruction, deep venous stenting resulted in a high rate of healing. However, a prolonged 10 month healing time was observed and despite high stent patency, wound recurrence rate was high.


Assuntos
Procedimentos Endovasculares/instrumentação , Extremidade Inferior/irrigação sanguínea , Stents , Úlcera Varicosa/terapia , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Úlcera Varicosa/patologia , Úlcera Varicosa/fisiopatologia , Grau de Desobstrução Vascular
2.
Ann Vasc Surg ; 83: 53-61, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34998937

RESUMO

OBJECTIVES: Congenital abnormalities of the first rib (ABNFR) are a rare cause of thoracic outlet syndrome (TOS). The range of abnormalities have not been clearly documented in the literature. Surgical decompression in these patients presents with increased complexity secondary to anomalous anatomy. Our goal is to review an institutional experience of first rib resection (FRR) performed for ABNFRs, to present a novel classification system, and to analyze outcomes according to clinical presentation. METHODS: A prospectively collected database was used to identify individuals with ABNFRs who underwent FRR for TOS between 1990-2021. These individuals were identified both by preoperative imaging and intraoperative descriptions of the first rib after resection. Demographic, clinical, perioperative and pathological data were reviewed. ABNFRs were classified into 3 categories according to anatomical criteria: (I) Hypoplastic, (II) Fused, and (III) Hyperplastic. Outcomes were rated using the standardized Quick Disability of Arm Shoulder and Hand Scores (QDS), Somatic Pain Scores (SPS) and Derkash Scores (DkS). RESULTS: Among the 2200 cases of TOS, there were 19 patients (0.8%) with ABNFR who underwent FRR. Average age at surgery was 30.5 (range 11-74), including 13 men and 6 women. Presentations included 9 arterial (ATOS), 6 neurogenic (NTOS), and 4 venous (VTOS) cases. There were 6 class I, 6 class II, and 7 class III ABNFRs. Among 6 NTOS patients there were 4 abnormal nerve conduction tests and 5 positive anterior scalene muscle blocks. Among the 9 patients with ATOS, thrombolysis was attempted in 5 patients, and of these, 3 ultimately required surgical thrombectomy. Of 4 VTOS cases, 2 were managed with thrombolysis, and 2 with anticoagulation alone. The approach for FRR was transaxillary in all patients. Secondary procedures included 1 pectoralis minor tenotomy, 1 scalenectomy, and 1 contralateral rib resection. No major neurological or vascular complications occurred. There was 1 patient who required surgical evacuation of a hematoma. Intraoperative chest tube placement was required in 5 patients secondary to pleural entry during dissection. There was an overall improvement in symptoms over an average follow-up of 7.4 months. QDS reduced from 49.7 pre-op to 22.1 (P < 0.05). SPS improved from 3.4 pre-op to 1.8. DkS scores were good to excellent in 79% of patients. Residual symptoms were noted in 7, and ATOS accounted for 5 (70%) of these. All patients were able to return to work. CONCLUSIONS: Despite increased complexity, ABNFRs may be safely resected via transaxillary approach with low incidence of complications, very good symptom relief, and excellent outcomes. Congenital ABNFRs may by classified into 3 categories (hypoplastic, fused, and hyperplastic) with a variety of presentations, including ATOS, NTOS, and VTOS. Classification of ABNFRs allows concise description of abnormal anatomy which facilitates comparison between series and provides direction for surgical management to ultimately optimize patient outcomes.


Assuntos
Síndrome do Desfiladeiro Torácico , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Estudos Prospectivos , Costelas/diagnóstico por imagem , Costelas/cirurgia , Síndrome do Desfiladeiro Torácico/diagnóstico por imagem , Síndrome do Desfiladeiro Torácico/cirurgia , Resultado do Tratamento
3.
Ann Vasc Surg ; 74: 111-121, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33556528

RESUMO

BACKGROUND: Frailty has been increasingly recognized as an important risk factor for vascular procedures. To assess the impact of frailty on clinical outcomes and resource utilization in patients undergoing carotid revascularization using a national cohort. METHODS: The 2005-2017 National Inpatient Sample was used to identify patients who underwent carotid endarterectomy (CEA) or carotid stenting (CAS). Patients were classified as frail using diagnosis codes defined by the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable regression was used to evaluate associations between frailty and in-hospital mortality, postoperative stroke, myocardial infarction (MI), hospitalization costs, and length of stay (LOS). RESULTS: Of 1,426,343 patients undergoing carotid revascularization, 59,158 (4.2%) were identified as frail. Among frail patients, 79.4% underwent CEA and 20.6% underwent CAS. Compared to CEA, a greater proportion of patients undergoing CAS were frail (6.0% vs. 3.8%, P < 0.001). Compared to the nonfrail cohort, frail patients had higher rates of mortality (2.2% vs. 0.5%, P < 0.001), postoperative stroke (2.6% vs. 1.0%, P < 0.001), MI (2.2% vs. 0.8%, P < 0.001), and stroke/death (4.4% vs. 1.4%, P < 0.001). After adjustment, frailty was associated with increased odds of mortality (AOR = 1.59, 95% CI: 1.30-1.80, P < 0.001), stroke (AOR = 1.66, 95% CI: 1.38-1.83 P < 0.001), MI (AOR = 1.51, 95% CI: 1.29-1.72, P < 0.001), and stroke/death (AOR = 1.62, 95% CI: 1.45-1.81, P < 0.001). Furthermore, frailty was associated with increased hospitalization costs (ß = +$5,980, 95% CI: $5,490-$6,470, P < 0.001) and LOS (ß = +2.6 days, 95% CI: 2.4-2.8, P < 0.001). CONCLUSIONS: Frailty is associated with adverse outcomes and greater resource use for those undergoing carotid revascularization. Risk models should include an assessment of frailty to guide management and improve outcomes for these high-risk patients.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Fragilidade/complicações , Mortalidade Hospitalar , Infarto do Miocárdio/etiologia , Complicações Pós-Operatórias/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Artérias Carótidas/cirurgia , Feminino , Idoso Fragilizado , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Stents , Resultado do Tratamento
4.
Ann Vasc Surg ; 76: 202-210, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34437963

RESUMO

INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection. METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed. RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.


Assuntos
Aorta/cirurgia , Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Remoção de Dispositivo , Procedimentos Endovasculares/efeitos adversos , Infecções Relacionadas à Prótese/cirurgia , Idoso , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/mortalidade , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
5.
Ann Vasc Surg ; 65: 25-32, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31715248

RESUMO

BACKGROUND: The en bloc resection of inferior vena cava (IVC) leiomyosarcoma often necessitates IVC reconstruction. The objective of this study is to examine outcomes after IVC reconstruction and determine optimal graft sizing. METHODS: A retrospective review was conducted of all IVC reconstructions after IVC leiomyosarcoma resection at a single institution. Cross-sectional dimensions at the IVC resection margins were measured on preoperative imaging. The tumor location was based on the most superiorly involved region of the IVC and was classified as infrarenal, between hepatic and renal veins, or superior to the hepatic veins. Perioperative details and long-term outcomes including graft sizing, graft patency, morbidity, and mortality were recorded. RESULTS: Between 2007 and 2017, 12 patients (6 females, mean age: 64.5 years, age range: 46-80 years) underwent IVC leiomyosarcoma resection and reconstruction. All reconstructions were performed with ringed polytetrafluoroethylene (PTFE); graft sizes ranged from 12 mm to 16 mm. The tumor location was exclusively infrarenal in seven patients, between the renal and hepatic veins in two patients, and involved multiple segments in three patients. Larger graft sizes were utilized in reconstructing more superior segments of the IVC. Grafts were typically undersized and based on the diameter of the superior resection margin with 12 mm grafts approximately correlating to a 20 mm diameter, 14 mm to 25 mm, and 16 mm to 30 mm. The average undersizing ratio was 0.6. At a mean follow-up time of 43 ± 27 months, radiographic graft patency was 92%, overall survival was 83%, and disease-free survival was 25%. CONCLUSIONS: After en bloc resection of IVC leiomyosarcoma, caval reconstruction with an undersized ringed PTFE has acceptable patency. Grafts sizes should be based on the IVC diameter superior to the tumor and undersizing by approximately 40% appears to be associated with acceptable patency rates. Further multiinstitutional studies should be performed to best determine the optimal treatment of this rarely encountered tumor.


Assuntos
Implante de Prótese Vascular/instrumentação , Prótese Vascular , Leiomiossarcoma/cirurgia , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/cirurgia , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Leiomiossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo , Neoplasias Vasculares/patologia , Grau de Desobstrução Vascular , Veia Cava Inferior/patologia
6.
J Vasc Surg ; 69(2): 592-595, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30154016

RESUMO

Termed hemosuccus pancreaticus by Sandblom in 1970, hemorrhage from the pancreatic duct into the gastrointestinal tract represents a rare and challenging problem. Patients present with repeated upper gastrointestinal bleeding that is intermittent but often self-limited. In most cases, this pathophysiologic process is secondary to pancreatitis, chronic inflammation, and subsequent splenic artery pseudoaneurysm bleeding. Previously treated with open splenectomy and distal pancreatectomy, hemosuccus pancreaticus is now often managed with minimally invasive endovascular means. We describe an uncommon presentation of hemosuccus pancreaticus in the absence of prior pancreatitis, requiring open splenectomy, distal pancreatectomy, and celiac artery ligation after failed endovascular intervention.


Assuntos
Falso Aneurisma/cirurgia , Artéria Celíaca/cirurgia , Hemorragia Gastrointestinal/cirurgia , Pancreatectomia , Pancreatopatias/cirurgia , Ductos Pancreáticos/cirurgia , Esplenectomia , Artéria Esplênica/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Falso Aneurisma/diagnóstico por imagem , Artéria Celíaca/diagnóstico por imagem , Embolização Terapêutica , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Ligadura , Masculino , Pancreatopatias/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Artéria Esplênica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Ann Vasc Surg ; 29(7): 1434-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26130434

RESUMO

BACKGROUND: To examine the value of routine postoperative surveillance duplex in identifying late graft-related complications after open aortic operations for occlusive and aneurysmal disease. METHODS: All open aortic operations performed at a single institution between 1998 and 2012 were retrospectively reviewed. All patients were scheduled for yearly postoperative surveillance duplex. Patients who had at least 30-day follow-up and at least 1 surveillance duplex were analyzed. RESULTS: Two hundred thirty-eight open aortic operations were performed during the study period, 140 of which met the inclusion criteria. Mean follow-up was 3.9 years. A tube graft was performed in 65 (46%), and the proximal anastomosis was in the infrarenal or juxtarenal position in 126 (90%). Overall survival at was 100% and 85.3% at 1 and 5 years, respectively. A mean of three surveillance duplexes was performed per patient. Surveillance duplex scanning identified 31 significant findings in 31 patients, including 13 significant velocity increases (>3:1) and 18 aneurysms/pseudoaneurysms. Thirteen (9%) patients required a graft-related operation at a mean of 3.5 years. Indications included anastomotic aneurysm/pseudoaneurysm (n = 7), limb occlusion (n = 3), graft stenosis (n = 2), and graft infection (n = 1). The indication for operation was identified by surveillance duplex in 5 of the 13 cases. The remainder were identified by physical examination and/or clinical presentation. Reintervention-free survival (RIFS) was 98.5% at 1 year and 80.4% at 5 years. On multivariable analysis, RIFS was improved only by the use of a tube graft during the index operation (hazard ratio, 0.73; 95% confidence interval, 0.54-0.96). CONCLUSIONS: Routine surveillance duplex identifies few findings that lead to reintervention. Patients with a non-tube-graft reconstruction are at greater risk for reintervention and may benefit from surveillance duplex after open aortic operations.


Assuntos
Aneurisma Aórtico/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Complicações Pós-Operatórias/diagnóstico por imagem , Ultrassonografia Doppler Dupla , Idoso , Aneurisma Aórtico/diagnóstico por imagem , Arteriopatias Oclusivas/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Análise Multivariada , Complicações Pós-Operatórias/cirurgia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
J Neurosci Res ; 92(12): 1621-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24989965

RESUMO

Glatiramer acetate (GA; Copaxone) is an approved drug for the treatment of multiple sclerosis (MS). The underlying multifactorial anti-inflammatory, neuroprotective effect of GA is in the induction of reactive T cells that release immunomodulatory cytokines and neurotrophic factors at the injury site. These GA-induced cytokines and growth factors may have a direct effect on axon function. Building on previous findings that suggest a neuroprotective effect of GA, we assessed the therapeutic effects of GA on brain and spinal cord pathology and functional correlates using the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Therapeutic regimens were utilized based on promising prophylactic efficacy. More specifically, C57BL/6 mice were treated with 2 mg/mouse/day GA for 8 days beginning at various time points after EAE post-induction day 15, yielding a thorough, clinically relevant assessment of GA efficacy within the context of severe progressive disease. Therapeutic treatment with GA significantly decreased clinical scores and improved rotorod motor performance in EAE mice. These functional improvements were supported by an increase in myelinated axons and fewer amyloid precursor protein-positive axons in the spinal cords of GA-treated EAE mice. Furthermore, therapeutic GA decreased microglia/macrophage and T cell infiltrates and increased oligodendrocyte numbers in both the spinal cord and corpus callosum of EAE mice. Finally, GA improved callosal axon conduction and nodal protein organization in EAE. Our results demonstrate that therapeutic GA treatment has significant beneficial effects in a chronic mouse model of MS, in which its positive effects on both myelinated and non-myelinated axons results in improved axon function.


Assuntos
Axônios/metabolismo , Encefalomielite Autoimune Experimental/complicações , Imunossupressores/uso terapêutico , Transtornos dos Movimentos/tratamento farmacológico , Condução Nervosa/efeitos dos fármacos , Peptídeos/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Axônios/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Acetato de Glatiramer , Imunossupressores/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/patologia , Proteína Básica da Mielina/metabolismo , Proteína Proteolipídica de Mielina/genética , Proteína Proteolipídica de Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos , Oligodendroglia/patologia , Peptídeos/farmacologia , Índice de Gravidade de Doença , Medula Espinal/patologia , Fatores de Tempo
9.
Vasc Endovascular Surg ; 58(8): 876-883, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39163873

RESUMO

BACKGROUND: Endovascular repair of thoracic aortic aneurysms (TAA) in elective settings has demonstrated successful clinical outcomes. However, life-threatening conditions such as rupture are more often managed with open surgical repair due to the high complexity of arch endovascular repair, lack of available off-the-shelf devices, and limited long-term data. CASE SUMMARY: A 49-year-old female with a recent history of prior ascending aortic repair for Type A10 aortic dissection presented with chest pain and dyspnea. Chest computed tomography angiogram (CTA) revealed acute bilateral pulmonary emboli and a 6.2 cm post dissection aneurysm of the posterior aortic arch with the dissection extending to the right iliac artery. She was treated with thrombolysis and subsequently became hemodynamically unstable. Repeat CTA revealed a massive left hemithorax with concern for aortic arch rupture. Given significant cardiorespiratory compromise and recent open repair, she was considered unfit for redo open repair. Thoracic endovascular aortic repair (TEVAR) with a physician-modified endograft (PMEG) was planned. An Alpha Zenith endograft was modified adding an internal branch for the innominate artery and a fenestration for the left common carotid artery. The left subclavian artery was occluded with a microvascular plug and coil embolization up to the level of the vertebral artery. TEVAR PMEG extension to the celiac artery was performed followed by deployment of a Zenith dissection stent to the aortic bifurcation. Completion angiogram demonstrated successful aneurysm exclusion and patency of target vessels. CONCLUSION: Endovascular treatment of ruptured TAA with PMEGs is feasible. This approach may be an alternative for unfit patients for open repair in emergent settings.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Ruptura Aórtica , Implante de Prótese Vascular , Prótese Vascular , Procedimentos Endovasculares , Desenho de Prótese , Stents , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/fisiopatologia , Feminino , Pessoa de Meia-Idade , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Procedimentos Endovasculares/instrumentação , Implante de Prótese Vascular/instrumentação , Resultado do Tratamento , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/cirurgia , Ruptura Aórtica/fisiopatologia , Aortografia , Aneurisma do Arco Aórtico
10.
Neurobiol Dis ; 56: 131-44, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23603111

RESUMO

The identification of a drug that stimulates endogenous myelination and spares axon degeneration during multiple sclerosis (MS) could potentially reduce the rate of disease progression. Using experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, we have previously shown that prophylactic administration of the estrogen receptor (ER) ß ligand 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) decreases clinical disease, is neuroprotective, stimulates endogenous myelination, and improves axon conduction without altering peripheral cytokine production or reducing central nervous system (CNS) inflammation. Here, we assessed the effects of therapeutic DPN treatment during peak EAE disease, which represents a more clinically relevant treatment paradigm. In addition, we investigated the mechanism of action of DPN treatment-induced recovery during EAE. Given that prophylactic and therapeutic treatments with DPN during EAE improved remyelination-induced axon conduction, and that ER (α and ß) and membrane (m)ERs are present on oligodendrocyte lineage cells, a direct effect of treatment on oligodendrocytes is likely. DPN treatment of EAE animals resulted in phosphorylated ERß and activated the phosphatidylinositol 3-kinase (PI3K)/serine-threonine-specific protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, a pathway required for oligodendrocyte survival and axon myelination. These results, along with our previous studies of prophylactic DPN treatment, make DPN and similar ERß ligands immediate and favorable therapeutic candidates for demyelinating disease.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Receptor beta de Estrogênio/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Bainha de Mielina/efeitos dos fármacos , Nitrilas/uso terapêutico , Oligodendroglia/efeitos dos fármacos , Proteína Oncogênica v-akt/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/fisiologia , Animais , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Calpaína/metabolismo , Caspase 3/metabolismo , Corpo Caloso/patologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Imuno-Histoquímica , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Equilíbrio Postural/efeitos dos fármacos , Medula Espinal/patologia
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