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1.
JACC Case Rep ; 3(3): 443-446, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34317554

RESUMO

Cardiac sympathetic denervation has been shown to reduce sustained ventricular arrhythmias and implantable cardioverter-defibrillator shocks by inhibiting sympathetic outflow to the heart. We describe the first case to our knowledge of cardiac sympathetic denervation in the left ventricular assist device population. (Level of Difficulty: Advanced.).

2.
J Heart Lung Transplant ; 40(11): 1382-1386, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34176726

RESUMO

The trends and outcomes of multiorgan heart-transplantation (HT) using hepatitis C virus (HCV) donors in the contemporary era are sparsely known. Using UNOS registry, 1322 adult multiorgan-HTs (n = 986 heart-kidney, n = 155 heart-lung, n = 181 heart-liver) between August-2015 and August-2020 were identified, of which 109 were performed using HCV-donors (n = 77 HCV nucleic-acid-amplification testing [NAT] positive irrespective of antibody status [HCV-viremic]; and n = 32 HCV Ab+/NAT-[HCV antibody + nonviremic]). The percentage of HCV-donors used for multiorgan-HT increased from 0% in 2015 to 14% in 2020 (p < 0.001), but there was wide variation across UNOS regions and center volumes. Recipients of multiorgan heart-kidney transplants from HCV-donors (n = 90) and HCV-naïve (HCV Ab-/NAT-) donors (n = 896) had similar 1-year survival using unadjusted and adjusted Cox-proportional hazards-regression models including in propensity-score matched cohorts. Post-HT rates of cardiac-allograft-vasculopathy (5.4% vs 5.8%) and chronic-dialysis (7.3% vs 4.9%) at 1-year were also similar. Use of HCV-donors (HCV-viremic, HCV Ab+ nonviremic) for multiorgan-HT has increased significantly. Encouraging 1-year outcomes in heart-kidney recipients from HCV-donors should support further expansion of heart-kidney transplantation using HCV-donors.


Assuntos
Transplante de Coração/métodos , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/análise , Hepatite C/virologia , Insuficiência de Múltiplos Órgãos/cirurgia , Sistema de Registros , Doadores de Tecidos , Adulto , Feminino , Seguimentos , Hepatite C/complicações , Humanos , Masculino , Insuficiência de Múltiplos Órgãos/complicações , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/métodos
3.
Curr Probl Diagn Radiol ; 50(5): 580-584, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32561151

RESUMO

BACKGROUND: The transition toward value-based payment models increases focus on the radiologist's direct impact on hospital-provided patient care. Radiology trainees understand inpatient hospital workflows and decision-making paradigms and are well positioned to interface directly with hospital physicians regarding clinical decision making related to diagnostic imaging and/or image guided interventions. A radiology resident-led project with internal medicine residents focused on Clinical Decision Support was designed, implemented, and reviewed, with the objectives of educating clinical teams and positively impacting patient care. MATERIALS AND METHODS: During the 2017-2018 academic year, senior radiology residents (PGY-5) led weekly rounds with medicine residents rotating through inpatient floor units. During these rounds, they discussed indications for and types of hospital inpatient imaging studies, exchanged clinical information, directed further imaging workup, and taught the essentials of image interpretation. Participating medical residents' degree of radiology-awareness and opinions were systematically surveyed at the conclusion of the academic year. Thirty-four out of a total of 161 (21%) Internal Medicine residents responded to the survey. Thirty one percent of these residents could identify an instance where radiology-led rounds altered patient management and 94% acknowledged an increase in medical knowledge. Sixty-one percent believed evidence-based choice for imaging orders was enhanced by attending radiology-led rounds and 64% developed a better understanding of resources available to guide image ordering. Forty-nine percent of residents made suggestions to their Internal Medicine attending physician or more senior trainee or otherwise applied something learned during radiology-led rounds and 42% cancelled or ordered a study based on what they learned or discussed in radiology rounds. Thirty-nine percent of medicine residents stated that these rounds changed their perception of the role of the radiologist and 75% expressed the desire to see increased participation by radiologists in their daily workflow. Radiology resident-led educational medicine rounds promote cross-specialty collaboration, further educate trainees, and directly affect patient management. It is therefore valuable for radiology trainees to directly engage in the teaching of other medical providers, to enhance their own consultative skill set, promote face-to-face interactions with other physicians, and to directly impact patient care.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Internato e Residência , Médicos , Radiologia , Visitas de Preceptoria , Humanos , Radiologia/educação
4.
Am J Cardiol ; 138: 80-84, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33058805

RESUMO

Peripheral venous pressure (PVP) monitoring is a noninvasive method to assess volume status. We investigated the correlation between PVP and central venous pressure (CVP) in heart failure (HF), heart transplant (HTx), and left ventricular assist device (LVAD) patients undergoing right heart catheterization (RHC). A prospective, cross-sectional study examining PVP in 100 patients from October 2018 to January 2020 was conducted. The analysis included patients undergoing RHC admitted for HF, post-HTx monitoring, or LVAD hemodynamic testing. Sixty percent of patients had HF, 30% were HTx patients, and 10% were LVAD patients. The mean PVP was 9.4 ± 5.3 mm Hg, and the mean CVP was 9.2 ± 5.8 mm Hg. The PVP and CVP were found to be highly correlated (r = 0.93, p < 0.00001). High correlation was also noted when broken down by HF (r = 0.93, p < 0.00001), HTx (r = 0.93, p < 0.00001), and LVAD groups (r = 0.94, p < 0.00005). In conclusion, there is a high degree of correlation between PVP and CVP in HF, HTx, and LVAD patients. PVP measurements can be used as a rapid, reliable, noninvasive estimate of volume status in these patient populations.


Assuntos
Determinação da Pressão Arterial/métodos , Pressão Venosa Central/fisiologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Coração Auxiliar , Pressão Venosa/fisiologia , Adulto , Idoso , Cateterismo Cardíaco , Estudos Transversais , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
Ann Thorac Surg ; 110(1): 76-84, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31816283

RESUMO

BACKGROUND: The impact of different types of regional wall motion abnormalities (RWMAs), including the Takotsubo syndrome-like (TTS-like) phenotype, on posttransplant outcomes when using donor hearts with transient left ventricular systolic dysfunction (LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis and posttransplant outcomes when using donor hearts with transient LVSD. METHODS: From all adult (≥18 years) heart transplants in United Network of Organ Sharing between January 2007 and September 2015, we identified 472 donor hearts with improving or transient LVSD, defined as left ventricular ejection fraction ≤ 40% on initial transthoracic echocardiogram (TTE) that improved to ≥50% on follow-up TTE during donor evaluation. These improved LVSD donors were then subdivided into 3 groups based on RWMAs on the initial TTE, TTS-like (49, 10.38%), non-TTS RWMAs (74, 15.68%), and diffuse global hypokinesis (349, 73.94%), and compared for baseline characteristics and posttransplant outcomes with follow up until June 2018. RESULTS: Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year posttransplant mortality. Posttransplant functional status scores of recipients (at 1 year) and donor left ventricular ejection fraction (at median follow-up of 3.6 years) improved in all 3 subgroups. Rates of stroke or pacemaker predischarge were also similar. CONCLUSIONS: In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE, but this was not associated with adverse posttransplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs.


Assuntos
Transplante de Coração , Cardiomiopatia de Takotsubo/fisiopatologia , Adulto , Cardiotônicos/uso terapêutico , Angiografia Coronária , Eletrocardiografia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fenótipo , Cardiomiopatia de Takotsubo/sangue , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/tratamento farmacológico , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Resultado do Tratamento , Troponina I/sangue , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
7.
J Neurol Sci ; 397: 117-122, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30612084

RESUMO

OBJECTIVE: Sleep deprivation has a negative effect on neurocognitive performance. The King-Devick test (KDT), which tests speed and accuracy of number-reading, requires integrity of saccades, visual processing, and cognition. This study investigated effects of sleep deprivation in on-call residents using KDT. METHODS: A prospective cohort study was conducted among 80 residents. KDT was performed at the beginning and end of an overnight call shift for the residents in the experimental group. A control group was tested at the beginning of 2 consecutive day shifts. Estimates of hours of sleep, Karolinska Sleepiness Scale (KSS)(1 = extremely alert, 9 = extremely sleepy), and time and accuracy of KDT were recorded. RESULTS: 42 residents were tested before and after overnight call shifts and 38 served as controls. Change in test time differed between the groups, with the experimental group performing 0.54(SD = 4.0) seconds slower after their night on call and the control group performing 2.32(SD = 3.0) seconds faster on the second day, p < 0.001. This difference was larger in surgical compared to medical residents. CONCLUSIONS: Sleep deprivation was inversely correlated with neurocognitive performance as measured by KDT, with more effect on surgical than medical residents. Further research could investigate whether this test could help determine fatigue level and ability to continue working after a long shift.


Assuntos
Movimentos Oculares/fisiologia , Fadiga/diagnóstico , Internato e Residência , Doenças Profissionais/diagnóstico , Privação do Sono/diagnóstico , Adulto , Cognição/fisiologia , Medições dos Movimentos Oculares , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos
8.
JACC Case Rep ; 1(3): 350-354, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34316824

RESUMO

Nonbacterial thrombotic endocarditis is characterized by sterile thrombi on cardiac valves. This report describes the case of nonbacterial endocarditis without pathologic findings of fibrin or platelet deposition. Quadrivalvular endocarditis was found to be due to immunoglobulin M heavy chain deposition. This was a case of nonbacterial, nonthrombotic quadrivalvular endocarditis, which was termed noninfective endocarditis. (Level of Difficulty: Intermediate.).

9.
Vascular ; 27(1): 90-97, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30056785

RESUMO

BACKGROUND: To study trends in the clinical presentation, electrocardiograms, and diagnostic imaging in patients with pulmonary embolism presenting as ST segment elevation. METHODS: We performed a systematic literature search for all reported cases of pulmonary embolism mimicking ST-elevation myocardial infarction. Pre-specified data such as clinical presentation, electrocardiogram changes, transthoracic echocardiographic findings, cardiac biomarkers, diagnostic imaging, therapy, and outcomes were collected. RESULTS: We identified a total of 34 case reports. There were 23 males. Mean age of the population was 56.5 ± 15.5 years. Patients presented with dyspnea (76.4%), chest pain (63.6%), and tachycardia (71.4%). All patients presented with ST-elevations, with the most common location being in the anterior-septal distribution, lead V3 (74%), V2 (71%), V1 (62%) and V4 (47%). ST-segment elevations in the inferior distribution were present in lead II (12%), III (18%), and aVF (21%). Presentation was least likely in the lateral distribution. Troponin was elevated in 78.9% of cases. Right ventricular strain was the most common echocardiographic finding. Over 80% of patients had findings consistent with elevated right ventricular pressure, with 50% reported RV dilatation and 20% RV hypokinesis. The most commonly used imaging modality was contrast-enhanced pulmonary angiography. There was a greater incidence of bilateral compared to unilateral pulmonary emboli (72.4% vs. 10%). About 65% patients received anticoagulation and 36.3% were treated with thrombolytics. Forty-six percent of patients required intensive care and 18.7% intubation. Overall mortality was 25.8%. CONCLUSIONS: A review of the literature reveals that in patients presenting with pulmonary embolism, electrocardiogram findings of ST-segment elevations will occur predominantly in the anterior-septal distribution.


Assuntos
Angiografia por Tomografia Computadorizada , Ecocardiografia , Eletrocardiografia , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Terapia Trombolítica , Resultado do Tratamento
10.
Circ Heart Fail ; 11(8): e004899, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30354557

RESUMO

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs. Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD. METHODS AND RESULTS: Charts of all adult patients implanted with CF-LVAD between February 2006 and February 2017 were reviewed with particular emphasis on occurrence and cause of GIB. Fifty-four of 199 patients (27%) experienced a GIB. Overall frequency of GIB was lower in the 64 patients receiving digoxin compared with the 135 patients not receiving digoxin (16% versus 33%, P=0.01). Multivariable-adjusted Cox regression analysis confirmed that digoxin use was independently associated with a reduced risk for overall GIB (hazard ratio, 0.49; 95% CI, 0.24-0.98; P=0.045). GIBs were then categorized as non-GIAD, GIAD, or likely GIAD. Although the incidence of non-GIAD was similar in both groups (11% versus 7%, P=0.41), the frequency of GIAD/likely GIAD bleeding was significantly reduced in the digoxin group (5% versus 25%, P=0.0003). Multivariable-adjusted analysis confirmed that digoxin use was independently associated with a reduced risk for GIAD/likely GIAD bleeding (hazard ratio, 0.18; 95% CI, 0.06-0.6; P=0.005). However, digoxin use was not associated with reduced risk for non-GIAD GIB (hazard ratio, 1.54; 95% CI, 0.58-4.08; P=0.39). CONCLUSIONS: Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.


Assuntos
Angiodisplasia/prevenção & controle , Cardiotônicos/uso terapêutico , Digoxina/uso terapêutico , Hemorragia Gastrointestinal/prevenção & controle , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Angiodisplasia/diagnóstico , Angiodisplasia/etiologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Fatores de Proteção , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
J Am Coll Cardiol ; 70(10): 1248-1258, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28859788

RESUMO

BACKGROUND: Left ventricular systolic dysfunction (LVSD) accounts for almost 25% of nonacceptance of potential donor hearts. Previous smaller, single-center studies showed that LVSD following brain death may be transient, and such hearts can be successfully resuscitated with resolution of LVSD, then transplanted. OBJECTIVES: This study evaluated outcomes of donor hearts with LVSD on initial transthoracic echocardiogram (TTE) that resolved during donor management. METHODS: We reviewed echocardiograms of all cardiac donors in the United Network of Organ Sharing database that were transplanted from January 1, 2007, to September 30, 2015, and identified 472 donor hearts with LVSD (left ventricular ejection fraction [LVEF] ≤40%) on initial TTE that resolved (LVEF ≥50%) during donor management on a subsequent TTE. These patients comprised the improved donor LVEF group. These were compared with donor hearts with normal LVEF (LVEF ≥55%) on the initial TTE for recipient mortality, cardiac allograft vasculopathy (CAV), and primary graft failure (PGF). RESULTS: There was no significant difference in recipient mortality at 30 days, 1 year, 3 years, and 5 years of follow-up, nor any difference in rates of PGF at 90 days and CAV at 5 years between recipients of donor hearts with improved LVEF and recipients of donor hearts with initially normal LVEF. Post-transplant length of stay was also similar between the 2 groups. Using propensity scores, 461 transplants in the improved-donor LVEF group were matched to 461 transplants in the normal-donor LVEF group. There was no significant difference in PGF at 90 days or recipient mortality after up to 5 years of follow-up. CONCLUSIONS: In the largest analysis of donor hearts with transient LVSD, we found that such hearts can be successfully resuscitated and transplanted without increasing recipient mortality, CAV, or PGF. These results underscore the importance of appropriate donor management and should help to increase utilization of donor hearts with transient LVSD.


Assuntos
Transplante de Coração , Doadores de Tecidos , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Adulto , Ecocardiografia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Transplantados , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/cirurgia , Adulto Jovem
13.
JACC Heart Fail ; 5(12): 879-887, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28822746

RESUMO

OBJECTIVES: This study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts. BACKGROUND: Despite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established. METHODS: All adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics. RESULTS: Of the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07). CONCLUSIONS: In this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts.


Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Transplantados , Adolescente , Adulto , Fatores Etários , Causas de Morte/tendências , Bases de Dados Factuais , Feminino , Seguimentos , Sobrevivência de Enxerto , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
14.
Int J Cardiol ; 225: 234-243, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27732927

RESUMO

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to surgical aortic-valve replacement (SAVR) for patients with severe symptomatic aortic stenosis (AS) who are at high operative risk. We sought to determine the long-term (≥1year follow-up) safety and efficacy TAVR compared with SAVR in patients with severe AS. METHODS: A comprehensive search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and relevant Web sites from inception through 10 April 2016. RESULTS: Fifty studies enrolling 44,247 patients met the inclusion criteria. The mean duration follow-up was 21.4months. No difference was found in long-term all-cause mortality (risk ratios (RR), 1.06; 95% confidence interval (CI) 0.91-1.22). There was a significant difference favoring TAVR in the incidence of stroke (RR, 0.82; 95% CI 0.71-0.94), atrial fibrillation (RR, 0.43; 95% CI 0.33-0.54), acute kidney injury (RR, 0.70; 95% CI 0.53-0.92), and major bleeding (RR, 0.57; 95% CI 0.40-0.81). TAVR had significant higher incidence of vascular complications (RR, 2.90; 95% CI 1.87-4.49), aortic regurgitation (RR, 7.00; 95% CI 5.27-9.30), and pacemaker implantation (PPM) (RR, 2.02; 95% CI 1.51-2.68). TAVR demonstrated significantly lower stroke risk compared to SAVR in high-risk patients (RR, 1.49; 95% CI 1.06-2.10); no differences in PPM implantation were observed in intermediate-risk patients (RR, 1.68; 95% CI 0.94-3.00). In a meta-regression analysis, the effect of TAVR baseline clinical features did not affect the long-term all-cause mortality outcome. CONCLUSION: TAVR and SAVR showed similar long-term survival in patients with severe AS; with important differences in treatment-associated morbidity.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/tendências , Estenose da Valva Aórtica/diagnóstico , Ensaios Clínicos como Assunto/métodos , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/tendências , Humanos , Análise de Regressão , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento
16.
Biochem Pharmacol ; 79(12): 1759-71, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20188076

RESUMO

NO-donating aspirin (NO-ASA, para isomer) has been reported to exhibit strong growth inhibitory effect in Jurkat T-acute lymphoblastic leukemia (T-ALL) cells mediated in part by beta-catenin degradation and caspase activation, but the mechanism(s) still remains unclear. In this study, DNA oligoarrays with 263 genes were used to examine the gene expression profiles relating to stress and drug metabolism, and characterize the stress responses at IC(50) and subIC(50) concentrations of p-NO-ASA (20 and 10microM, respectively) in Jurkat T cells. A total of 22 genes related to heat shock response, apoptosis signaling, detoxifiers and Phase II enzymes, and regulators of cell growth were altered in expression by array analysis based on the expression fold change criteria of > or =1.5-fold or < or =0.65-fold. Real time quantitative RT-PCR confirmed that 20microM p-NO-ASA strongly upregulated the mRNA levels of two heat shock genes HSPA1A (41.5+/-7.01-fold) and HSPA6 (100.4+/-8.11-fold), and FOS (16.2+/-3.2-fold), moderately upregulated HSPH1 (1.71+/-0.43-fold), FMO4 (4.5+/-1.67-fold), CASP9 (1.77+/-0.03-fold), DDIT3 (5.6+/-0.51-fold), and downregulated NF-kappaB1 (0.54+/-0.01-fold) and CCND1 (0.69+/-0.06-fold). Protein levels of Hsp70, the product of HSPA1A, and fos were increased in p-NO-ASA-treated Jurkat T and HT-29 colon cancer cells in a dose-dependent manner. Silencing of Hsp70 enhanced the growth inhibitory effect of p-NO-ASA at low concentrations. The altered gene expression patterns by NO-ASA in Jurkat T cells suggest mechanisms for carcinogen metabolism, anti-proliferative activity and possible chemoprotective activity in T-ALL.


Assuntos
Antineoplásicos/farmacologia , Aspirina/análogos & derivados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leucemia de Células T/tratamento farmacológico , Antineoplásicos/química , Aspirina/química , Aspirina/farmacologia , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Inativação Gênica , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Células Jurkat , Estrutura Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Interferência de RNA
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