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1.
Stem Cell Rev Rep ; 13(5): 644-658, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28733800

RESUMO

Orthotopic liver transplant (OLT) remains the standard of care for end stage liver disease. To circumvent allo-rejection, OLT subjects receive gluococorticoids (GC). We investigated the effects of GC on endogenous mesenchymal stem (stromal) cells (MSCs) in OLT. This question is relevant because MSCs have regenerative potential and immune suppressor function. Phenotypic analyses of blood samples from 12 OLT recipients, at pre-anhepatic, anhepatic and post-transplant (2 h, Days 1 and 5) indicated a significant decrease in MSCs after GC injection. The MSCs showed better recovery in the blood from subjects who started with relatively low MSCs as compared to those with high levels at the prehepatic phase. This drop in MSCs appeared to be linked to GC since similar change was not observed in liver resection subjects. In order to understand the effects of GC on decrease MSC migration, in vitro studies were performed in transwell cultures. Untreated MSCs could not migrate towards the GC-exposed liver tissue, despite CXCR4 expression and the production of inflammatory cytokines from the liver cells. GC-treated MSCs were inefficient with respect to migration towards CXCL12, and this correlated with retracted cytoskeleton and motility. These dysfunctions were partly explained by decreases in the CXCL12/receptor axis. GC-associated decrease in MSCs in OLT recipients recovered post-transplant, despite poor migratory ability towards GC-exposed liver. In total, the study indicated that GC usage in transplant needs to be examined to determine if this could be reduced or avoided with adjuvant cell therapy.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacologia , Transplante de Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Metilprednisolona/farmacologia , Estudos de Casos e Controles , Contagem de Células , Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12/genética , Quimiocina CXCL12/imunologia , Doença Hepática Terminal/genética , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/patologia , Regulação da Expressão Gênica , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/patologia , Cultura Primária de Células , Receptores CXCR4/genética , Receptores CXCR4/imunologia , Recuperação de Função Fisiológica/fisiologia , Transdução de Sinais
2.
Pain Med ; 15(3): 465-72, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24330381

RESUMO

OBJECTIVE: Continuous lumbar plexus blocks provide excellent analgesia for total hip arthroplasty (THA), but their utility has been questioned as they may increase motor weakness. The aim of this study was to compare the efficacy of two different concentrations of ropivacaine on both postoperative analgesia and motor function. METHODS: Thirty patients were examined in this prospective, single center, double-blinded, parallel group, comparative, randomized controlled trial in patients undergoing primary THA. Lumbar plexus catheters were inserted preoperatively. After surgery, patients were randomly assigned to receive an infusion of ropivacaine at a concentration of either 0.1% (group 0.1%) or 0.2% (group 0.2%) at a standardized volume of 7 mL per hour for 24 hours. Patients were also given free access to patient-controlled analgesia hydromorphone for 24 hours, supplemental intravenous (IV) opiates, and boluses of their assigned local anesthetic concentration via the lumbar plexus catheter. The primary endpoint was total hydromorphone consumption in 24 hours. Secondary endpoints included pain scores, sensory and motor function, and patient satisfaction. RESULTS: There was no significant difference in hydromorphone consumption in the first 24 hours postoperatively (mean [95% confidence interval]) between group 0.1% (8.02 mg [6.02-10.02]) and group 0.2% (8.21 mg [5.75-10.69], P = 0.90). The volume of local anesthetic received, pain scores, sensory and motor function, and patient satisfaction did not vary between groups. CONCLUSIONS: Following primary THA, lumbar plexus perineural infusion of 0.1% ropivacaine provided similar benefits for postoperative analgesia and functional recovery as 0.2% ropivacaine.


Assuntos
Amidas/uso terapêutico , Analgésicos Opioides/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Plexo Lombossacral/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/administração & dosagem , Anestésicos Locais/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Ropivacaina
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