RESUMEN
Both in the intensive care setting and during surgery, mechanical ventilation plays an important role in the treatment of critically ill patients with lung injury, but also in lung healthy patients. Mechanical ventilation is noncurative and is accompanied by various severe side effects. It is hypothesized that multiorgan failure can be induced by mechanical ventilation. Furthermore, there is evidence to suggest cross-talk between lungs and other organs. In particular, the activation of specific cells and cell programs in peripheral organs is an important step on the way to multiorgan failure. In addition to bidirectional connection between the lung and brain, nonprotective ventilation leads to cell apoptosis in the kidney and intestine and leads to an increase of biomarkers for organ dysfunction. It is believed that both inflammation mediators and pro-apoptotic factors are responsible for organ dysfunction.
Asunto(s)
Unidades de Cuidados Intensivos , Insuficiencia Multiorgánica/etiología , Respiración Artificial/efectos adversos , Sepsis/etiología , Procedimientos Quirúrgicos Operativos , Factor Inductor de la Apoptosis/sangre , Biomarcadores/sangre , Encéfalo/fisiopatología , Humanos , Mediadores de Inflamación/sangre , Pulmón/fisiopatología , Lesión Pulmonar/etiología , Lesión Pulmonar/fisiopatología , Insuficiencia Multiorgánica/fisiopatología , Sepsis/fisiopatologíaRESUMEN
OBJECTIVES: To compare the effects of propofol, sevoflurane, and the combination of the 2 on circulating lymphocytes in patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: One hundred five patients undergoing elective OPCAB surgery. INTERVENTIONS: Participants were randomized to receive sevoflurane (group S), propofol (group P), or coadministration (group C) of sevoflurane- and propofol-maintained anesthesia. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained before, during, and after surgery. Caspase-3 and apoptosis-inducing factor in lymphocytes were evaluated by Western blot. During surgery, 5 minutes after revascularization of the left anterior descending artery, 5 minutes after all anastomoses (T4), and after the sternal closure (T5), caspase-3 expression of group S was higher than that of group P (p = 0.02) and group C (p = 0.02). At T4 and T5, expression of active apoptosis-inducing factor in group S was higher than that in the other 2 groups (p = 0.03 and p = 0.04, respectively). 24 hours after surgery, the lymphocyte count of group S (0.55/nL) was lower than that of group P (0.73/nL, p = 0.02) and group C (0.73/nL, p = 0.03). Intensive care unit stay of group S (3.0 days) was longer than that of the other 2 groups (2.2 days, p = 0.02 and 2.1 days, p = 0.01). CONCLUSIONS: OPCAB surgery was associated with postoperative lymphopenia. Regarding a protective effect for circulating lymphocytes, propofol and the combination of sevoflurane- and propofol-maintained anesthesia were both superior to sevoflurane-maintained anesthesia.
Asunto(s)
Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Puente de Arteria Coronaria Off-Pump , Linfocitos/efectos de los fármacos , Éteres Metílicos/farmacología , Propofol/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos por Inhalación/sangre , Anestésicos Intravenosos/sangre , Factor Inductor de la Apoptosis/sangre , Factor Inductor de la Apoptosis/efectos de los fármacos , Western Blotting , Caspasa 3/sangre , Caspasa 3/efectos de los fármacos , Quimioterapia Combinada , Humanos , Masculino , Éteres Metílicos/sangre , Persona de Mediana Edad , Propofol/sangre , Estudios Prospectivos , Sevoflurano , Adulto JovenRESUMEN
OBJECTIVE: To identify the serum protein markers for the gestational diabetes mellitus (GDM) complicated by pregnancy-induced hypertensive (PIH) syndrome to provide a molecular biological basis for the screening, prevention and therapy of the related diseases. METHODS: Serum samples were collected from the patients with GDM, PIH syndrome, and GDM complicated by PIH syndrome. IgG and albumins were removed from the samples before SDS -PAGE. The protein bands showing significant differences among the 3 samples were collected, digested and identified with mass spectrometry, and the function of the identified proteins was analyzed. RESULTS: Three SDS-PAGE were performed in parallel to confirm the differentially expressed proteins. Mass spectrometry indicated that the proteins showing obvious differences among the 3 samples were haptoglobin, protein SMG8 and apoptosis-inducing factor-1. CONCLUSIONS: The protein markers identified in GDM complicated by PIH syndrome may be integrated into the proteomic database of gestational metabolic diseases. Identification of the associated protein markers may provide significant experimental data for the prevention, diagnosis and therapy of the related diseases.
Asunto(s)
Diabetes Gestacional/sangre , Haptoglobinas/análisis , Hipertensión Inducida en el Embarazo/sangre , Adulto , Factor Inductor de la Apoptosis/sangre , Biomarcadores/sangre , Diabetes Gestacional/diagnóstico , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Embarazo , Proteómica/métodos , Adulto JovenRESUMEN
Intensive bone cell apoptosis contributes to osteonecrosis of femoral head (ONFH). Dickkopf-1 (DKK1) reportedly mediates various types of skeletal disorders. This study investigated whether DKK1 was linked to the occurrence of ONFH. Thirty-nine patients with various stages of ONFH were recruited. Bone specimens were harvested from 34 ONFH patients underwent hip arthroplasty, and from 10 femoral neck fracture patients. Bad, Bcl2 TNFalpha, DKK1, Wnt3a, LRP5, and Axin1 expressions were analyzed by quantitative RT-PCR and ELISA. Apoptotic cells were assayed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL). Primary bone-marrow mesenchymal cells were treated with DKK1 RNA interference and recombinant DKK1 protein. ONFH patients with the histories of being administrated corticosteroids and excessive alcohol consumption had significantly higher Bad and DKK1 mRNA expressions in bone tissue and DKK1 abundances in serum than femoral neck fracture patients. Bone cells adjacent to osteonecrotic bone displayed strong DKK1 immunoreactivity and TUNEL staining. Increased DKK1 expression in bone tissue and serum correlated with Bad expression and TUNEL staining. Serum DKK1 abundance correlated with the severity of ONFH. The DKK1 RNA interference and recombinant DKK1 protein regulated Bad expression and apoptosis of primary bone-marrow mesenchymal cells. Knock down of DKK1 reduced dexamethasone-induced apoptosis of mesenchymal cells. Taken together, promoted DKK1 expression was associated with bone cell apoptosis in the occurrence of ONFH patients with the histories of corticosteroid and alcohol intake and progression of ONFH. DKK1 expression in injured tissue provides new insight into ONFH pathogenesis.