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1.
Clin Transplant ; 33(10): e13659, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31278776

RESUMO

Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy-one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5-8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up-to-date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.


Assuntos
Transplante de Órgãos/normas , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Especialidades Cirúrgicas/estatística & dados numéricos , Especialidades Cirúrgicas/normas , Cirurgiões/normas , Recursos Humanos/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
2.
Curr Transplant Rep ; 5(1): 45-54, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29805957

RESUMO

PURPOSE OF REVIEW: This paper describes the background, rationale, and design of an NIH-funded, single-center study to test the impact of offering reimbursement for donor lost wages incurred during the post-nephrectomy recovery period on the live donor kidney transplant (LDKT) rate in newly evaluated kidney transplant candidates, to examine whether offering reimbursement for donor lost wages reduces racial disparity in LDKT rates, and to determine whether higher reimbursement amounts lead to higher LDKT rates. RECENT FINDINGS: LDKT is the optimal treatment for renal failure. However, living kidney donation has declined in the past decade, particularly among men, younger adults, blacks, and low-income adults. There is evidence that donation-related costs may deter both transplant candidates and potential donors from considering LDKT. Lost wages is a major source of financial loss for some living donors and, unlike travel and lodging expenses, is not reimbursed by financial assistance programs. SUMMARY: The study addresses the transplant community's call to reduce the financial burden of living donation and examine its impact on LDKT rates. Findings have the potential to influence policy, clinical practice, LDKT access, and income-related and racial disparities in LDKT and living donation.

3.
J Clin Psychol Med Settings ; 22(2-3): 160-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26123551

RESUMO

This article describes the development and implementation of an initiative at one transplant center to annually assess psychosocial outcomes of living kidney donors. The current analysis focuses on a cohort of adults (n = 208) who donated a kidney at BIDMC between September 2005 and August 2012, in which two post-donation annual assessments could be examined. One and two year post-donation surveys were returned by 59 % (n = 123) and 47 % (n = 98) of LKDs, respectively. Those who did not complete any survey were more likely to be younger (p = 0.001), minority race/ethnicity (p < 0.001), and uninsured at the time of donation (p = 0.01) compared to those who returned at least one of the two annual surveys. The majority of donors reported no adverse physical or psychosocial consequences of donation, high satisfaction with the donation experience, and no donation decision regret. However, a sizable minority of donors felt more pain intensity than expected and recovery time was much slower than expected, and experienced a clinically significant decline in vitality. We describe how these outcomes are used to inform clinical practice at our transplant center as well as highlight challenges in donor surveillance over time.


Assuntos
Transplante de Rim/psicologia , Transplante de Rim/estatística & dados numéricos , Doadores Vivos/psicologia , Doadores Vivos/estatística & dados numéricos , Avaliação de Resultados da Assistência ao Paciente , Adolescente , Adulto , Distribuição por Idade , Idoso , Boston , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Adulto Jovem
4.
Liver Transpl ; 21(5): 572-80, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25644857

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) and resection are curative treatment options for well-selected patients with HCC, whereas loco-ablative therapy has been shown to prolong survival. Organ and treatment allocations for these patients are currently based on the number and size of tumors, as defined by the Milan criteria, and on functional capacity, and they are incorporated into the Barcelona Clinic Liver Cancer staging system and treatment strategy. Even though these staging criteria have markedly improved the outcomes of patients with HCC, they still lack accuracy in predicting the risk of tumor recurrence because they do not incorporate markers of tumor biology and behavior. Positron emission tomography (PET) and computed tomography (CT) with [(18) F]fludeoxyglucose ([(18) F]FDG) constitute an imaging modality for detecting tumor tissue that is metabolically active. Uptake of [(18) F]FDG is highly associated with tumor aggressiveness. In this review, we present the accumulating data on the use of [(18) F]FDG PET-CT as an in vivo biomarker and its predictive value in identifying patients at risk for HCC recurrence after liver transplantation, resection, or ablation. These data suggest that the introduction of [(18) F]FDG PET-CT into the imaging algorithm of patients planned for liver transplantation, resection, or ablation may improve outcomes.


Assuntos
Carcinoma Hepatocelular/cirurgia , Fluordesoxiglucose F18/química , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Análise Custo-Benefício , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Invasividade Neoplásica , Metástase Neoplásica , Tomografia por Emissão de Pósitrons/economia , Prognóstico , Compostos Radiofarmacêuticos/química , Recidiva , Resultado do Tratamento
5.
J Gastrointest Surg ; 18(10): 1777-83, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25091839

RESUMO

BACKGROUND: Emergent surgery in the setting of decompensated cirrhosis is highly morbid. We sought to determine the clinical factors associated with negative intraoperative findings at emergent laparotomy. METHODS: We performed a retrospective cohort study of consecutive inpatients with a diagnosis of cirrhosis (ICD-9 571) admitted to the Beth Israel Deaconess Medical Center (Boston, MA) who underwent emergent, nonhepatic, abdominal surgery between May 6, 2005 and September 3, 2012. RESULTS: Eighty-six patients with cirrhosis were included with a mean model for end-stage liver disease score of 21.3 ± 7.95 and a 90-day mortality rate of 39.5%. Twelve (16.2%) patients had negative laparotomies. Negative intraoperative findings were independently associated with (1) paracentesis prior to a preoperative diagnosis of perforated viscus (P = 0.006), (2) development of an indication for emergent surgery after 24 h into hospital admission for another reason (P = 0.020), and (3) a preoperative diagnosis of bowel ischemia (P = 0.005), with odds ratios of 10.1 (CI 1.92-66.83), 5.80 (CI 1.32-33.39), and 11.1 (CI 2.08-77.4), respectively. Free air on computed tomography (CT) imaging was found in 64.3% (9/14) of patients who had a paracentesis within the preceding 48 h compared to 10.1% (7/72) among patients who did not undergo a paracentesis (P < 0.001). Only 45% of patients with free air following a paracentesis had positive findings at laparotomy compared to 100% in those without a preceding paracentesis (P = 0.038). Negative laparotomy was independently predictive of in-hospital mortality (OR 4.7; P = 0.034). CONCLUSION: The possibility of a negative laparotomy is suggested by preoperative clinical factors. In particular, free air following a paracentesis does not necessarily indicate that operative intervention is required. Consideration of close observation before laparotomy in these patients is reasonable.


Assuntos
Complicações Intraoperatórias/epidemiologia , Laparotomia/métodos , Cirrose Hepática/cirurgia , Causas de Morte/tendências , Emergências , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Período Intraoperatório , Tempo de Internação/tendências , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
6.
J Trauma Acute Care Surg ; 75(3): 404-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24089110

RESUMO

BACKGROUND: The optimal treatment for abdominal wall hernias in the setting of ascites is not clear. We describe our experience with emergent surgery for hernias in patients with cirrhosis and ascites and assess variables associated with poor short- and long-term outcomes to inform decisions about aggressive early repair. METHODS: We performed a retrospective review of all emergency abdominal wall hernia repairs admitted from the emergency department from January 2000 to December 2011 in all patients with ascites caused by liver cirrhosis. Demographic data, comorbidities, complications, operative details, hospital length of stay, and admission model of end-stage liver disease (MELD) score was determined. Follow-up was detailed via comprehensive liver service electronic records. RESULTS: There were 69 emergent hernia surgeries in 68 patients during the study period. There were two early deaths (both MELD score> 20). Multivariate analysis revealed MELD score (18% increase in risk with each point of MELD), preoperative anemia (sevenfold increase in risk), and preoperative small bowel obstruction (ninefold increase in risk) as predictive factors of major complication. In patients with MELD score greater than 10, morbidity was more than 50%, and major morbidity is greater than 12% when MELD score is greater than 20. CONCLUSION: Emergent hernia surgery in patients with ascites has low mortality but high morbidity and requires intense use of resources. To decrease the incidence of emergent hernia surgery, we recommend the aggressive use of elective repair. Emergent hernia repair, when necessary, should be performed at experienced centers and must include adequate ascites control with diuretic therapy and percutaneous paracentesis. Preoperative anemia and electrolyte abnormalities should be aggressively treated. Finally, while wound complications are common and frequently require reintervention, they are not associated with increased mortality. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level V.


Assuntos
Ascite/complicações , Hérnia Ventral/cirurgia , Idoso , Ascite/cirurgia , Emergências , Feminino , Hérnia Ventral/complicações , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
7.
Transplantation ; 93(5): 530-5, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22245875

RESUMO

BACKGROUND: Debate continues about which liver transplantation candidates with impaired renal function should undergo liver transplant alone versus simultaneous liver-kidney transplantation (SLK). Identifying predictors of native kidney function recovery after SLK requires an accurate measure of the relative function of all three kidneys in patients with SLK. METHODS: The distance of a transplanted kidney from the renal scan camera can be substantially different from that of native kidneys. We developed a technique to correct attenuation of counts of all three kidneys based on their depth. RESULTS: In our series of 13 SLK recipients, attenuation correction increased the measured renal function of native kidneys by up to 40%, demonstrating the importance of this procedure for accurately measuring kidney function. Eight patients met the United Network for Organ Sharing (UNOS)-proposed criteria for receiving a SLK, but four of these still had significant native kidney function (>40% of total function) after transplant. Five patients did not meet the UNOS-proposed criteria for SLK, yet only one of these had native kidney function recovery. CONCLUSION: The criteria proposed by UNOS to determine that SLK is indicated, and thus that native kidney recovery is not expected, are not always accurate. Further study of factors associated with native kidney recovery after SLK is required.


Assuntos
Transplante de Rim , Rim/cirurgia , Transplante de Fígado , Adulto , Idoso , Boston , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Seleção de Pacientes , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Curr Opin Organ Transplant ; 16(4): 385-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21709554

RESUMO

PURPOSE OF REVIEW: The present review describes the recent experience with kidney transplantation using donation after circulatory determination of death (DCDD) including efforts to expand the potential pool of DCDD donors. RECENT FINDINGS: The use of DCDD kidneys represents a growing source of kidneys for transplantation in the USA, although not to the same extent as in Europe. Expansion of the potential donor pool has included the use of kidneys with extended time to donor arrest and pediatric donors. The use of machine perfusion for DCDD kidneys has failed to demonstrate significant benefit. SUMMARY: DCDD kidneys continue to demonstrate increased rates of delayed graft function and primary nonfunction when compared with kidneys recovered after donation after brain death (DBD) likely due to increased warm ischemic time during recovery. Despite early complications, DCDD kidneys show comparable function and survival after the immediate postoperative period and have been demonstrated to provide a survival benefit to recipients over waiting for DBD kidneys. The effect of machine perfusion on DCDD kidneys may decrease delayed graft function but has no effect on long-term function. Despite concerns, the increasing number of DCDD donors does not appear to be directly responsible for decreased numbers of DBD donors.


Assuntos
Morte , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos , Animais , Função Retardada do Enxerto/etiologia , Humanos , Transplante de Rim/efeitos adversos , Perfusão , Coleta de Tecidos e Órgãos/efeitos adversos , Coleta de Tecidos e Órgãos/métodos , Resultado do Tratamento , Listas de Espera
9.
Fetal Diagn Ther ; 24(2): 119-25, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18648212

RESUMO

OBJECTIVES: Neuroblastoma is the most common extracranial solid tumor of childhood, and the most common malignancy diagnosed during infancy. In comparison, neonatal neuroblastoma is relatively rare. Improvements in prenatal imaging and widespread use of fetal ultrasonography have led to an increased rate of prenatal diagnoses. METHODS: Case report and literature review. RESULTS: We report a case of an intermediate-risk neuroblastoma, diagnosed at 36 weeks' gestation by ultrasound and subsequently visualized by fetal MRI, that resulted in spinal cord compression and decreased fetal movement. A multidisciplinary team approach resulted in rapid delivery, evaluation, biopsy, staging, and treatment implementation in a successful effort to preserve lower extremity function. CONCLUSION: Prenatal diagnosis of neuroblastoma, management and outcomes are reviewed. Prompt diagnosis can strongly influence perinatal management and improve prognosis.


Assuntos
Doenças Fetais/patologia , Neuroblastoma/patologia , Diagnóstico Pré-Natal , Neoplasias da Coluna Vertebral/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Parto Obstétrico , Feminino , Movimento Fetal , Idade Gestacional , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neuroblastoma/complicações , Neuroblastoma/tratamento farmacológico , Neuroblastoma/embriologia , Gravidez , Compressão da Medula Espinal/embriologia , Compressão da Medula Espinal/patologia , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/embriologia , Resultado do Tratamento , Ultrassonografia Pré-Natal
10.
J Gastrointest Surg ; 10(3): 455-64, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16504896

RESUMO

Enterocutaneous fistulas, defined as abnormal communications between bowel and skin, are among the most challenging conditions managed by the general surgeon. In an era when the mortality from pancreaticoduodenectomy is less than 3%, the mortality of enterocutaneous fistulas remains 10 to 30% due to the often-present complications of sepsis, malnutrition, and electrolyte abnormalities. Taking advantage of recent advances in techniques of pre- and post-surgical management and support, employing a multidisciplinary team approach, and executing a well-delineated management plan provide the patient and surgeon with the best possibility of success in treating this potentially devastating condition.


Assuntos
Fístula Cutânea/cirurgia , Fístula Intestinal/cirurgia , Fístula Cutânea/complicações , Fístula Cutânea/etiologia , Fístula Cutânea/mortalidade , Drenagem , Humanos , Fístula Intestinal/complicações , Fístula Intestinal/etiologia , Fístula Intestinal/mortalidade , Apoio Nutricional , Complicações Pós-Operatórias/terapia , Procedimentos de Cirurgia Plástica , Equilíbrio Hidroeletrolítico
11.
Am J Physiol Regul Integr Comp Physiol ; 290(6): R1589-97, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16455766

RESUMO

Muscle wasting in sepsis is a significant clinical problem because it results in muscle weakness and fatigue that may delay ambulation and increase the risk for thromboembolic and pulmonary complications. Treatments aimed at preventing or reducing muscle wasting in sepsis, therefore, may have important clinical implications. Recent studies suggest that sepsis-induced muscle proteolysis may be initiated by calpain-dependent release of myofilaments from the sarcomere, followed by ubiquitination and degradation of the myofilaments by the 26S proteasome. In the present experiments, treatment of rats with one of the calpain inhibitors calpeptin or BN82270 inhibited protein breakdown in muscles from rats made septic by cecal ligation and puncture. The inhibition of protein breakdown was not accompanied by reduced expression of the ubiquitin ligases atrogin-1/MAFbx and MuRF1, suggesting that the ubiquitin-proteasome system is regulated independent of the calpain system in septic muscle. When incubated muscles were treated in vitro with calpain inhibitor, protein breakdown rates and calpain activity were reduced, consistent with a direct effect in skeletal muscle. Additional experiments suggested that the effects of BN82270 on muscle protein breakdown may, in part, reflect inhibited cathepsin L activity, in addition to inhibited calpain activity. When cultured myoblasts were transfected with a plasmid expressing the endogenous calpain inhibitor calpastatin, the increased protein breakdown rates in dexamethasone-treated myoblasts were reduced, supporting a role of calpain activity in atrophying muscle. The present results suggest that treatment with calpain inhibitors may prevent sepsis-induced muscle wasting.


Assuntos
Glicoproteínas/farmacologia , Proteínas Musculares/genética , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/metabolismo , Proteínas Ligases SKP Culina F-Box/genética , Sepse/complicações , Ubiquitina-Proteína Ligases/genética , Animais , Proteínas de Ligação ao Cálcio/genética , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Linhagem Celular , Inibidores de Cisteína Proteinase/farmacologia , Dexametasona/farmacologia , Dipeptídeos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Peróxido de Hidrogênio/farmacologia , Masculino , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Pepstatinas/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma , Ratos , Ratos Sprague-Dawley , Transfecção , Proteínas com Motivo Tripartido
12.
Surgery ; 138(6): 1166-74; discussion 1174-5, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16360405

RESUMO

BACKGROUND: Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) has become an important tool in the postoperative management of de-differentiated thyroid cancer. The utility of this imaging modality in the preoperative assessment of thyroid nodules is unclear. This study was designed to determine whether (18)FDG-PET/CT improves the preoperative diagnosis of thyroid nodules. METHODS: A total of 31 patients with 48 lesions underwent fine-needle aspiration and (18)FDG-PET/CT before surgical resection of thyroid nodules. PET/CT images were obtained 1 hour after intravenous administration of (18)FDG. Standard uptake values were calculated for regions of increased (18)FDG uptake. CT scans were evaluated to identify thyroid pathology. Final pathologic diagnoses were compared with PET/CT findings. RESULTS: Fifteen of 48 lesions were malignant and 33 were benign. Nine of 15 malignant lesions were (18)FDG-avid (sensitivity 60%). Thirty of 33 benign lesions were (18)FDG-cold (specificity 91%). Positive and negative predictive values were 75% and 83%, respectively. CONCLUSIONS: (18)FDG-PET/CT provides a high negative predictive value for malignancy, making this a potentially useful tool in the evaluation of thyroid nodules with indeterminate fine-needle aspiration. However further studies with larger sample sizes are needed to determine the true efficacy of this test.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico por imagem , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia , Tomografia Computadorizada por Raios X
13.
Int J Biochem Cell Biol ; 37(10): 2226-38, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16051512

RESUMO

Sepsis is associated with muscle wasting, mainly reflecting increased muscle proteolysis. Recent studies suggest that inhibition of GSK-3beta activity may counteract catabolic stimuli in skeletal muscle. We tested the hypothesis that treatment of muscles from septic rats with the GSK-3beta inhibitors LiCl and TDZD-8 would reduce sepsis-induced muscle proteolysis. Because muscle wasting during sepsis is, at least in part, mediated by glucocorticoids, we also tested the effects of GSK-3beta inhibitors on protein degradation in dexamethasone-treated cultured myotubes. Treatment of incubated extensor digitorum longus muscles with LiCl or TDZD-8 reduced basal and sepsis-induced protein breakdown rates. When cultured myotubes were treated with LiCl or one of the GSK-3beta inhibitors SB216763 or SB415286, protein degradation was reduced. Treatment of incubated muscles or cultured myotubes with LiCl, but not the other GSK-3beta inhibitors, resulted in increased phosphorylation of GSK-3beta at Ser9, consistent with inactivation of the kinase and suggesting that the other inhibitors used in the present experiments inhibit GSK-3beta by phosphorylation-independent mechanisms. The present results suggest that GSK-3beta inhibitors may be used to prevent or treat sepsis-induced, glucocorticoid-regulated muscle proteolysis.


Assuntos
Dexametasona/farmacologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Fibras Musculares Esqueléticas/efeitos dos fármacos , Sepse/metabolismo , Animais , Células Cultivadas , Dexametasona/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Cloreto de Lítio/farmacologia , Masculino , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Ligases SKP Culina F-Box/efeitos dos fármacos , Proteínas Ligases SKP Culina F-Box/metabolismo , Tiadiazóis/farmacologia , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo
14.
Curr Surg ; 62(4): 374-82, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15964458
15.
Endocrinology ; 146(7): 3141-9, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15802492

RESUMO

We reported previously that IGF-I inhibits burn-induced muscle proteolysis. Recent studies suggest that activation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway with downstream phosphorylation of Forkhead box O transcription factors is an important mechanism of IGF-I-induced anabolic effects in skeletal muscle. The potential roles of other mechanisms in the anabolic effects of IGF-I are less well understood. In this study we tested the roles of mammalian target of rapamycin and glycogen synthase kinase-3beta (GSK-3beta) phosphorylation as well as MAPK- and calcineurin-dependent signaling pathways in the anticatabolic effects of IGF-I by incubating extensor digitorum longus muscles from burned rats in the presence of IGF-I and specific signaling pathway inhibitors. Surprisingly, the PI3K inhibitors LY294002 and wortmannin reduced basal protein breakdown. No additional inhibition by IGF-I was noticed in the presence of LY294002 or wortmannin. Inhibition of proteolysis by IGF-I was associated with phosphorylation (inactivation) of GSK-3beta. In addition, the GSK-3beta inhibitors, lithium chloride and thiadiazolidinone-8, reduced protein breakdown in a similar fashion as IGF-I. Lithium chloride, but not thiadiazolidinone-8, increased the levels of phosphorylated Foxo 1 in incubated muscles from burned rats. Inhibitors of mammalian target of rapamycin, MAPK, and calcineurin did not prevent the IGF-I-induced inhibition of muscle proteolysis. Our results suggest that IGF-I inhibits protein breakdown at least in part through a PI3K/Akt/GSK3beta-dependent mechanism. Additional experiments showed that similar mechanisms were responsible for the effect of IGF-I in muscle from nonburned rats. Taken together with recent reports in the literature, the present results suggest that IGF-I inhibits protein breakdown in skeletal muscle by multiple mechanisms, including PI3K/Akt-mediated inactivation of GSK-3beta and Foxo transcription factors.


Assuntos
Queimaduras/metabolismo , Inibidores Enzimáticos/farmacologia , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas Musculares/metabolismo , Peptídeo Hidrolases/metabolismo , Animais , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática/fisiologia , Fatores de Transcrição Forkhead , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Membro Posterior , Cloreto de Lítio/farmacologia , Masculino , Músculo Esquelético/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Peptídeo Hidrolases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/fisiologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Tiadiazóis/farmacologia , Dedos do Pé
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