RESUMO
PURPOSE: Cryofibrinogenemia is a rare cryopathy presenting as acrocyanosis following exposure to cold. Familial presentation has been described but the underlying molecular cause remained undetermined. METHODS: Forty (40) members from a large family with an initial diagnosis of familial cryofibrinogenemia were interviewed and examined to determine affected status and collect DNA. Exome sequencing was performed on three affected individuals from distinct branches of the pedigree. RESULTS: Seventeen (17) family members reported a history of acrocyanosis with cold exposure. None reported symptoms were suggestive of lupus. Exome sequencing of three subjects identified the heterozygous mutation D18N in the TREX1 gene which was then confirmed by Sanger sequencing in all affected as well as 2 unaffected family members. The mutation is already being associated with familial chilblain lupus erythematosus (CHLE), and a systematic review of literature was undertaken to compare reports of familial CHLE and cryofibrinogenemia. Both entities were found to share highly similar clinical presentations suggesting they are part of a same syndrome in which cryofibrinogenemia and lupus manifestations have variable penetrance. CONCLUSIONS: Familial cryofibrinogenemia without lupus should be added to the spectrum of TREX1-related disease.
Assuntos
Crioglobulinemia/genética , Exodesoxirribonucleases/genética , Fosfoproteínas/genética , Adulto , Pérnio/genética , DNA/genética , Feminino , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Lúpus Eritematoso Cutâneo/genética , Lúpus Eritematoso Sistêmico/genética , Masculino , Mutação/genética , LinhagemRESUMO
The goals of distal radius fracture treatment in patients above 65 years of age would not change over time if the fracture were the only factor to consider. However, people change, and fixation methods also change. Since this fracture heals in nearly every case and volar plates have eliminated the worry of malunion, we are left with two main goals. In active patients with weakened bones, the aim is to help them regain their quality of life as quickly as possible while avoiding iatrogenic conditions. This compromise is possible because of new tools-but at what price?
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Redução Fechada/métodos , Fixação Interna de Fraturas , Osteoporose/epidemiologia , Fraturas do Rádio , Rádio (Anatomia) , Idoso , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Humanos , Seleção de Pacientes , Prognóstico , Rádio (Anatomia)/lesões , Rádio (Anatomia)/patologia , Fraturas do Rádio/diagnóstico , Fraturas do Rádio/epidemiologia , Fraturas do Rádio/etiologia , Fraturas do Rádio/terapia , Risco Ajustado/métodosRESUMO
INTRODUCTION: Quadriceps tendon avulsions are typically treated by reattaching the tendon through bone tunnels, with or without tendon or hardware augmentation. The operated knee joint can be moved right away; however, tendon grafting or tension banding will be required to protect the repair, and the hardware must be removed later on. The goal of this study was to evaluate the clinical and functional outcomes when suture anchors are used to reattached torn quadriceps tendon, and also to assess tendon healing using MRI. MATERIALS AND METHODS: Thirteen consecutive patients with avulsed quadriceps tendons were operated and then followed prospectively. The surgical technique consisted of tendon reattachment using at least three anchors, in addition to intratendinous weaving of the sutures. Weight bearing was allowed while using a splint. Rehabilitation was initiated immediately after surgery according to a set protocol. RESULTS: Eleven patients were followed for a mean of 14.7 months. Two retears occurred in patients who did not wear the splint. Eighty-two per cent of patients were satisfied or very satisfied with the outcome. The mean knee flexion was 124.5°. All patients were able to return to their pre-injury activity levels. The mean time for clinical and functional recovery was 3 months. MRI performed 6 months after the surgical repair revealed good tendon healing. DISCUSSION: This was the first prospective study performed on quadriceps avulsion patients undergoing suture anchor repair. Prior clinical case reports have shown that this method leads to predictable clinical and functional results. Our results were comparable to those in published cases. CONCLUSION: The procedure is simpler when only suture anchors are used. Tendon healing was observed on MRI in all cases. This simple, reproducible technique is free of the drawbacks associated with the typical repair augmentation.
Assuntos
Âncoras de Sutura , Traumatismos dos Tendões/cirurgia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/reabilitação , Traumatismos em Atletas/cirurgia , Humanos , Traumatismos do Joelho/reabilitação , Traumatismos do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Duração da Cirurgia , Satisfação do Paciente , Estudos Prospectivos , Músculo Quadríceps/fisiologia , Músculo Quadríceps/cirurgia , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica/fisiologia , Volta ao Esporte , Fatores de Risco , Ruptura/fisiopatologia , Ruptura/reabilitação , Ruptura/cirurgia , Traumatismos dos Tendões/fisiopatologia , Traumatismos dos Tendões/reabilitação , Tempo para o Tratamento , Resultado do Tratamento , Suporte de Carga/fisiologia , Cicatrização/fisiologiaRESUMO
Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant Staphylococcus aureus. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array-high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for Staphylococcus aureus in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of Staphylococcus aureus bone and joint infections.
Assuntos
Antibacterianos/farmacocinética , Artroplastia de Substituição , Osso e Ossos/metabolismo , Daptomicina/farmacocinética , Líquido Sinovial/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
The posterior interosseous flap on the posterolateral aspect of the forearm is appreciated for its thinness and the length of its vascular pedicle. Arterial supply to the flap comes from the posterior interosseous artery, which gives off several cutaneous branches. This flap is most often used with its distal pedicle as its artery presents anastomoses with the anterior interosseous artery and the dorsal arterial carpal network. However, its dissection is often difficult because of anatomical variants and is not reliable in case of traumatic history at the distal forearm. A case is reported where no posterior interosseous pedicle was found and the flap was subsequently transferred as a free flap supplied by a perforating branch arising from the anterior interosseous artery.
Assuntos
Artérias/anatomia & histologia , Antebraço/irrigação sanguínea , Antebraço/cirurgia , Traumatismos da Mão/cirurgia , Terapia de Salvação/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Feminino , HumanosRESUMO
There are very few published studies describing the treatment of segmental bone defects of the forearm using the induced membrane technique. The objectives of this study were to evaluate the time to bone union, the function of the joints above and below the treated bone segment and the patients' quality of life over the long-term. We performed a retrospective study in all patients treated by the induced membrane for a forearm bone defect over at 13-year period. Demographics, bone union, complications, functional outcomes and occupational status were collected. Six patients were included: 2 posttraumatic injuries, 1 osteomyelitis, 1 septic arthritis, 1 aseptic nonunion, 1 tumor. The average defect length was 64mm (48-110). All defects were treated with internal fixation. Bone graft was harvested from the iliac crest in two patients, the femur (using the Reamer Irrigator Aspirator technique) in three patients and the radius in one patient. Five patients achieved bone union after a mean of 4months (3-6). Three complications were observed: 1 radioulnar instability, 1 infection of the fixation device, 1 abscess. At an average 8½ years' follow-up, the pain level on the VAS was 0.6 (0-3), the Mayo Elbow Performance Score was 98 (90-100), the Herzberg score was 108 (85.6-140) and the QuickDASH was 14.9 (2.7-35). All patients returned to work. Using the induced membrane technique avoids the complications associated with vascularized autograft and yields good functional outcome and quality of life.
Assuntos
Fraturas não Consolidadas , Antebraço/cirurgia , Fraturas não Consolidadas/cirurgia , Humanos , Ílio/transplante , Qualidade de Vida , Estudos RetrospectivosRESUMO
Atmospheric nuclear weapons tests carried out by the United States, the former Soviet Union, the United Kingdom, France and China between 1945 and 1980 resulted in radioactive fallout over the earth's surface of long-lived radionuclides, such as 137Cs, 239+240Pu and 238Pu that could be detected more than 50 years after their production. In addition, the burnup in the upper atmosphere of a thermoelectric generator fueled by 238Pu, SNAP-9A, contributed to the inventory of 238Pu deposited on the ground. In order to estimate the deposition densities of 137Cs, 239+240Pu and 238Pu in French Polynesia, we collected undisturbed soil samples up to 30â¯cm deep at eight sites in two islands (Hiva Oa, 139°W - 10°S and Raivavae, 148°W - 24°S) in 2015-2016. The top 0-10â¯cm of the soil cores were sliced into five 2-cm layers and the bottom 10-30â¯cm into four 5-cm layers for gamma spectrometry and alpha spectrometry measurements. We found that more than 50% of the radioactive inventories are still contained within the first 10â¯cm and that the average vertical migration velocities of 137Cs and Pu are less than 0.2â¯cmâ¯y-1. The average accumulated depositions, deduced from the profile measurements, are 236⯱â¯11 Bq.m-2 and 313⯱â¯39 Bq.m-2 for 137Cs, 12.1⯱â¯1.5 Bq.m-2 and 22.1⯱â¯1.7 Bq.m-2 for 239+240Pu, and 1.23⯱â¯0.46 Bq.m-2 and 1.58⯱â¯0.60 Bq.m-2 for 238Pu, in Hiva Oa and Raivavae, respectively. The 238Pu/239+240Pu ratios are 0.102⯱â¯0.050â¯at Hiva Oa and 0.072⯱â¯0.033â¯at Raivavae. Both values are higher than the ratio in nuclear weapons tests fallout estimated to be 0.016 in 2016 (Hardy et al., 1973), because of the contribution of 238Pu fallout from SNAP-9A, which is latitude dependent. The 137Cs/239+240Pu ratios, 19.5⯱â¯3.2â¯at Hiva Oa and 14.2⯱â¯2.8â¯at Raivavae are in the lower part of the range of values observed in other regions of the world.
Assuntos
Radioisótopos de Césio/análise , Plutônio/análise , Monitoramento de Radiação , Cinza Radioativa/análise , Poluentes Radioativos do Solo/análise , Ilhas , Polinésia , Solo , Poluentes Radioativos da Água/análiseRESUMO
BACKGROUND: Patients with both vascular and osteoarticular injuries require multidisciplinary management. Vascular injuries may be function- and/or life-threatening. The lower limbs are predominantly affected. Traffic, domestic, and work-related accidents contribute most of the cases. The primary objective of this study was to describe the management of patients with concomitant vascular and osteo-articular injuries, with special attention to the rates of amputation and fasciotomy. The secondary objective was to suggest a management sequence to optimise our surgical practice. HYPOTHESIS: The management sequence is a crucial consideration in patients with both vascular and osteo-articular injuries. MATERIAL AND METHODS: A 6-year, retrospective, observational study was conducted in patients with concomitant vascular and osteo-articular injuries. RESULTS: The study included 36 patients with a mean age of 40.6±22.1 years. The main sources of injury were traffic accidents (n=19, 52.8%), crush injury (n=8, 22.2%), and falls (n=5, 13.9%). A compound fracture was present in 20 (55.6%) patients. Evidence of ischaemia in 25 (69.4%) patients, and bleeding in 11 (30.6%) patients. Pre-operative imaging, by ultrasonography or computed tomography, was performed in 27 (75.0%) patients. The lower limb was involved in 30 (83.3%) patients, who had osteoarticular injuries to the femur and leg combined with injury to the popliteal artery. Fasciotomy was performed in 11 (30.6%) patients and secondary amputation in 7 (19.4%) patients. The limb salvage rate was 80.6%. Median patient survival was 9.3 [0-74.8] months. DISCUSSION: Coordinated work by two surgical teams is crucial to manage concomitant vascular and osteo-articular injuries. The management sequence must be defined clearly. Computed tomography angiography is the investigation of choice and should be performed at the slightest suspicion of vascular injury. LEVEL OF EVIDENCE: IV, retrospective observational study.
Assuntos
Fraturas Expostas/cirurgia , Articulações/lesões , Traumatismo Múltiplo/cirurgia , Equipe de Assistência ao Paciente/organização & administração , Lesões do Sistema Vascular/cirurgia , Adolescente , Adulto , Idoso , Amputação Cirúrgica , Fasciotomia , Feminino , Fraturas Expostas/complicações , Hemorragia/etiologia , Hemorragia/cirurgia , Humanos , Isquemia/etiologia , Isquemia/cirurgia , Traumatismos da Perna/cirurgia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/complicações , Artéria Poplítea/lesões , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Lesões do Sistema Vascular/complicações , Adulto JovemRESUMO
The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.
Assuntos
Angioplastia com Balão , Arteriosclerose/terapia , Luciferases/genética , Transfecção , Angiografia , Animais , Artérias/patologia , Lipossomos/administração & dosagem , Luciferases/análise , Hibridização de Ácido Nucleico , CoelhosRESUMO
Human atheromata obtained in vivo were used to test the hypothesis that transforming growth factor-beta 1 plays a role in the development of vascular restenosis. We analyzed 28 specimens from patients with primary atherosclerotic or restenotic lesions; 26 of these were obtained by directional atherectomy and 2 at the time of coronary bypass surgery. Seven control tissues included operatively excised segments of human internal mammary artery, myocardium, and unused portions of vein graft obtained intraoperatively. From these 35 specimens, 210 sections were examined using in situ hybridization. Measurement of silver grains/nucleus disclosed that expression of transforming growth factor-beta 1 mRNA was highest in restenotic tissues (P < 0.001 vs. primary atherosclerotic tissues) and lowest in nonatherosclerotic (control) tissues. In cultures of human vascular smooth muscle cells grown from explants of internal mammary artery, expression of mRNA for transforming growth factor-beta 1 was significantly greater in subconfluent than in confluent smooth muscle cells (P = 0.05). Transforming growth factor type-beta III receptor was expressed in cell cultures and undetectable in the tissue specimens. Sections taken adjacent to those studied by in situ hybridization were examined by immunohistochemistry using antibodies against transforming growth factor-beta 1 and alpha-actin (as a marker for smooth muscle cells) and disclosed transforming growth factor-beta 1 in smooth muscle cells present in these sections. These findings are consistent with the concept that transforming growth factor-beta 1 plays an important role in modulating repair of vascular injury, including restenosis, after balloon angioplasty.
Assuntos
Fator de Crescimento Transformador beta/análise , Doenças Vasculares/metabolismo , Actinas/análise , Arteriosclerose/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Fator de Crescimento Derivado de Plaquetas/fisiologia , RNA Mensageiro/análise , Receptores de Superfície Celular/análise , Receptores de Fatores de Crescimento Transformadores beta , Recidiva , Fator de Crescimento Transformador beta/genéticaRESUMO
Arterial gene transfer represents a novel strategy that is potentially applicable to a variety of cardiovascular disorders. Attempts to perform arterial gene transfer using nonviral vectors have been compromised by a low transfection efficiency. We investigated the hypothesis that cellular proliferation induced by arterial injury could augment gene expression after liposome-mediated gene transfer. Nondenuded and denuded rabbit arterial strips were maintained in culture for up to 21 d, after which transfection was performed with a mixture of the plasmid encoding firefly luciferase and cationic liposomes. In non-denuded arteries, the culture interval before transfection did not affect the gene expression. In contrast, denuded arteries cultured for 3-14 d before transfection yielded 7-13-fold higher expression (vs. day 0; P < 0.005). Transfection was then performed percutaneously to the iliac arteries of live rabbits with or without antecedent angioplasty. Gene expression increased when transfection was performed 3-7 d postangioplasty (P < 0.05). Proliferative activity of neointimal cells assessed in vitro by [3H]thymidine incorporation, and in vivo by immunostaining for proliferating cell nuclear antigen, increased and declined in parallel with gene expression. These findings thus indicate that the expression of liposome-mediated arterial gene transfer may be augmented in presence of ongoing cellular proliferation.
Assuntos
Aorta Torácica/lesões , Aorta Torácica/metabolismo , Cateterismo/efeitos adversos , Expressão Gênica , Luciferases/biossíntese , Músculo Liso Vascular/metabolismo , Transfecção/métodos , Animais , Aorta Torácica/citologia , Divisão Celular , Portadores de Fármacos , Terapia Genética/métodos , Lipossomos , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/lesões , Técnicas de Cultura de Órgãos , Plasmídeos/administração & dosagem , CoelhosRESUMO
The induced membrane technique is used for bone reconstruction. It is based on the osteoinductive properties of a membrane induced by the insertion of a PMMA cement spacer. We will describe a simple, cost-effective method in which the body of a syringe is used to facilitate the cement introduction, allow insertion of a regular spacer, contain the cement volume in the extension of the diaphysis and protect the underlying tissues from the exothermic reaction during PMMA polymerisation.
Assuntos
Cimentos Ósseos/uso terapêutico , Regeneração Óssea/fisiologia , Procedimentos Ortopédicos/métodos , Polimetil Metacrilato/uso terapêutico , Análise Custo-Benefício , Humanos , Teste de Materiais , Polimerização , Procedimentos de Cirurgia Plástica/métodos , SeringasRESUMO
Folypoly-gamma-glutamate synthetase (FPGS) is essential for the cytotoxicity of "classical" antifolates and their efficacy in cancer chemotherapy. The expression of the FPGS gene appears controlled by both tissue/lineage-specific and proliferation-dependent mechanisms. Four alternative exon 1 splice variants of the FPGS gene have been described previously, but their significance in gene regulation has not been determined. Furthermore, alternative splicing of the human FPGS gene in normal or transformed cells in vivo has not been reported. We have examined the mRNA expression of these FPGS splice variants in primary human leukemia cells, cell lines, and normal human hematopoietic progenitors using reverse transcription-PCR. Specific primers were designed to amplify splice variants 1, 1A, 1B, and 1C; and full-length FPGS mRNA was amplified using primers for exons 14 and 15 at the 3' end of the gene. In this study, we demonstrate that all four alternative exon 1 variants are expressed in all primary leukemia cells and cell lines (ALL and AML), as well as in normal human hematopoietic progenitors. No significant differences in mRNA expression were detected in primary cells or cell lines for the four exon 1 splice variants. Normal circulating human lymphocytes (peripheral blood mononuclear cells) also expressed mRNA amplified from full-length FPGS and the four exon 1 splice variants, although no detectable FPGS activity was found. Using Western immunoblotting, we show that FPGS protein is expressed in these peripheral blood mononuclear cells; thus, we propose that posttranslational modification(s) is required for expression of a functional FPGS protein in human lymphohematopoietic cells. In addition, poly(A)(+) RNA from normal human adult and fetal tissues and leukemia cell lines was analyzed by Northern blot methodology. Total FPGS mRNA expression showed tissue-specificity, and higher levels were observed in human fetal tissues compared with adult tissues. The data presented herein demonstrate the existence of these FPGS mRNA splice variants in normal and transformed human hematopoietic cells and indicate that alternative splicing of the 5' end of the human FPGS gene does occur in primary cells in vivo. However, its role in regulating the expression of its mRNA remains to be determined.
Assuntos
Processamento Alternativo , Leucemia/genética , Peptídeo Sintases/genética , Células da Medula Óssea/enzimologia , Catálise , Linhagem Celular , Éxons , Feto/enzimologia , Expressão Gênica , Células HL-60 , Células-Tronco Hematopoéticas/enzimologia , Humanos , Células K562 , Leucemia/enzimologia , Leucemia/patologia , Peptídeo Sintases/biossíntese , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Stents permanently maximize the arterial lumen following percutaneous transluminal coronary angioplasty (PTCA) at the cost of a vascular injury caused by the deployment of the prosthesis. Even though clinical trials show progressive reduction of restenosis and thrombosis rates in implanted coronary stents, these two events continue to represent a potential limitation to their clinical use. This review is focused on the arterial pathobiology related to the use of permanent and temporary stents. © 1997, Elsevier Science Inc. (Trends Cardiovasc Med 1997;7:24-28).
RESUMO
Directional atherectomy has provided the opportunity to study the pathology of restenosis in human tissue specimens from live patients. The restenosis lesion is characterized by two distinctive features: a focus of hypercellularity, comprised of cells with phenotypic features of proliferative vascular smooth muscle cells (SMCs), and a rich, loose extracellular matrix (ECM). Analysis of restenosis lesions by in situ hybridization, immunohistochemistry, and cell culture has disclosed evidence of activated SMCs, and in many cases-particularly lesions from the peripheral vasculature-ongoing cellular proliferation. The ECM of restenosis lesions is biglycan rich and decorin poor, a finding that is associated with increased expression of transforming growth factor beta (TGF-ß). While certain restenosis lesions contain foci of microangiogenesis, the pathogenetic significance of this feature remains uncertain.
RESUMO
Current generations of monotherapy drug-eluting stents only inhibit neointimal hyperplasia. However, these stent designs have other drawbacks such as delayed arterial healing, hypersensitivity, late stent thrombosis, and neoatherosclerosis, creating a need for a new generation of safer devices. The novel 'pro-healing' COMBOTM dual therapy stent aims to address these issues by reducing neointimal hyperplasia via an abluminal bioabsorbable polymer eluting sirolimus, and by simultaneously capturing circulating endothelial progenitor cells via luminally immobilized anti-CD34+ antibodies. Short-term preclinical data shows promising results as compared to 1st generation and 2nd generation drug-eluting stents; however long-term literature remains unavailable until now. This review aims to evaluate, histopathologically, drawbacks of the current era of stents at autopsy, review short-term preclinical and clinical data from the REMEDEE trial, and present original long-term preclinical data. To date, preclinical data shows good performance of the COMBOTM stent comparable with the safety profile of bare metal stents with minimal inflammation, increased endothelialization, and acceptable neointimal hyperplasia with no statistical evidence of late catch-up. Clinical data from the REMEDEE trial at 12 months shows non-inferiority to paclitaxel drug-eluting stents, no evidence of late stent thrombosis, and a low rate of adverse clinical events.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Stents Farmacológicos , Sirolimo/administração & dosagem , Anticorpos Monoclonais/imunologia , Antígenos CD34/imunologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Neointima/prevenção & controle , Paclitaxel/administração & dosagem , Polímeros/química , Desenho de Prótese , Trombose/prevenção & controleRESUMO
Intimal proliferation and functional changes involving vascular smooth muscle cells are key events in the development of atherosclerosis, including restenosis after percutaneous transluminal angioplasty. Nonmuscle myosin (NMM) is required for cytokinesis and has been shown in cultures of vascular smooth muscle cells to undergo changes of isoform expression depending on the stage of proliferation and differentiation. The purpose of this study was to examine the differential expression of the two most recently identified nonmuscle myosin heavy chain isoform II (NMMHC-II) isoforms A and B in atherosclerotic plaque. Primary atherosclerotic and restenotic atherectomy specimens and non-atherosclerotic controls, were analyzed by Western Blot analysis, immunohistochemistry and in situ hybridization. Nonmuscle myosin heavy chain isoform IIA (NMMHC-IIA) was equally expressed in all types of tissue specimens both at the protein and mRNA levels. In contrast, NMMHC-IIB protein was found in restenotic specimens and normal artery but was at very low levels in primary atherosclerotic plaque. By in situ hybridization NMMHC-IIB mRNA levels were significantly greater in restenotic versus primary atherosclerotic lesions. NMMHC-IIB expression is associated with vascular restenosis but is downregulated in stable atherosclerotic lesions, whereas NMMHC-IIA is expressed in both. These results indicate that these new myosin isoforms have different functions and should be regarded separately with respect to smooth muscle proliferation and restenosis. They should prove to be useful molecular markers for the study of atherosclerosis and restenosis.
Assuntos
Artérias/química , Arteriosclerose/metabolismo , Cadeias Pesadas de Miosina/análise , Idoso , Especificidade de Anticorpos , Arteriosclerose/terapia , Aterectomia , Western Blotting , Células Cultivadas , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Músculo Liso Vascular/química , Cadeias Pesadas de Miosina/imunologia , Subfragmentos de Miosina/imunologia , RecidivaRESUMO
PURPOSE: Late thrombosis of irradiated vascular segments may be the consequence of endothelial cell (EC) dysfunction after radiation therapy. We investigated the effects of beta ionizing radiation on human EC viability, thymidine uptake, and differentiation. METHODS AND MATERIALS: Endothelial cells were exposed to (32)P-labeled DNA oligonucleotides in incremental doses of 2, 6, and 10 Gy. The modulation of the VEGFR2 receptor expression after irradiation and the overall potential radioprotective effect of VEGF(165) on these functions were assayed. RESULTS: A dose-dependent inhibitory effect of beta irradiation on ECs' thymidine uptake and differentiation was observed. EC viability, however, was not affected at levels of radiation up to 10 Gy. VEGF(165) proved to have a radioprotective effect as ECs' thymidine uptake, after radiation doses of 2, 6, and 10 Gy, was increased by 1.5-, 2-, and 4-fold, respectively, in the presence of 10 ng/ml of VEGF(165) (p < 0.05 vs. LacZ). This concentration of VEGF(165) also proved beneficial in maintaining cell differentiation at 16 h postirradiation when compared to controls. These biologic effects were in direct correlation with the upregulation of VEGFR2 receptor expression in irradiated ECs. CONCLUSIONS: beta irradiation interacts directly with EC functions by significantly reducing their ability to differentiate and proliferate, associated with upregulation of VEGFR2. These effects can be prevented in part by pretreating cells with VEGF(165), an effect potentially favored by the upregulation of VEGFR2 receptor expression after irradiation.
Assuntos
Fatores de Crescimento Endotelial/fisiologia , Endotélio Vascular/efeitos da radiação , Linfocinas/fisiologia , Receptores Proteína Tirosina Quinases/biossíntese , Receptores de Fatores de Crescimento/biossíntese , Timidina/farmacocinética , Adenovírus Humanos/genética , Partículas beta , Diferenciação Celular/efeitos da radiação , Divisão Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Humanos , Linfocinas/biossíntese , Linfocinas/genética , Linfocinas/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiologia , Músculo Liso Vascular/virologia , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento do Endotélio Vascular , Regulação para Cima/efeitos da radiação , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
New beta-adrenergic blocking agents, most of which do not contain an aromatic nucleus, were synthesized. They were derived either from alkylamino-aliphatic oxime ethers or alkylamino-aliphatic ethers. Most active among these are O-[3-(tert-butylamino)-2-hydroxypropyl]acetoxime (8; trachea pA2 = 7.65) and 1-isobutoxy-3-(tert-butylamino)-2-propanol (15; trachea pA2 = 7.49), both of which displayed bronchoselectivity (beta 2/beta 1 ratio approximately 15). The role and importance of the aromatic nucleus in this class of compounds are discussed.