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BACKGROUND: The association of lipoprotein(a) [Lp(a)] and stroke functional outcomes was conflicting. The aim of the study was to clarify whether high Lp(a) is associated with unfavorable functional outcomes in patients with ischemic stroke. METHODS: A total of 9709 individuals from the third China National Stroke Registry cohort were recruited. Plasma level of Lp(a) at admission was measured with enzyme-linked immunosorbent assay. The cut-off was set at the median for Lp(a). Functional outcome was assessed using the modified Rankin scale (mRS) at 3 months and 1 year after ischemic stroke. The association between Lp(a) and functional outcomes was evaluated using a logistic regression model. RESULTS: The median age was 63.0 years, and 31.1% participants were women. Patients in higher Lp(a) group had higher incidences of unfavorable functional outcomes at 3 months. In logistic regression model, elevated Lp(a) levels were associated with unfavorable functional outcomes at 3 months (Q4 vs. Q1: odds ratio 1.33, 95% confidence interval 1.11-1.61). Subgroup analysis showed that in the lower Lp-PLA2 group, Lp(a) level was not associated with functional outcomes, but in the higher Lp-PLA2 group, Lp(a) level was significantly associated with functional outcomes. After grouped by different levels of Lp(a) and Lp-PLA2, the Lp(a) high/ Lp-PLA2 high group showed the highest incidence of unfavorable functional outcomes at 3 months and 1 year. CONCLUSIONS: Elevated Lp(a) level is associated with unfavorable functional outcomes in patients with ischemic stroke. The increment in both Lp(a) and Lp-PLA2 are associated with unfavorable functional outcomes at 3 months and 1 year after ischemic stroke.
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Accidente Cerebrovascular Isquémico/diagnóstico , Lipoproteína(a)/sangre , Fosfolipasas A2/sangre , 1-Alquil-2-acetilglicerofosfocolina Esterasa , Anciano , Biomarcadores/sangre , Femenino , Humanos , Accidente Cerebrovascular Isquémico/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Sistema de Registros , Resultado del TratamientoRESUMEN
Acute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in 'lure and kill' mechanism (denoted 'MΦ-NP(L&K)') for the treatment of acute pancreatitis. MΦ-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MΦ-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders.
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Enfermedad Aguda/terapia , Macrófagos , Nanopartículas/uso terapéutico , Pancreatitis/terapia , Animales , Citocinas , Modelos Animales de Enfermedad , Femenino , Humanos , Inflamación , Meliteno , Ratones , Fosfolipasas A2/sangre , Células THP-1RESUMEN
It was established that the administration of an aqueous solution of bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium to animals daily for 2 months at a dose of the active substance of 10 mg/kg of the animal's weight leads to inhibition of the total activity of the alkaline phospholipase A2 of mononuclear cells. The results of the study can be used to correct lipid metabolism in the development of disorders in hyperlipidemia. This makes it possible to expand the scope of use of the studied substance and create new pharmaceuticals based on bis(µ-tartrato)di(µ-hydroxy) germanate (IV) triethanolammonium prevent and inhibit the development of hyperlipidemia.
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Etanolaminas/farmacología , Hiperlipidemias/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Inhibidores de Fosfolipasa A2/farmacología , Fosfolipasas A2/metabolismo , Animales , Colesterol/sangre , Germanio/química , Germanio/farmacología , Hiperlipidemias/enzimología , Hiperlipidemias/patología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/enzimología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Fosfolipasas A2/sangre , ConejosRESUMEN
OBJECTIVES: All patients who undergo cardiopulmonary bypass (CPB) experience some degree of ischemia reperfusion injury (IRI). Severe IRI-induced acute kidney injury (AKI) occurs in approximately 1-2% of patients undergoing CPB. Previous studies using activity-based protein profiling of urine identified group XV phospholipase A2, PLA2G15/LPLA2, as potentially associated with patients who develop AKI post CPB. The present study examined urinary PLA2G15/LPLA2 activity during CPB and in the near postoperative period for associations with subsequent AKI development. DESIGN & METHODS: Samples were collected in a nested case controlled cohort of 21 patients per group who either did (AKI) or did not (non-AKI) develop AKI post-operatively. Serum and urine samples from each patient before, during and after CPB were assayed for PLA2G15/LPLA2 activity. RESULTS: Urine activity significantly increased during the intra operative period. In contrast the activities in paired sera were markedly decreased during CPB. There was no correlation between the serum and urine activity levels of patients. There were no significant differences in activity levels of PLA2G15/LPLA2 in the urine or sera from patients that did and did not develop AKI. CONCLUSIONS: The lack of correlation between serum and urine activity levels suggests that the rapid intraoperative increases in PLA2G15/LPLA2 activity may originate from the kidney and as such offer an intraoperative indicator of early renal response to CPB associated stressors.
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Lesión Renal Aguda/enzimología , Aciltransferasas/sangre , Aciltransferasas/orina , Puente Cardiopulmonar , Fosfolipasas A2/sangre , Fosfolipasas A2/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Puente Cardiopulmonar/efectos adversos , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/enzimología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Periodo Posoperatorio , Factores de RiesgoRESUMEN
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.
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Infecciones por Coronavirus/metabolismo , Metaboloma , Neumonía Viral/metabolismo , Anciano , Anciano de 80 o más Años , Aminoácidos/sangre , Ácido Araquidónico/sangre , Biomarcadores/sangre , COVID-19 , Ciclo del Ácido Cítrico , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/patología , Femenino , Gluconeogénesis , Humanos , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Pandemias , Fosfatidilcolinas/sangre , Fosfatidiletanolaminas/sangre , Fosfolipasas A2/sangre , Neumonía Viral/sangre , Neumonía Viral/patología , Triglicéridos/sangreRESUMEN
BACKGROUND: Mastocytosis is a condition characterized by the expansion and accumulation of mast cells (MCs) in various organs. The symptoms are related to the increased release of MC-derived mediators that exert local and distant effects. MCs are a source and target of phospholipase enzymes (PLs), which catalyze the cleavage of membrane phospholipids releasing lipid mediators (e.g., diacylglycerols (DAGs) and the endocannabinoid (EC) 2-arachidonoylglycerol (2-AG)). To date, there are no data on the role of these lipid mediators in mastocytosis. Here, we analyzed plasma levels of PLA2, PLC, DAG, ECs, and EC-related N-acylethanolamines in patients with mastocytosis. METHODS: In 23 patients with mastocytosis and 23 healthy individuals, we measured plasma PLA2 and PLC activities, DAG, 2-AG, anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA). RESULTS: Plasma PLA2 and PLC activities were increased in mastocytosis patients compared to controls. Concentrations of DAG (18:1 20:4 and 18:0 20:4), two second messengers produced by PLC, were higher in mastocytosis compared to controls, whereas the concentrations of their metabolite, 2-AG, were not altered. AEA was decreased in mastocytosis patients compared to controls; by contrast, AEA congener, PEA, was increased. PLA2 and PLC activities were increased only in patients with mediator-related symptoms. Moreover, PLC activity was positively correlated with disease severity and tryptase concentrations. By contrast, AEA was negatively correlated with tryptase concentrations. CONCLUSIONS: PLs and some lipid mediators are altered in patients with mastocytosis. Our results may pave the way for investigating the functions of these mediators in the pathophysiology of mastocytosis and provide new potential biomarkers and therapeutic targets.
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Diglicéridos/metabolismo , Endocannabinoides/sangre , Etanolaminas/sangre , Mastocitosis/metabolismo , Fosfolipasas A2/metabolismo , Fosfolipasas de Tipo C/metabolismo , Adulto , Anciano , Ácidos Araquidónicos/sangre , Biomarcadores/sangre , Diglicéridos/sangre , Femenino , Humanos , Masculino , Mastocitosis/sangre , Mastocitosis/enzimología , Mastocitosis/patología , Persona de Mediana Edad , Fosfolipasas A2/sangre , Alcamidas Poliinsaturadas/sangre , Triptasas/sangre , Fosfolipasas de Tipo C/sangreRESUMEN
The increment of eryptosis in lead-exposed workers has been associated with oxidative stress, having as the main mediator [Ca2+]i. However, other molecules could participate as signals, such as PLA2 and SMase, which have been proposed to increase PGE2 and ceramides, both involved in the increment of PS externalization due to osmotic stress. To study the role of these enzymes in lead intoxication, we studied 30 lead exposed workers and 27 non-lead exposed individuals. We found, compared to non-exposed subjects, lead intoxication characterized by high blood lead concentration (medianâ¯=â¯39.1⯵g/dL), and low δ-ALAD activity (medianâ¯=â¯348â¯nmol of porphobilinogen/h/mL); oxidative stress with high lipid peroxidation (medianâ¯=â¯1.31â¯nmol of malondialdehyde/mL) and low TAC (medianâ¯=â¯370â¯mM Trolox equivalents); a higher enzymatic activity of PLA2 (medianâ¯=â¯518 AFU/mg) and SMase (medianâ¯=â¯706 AFU/mg) and higher eryptosis (medianâ¯=â¯0.92% PS externalization). Correlation and conditional probability analyses permit to associate oxidative stress and eryptosis with high PLA2 activity. However, high SMase activity was only associated with PLA2 activity. The role of these enzymes in the signal path to eryptosis induced by oxidative stress in lead-exposed workers is discussed.
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Contaminantes Ambientales/efectos adversos , Eriptosis/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Intoxicación por Plomo/etiología , Plomo/efectos adversos , Exposición Profesional/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Fosfolipasas A2/sangre , Esfingomielina Fosfodiesterasa/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Contaminantes Ambientales/sangre , Eritrocitos/enzimología , Eritrocitos/patología , Humanos , Plomo/sangre , Intoxicación por Plomo/sangre , Intoxicación por Plomo/enzimología , Intoxicación por Plomo/patología , Peroxidación de Lípido/efectos de los fármacos , Persona de Mediana Edad , Porfobilinógeno Sintasa/sangre , Medición de Riesgo , Transducción de Señal , Adulto JovenRESUMEN
OBJECTIVES: Expression of phospholipids and related molecules could provide panels of multiple biomarkers searching for the signature of Alzheimer's disease (AD). The aim of the present study was to quantify ten phospholipids and simultaneously determine phospholipase A2 (PLA2) activity in blood of mild cognitive impairment (MCI) and AD patients. METHODS: Thirty-four AD, 20 MCI and 25 controls were enrolled. The phospholipids where analysed using the AbsoluteIDQ® p180 Kit. PLA2 activities were accessed in platelets by a radio-enzymatic assay. RESULTS: The study failed to fix the ten phospholipids as a panel to predict AD; the levels of PCaaC36:6, PCaaC40:6 and C16:1-OH were lower in MCI than in controls (P = 0.041, P = 0.012, P = 0.044 respectively). PCaaC40:2 levels were lower in MCI than in AD (P = 0.041). The converters MCI-AD showed at baseline lower levels of PCaaC40:2 (P = 0.050) and PCaaC40:6 (P = 0.037) than controls. iPLA2 activity was reduced in AD and MCI than in controls (P < 0.001). We found positive correlation in the control group between PCaaC38:6 and tPLA2 (r = 0.680; P = 0.001) and sPLA2 (r = 0.601; P = 0.004); PCaaC40:1 and iPLA2 (r = 0.503; P = 0.020); PCaaC40:6 and tPLA2 (r = 0.532; P = 0.013) and sPLA2 (r = 0.523; P = 0.015). CONCLUSIONS: Lipids metabolites in plasma might indirectly indicate changes in neuronal membrane and this deregulation can outline the transition between healthy and diseased brains.
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Enfermedad de Alzheimer/enzimología , Disfunción Cognitiva/enzimología , Fosfolipasas A2/sangre , Fosfolípidos/sangre , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Biomarcadores/sangre , Plaquetas/enzimología , Estudios de Casos y Controles , Disfunción Cognitiva/sangre , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: PLAC® mass test (diaDexus, Inc.) does not detect all Lp-PLA2 proteins in the circulation. The total circulating Lp-PLA2 mass can be quantized by using the CHAPS modified PLAC® mass test. To compare the difference of the PLAC® mass, CHAPS modified PLAC® mass and PLAC® activity tests in risk assessment of CVD, the 3 Lp-PLA2 quantization methods were characterized using a collection of serum and plasma from CVD patents and matched non-symptomatic controls. Improvement on risk assessment for ischemic stroke by Lp-PLA2 and lipids were also investigated. METHODS: Ninety one human sera and plasma from elderly patients with first CVD incidents and 78 matched controls were collected at clinics. Lp-PLA2 was assessed by PLAC® mass, CHAPS modified PLAC® mass and PLAC® activity tests and data were subjected to statistical analyses. Correlation with lipid cholesterols or Apo proteins was compared for all formats of PLAC® tests. Ratios of Lp-PLA2 by different PLAC® tests to different lipids were assessed for synergistic enhancement in the indication of ischemic stroke. RESULTS: The PLAC® mass test was superior to other formats of PLAC® tests in the assessment of CVD and is independent of lipids. The Lp-PLA2 by the CHAPS modified PLAC® mass test has no separation between the CVD and control groups. CONCLUSIONS: Both PLAC® mass and PLAC® activity tests are effective but the CHAPS modified PLAC® mass test has no or less utility in the risk assessment of CVD. The ratio of Lp-PLA2 by either PLAC® mass or PLAC® activity over ApoA1 or (Apo A1â¯+â¯Apo B) synergistically enhance the risk assessment power for ischemic stroke.
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Enfermedades Cardiovasculares/diagnóstico , Lipoproteínas/sangre , Fosfolipasas A2/sangre , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/metabolismo , Femenino , Humanos , Lipoproteínas/metabolismo , Masculino , Fosfolipasas A2/metabolismoRESUMEN
BACKGROUND: Fluid restriction in patients with acute respiratory distress syndrome increases ventilator-free days while lowering plasma angiopoietin-2 (Ang-2), a marker of pulmonary endothelial injury. We hypothesised that fluid resuscitation may lead to endothelial injury after cardiac surgery and analysed Ang-2, angiopoietin-1 (Ang-1) and phospholipase A2 (PLA2) levels and the impact of fluid management on ventilation time. METHODS: Patients enrolled in a single-centre, prospectively randomised interventional study of liberal or conservative fluid resuscitation strategy had plasma Ang-2, Ang-1 and PLA2 levels measured at baseline (pre-operative), 6 and 24 hours after commencement of cardiopulmonary bypass, and analysed by linear mixed models as liberal v conservative (intention to treat) or high v low fluid group (actual treatment, ≥ 3250 mL of fluid administered), and further subclassified as EuroSCORE (European System for Cardiac Operative Risk Evaluation) II ≥ 0.9 or < 0.9. RESULTS: Over 9 months, 144 patients were randomly allocated to either liberal (n =74) or conservative (n =70) fluid. Patients in the liberal fluid arm tended to an increased Ang-2 (P =0.12) and had higher PLA2 levels (P =0.03). Based on actual fluid administered, Ang-2 levels were higher, the Ang-1/Ang-2 ratio lower, and the length of mechanical ventilation and intensive care unit (ICU) stay was longer in the high fluid group (P < 0.001). The highest levels of Ang- 2 and corresponding lowest Ang-1/Ang-2 ratio, along with longest length of mechanical ventilation and ICU stay, were found with both the liberal and high fluid groups in patients with a EuroSCORE II ≥ 0.9 (P < 0.01). CONCLUSION: Liberal fluid resuscitation after cardiac surgery was associated with both pulmonary endothelial injury and prolonged length of mechanical ventilation. CLINICAL TRIAL REGISTRATION: ACTRN12612000754842.
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Angiopoyetina 2/sangre , Procedimientos Quirúrgicos Cardíacos , Fluidoterapia/métodos , Respiración Artificial/estadística & datos numéricos , Angiopoyetina 1/sangre , Endotelio Vascular/lesiones , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Selectina-P/sangre , Fosfolipasas A2/sangre , Estudios ProspectivosRESUMEN
BACKGROUND: Myeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined. METHODS: This study concerned 67 SCAD patients divided into groups: all patients, patients with MPO < 200 ng/ml, MPO 200-300 ng/ml, MPO > 300 ng/ml concentration and 15 controls. ApoAI, apoB and hsCRP levels were examined using the immunonephelometric method, and MPO, LpPLA2, IL-6, TNF-α concentration was performed by using Quantikine ELISA kit R&D Systems. RESULTS: In the all patients, and in group with MPO 200-300 ng/ml TC, LDL-C, nonHDL-C, LpPLA2 concentration and TC/HDL-C, LDL-C/HDL-C ratios were insignificant, and significantly higher concentration of TG, apoB, MPO, inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios but HDL-C, apoAI level and HDL-C/apoAI ratio were significantly reduced. In the group of patients with MPO < 200 ng/ml, level of TC, LDL-C, nonHDL-C, apoAI, apoAII, LpPLA2 and MPO and LDL-C/HDL-C ratio were in-significant, HDL-C was decreased but apoB, TG, inflammatory markers, apoB/apoAI, TG/HDL-C, MPO/apoAI, MPO/HDL-C ratio were significantly increased. In the group of patients with MPO > 300 ng/ml concentration of TC, LDL-C, nonHDL-C, apoAII, LpPLA2 and LDL-C/HDL-C ratios were not significant, but HDL-C and apoAI concentrations were significantly decreased. The concentrations of TG, apoB, MPO and inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios were significantly increased compared to the controls. The apoAI concentration was significantly decreased and the concentration of MPO and hsCRP as well as MPO/apoAI and MPO/HDL-C ratios were significantly higher as compared to the group of patients with MPO < 200 ng/ml. Spearman's correlation test showed a positive correlation between MPO concentration and MPO/apoAI and MPO/HDL-C ratios in all patients and MPO < 200 ng/ml, MPO 200-300 ng/ml. The patients with MPO > 300 ng/ml showed a positive correlation between the concentration of MPO and the level of hsCRP and IL-6, and a negative correlation between MPO/apoAI ratio and the concentration of HDL-C, apoAI and apoAII. CONCLUSION: The results suggest that moderate dyslipidemia and dyslipoproteinemia deepening of inflammation, and inflammation slowly induce increase MPO concentration which decrease apoAI and HDL-C level and disturb HDLs function. The increasing MPO level and MPO/HDL-C, MPO/apoAI ratios can differentiate the SCAD patients at the risk of acute coronary syndrome (ACAD) and stroke.
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Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Lípidos/sangre , Peroxidasa/sangre , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/etiología , Anciano , Apolipoproteína A-I/sangre , Apolipoproteína B-100/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Fosfolipasas A2/sangre , Factor de Necrosis Tumoral alfa/sangreAsunto(s)
Amilasas/sangre , Hipertrigliceridemia/complicaciones , Lipasa/sangre , Pancreatitis/etiología , Dolor Abdominal/etiología , Enfermedad Aguda , Adulto , Humanos , Masculino , Pancreatitis/diagnóstico por imagen , Fosfolipasas A2/sangre , Tomografía Computarizada por Rayos X , Tripsina/sangreRESUMEN
INTRODUCTION: This study was aimed to compare the diagnostic value of multi-slice spiral computed tomography (CT) and secretary phospholipase A2-IIa (sPLA2-IIa) in differentiating between malignant and benign solitary pulmonary nodules (SPNs). METHODS: A total of 223 patients with SPNs (91 patients with malignant SPNs and 132 patients with benign SPNs) were included from Weihai Central Hospital during October 2014 to December 2016. SPN diagnosis was confirmed in all patients using needle biopsy, surgery and bronchoscopy. The patients were managed with dynamic multi-slice CT scans, and their sPLA2-IIa levels were also detected. By selecting the area of interest of focus, the perfusion parameters of multi-slice CT targeting the focus were obtained. RESULTS: The levels of MTT, PS, BV, BF and sPLA2-IIa significantly increased with increasing severity of SPNs (P<.05). Notably, BV (area under the ROC curve [AUC]=0.915; 95%CI: 0.88-0.95; sensitivity=91.21%; specificity=78.79%) showed a higher potential to discriminate patients with malignant SPNs from those with benign SPNs than did BF (AUC=0.712; 95%CI: 0.65-0.78; sensitivity=72.50%; specificity=59.10%), PS (AUC=0.772; 95%CI: 0.71-0.84; sensitivity=65.93%; specificity=82.58%) and MTT (AUC=0.600; 95%CI: 0.52-0.68; sensitivity=52.75%; specificity=78.03%). Finally, the combined diagnostic value of BV and sPLA2-IIa was quite ideal (AUC=0.947; 95%CI: 0.92-0.97; sensitivity=85.70%; specificity=92.70%) for malignant and benign SPNs. CONCLUSIONS: The combined diagnostic value of BV and sPLA2-IIa appeared as a desirable detection method for malignant and benign SPNs.
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Interpretación de Imagen Asistida por Computador/métodos , Fosfolipasas A2/sangre , Nódulo Pulmonar Solitario/sangre , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/epidemiologíaRESUMEN
There is a strong association between lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and atherosclerosis-related diseases. The aim of this study was to investigate the role of Lp-PLA2 in the ischemic stroke and further offer clinical evidence that measuring Lp-PLA2 helps predict the risk of stroke occurrence and recurrence. A total of 328 hospitalized patients were recruited, including 179 cases of acute cerebral infarction (ACI) and 149 non-ACI controls. The serum level of Lp-PLA2 in ACI was significantly higher than non-ACI. The serum level of Lp-PLA2 in the recurrence of ACI was significantly higher than the nonrecurrence. The serum levels of Lp-PLA2 in large-artery atherosclerosis subtype were the highest among the subtypes of the Trial of Org 10172 in Acute Stroke Treatment and non-ACI controls. The level of Lp-PLA2 in large-artery atherosclerosis and the cardioembolism group was statistically significantly higher than that of the control cases. There was no statistically significant difference between the small-vessel occlusion group and the control cases. The present study confirmed that the elevated Lp-PLA2 level can be a risk factor for ischemic stroke in the Chinese population. The serum level of Lp-PLA2 may be a predictive factor for the recurrence of ACI.
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Infarto Cerebral/sangre , Infarto Cerebral/enzimología , Fosfolipasas A2/sangre , Adulto , Biomarcadores/sangre , Infarto Cerebral/terapia , China , Femenino , Hospitalización , Humanos , Arteriosclerosis Intracraneal/sangre , Arteriosclerosis Intracraneal/enzimología , Arteriosclerosis Intracraneal/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Factores de RiesgoRESUMEN
OBJECTIVE: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. METHODS: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). RESULTS: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)-not working memory (p = 0.113). CONCLUSION: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made.
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Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Anciano , Pueblo Asiatico , China , Disfunción Cognitiva/sangre , Dieta , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Método Doble Ciego , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Omega-3/sangre , Femenino , Humanos , Interleucina-6/sangre , Lipooxigenasa/sangre , Masculino , Fosfolipasas A2/sangre , Prostaglandina-Endoperóxido Sintasas/sangre , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND AND AIM: Acute pancreatitis is one of the less frequently diagnosed lethal abdominal complications of cardiac surgery. The incidence of early postoperative period hyperamylasaemia was reported to be 30-70% of patients who underwent coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). The mechanism of pancreatic enzyme elevation after cardiac surgery is not clear. Our aim was to determine the relationship between ischaemia associated temporary renal dysfunction and elevation of pancreatic enzymes after CABG. METHODS: Forty-one consecutive patients undergoing CABG under CPB were prospectively studied to determine serum total amylase, phospholipase A2, macroamylase, Cystatin C and urine NAG levels. RESULTS: Hyperamylasaemia was observed in 88% of the cases, with a distribution of 6% at the beginning of cardioplegic arrest, 5% at the 20th minute after cardioplegic arrest, 7% at the 40th minute after cardioplegic arrest, 14% when the heart was re-started, 26% at the 6th hour of intensive care and 30% at the 24th hour of intensive care. All of these patients had asymptomatic isolated hyperamylasaemia, and none of them presented with clinical pancreatitis. As indicators of renal damage; Cystatin C and NAG levels were higher compared to baseline values. CONCLUSION: Amylase began to rise during initial extracorporeal circulation and reached a maximum level postoperatively at 6 and 24hours. Decreased amylase excretion is the main reason for post CABG hyperamylasaemia.
Asunto(s)
Acetilglucosaminidasa/orina , Amilasas/sangre , Puente de Arteria Coronaria , Cistatina C/sangre , Hiperamilasemia , Fosfolipasas A2/sangre , Complicaciones Posoperatorias , Anciano , Humanos , Hiperamilasemia/sangre , Hiperamilasemia/etiología , Hiperamilasemia/orina , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/orinaRESUMEN
Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A2 enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A2 activity, and brain WM microstructure in healthy subjects aged 9-20years (n=30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A2 activity (inPLA2). Plasma inPLA2 activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological inPLA2 activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by inPLA2. These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin-related neurodevelopmental disorders.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Fosfolipasas A2/sangre , Sustancia Blanca/crecimiento & desarrollo , Sustancia Blanca/metabolismo , Adolescente , Encéfalo/diagnóstico por imagen , Niño , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora , Ácido Eicosapentaenoico/metabolismo , Eritrocitos/metabolismo , Femenino , Humanos , Masculino , Vaina de Mielina/metabolismo , Factores Sexuales , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk. OBJECTIVE: This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population. DESIGN: A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6g/d, EPA 600mg/d, EPA 1800mg/d, or DHA 600mg/d. The EPA was derived from genetically modified yeast. RESULTS: The subjects tolerated the supplements well with no safety issues; and the expected treatment-specific increases in plasma EPA and DHA levels were observed. Compared to placebo, the DHA group had significant decreases in postprandial triglyceride (TG) concentrations (-20%, -52.2mg/dL, P=0.03), significant increases in fasting and postprandial low-density lipoprotein cholesterol (LDL-C) (+18.4%, 17.1mg/dL, P=0.001), with no significant changes in inflammatory biomarkers. No significant effects were observed in the EPA 600mg/d group. The high-dose EPA group had significant decreases in lipoprotein-associated phospholipase A2 concentrations (Lp-PLA2) (-14.1%, -21.4ng/mL, P=0.003). CONCLUSIONS: The beneficial effects of EPA 1800mg/d on CVD risk reduction may relate in part to the lowering of Lp-PLA2 without adversely affecting LDL-C. In contrast, DHA decreased postprandial TG, but raised LDL-C. Our observations indicate that these dietary fatty acids have divergent effects on cardiovascular risk markers.
Asunto(s)
Cardiotónicos/farmacología , Enfermedades Cardiovasculares/epidemiología , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Apolipoproteínas/sangre , Apolipoproteínas B/sangre , Biomarcadores/sangre , LDL-Colesterol/sangre , Método Doble Ciego , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Aceite de Oliva/farmacología , Fosfolipasas A2/sangre , Factores de Riesgo , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
OBJECTIVE: To observe the effects of Danlou Tablet (DT) on inflammatory reaction, and expressions of lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2), and to analyze potential mechanisms. METHODS: Forty male Wistar rats were randomly and equally divided into five groups, i.e., the normal control group, the model group, the Western medicine (WM) group, the low dose DT group, the high dose DT group, 8 in each group. Rats in the normal control group were fed with basic forage for 12 successive weeks, while AS rat model was established in rats of the other four groups by feeding high fat and sugar forage plus intraperitoneal injection of vitamin D3. Normal saline, atorvastatin calcium suspension (at the daily dose of 1.8 mg/kg), low dose DT suspension (at the daily dose of 450 mg/kg), and high dose DT suspension (at the daily dose of 900 mg/kg) were administered to rats in the model group, the WM group, the low dose DT group, the high dose DT group respectively by gastragavage for 8 successive weeks. The general condition of all rats was observed. Rats were sacrificed after gastric administration and their serum collected. Serum levels of lipids (TC, TG, HDL-C, LDL-C) and inflammatory factors [IL-6, TNF-α, monocyte chemoattractant protein 1 (MCP-1), oxidized low-density lipoprotein (ox-LDL), lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase A2 (sPLA2)] were detected. Pathological changes of thoracic aorta were observed by HE staining. Protein and gene expressions of LP-PLA2 and sPLA2 in thoracic aorta were measured by Western blot and real-time fluorescent quantitative PCR respectively. RESULTS: Compared with the normal control group, rats in the model group were in low spirits and responded poorly. Typical atherosclerotic plaque could be seen in thoracic aorta of rats in the model group. Serum levels of TC, TG, LDL-C, IL-6, TNF-α, MCP-1, ox-LDL, LP-PLA2, and sPLA2 significantly increased (P < 0.05); protein and gene expressions of LP-PLA2 and sPLA2 in rat thoracic aorta increased (P < 0.05) in the model group. After 8 weeks of intervention, rats in 3 medication groups appeared active, and HE staining showed subsidence of plaque in rat thoracic aorta. Compared with the model group, serum levels of TC, TG, LDL-C, IL-6, TNF-α, MCP-1, ox-LDL, and LP-PLA2 decreased in 3 medication groups (P < 0.01, P < 0.05); serum sPLA2 level decreased, protein and mRNA expressions of LP-PLA2 and sPLA2 in rat thoracic aorta decreased in the WM group (P < 0.01, P < 0.05); protein and mRNA expressions of LP-PLA2 in rat thoracic aorta significantly decreased in the low dose DT group (P < 0.01, P < 0.05), and those of LP-PLA2 and sPLA2 decreased in the high dose DT group (P < 0.01, P < 0.05). CONCLUSION: DT could fight against inflammatory reaction and AS possibly through inhibiting LP-PLA2 expression and reducing ox-LDL production.