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1.
J Arthroplasty ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094013

RESUMO

BACKGROUND: The direct anterior (DA) approach is becoming increasingly popular for primary total hip arthroplasty (THA). The aim of this study is to evaluate early postoperative complication and revision rates based on surgical approach, comparing DA, posterolateral (PL), and direct superior (DS) approaches. METHODS: After institutional review board approval, a total joint arthroplasty database from a single institution was used to identify all patients who underwent elective primary THA between July 2013 and November 2017 with a DA, PL, or DS hip approach. Patients were followed for complications out to 90 days postsurgery. Patients were divided into groups based on surgical approach and compared on length of stay, discharge disposition, and 90-day complication and revision rates. RESULTS: There were 5341 THA procedures performed, with 3162 PL, 1846 DA, and 333 DS approaches. Length of stay was shorter for DS (1.7 ± 0.9 days) and DA (1.8 ± 0.9 days) than for PL approaches (2.3 ± 1.4 days, P < .001) The DS approach had the highest rate of home discharges (93.1%), but the highest short-term revision rate (1.5%, P = .011). The DA approach had the lowest intraoperative fracture rate (0.1%, P = .019) but the highest incidence of postoperative fractures (1.3%, P = .021). There were no differences in readmission (P = .056), 90-day events (P = .062), emergency department visits (P = .210), dislocations (P = .090), combined perioperative fractures (P = .289), venous thromboembolic events (P = .059), or acute infection rates (P = .287). CONCLUSION: In the era of bundled payments, the DA, PL, and DS approaches can all be effectively used. LEVEL OF EVIDENCE: Level III; retrospective comparative study.

2.
Orthopedics ; 42(6): e528-e531, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31185123

RESUMO

Primary total joint arthroplasty (TJA) of the hip and knee are effective procedures for improving pain and function in patients with arthritis. This study examined whether order of surgery (TKA or THA first) affects length of stay (LOS) and discharge disposition among patients with coexisting knee and hip arthritis. A total joint arthroplasty database review was performed to collect all available data for arthroplasties performed at 2 campuses of a single institution between July 2013 and April 2017. Inclusion criteria were patients who underwent both primary THA and TKA within 18 months and were age 18 years or older. Patients were divided into 2 groups based on whether THA or TKA was performed first. For all procedures, the following data were collected: age, body mass index (BMI), time between cases, LOS, discharge disposition, and the number of 90-day adverse postoperative events. Adverse 90-day events included deep infection, fracture, hardware failure, urinary tract infection, other return to the operating room, emergency department visit, readmission, or death. A total of 211 patients underwent both THA and TKA within 18 months; 124 patients underwent THA first and 87 underwent TKA first. There was no difference in age or BMI between the 2 groups. There was a significantly longer time between the first and second arthroplasty in patients with TKA first by a mean of 2 months (P=.001). There was no difference in 90-day adverse postoperative events following THA whether done first or second (P=.371), and no difference in 90-day events following TKA whether done first or second (P=.524). There was no difference in discharge disposition (P=.833 and P=.395) or LOS (P=.695 and P=.473) between groups for the first or second procedure, respectively. In a patient with coexisting hip and knee arthritis, the current results do not support recommending THA or TKA first based on cost related to LOS and discharge disposition. [Orthopedics. 2019; 42(6):e528-e531.].


Assuntos
Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Tempo de Internação , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , Idoso , Custos e Análise de Custo , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/complicações , Osteoartrite do Joelho/complicações , Alta do Paciente , Período Pós-Operatório , Fatores de Risco , Resultado do Tratamento
3.
J Arthroplasty ; 34(6): 1273-1278, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30853157

RESUMO

BACKGROUND: Dual-mobility (DM) total hip arthroplasty (THA) systems are designed to increase stability while potentially avoiding problems associated with large femoral heads. Complications of these systems are not yet fully understood. This study aims at characterizing in vivo performance of DM hip systems and assessing modes of clinical failure. METHODS: Under an institutional review board-approved implant retrieval protocol, 18 DM THA systems from 17 patients were included. Implants were graded at the head-neck junction for fretting and corrosion based on the system of Goldberg et al. Components were also macroscopically examined for different damage modes. Demographics and surgical data were collected from medical records, and radiographs were assessed for component positioning. Data were analyzed through Spearman rank-order correlation and Mann-Whitney U-tests, with α = 0.05. RESULTS: The average length of implantation was 13.4 months with mild to moderate fretting corrosion damage. Polyethylene (PE) liners exhibited edge deformation, scratching, and pitting damage. Metallic components exhibited burnishing and scratching damage. Summed fretting and corrosion scores were strongly correlated (ρ = 0.967, P < .0001). Summed corrosion score was moderately correlated with presence of embedding on the PE liner (ρ = 0.690, P = .017). PE liner abrasion and edge deformation of the femoral stem taper were moderately positively correlated (ρ = 0.690, P = .017). Fretting and corrosion damage were not significantly correlated with patient demographics or radiographic positioning of implants. There were no differences in scores between modular and monoblock designs. CONCLUSION: These findings demonstrate that dual-mobility THA systems may be susceptible to the same fretting and corrosion damage observed in traditional modular THA systems. Future studies are needed to confirm these results and clinical significance.

4.
J Arthroplasty ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31924488

RESUMO

BACKGROUND: The purpose of this study is to compare open reduction and internal fixation (ORIF) to distal femoral replacement (DFR) for treatment of displaced periprosthetic distal femur fractures. METHODS: We identified 72 patients with minimum 2-year follow-up following a displaced periprosthetic distal femur fracture: 50 were treated with ORIF and 22 with DFR. Outcomes were assessed with multivariate regression analysis and include Knee Society Scores (KSS), infection rates, revision incidence, and mortality. RESULTS: Patients treated with DFR had a higher Charlson comorbidity index (5.2 vs 3.8; P = .006). The mean postoperative KSS were similar between groups, but the Knee Society Functional Scores were higher in the ORIF group (P = .01). Six ORIF patients (12%) and 3 DFR patients (14%) underwent a revision surgery (P = .1). In the ORIF group, 3 revisions were associated with periprosthetic infection, and 3 revisions occurred for aseptic nonunion. In the DFR group, 1 infection was treated with irrigation and debridement, and 2 cases of patellar maltracking resulted in 1 liner exchange with soft tissue release and 1 femoral revision for malrotation. More patients in the ORIF group required repeat revisions, with twice as many total revisions (P < .001). Six ORIF patients and 7 DFR patients died within 2 years (P = .26). CONCLUSION: The Knee Society Functional Score favored ORIF, but the total incidence of revision was higher in the ORIF cohort. Given the high mortality and the substantial risk of reoperation in both groups, additional studies are needed regarding the prevention of and optimal treatment for patients with periprosthetic distal femur fractures.

5.
Orthopedics ; 41(6): e747-e755, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321439

RESUMO

Patella fractures comprise 1% of all fractures. Treatment options vary based on fracture displacement, classification, and patient factors. Traditionally, nonoperative treatment has been reserved for nondisplaced fractures. Many operative treatments are available with differing indications and levels of success. Tension band constructs have been the most commonly employed approach to fixation, with cerclage wiring for comminuted fractures. Recently, plate fixation of patella fractures has become more popular. Plating constructs offer a low-profile design with stable fixation, allowing for earlier mobilization and potentially improved functional outcomes. Data regarding the long-term outcomes of plating techniques are limited, and further studies are needed. [Orthopedics. 2018; 41(6):e747-e755.].


Assuntos
Fixação Interna de Fraturas/métodos , Fraturas Ósseas/terapia , Fraturas Cominutivas/cirurgia , Traumatismos do Joelho/terapia , Patela/lesões , Patela/cirurgia , Placas Ósseas , Fios Ortopédicos , Humanos , Patela/anatomia & histologia
6.
J Arthroplasty ; 33(11): 3416-3421, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30057269

RESUMO

BACKGROUND: More emphasis is being placed on patient-reported outcome measures (PROMs), but the myriad of PROMs makes standardization and cross-study comparison difficult. As the era of big data and massive total joint registries matures, it will be critical to identify and implement the best PROMs. METHODS: All abstracts published in the years 2004, 2009, 2014, and 2016 in the Journal of Bone and Joint Surgery-American volume, the Bone and Joint Journal, Clinical Orthopedics and Related Research, and the Journal of Arthroplasty were reviewed. A PubMed search was performed with filters limiting results only to total knee, total hip, and unicompartmental knee arthroplasty articles with available abstracts. Each abstract was reviewed to identify all PROMs. Trends over time were evaluated using the Cochran-Armitage test. In the non-trend analysis, Pearson chi-square tests and one-way analysis of variance were performed. RESULTS: A total of 42 unique PROMs were used 1073 times across 644 studies. The number of PROMs in these 4 journals increased from 97 in 2004 to 228 in 2016 (P < .0001). The proportion of articles with more than one PROM increased from 20.6% in 2004 to 47.8% in 2016 (P = .0001). The most common PROMs used in total knee, total hip, and unicompartmental knee arthroplasty studies were the Knee Society Score, the Harris Hip Score, and the Oxford Knee Score, respectively. CONCLUSION: Providers and registries should consider the relative prevalence of published outcome measures when selecting which PROMs to use, to better facilitate future cross-study comparison.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Ortopedia/tendências , Medidas de Resultados Relatados pelo Paciente , Humanos , Articulação do Joelho/cirurgia , Ortopedia/estatística & dados numéricos , Amplitude de Movimento Articular , Resultado do Tratamento
7.
Orthopedics ; 41(3): 171-176, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29570760

RESUMO

Aspirin and unfractionated heparin (UH) are accepted options for venous thromboembolism (VTE) prophylaxis after total joint arthroplasty (TJA). The use of aspirin in addition to UH in preventing VTE after TJA has yet to be studied. The primary objective of this study was to determine VTE rates in patients receiving aspirin monotherapy and those receiving aspirin and UH combination therapy immediately following TJA. A TJA database from a single hospital system was retrospectively reviewed to identify all patients who underwent primary hip or knee arthroplasty from 2013 to 2016. Patients were divided into 3 groups based on postoperative VTE chemoprophylaxis: aspirin only, aspirin with 1 dose of UH, and aspirin with multiple doses of UH. There were 5350 patients included: 1024 aspirin only, 1695 aspirin plus 1 dose of UH, and 2631 aspirin plus multiple doses of UH. Deep venous thrombosis and pulmonary embolus rates did not vary significantly between groups (deep venous thrombosis: 1.1%, 0.9%, and 1.2%, respectively, P=.701; pulmonary embolus: 0.3%, 0.3%, and 0.2%, respectively, P=.894). Transfusion rates were significantly greater with 1 dose of UH (1.8%) and multiple doses of UH (4.3%) compared with aspirin only (0.9%) (P<.001). Additionally, the postoperative hemoglobin decreased significantly more postoperatively with the use of UH (P<.001). Aspirin and UH combination therapy did not decrease VTE incidence compared with aspirin monotherapy. Additionally, there was greater perioperative blood loss and an increased rate of blood transfusion in patients receiving UH. On the basis of these findings, the authors do not recommend UH as an additional mode of VTE prophylaxis when prescribing aspirin after elective TJA. [Orthopedics. 2018; 41(3):171-176.].


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Aspirina/uso terapêutico , Heparina/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Quimioterapia Combinada , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Embolia Pulmonar/etiologia , Embolia Pulmonar/prevenção & controle , Estudos Retrospectivos , Tromboembolia Venosa/etiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
8.
J Arthroplasty ; 33(2): 320-323, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28988612

RESUMO

BACKGROUND: Simultaneous vs staged bilateral total knee arthroplasty (BTKA) has long been debated. The primary objective of this study was to compare actual hospital costs and complication rates in patients undergoing simultaneous BTKA (simBTKA) and staged BTKA (staBTKA) at a single institution. METHODS: A total joint arthroplasty database from a single hospital was used to identify all patients who underwent primary BTKA from 2013 to 2016 and divided into simultaneous and staged groups. StaBTKA patients were included if both procedures were performed within 1 year by the same surgeon. The combined total hospital cost of both procedures was used, and inpatient rehabilitation (IPR) costs were added for all patients discharged to IPR. RESULTS: There were 225 simBTKA and 337 staBTKA patients. SimBTKA patients were younger (61 ± 8 vs 66 ± 8 years, P < .001), had lower body mass index (31.3 ± 5.9 vs 34.0 ± 7.2, P < .001), were more predominately male (48% vs 38%, P = .029), and more likely to require IPR as compared with staBTKA patients. There was no difference in total hospital cost for simBTKA as compared with staBTKA ($24,596 ± $5652 vs $24,915 ± $5756, P = .586). Complications were more prevalent in the simBTKA group, including venous thromboembolism (5.4% vs 1.4%, P = .006) and blood transfusions (15.8% vs 6.2%, P < .001). CONCLUSION: There were higher complication rates with no significant cost savings in actual hospital costs associated with simBTKA, when accounting for the cost of IPR, as compared with staBTKA. The total cost analysis of simBTKA vs staBTKA, using actual cost data, merits further evaluation.


Assuntos
Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/economia , Custos Hospitalares/estatística & dados numéricos , Osteoartrite do Joelho/cirurgia , Idoso , Artroplastia do Joelho/métodos , Artroplastia do Joelho/estatística & dados numéricos , Custos e Análise de Custo , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Clin Orthop Relat Res ; 473(10): 3272-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25800376

RESUMO

BACKGROUND: Patients with Parkinson's disease are at increased risk for falls and associated hip fractures as a result of tremor, bradykinesia, rigidity, and postural instability. The available literature is limited and conflicting regarding the optimal surgical treatment and risk for postoperative complications and mortality in this unique patient population. QUESTIONS/PURPOSES: We asked: (1) Is there a difference in mortality after surgical treatment of hip fractures in patients with Parkinson's disease compared with similar patients with hip fractures without Parkinson's disease? (2) Does Parkinson's disease lead to a higher rate of reoperation after operative treatment of femoral neck fractures? (3) Does Parkinson's disease lead to a higher rate of dislocation after hemiarthroplasty for displaced femoral neck fractures, and (4) does the operative approach affect dislocation rates? METHODS: In this case-controlled study, we retrospectively reviewed 141 patients with a diagnosis of Parkinson's disease and a fracture of the femoral neck. Each patient with Parkinson's disease was matched with two control patients (n = 282) without Parkinson's disease stratified by age, sex, American Society of Anesthesiologists classification, and fracture type (nondisplaced/displaced). Clinical outcomes included mortality after surgical intervention, rate of reoperation, dislocation events after hemiarthroplasty, and the rate of failure after internal fixation for nondisplaced fractures. RESULTS: The median survival time of the patients with Parkinson's disease after fracture was 31 months (95% CI, 25-37 months) compared with 45 months (95% CI, 39-50 months) in our control group (p = 0.007). The rate of reoperation for displaced and nondisplaced fractures was higher in the Parkinson's disease group compared with the control group (11% versus 4%; p = 0.005). Failure of fixation for patients treated with internal fixation of nondisplaced femoral neck fractures was significantly higher in the Parkinson's disease group compared with our control group (22% versus 5%; p = 0.01). Dislocation rates after hemiarthroplasty were significantly higher in the Parkinson's disease group compared with the control group (8% versus 1%; p = 0.003). Patients treated with a hemiarthroplasty through an anterolateral approach had a significantly lower dislocation rate compared with those treated with a posterior approach (2% versus 15%; p = 0.002). CONCLUSIONS: Parkinson's disease is an independent predictor of mortality after femoral neck fracture and is associated with an increased rate of dislocation, revision surgery, and failure of internal fixation. Although patients with Parkinson's disease with a nondisplaced or valgus impacted femoral neck fracture may be treated with internal fixation, they are at significantly higher risk of failure of fixation compared with patients without Parkinson's disease. Use of a hemiarthroplasty through an anterolateral approach may reduce the likelihood of requiring a revision operation. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Fraturas do Colo Femoral/mortalidade , Fraturas do Colo Femoral/cirurgia , Doença de Parkinson/complicações , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fraturas do Colo Femoral/complicações , Humanos , Masculino , Complicações Pós-Operatórias/mortalidade , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
11.
Foot Ankle Int ; 33(10): 870-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23050712

RESUMO

BACKGROUND: Diagnosis of syndesmotic injuries is primarily based upon the assessment of ankle radiographs. The purpose of our study was to redefine the radiographic relationships of the ankle syndesmosis based on a large series of normal ankle radiographs in living subjects. METHODS: The study involved 392 patients (218 females, 174 males) with ankle radiographs without known clinical or radiographic evidence of abnormality. Eighty-three of the 392 patients had also had normal contralateral radiographs. Tibiofibular overlap and tibiofibular clear space were measured on anteroposterior (AP) and mortise radiographs. The radiographic measurements were used to calculate means, standard deviations, and intra- and interobserver reliabilities, and compare genders and side-to-side radiographs. RESULTS: The mean overlap was 8.3 mm on the AP and 3.5 mm on the mortise while the mean clear space was 4.6 mm on the AP and 4.3 mm on the mortise view. The least amount of overlap on the AP view was 1.8 mm. On the mortise view, there was a subset of patients that had a complete lack of overlap (less than 0 mm) with the greatest gap noted to be 1.9 mm. The greatest clear space on AP was 8 mm and on the mortise was 7.6 mm. Mortise clear space was the most accurate measure when obtaining contralateral radiographs, with a mean side-to-side difference of 0.7 ± 0.7 mm. CONCLUSION: Lack of overlap on the mortise view can represent a normal variant, which has not been definitively reported in prior investigations. CLINICAL RELEVANCE: Our data form the basis for revised radiographic criteria to evaluate the distal tibiofibular syndesmosis which may influence clinical management of these patients.


Assuntos
Articulação do Tornozelo/diagnóstico por imagem , Fíbula/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Ligamentos Articulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radiografia , Reprodutibilidade dos Testes , Caracteres Sexuais , Adulto Jovem
12.
Arthroscopy ; 27(5): 681-94, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21663724

RESUMO

Failure of primary shoulder stabilization procedures is often related to uncorrected anatomic pathology. Orthopaedic surgeons must recognize excessive capsular laxity or large glenohumeral bone defects preoperatively to avoid recurrence of instability. When history, physical examination, and radiographic evaluation are used in conjunction, patients at risk for failure can be identified. The instability severity index score permits precise identification of patients at risk. When treating patients in whom prior surgical intervention has failed, the success of revision procedures correlates to the surgeon's ability to identify the essential pathology and use lesion-specific treatment strategies. Revision procedures remain technically demanding. Keen preoperative and intraoperative judgment is required to avoid additional recurrence of instability after revision procedures, particularly because results deteriorate with each successive operation. Glenoid or humeral defects with greater than 25% bone loss compromise stability provided through the mechanism of concavity compression. These defects must be specifically addressed to avoid recurrence of instability. We prefer anatomic reconstruction techniques combined with capsulolabral repair and, if bone defects are present, anatomic reconstruction with osteochondral allograft.


Assuntos
Instabilidade Articular/cirurgia , Luxação do Ombro/cirurgia , Articulação do Ombro/cirurgia , Artroscopia/métodos , Transplante Ósseo , Cartilagem Articular/lesões , Cartilagem Articular/cirurgia , Fraturas Ósseas/complicações , Fraturas Ósseas/cirurgia , Humanos , Cápsula Articular/cirurgia , Instabilidade Articular/diagnóstico , Instabilidade Articular/reabilitação , Exame Físico , Cuidados Pré-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco , Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador , Escápula/lesões , Índice de Gravidade de Doença , Luxação do Ombro/etiologia , Luxação do Ombro/prevenção & controle , Luxação do Ombro/reabilitação , Fraturas do Ombro/complicações , Fraturas do Ombro/cirurgia , Estresse Mecânico
13.
Behav Brain Res ; 157(1): 79-90, 2005 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-15617774

RESUMO

Previous studies in humans have demonstrated a high co-morbidity between alcoholism and smoking. This co-morbidity between alcohol and nicotine dependence can be attributed, in part, to common genetic factors. In rodents, behavioral and physiological responses to alcohol and nicotine also appear to share common genetic influences. In this report, the genetic correlation between free-choice oral nicotine and oral alcohol consumption was evaluated using an ascending two-bottle choice paradigm in C57BL/6xC3H/HeJ F2 intercross mice. For all concentrations of nicotine (25, 50, and 100 microg/ml) and alcohol (3, 6, and 10%) tested, nicotine consumption was significantly correlated with alcohol consumption. Nicotine consumption at the highest nicotine concentration tested (100 microg/ml) showed low, but significant, correlations with the number of [3H]-cytisine binding sites in the hippocampus (r=0.307) and the number of [125I]-alpha-bungarotoxin binding sites in the cortex (r=-0.328). No significant correlations between alcohol consumption and the number of either [3H]-cytisine or [125I]-alpha-bungarotoxin binding sites was observed. A polymorphism in the nicotinic receptor alpha4 subunit gene, Chrna4, showed a trend with nicotine consumption and a significant association with alcohol consumption in female but not male mice. These results indicate that common genetic factors influence nicotine and alcohol consumption in mice. However, neither individual differences in the expression of [3H]-cytisine or [125I]-alpha-bungarotoxin binding nicotinic receptors nor the polymorphism in Chrna4 likely contribute to the genetic overlap that influences the consumption of both of these drugs of abuse in C57BL/6xC3H/HeJ F2 mice.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Comportamento de Escolha/fisiologia , Etanol/metabolismo , Nicotina/metabolismo , Receptores Nicotínicos/metabolismo , Fumar/genética , Paladar/fisiologia , Consumo de Bebidas Alcoólicas/metabolismo , Alcaloides/genética , Alcaloides/metabolismo , Animais , Azocinas/metabolismo , Bungarotoxinas/metabolismo , Córtex Cerebral/metabolismo , Ingestão de Líquidos/fisiologia , Feminino , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Nicotina/antagonistas & inibidores , Polimorfismo Genético , Quinolizinas/metabolismo , Receptores Nicotínicos/genética , Fatores Sexuais , Especificidade da Espécie , Paladar/genética , Receptor Nicotínico de Acetilcolina alfa7
14.
J Neurochem ; 91(5): 1138-50, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15569257

RESUMO

Mouse alpha4beta2 nicotinic acetylcholine receptors (nAchRs) were stably expressed in HEK293T cells. The function of this stable cell line, termed mmalpha4beta2, was assessed using an aequorin-based luminescence method that measures agonist-evoked changes in intracellular calcium. Agonist-elicited changes in intracellular calcium were due primarily to direct entry of calcium through the alpha4beta2 channel, although release of calcium from intracellular stores contributed approximately 28% of the agonist-evoked response. Agonist pharmacologies were very similar between the mmalpha4beta2 cells and most cell lines that stably express human alpha4beta2 nAchRs. Based on agonist profiles and sensitivity to the antagonist dihydro-beta-erythroidine (DHbetaE), the predominant alpha4beta2 nAchR expressed in the mmalpha4beta2 cells exhibits a pharmacology that most resembles the DHbetaE-sensitive component of 86Rb+ efflux from mouse brain synaptosomes. However, when evaluated with the aequorin assay, the mmalpha4beta2 nAchR was found to be atypically sensitive to blockade by the presumed alpha7-selective antagonist methyllycaconitine (MLA), exhibiting an IC50 value of 31 +/- 0.1 nm. Similar IC50 values have been reported for the MLA inhibition of nicotine-stimulated dopamine release, a response that is mediated by beta2-subunit-containing nAchRs and not alpha7-subunit-containing nAchRs. Consequently, at low nanomolar concentrations, MLA may not be as selective for alpha7-containing nAchRs as previously thought.


Assuntos
Expressão Gênica/fisiologia , Receptores Nicotínicos/fisiologia , Acetilcolina/farmacologia , Equorina/metabolismo , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Cloreto de Cádmio/farmacologia , Cálcio/metabolismo , Cálcio/farmacologia , Linhagem Celular , Relação Dose-Resposta a Droga , Interações de Medicamentos , Inibidores Enzimáticos/farmacologia , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Compostos Macrocíclicos , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Agonistas Nicotínicos/farmacocinética , Agonistas Nicotínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Oxazóis/farmacologia , Técnicas de Patch-Clamp/métodos , Piridinas/farmacocinética , Piridinas/farmacologia , Ensaio Radioligante/métodos , Receptores Nicotínicos/genética , Radioisótopos de Rubídio/metabolismo , Rianodina/farmacologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Transfecção/métodos
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