RESUMEN
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major postoperative complication that results in significant morbidity and mortality. Causes are heterogeneous, treatment strategies are largely supportive, and data on outcomes, such as potential for recovery, are lacking. This literature review explores the evidence on how furosemide may alter the course and outcome of postoperative fluid overload in patients with CSA-AKI. Nephrology nurse practitioners need to employ tailored preventive therapies at the preoperative, intraoperative, and postoperative points of care. This article discusses the unique methods for CSA-AKI mechanisms, hemodynamic monitoring strategies employed at the point of care recommended by clinical practice guidelines and recent evidence, and emerging biomarkers of AKI.
Asunto(s)
Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Humanos , Adulto , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Periodo Posoperatorio , Factores de RiesgoRESUMEN
Clinicians routinely perform bone marrow aspiration and biopsy (BMAB) to diagnose cancer and evaluate disease status; however, few studies address pain and distress with BMAB. A prospective descriptive-correlational design examined patients' (N = 152) ratings of pain intensity (numeric rating scale, 0-10) and distress (distress thermometer) at baseline and 5 min and 1 hr postprocedure. Data were analyzed using descriptive statistics, chi-square, and linear regression models. Mean postprocedure pain intensity at 5 min was moderate, 5.56 (SD = 3.03), and opioid use was associated with decreased pain at 1 hr (p < .001). Preprocedure administration of anxiolytics had no significant effect on distress reduction (p = .88). Being female, first-time biopsy, and increased preprocedure pain were significant predictors of postprocedure distress (p < .001). Treating anxiety alone may not be sufficient to lessen pain and distress. Individualized plans of care should be based on patient risk and response to procedure.
Asunto(s)
Dimensión del Dolor , Dolor , Adulto , Biopsia , Biopsia con Aguja , Médula Ósea , Femenino , Humanos , Análisis Multivariante , Estudios ProspectivosRESUMEN
Due to poor tumour-associated vasculature, tumour cells are subjected to a fluctuating microenvironment with periods of limited oxygen and glucose availability. Adaptive mechanisms to adverse microenvironments are important for tumour cell survival. The cyclooxygenase (COX)-2/prostaglandin E(2) (PGE(2)) pathway has key roles in colorectal tumorigenesis. Although glucose is important as an energy source and in maintaining endoplasmic reticulum homeostasis, relatively little is known regarding how tumour cells adapt to the microenvironmental stress of reduced glucose availability. Here, we report the novel findings that glucose deprivation of colorectal tumour cells not only increases COX-2 expression but also decreases 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, resulting in increased extracellular PGE(2). Furthermore, we have shown that PGE(2) promotes tumour cell survival during glucose deprivation. Glucose deprivation enhances phosphoinositide 3-kinase/Akt activity, which has a role in both the up-regulation of COX-2 and down-regulation of 15-PGDH. Glucose deprivation also activates the unfolded protein response (UPR) resulting in elevated C/EBP-homologous protein (CHOP) expression. Interestingly, inhibiting CHOP expression by small interfering RNA during glucose deprivation attenuates the reduction in 15-PGDH expression. This is the first report linking activation of the UPR with a reduction in expression of tumour-suppressive 15-PGDH and may have implications for tumour cells' ability to survive exposure to therapeutic agents that activate the UPR. Our data suggest that diverse microenvironmental stresses converge to regulate PGE(2) as a common and crucial mediator of cell survival during adaptation to the tumour microenvironment and may lead to novel chemopreventive and therapeutic strategies.
Asunto(s)
Proliferación Celular , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Glucosa/deficiencia , Hidroxiprostaglandina Deshidrogenasas/metabolismo , Western Blotting , Neoplasias del Colon/genética , Ciclooxigenasa 2/genética , Elafina/genética , Elafina/metabolismo , Humanos , Hidroxiprostaglandina Deshidrogenasas/genética , Hipoxia , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , Microambiente Tumoral , Respuesta de Proteína DesplegadaRESUMEN
Evidence points towards a pivotal role for cyclooxygenase (COX)-2 in promoting colorectal tumorigenesis through increasing prostaglandin E(2) (PGE(2)) levels. PGE(2) signalling is closely associated with the survival, proliferation and invasion of colorectal cancer cells. Recently, a reduction in PGE(2) inactivation, a process mediated by the nicotinamide adenine dinucleotide (NAD+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), has also been shown to promote tumoral PGE(2) accumulation. The hepatocyte growth factor (HGF) receptor, Met, is frequently over-expressed in colorectal tumours and promotes cancer growth, metastasis and resistance to therapy, although the mechanisms for this have not been fully elucidated. Here, we report that HGF/Met signalling can promote PGE(2) biogenesis in colorectal cancer cells via COX-2 up-regulation and 15-PGDH down-regulation at the protein and messenger RNA level. Pharmacological inhibition of MEK and PI3K suggested that both extracellular signal-regulated kinase (ERK) and AKT signalling are required for COX-2 protein up-regulation and 15-PGDH down-regulation downstream of Met. Notably, inhibition of Met with the small molecule inhibitor SU11274 reduced COX-2 expression and increased 15-PGDH expression in high Met-expressing cells. We also show that hypoxia potentiated HGF-driven COX-2 expression and enhanced PGE(2) release. Furthermore, inhibition of COX-2 impeded the growth-promoting effects of HGF, suggesting that the COX-2/PGE(2) pathway is an important mediator of HGF/Met signalling. These data reveal a critical role for HGF/Met signalling in promoting PGE(2) biogenesis in colorectal cancer cells. Targeting the crosstalk between these two important pathways may be useful for therapeutic treatment of colorectal cancer.
Asunto(s)
Adenoma/genética , Neoplasias Colorrectales/genética , Ciclooxigenasa 2/genética , Hidroxiprostaglandina Deshidrogenasas/genética , Proteínas Proto-Oncogénicas/fisiología , Receptores de Factores de Crecimiento/fisiología , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/terapia , Ciclooxigenasa 2/metabolismo , Dinoprostona/biosíntesis , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-met , Transducción de Señal , Regulación hacia ArribaRESUMEN
It is widely accepted that alterations to cyclooxygenase-2 (COX-2) expression and the abundance of its enzymatic product prostaglandin E(2) (PGE(2)) have key roles in influencing the development of colorectal cancer. Deregulation of the COX-2/PGE(2) pathway appears to affect colorectal tumorigenesis via a number of distinct mechanisms: promoting tumour maintenance and progression, encouraging metastatic spread, and perhaps even participating in tumour initiation. Here, we review the role of COX-2/PGE(2) signalling in colorectal tumorigenesis and highlight its ability to influence the hallmarks of cancer--attributes defined by Hanahan and Weinberg as being requisite for tumorigenesis. In addition, we consider components of the COX-prostaglandin pathway emerging as important regulators of tumorigenesis; namely, the prostanoid (EP) receptors, 15-hydroxyprostaglandin dehydrogenase and the prostaglandin transporter. Finally, based on recent findings, we propose a model for the cellular adaptation to the hypoxic tumour microenvironment that encompasses the interplay between COX-2, hypoxia-inducible factor 1 and dynamic switches in beta-catenin function that fine-tune signalling networks to meet the ever-changing demands of a tumour.