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1.
J Surg Res ; 193(1): 102-10, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25066187

RESUMEN

BACKGROUND: Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. MATERIALS AND METHODS: Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. RESULTS: One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75-8) were scored the lowest by care providers. CONCLUSIONS: ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components.


Asunto(s)
Actitud del Personal de Salud , Vías Clínicas , Procedimientos Quirúrgicos del Sistema Digestivo/normas , Enfermedades Gastrointestinales/cirugía , Satisfacción del Paciente , Abdomen/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos del Sistema Digestivo/psicología , Esófago/cirugía , Femenino , Encuestas de Atención de la Salud/normas , Encuestas Epidemiológicas/normas , Humanos , Hígado/cirugía , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Evaluación de Procesos y Resultados en Atención de Salud/normas , Recuperación de la Función , Encuestas y Cuestionarios/normas
2.
HPB (Oxford) ; 14(4): 236-41, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22404261

RESUMEN

OBJECTIVES: Excessive blood loss during liver surgery contributes to postoperative morbidity and mortality and the minimizing of blood loss improves outcomes. This study examines pre- and intraoperative factors contributing to blood loss and identifies areas for improvement. METHODS: All patients who underwent elective hepatic resection between June 2007 and June 2009 were identified. Detailed information on the pre- and perioperative clinical course was analysed. Univariate and multivariate analyses were used to identify factors associated with intraoperative blood loss. RESULTS: A total of 175 patients were studied, of whom 95 (54%) underwent resection of three or more segments. Median blood loss was 782 ml. Greater blood loss occurred during major resections and prolonged surgery and was associated with an increase in postoperative complications (P= 0.026). Peak central venous pressure (CVP) of >10 cm H(2)O was associated with increased blood loss (P= 0.01). Although no differences in case mix were identified, blood loss varied significantly among anaesthetists, as did intraoperative volumes of i.v. fluids and transfusion practices. CONCLUSIONS: This study confirms a relationship between CVP and blood loss in hepatic resection. Intraoperative CVP values were higher than those described in other studies. There was variation in the intraoperative management of patients. Collaboration between surgical and anaesthesia teams is required to minimize blood loss and the standardization of intraoperative anaesthesia practice may improve outcomes following liver surgery.


Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Hepatectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anestesia General/efectos adversos , Presión Venosa Central , Distribución de Chi-Cuadrado , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Atención Perioperativa , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Escocia , Reacción a la Transfusión , Adulto Joven
3.
HPB (Oxford) ; 13(3): 206-11, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21309939

RESUMEN

OBJECTIVES: Epidural analgesia is often considered the reference standard for pain relief following major abdominal surgery; however, the provision of analgesia in the context of liver surgery raises unique challenges. This study investigated the effectiveness of analgesia and the postoperative course of patients who did or did not receive epidural analgesia following liver resection. METHODS: Data were collected retrospectively on 177 patients who underwent open liver resection between June 2007 and June 2009. Patients were divided into two groups consisting, respectively, of those who received epidural analgesia (Epidural group, n= 148) and those who did not (No-Epidural group, n= 29). RESULTS: In the Epidural group, 27 patients (18%) required i.v. opiate analgesia on the day of surgery (DoS) or the first postoperative day (POD1). The Epidural group received significantly more i.v. colloid solution on the DoS (median: 1500 ml vs. 750 ml, range: 0-12,000 ml vs. 0-3500 ml; P= 0.004) and POD1 (median: 0 ml vs. 0 ml, range: 0-5000 ml vs. 0-1000 ml; P= 0.018), and total fluid on the DoS and POD1 combined (median: 6522 ml vs. 5453 ml, range: 2150-21 300 ml vs. 2875-15,886 ml; P= 0.032). CONCLUSIONS: Epidural analgesia provided inadequate postoperative pain relief in approximately 20% of liver resection patients and was associated with the administration of significantly greater volumes of i.v. colloid solution.


Asunto(s)
Analgesia Epidural , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/epidemiología , Colangiocarcinoma/epidemiología , Colangiocarcinoma/cirugía , Comorbilidad , Femenino , Fluidoterapia/métodos , Humanos , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
5.
Emerg Med J ; 27(5): 355-8, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20442163

RESUMEN

BACKGROUND: Early goal-directed therapy (EGDT) has been shown to improve outcome in patients presenting to the emergency department (ED). Uptake of EGDT in EDs in the UK has been slow. OBJECTIVE: To establish the level of awareness and skills necessary for EGDT to be implemented by emergency medicine (EM) specialist registrars (SpR) working in Scottish EDs. METHOD: A cross-sectional web-based survey of all 49 Scottish EM SpRs was performed. RESULTS: 42 responses were obtained (86%). Only 19 (45%) EM SpRs possessed the full complement of skills and knowledge necessary to fully implement EGDT independently within the ED. The 4 h target for time to admission was seen by 78% of SpRs as a barrier to the implementation of EGDT in the ED. The preference of most respondents was for initiation of EGDT delivery in the ED and referral to critical care for full implementation. CONCLUSION: Full delivery of EGDT by ED staff would require significant consultant support, improved training of juniors and flexibility in the 4 h target. This study suggests that it may be practical for EGDT to be initiated in the ED and that early referral to critical care will remain essential if patients are to receive the full benefit of this intervention.


Asunto(s)
Protocolos Clínicos , Cuidados Críticos/normas , Servicio de Urgencia en Hospital/normas , Cateterismo Venoso Central/normas , Competencia Clínica/normas , Estudios Transversales , Objetivos , Humanos , Cuerpo Médico de Hospitales/normas , Admisión del Paciente , Escocia , Factores de Tiempo , Resultado del Tratamiento
6.
Int J Mol Med ; 19(1): 165-72, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17143561

RESUMEN

Curcumin is a naturally occurring compound which is known to induce heme oxygenase 1 (HO-1), although the underlying mechanism has not been fully elucidated. This study investigates in detail the mechanism of HO-1 induction by curcumin in human hepatoma cells. There was increasing toxicity of curcumin at concentrations higher than 10 microM. Curcumin was found to induce HO-1 at doses of 10 to 25 microM. At both non-toxic and toxic doses, HO-1 induction was found to correlate with production of reactive oxygen species (ROS), suggesting a causative relationship. This was reinforced by the finding that pretreatment with the antioxidants N-acetylcysteine, vitamin E and catalase prevented HO-1 induction by curcumin. ROS production appeared to be mitochondrial in origin, and curcumin treatment resulted in depolarisation of the mitochondrial membrane potential. Nrf2 was induced by curcumin treatment, which was also partly ROS dependent. Using siRNA, Nrf2 was demonstrated to contribute to HO-1 induction. A panel of kinase inhibitors was used to examine the contribution of MAP kinases to the induction of HO-1 by curcumin. PKC and p38 MAPK activity are required for full induction of HO-1. Furthermore, curcumin also inhibited protein phosphatase activity. In conclusion, curcumin treatment results in ROS generation, activation of Nrf2 and MAP kinases and the inhibition of phosphatase activity in hepatocytes, and when curcumin is not administered in toxic doses, these multiple pathways converge to induce HO-1.


Asunto(s)
Curcumina/farmacología , Hemo-Oxigenasa 1/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Antioxidantes/farmacología , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular , Relación Dosis-Respuesta a Droga , Antagonismo de Drogas , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Mitocondrias/fisiología , Modelos Biológicos , Factor 2 Relacionado con NF-E2/fisiología , Monoéster Fosfórico Hidrolasas/metabolismo , Proteína Quinasa C/metabolismo , Proteína Quinasa C/fisiología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/fisiología
7.
Int J Mol Med ; 19(3): 413-20, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17273789

RESUMEN

Expression of inducible heat shock protein (HSP70) requires activation of heat shock transcription factor-1 (HSF-1). Recent evidence suggests that interleukin-6 (IL-6) can modify the response of HSF-1 to heat. We hypothesized that IL-6 would prime the HSP response by causing de-repression of HSF-1 resulting in augmented HSP expression in stressed cells. In this study we show that IL-6 has no direct effect on HSP70 expression at 37 degrees C but does augment HSP70 expression in response to heat. IL-6 treatment decreased active MAPK/pERK and glycogen synthase kinase 3beta (GSK3beta) expression and GSK3beta kinase activity. In IL-6-treated cells, monomeric HSF-1 accumulated in the cytoplasm and nucleus, bound DNA but was transcriptionally inactive. On exposure to heat shock this modified monomer assumed the transcriptionally active phenotype with trimerization and hyperphosphorylation evident. The increased induction of HSP70 in IL-6 and heat-treated cells was inhibited using PI3-kinase inhibitors or Akt inhibition and was HSF-1 dependent. IL-6, via the PI3-kinase/Akt pathway leads to inhibition of the repressive kinases MAPK/pERK and GSK3beta, and this converts inactive HSF-1 to an intermediate DNA-binding form augmenting transcriptional activation in the presence of a second stressor.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/enzimología , Interleucina-6/farmacología , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factores de Transcripción/metabolismo , Androstadienos/farmacología , Núcleo Celular/efectos de los fármacos , Células Cultivadas , Cromonas/farmacología , Citoplasma/efectos de los fármacos , Proteínas de Unión al ADN/química , Activación Enzimática/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Factores de Transcripción del Choque Térmico , Hepatocitos/citología , Humanos , Hipertermia Inducida , Morfolinas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Isoformas de Proteínas/metabolismo , Estructura Cuaternaria de Proteína/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/química , Transcripción Genética/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Wortmanina
8.
FEBS J ; 273(11): 2345-56, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16704410

RESUMEN

Heme oxygenase-1 catalyzes the breakdown of heme and is protective in models of kidney transplantation. In this study we describe the induction of heme oxygenase-1 mRNA and protein by insulin. Following treatment with insulin, a five-fold increase in heme oxygenase-1 mRNA and a four-fold increase in protein expression were observed in renal adenocarcinoma cells; insulin-induced heme oxygenase-1 expression was also demonstrated in mouse primary tubular epithelial cells. The induction of heme oxygenase-1 in renal adenocarcinoma cells was blocked by actinomycin D and cycloheximide and was abolished by the phosphatidylinositol 3-kinase inhibitor, LY294002, but not by the inactive analog LY303511. Overexpressing a dominant-negative form of Akt abrogated the heme oxygenase-1-inducing effects of insulin, whereas cells transfected with a constitutively active Akt construct demonstrated an increase in heme oxygenase-1 promoter activity and protein expression. The transcription factor NF-E2-related factor-2 was found to translocate to the nucleus following insulin treatment in a phosphatidylinositol 3-kinase-dependent manner. Pretreatment with NF-E2-related factor-2 small-interfering RNA abolished insulin-induced heme oxygenase-1 induction. Insulin was also found to activate the mitogen-activated protein kinase cascades p38 and extracellular signal-related kinase; however, inhibition of these pathways with SB202190 and PD98059 did not alter insulin-induced heme oxygenase-1 expression. Thus, insulin induces heme oxygenase-1 mRNA and protein expression in renal cells in a phosphatidylinositol 3-kinase/Akt and NF-E2-related factor-2-dependent manner.


Asunto(s)
Hemo-Oxigenasa 1/genética , Insulina/farmacología , Túbulos Renales/enzimología , Factor 2 Relacionado con NF-E2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adenocarcinoma , Animales , Línea Celular Tumoral , Inducción Enzimática , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Hemo-Oxigenasa 1/biosíntesis , Humanos , Neoplasias Renales , Túbulos Renales/citología , Túbulos Renales/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa , Interferencia de ARN , ARN Mensajero/genética , Transcripción Genética
9.
Transplantation ; 81(4): 623-6, 2006 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-16495813

RESUMEN

Preconditioning treatments hold significant potential for improving outcomes in solid organ transplantation. Protective phenotypes can be induced using certain drugs. Curcumin is a biologically active component of turmeric and has been reported to induce stress proteins in certain cell lines, leading to cell protection. This study investigates in detail the effect of curcumin on the stress-response in human hepatocytes, in particular its effect on heme oxygenase 1 (HO-1) and its cytoprotective effect. Pretreatment with curcumin protected hepatocytes in a model of oxidative injury and this protection was mediated through HO-1. In a model of cold preservation injury, curcumin pretreatment resulted in elevation of HO-1 throughout the cold storage and rewarming period, and was cytoprotective against oxidative injury. This is the first study to demonstrate that curcumin induces HO-1 in human hepatocytes, and that the protective effects of curcumin pretreatment may have clinical potential in hepatic transplantation.


Asunto(s)
Curcumina/farmacología , Hemo-Oxigenasa 1/genética , Hepatocitos/enzimología , Daño por Reperfusión/enzimología , Adenosina , Alopurinol , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glutatión , Proteínas HSP70 de Choque Térmico/genética , Hemo-Oxigenasa 1/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Humanos , Insulina , Circulación Hepática , Trasplante de Hígado/fisiología , Soluciones Preservantes de Órganos , Reacción en Cadena de la Polimerasa , Rafinosa , Conservación de Tejido/métodos , Acondicionamiento Pretrasplante
10.
Transplantation ; 100(1): 176-83, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26680374

RESUMEN

BACKGROUND: The enzyme heme oxygenase-1 (HO-1) degrades heme and protects against ischemia-reperfusion injury. Monocytes/macrophages are the major source of HO-1 and higher levels improve renal transplant outcomes. Heme arginate (HA) safely induces HO-1 in humans. METHODS: The Heme Oxygenase-1 in renal Transplantation study was a randomized, placebo-controlled, IIb trial to evaluate HA effect on HO-1 upregulation after deceased donor kidney transplantation. 40 recipients were randomized to either 3 mg kg HA or placebo (0.9% NaCl), given preoperatively (day 0) and again on day 2. Recipient blood and urine were collected daily. Graft biopsies were taken preoperatively and on day 5. Primary outcome was HO-1 upregulation in peripheral blood mononuclear cells (PBMCs). Secondary outcomes were graft HO-1 upregulation and injury, urinary biomarkers, and renal function. RESULTS: The HA upregulated PBMC HO-1 protein more than placebo at 24 hours: HA 11.1 ng/mL versus placebo 0.14 ng/mL (P = < 0.0001). The PBMC HO-1 messenger RNA also increased: HA 2.73-fold versus placebo 1.41-fold (P = 0.02). Heme arginate increased day 5 tissue HO-1 protein immunopositivity compared with placebo: HA 0.21 versus placebo -0.03 (P = 0.02) and % HO-1-positive renal macrophage also increased: HA 50.8 cells per high power field versus placebo 22.3 (P = 0.012). Urinary biomarkers were reduced after HA but not significantly. Histological injury and renal function were similar but the study was not powered for this. Adverse events were equivalent between groups. CONCLUSIONS: The primary outcome was achieved and demonstrated for the first time that HA safely induces HO-1 in transplant recipients. Planned larger studies will determine the impact of HO-1 upregulation on clinical outcomes and evaluate the benefit to patients at risk of ischemia-reperfusion injury.


Asunto(s)
Arginina/administración & dosificación , Hemo-Oxigenasa 1/biosíntesis , Hemo/administración & dosificación , Trasplante de Riñón/métodos , Riñón/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Receptores de Trasplantes , Adulto , Anciano , Biomarcadores/orina , Biopsia , Esquema de Medicación , Inducción Enzimática , Femenino , Hemo-Oxigenasa 1/genética , Humanos , Riñón/enzimología , Riñón/patología , Riñón/fisiopatología , Trasplante de Riñón/efectos adversos , Leucocitos Mononucleares/enzimología , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Masculino , Persona de Mediana Edad , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Escocia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
11.
Transplantation ; 78(10): 1479-87, 2004 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-15599312

RESUMEN

Intermittent clamping of the porta hepatis (PHC) is commonly performed during liver surgery to reduce blood loss and has been reported to precondition livers resulting in improved outcome after liver surgery (humans) and transplantation (animals). This study investigated the early expression of cytoprotective stress proteins during ischemia-reperfusion induced by PHC. Liver samples were taken before and after each event in a two-cycle ischemia-reperfusion protocol using 15 minutes of PHC followed by 5 minutes of reperfusion. Liver tissue was analyzed by real-time polymerase chain reaction for heme oxygenase (HO)-1 and heat shock protein (HSP)-70 mRNA expression. Extracted protein was analyzed by Western blot for HO-1, and HSP-70 and nuclear extracts were analyzed by DNA mobility shift assay for hypoxia inducible factor (HIF)-1alpha and heat shock factor (HSF)-1. Within minutes of PHC, significant increases in HO-1 mRNA expression were detected, and these were maintained throughout the protocol (P < 0.01). Protein expression of HO-1 (P < 0.03) and HO-1 activity (P < 0.05) were similarly increased between the start and end of ischemia- reperfusion (40 minutes). Binding of active HIF-1alpha to its consensus sequence was increased within 15 minutes of the start of the ischemia-reperfusion cycle. Although evidence of the transcriptionally active form of HSF-1 was detected at the same time point, this was not reflected in measurable changes in HSP-70 mRNA or protein. In conclusion, expression of the cytoprotective protein HO-1 is significantly up-regulated in the liver within minutes of PHC. It is likely that HO-1 contributes to the early protective effects of ischemic preconditioning.


Asunto(s)
Regulación de la Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Hepatectomía/métodos , Precondicionamiento Isquémico/métodos , Adenosina Trifosfato/metabolismo , Adulto , Anciano , Neoplasias Colorrectales/cirugía , Femenino , Glucosa Oxidasa/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo-Oxigenasa 1 , Humanos , Inmunohistoquímica , Macrófagos del Hígado/enzimología , Pruebas de Función Hepática , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Modelos Biológicos , Reacción en Cadena de la Polimerasa
12.
Am J Physiol Renal Physiol ; 295(2): F397-405, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18562631

RESUMEN

Heat shock proteins (Hsps) are protective in models of transplantation, yet practical strategies to upregulate them remain elusive. The heat shock protein 90-binding agent (HBA) geldanamycin and its analogs (17-AAG and 17-DMAG) are known to upregulate Hsps and confer cellular protection but have not been investigated in a model relevant to transplantation. We examined the ability of HBAs to upregulate Hsp expression and confer protection in renal adenocarcinoma (ACHN) cells in vitro and in a mouse model of kidney ischemia-reperfusion (I/R) injury. Hsp70 gene expression was increased 30-40 times in ACHN cells treated with HBAs, and trimerization and DNA binding of heat shock transcription factor-1 (HSF1) were demonstrated. A three- and twofold increase in Hsp70 and Hsp27 protein expression, respectively, was found in ACHN cells treated with HBAs. HBAs protected ACHN cells from an H2O2-mediated oxidative stress, and HSF1 short interfering RNA was found to abrogate HBA-mediated Hsp induction and protection. In vivo, Hsp70 was upregulated in the kidneys, liver, lungs, and heart of HBA-treated mice. This was associated with a functional and morphological renal protection from I/R injury. Therefore, HBAs mediate upregulation of protective Hsps in mouse kidneys which are associated with reduced I/R injury and may be useful in reducing transplant-associated kidney injury.


Asunto(s)
Benzoquinonas/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , Riñón/metabolismo , Lactamas Macrocíclicas/farmacología , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/prevención & control , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Proteínas de Choque Térmico HSP27 , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/efectos de los fármacos , Proteínas de Choque Térmico/metabolismo , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Chaperonas Moleculares , Proteínas de Neoplasias/metabolismo , ARN Interferente Pequeño/farmacología , Daño por Reperfusión/metabolismo
13.
Am J Physiol Gastrointest Liver Physiol ; 290(5): G903-11, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16339299

RESUMEN

The relationship between the stress protein response and the acute phase response (APPR) was studied in human hepatoma cells to investigate the hierarchy of regulation of these survival responses. Huh-7 cells were subjected to heat treatment (febrile-range temperature 40 degrees C or heat shock 43 degrees C) followed by recovery at 37 degrees C in the presence or absence of IL-6 given either before or after heat treatment. The effects on total, fractional, and acute phase protein synthesis were then analyzed by metabolic labeling, ELISA, real-time PCR, Northern blot analysis, and activation of an alpha(1)-antitrypsin reporter plasmid. Cell energetics were studied under the same conditions using an index of mitochondrial activity and measurement of cellular ATP levels. Febrile-range temperature (40 degrees C) augmented acute phase protein production when cells had been pretreated with IL-6. Pretreatment of cells with IL-6 also prevented heat shock-induced suppression of alpha(1)-antichymotrypsin (ACT) but not transferrin. mRNA expression of ACT and alpha(1)-antitrypsin reporter activation studies was consistent with transcriptional regulation of these proteins. Expression of mRNA transcripts for transferrin was increased despite protein expression being reduced by heat shock. The effects of heat shock on acute phase protein synthesis can be modified by preincubation with IL-6, whereas addition of this ligand after heat treatment has no effect on the suppressive effect of heat on the APPR. The mechanism of this action appears to be transcriptionally regulated in the case of ACT, but in the case of transferrin, it may be mediated by another process such as posttranslational modification.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Respuesta al Choque Térmico/fisiología , Calor , Interleucina-6/farmacología , Proteínas de Fase Aguda/metabolismo , Adenosina Trifosfato/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Fiebre/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Respuesta al Choque Térmico/efectos de los fármacos , Humanos , Mitocondrias/metabolismo , Regiones Promotoras Genéticas , Transferrina/metabolismo , alfa 1-Antiquimotripsina/metabolismo , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo
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