New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2

Background Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.

Advances in the pathogenesis of pancreaticobiliary maljunction / 中华肝胆外科杂志

Pancreaticobiliary maljunction means the common bile duct and the main pancreatic duct in the duodenal wall, or is the formation of a long common channel leading to biliopancreatic reflux, resulting a series of biliopancreatic diseases, and even the occurrence of biliary malignancy. The pathogenesis of pancreaticobiliary maljunction is complex, involving biliary fluid dynamics, the activation of phospholipase A2, protease activation, amino acids, fat metabolism, gene mutation. This paper summarized the latest study of the pathogenesis of the pancreaticobiliary maljunction to let clinicians understand pancreaticobiliary maljunction diseases, and provide new treatment ideas.

Clinical value of monitoring serum CTRP3 and Lp-PLA2 levels in patients with coronary heart disease / 中华检验医学杂志

Objective:To investigate the clinical value of monitoring serum complement C1q/tumor necrosis factors-associated protein 3 (CTRP3) and lipoprotein-associated phospholipase A2(Lp-PLA2) levels in patients with coronary heart disease, especially patients with acute myocardial infarction (AMI).Methods:This case-control study included 99 patients with angina pectoris aged (60.4±10.4) years, 105 patients with AMI aged (61.7±14.3) years, and 60 healthy individuals aged (43.6±9.5) years. Serum CTRP3 was detected by ELISA, and Lp-PLA2 was detected by automatic biochemical analyzer. Logistic regression analysis was performed to determine the correlation between CTRP3, Lp-PLA2 in angina pectoris and AMI patients. The diagnostic efficiency of each index was analyzed by receiver operating characteristic (ROC) curve.Results:Serum Lp-PLA2 was significantly higher in AMI group than in angina pectoris group ([313.1±68.1] U/L vs [205.8±71.4] U/L, P<0.001), while CTRP3 was significantly lower in AMI group than in angina pectoris group ([64.2±18.5] μg/L vs [84.8±25.0] μg/L, P<0.001). Logistic regression showed that serum CTRP3 was negatively correlated with AMI ( OR=0.964, 95% CI 0.935-0.993, P=0.019), and Lp-PLA2 was positively correlated with AMI ( OR=1.020, 95% CI 1.008-1.032, P=0.001). ROC analysis showed that the AUC (95% CI) of AMI diagnosed by CTRP3 was 0.753 (0.685-0.821), P<0.001; the AUC (95% CI) of AMI diagnosed by Lp-PLA2 was 0.884 (0.833-0.935), P<0.001; the AUC (95% CI) of diagnosis efficacy by combined indices was 0.910 (0.870-0.950), P<0.001. Conclusions:Lower serum CTRP3 and higher serum Lp-PLA2 levels are associated with increased risk for AMI. Combined detection of both indices can improve the diagnostic efficacy of AMI.

Progress in the treatment of elderly patients with primary membranous nephropathy / 中华老年医学杂志

Membranous nephropathy(MN)is the most common cause of nephrotic syndrome in the elderly.In recent years, the prevalence of MN has been increasing every year.The diagnosis and treatment of MN has entered the new era of molecular medicine with the identification of autoantibodies against the phospholipase A2 receptor(PLA2R). This review focuses on recent advances in the treatment and diagnosis of MN based on the 2020 Kidney Disease: Improving Global Outcomes(KDIGO)guidelines.

Effects of Danhong injection combined with intravenous thrombolysis on cardiac function, myocardial zymogram and lipoprotein-associated phospholipase A2 level in older adult patients with acute myocardial infarction / 中国基层医药

Objective:To investigate the effects of Danhong injection combined with intravenous recombinant tissue plasminogen activator (rt-PA) on cardiac function, myocardial zymogram and lipoprotein associated phospholipase A2 (Lp-PLA2) level in older adult patients with acute myocardial infarction (AMI). Methods:Eighty older adult patients with acute myocardial infarction who received treatment in Community-based General Hospital of Shaoxing Central Hospital, China between January 2017 and December 2019 were included in this study. They were randomly assigned to receive either intravenous thrombolysis with rt-PA (control group, n = 40) or Danhong injection combined with intravenous thrombolysis with rt-PA (observation group, n = 40). The changes in traditional Chinese medicine syndrome score, left ventricular ejection fraction, left ventricular end diastolic diameter, creatine kinase, creatine kinase-MB and lipoprotein associated phospholipase A2 level as well as adverse cardiovascular events were compared between the control and observation groups. Results:After treatment, the score of chest tightness, dark purple tongue, palpitation and shortness of breath in the two groups were decreased. After treatment, the score of chest tightness, dark purple tongue, palpitation and shortness of breath in the observation group was (2.13 ± 0.31) points, (1.98 ± 0.41) points, (1.77 ± 0.29) points, respectively, which was significantly lower than that in the control group [(2.98 ± 0.37) points, (2.52 ± 0.56) points, (2.13 ± 0.32) points, t = 11.137, 4.920, 5.272, all P < 0.001]. After treatment, left ventricular end diastolic diameter in each group was decreased compared with before treatment. After treatment, left ventricular end diastolic diameter in the observation group was significantly lower than that in the control group [(46.12 ± 4.11) mm vs. (49.74 ± 4.32) mm], and left ventricular ejection fraction in the observation group was significantly higher than that in the control group [(47.02 ± 3.55) % vs. (43.25 ± 4.10) %, t = 3.839, 4.396, both P < 0.001). After treatment, Lp-PLA2, creatine kinase, creatine kinase-MB levels in each group were decreased compared with before treatment. After treatment, Lp-PLA2, creatine kinase, creatine kinase-MB levels in the observation group were (171.02 ± 12.52) μg /L, (10.52 ± 2.11) U/L, (24.12 ± 3.52) U/L), respectively, which were significantly lower than those in the control group [(189.63 ± 11.98) μg/L, (14.71 ± 2.62) U/L, (32.79 ± 4.79) U/L), t = 6.792, 7.877, 9.224, all P < 0.001]. The incidence of adverse cardiovascular events in the observation group was significantly lower than that in the control group (5.00% vs. 22.50%, χ2 = 5.165, P < 0.05). Conclusion:Danhong injection combined with intravenous rt-PA for the treatment of acute myocardial infarction in older adult patients can greatly decrease traditional Chinese medicine syndrome score, improve cardiac function, regulate myocardial zymogram and Lp-PLA2 levels, and decrease the incidence of adverse cardiovascular events.

Neurotoxical activity of Micrurus snake venom and methods for its analysis. A literature review / Actividad neurotóxica del veneno de serpientes del género Micrurus y métodos para su análisis. Revisión de la literatura

Abstract Introduction: Snakes of the genus Micrurus have fossorial habits, passive temperament and scarce production of powerful venom with neurotoxic characteristics that block the synaptic transmission at the neuromuscular junction. Objective: To present an overview of the neurotoxicity of the Micrurus snake venom, and its functional characterization by ex vivo analysis methods. Materials and methods: A literature review was conducted in MedLine and ScienceDirect using specific terms and their combinations. Search strategy: type of studies: articles on the neurotoxicity of Micrurus snake venom and techniques to determine its neurotoxic activity by in vitro, in vivo and ex vivo models; publication period: articles published until June 2018; publication language: English and Spanish. Results: Out of 88 studies identified in the initial search, 28 were excluded because they did not meet the inclusion criteria (based on reading their titles and abstracts). 8 additional articles (books and reports) were included, since, according to the authors' opinion, they complemented the information reported by the selected studies. The studies included in the review (n=68) were original research papers (n=44), review articles (n = 16), and book chapters, reports, guides and online consultations (n=8). Conclusions: Studies performed using ex vivo muscle and nerve preparations to evaluate the effect of neurotoxins provide a good model for the characterization of the pre-synaptic and post-synaptic effect of the venom produced by snakes of the genus Micrurus.

Resumen Introducción. Las serpientes del género Micrurus son animales de hábitos fosoriales, de temperamento pasivo y escasa producción de un potente veneno con características neurotóxicas que bloquean la transmisión sináptica en la placa neuromuscular. Objetivo. Presentar un panorama general de la neurotoxicidad del veneno de las serpientes Micrurus y su caracterización funcional mediante métodos de análisis ex vivo. Materiales y métodos. Se realizó una revisión de la literatura en MedLine y ScienceDirect usando términos específicos y sus combinaciones. Estrategia de búsqueda: tipo de estudios: artículos sobre la neurotoxicidad del veneno de serpientes Micrurus y técnicas para determinar su actividad neurotóxica mediante modelos in vitro, in vivo y ex vivo; periodo de publicación: sin límite inicial a junio de 2018; idiomas: inglés y español. Resultados. De los 88 estudios identificados en la búsqueda inicial, se excluyeron 28 por no cumplir los criterios de inclusión (basándose en la lectura de títulos y resúmenes); además, se incluyeron 8 documentos adicionales (libros e informes), que, a criterio de los autores, complementaban la información reportada por las referencias seleccionadas. Los estudios incluidos en la revisión (n=68) correspondieron a las siguientes tipologías: investigaciones originales (n=44), artículos de revisión (n=16) y capítulos de libros, informes, guías y consultas en internet (n=8). Conclusiones. Los estudios que describen el uso de preparaciones ex vivo de músculo y nervio para evaluar el efecto de neurotoxinas ofrecen un buen modelo para la caracterización del efecto presináptico y postsináptico del veneno producido por las serpientes Micrurus.

Relationship between lipoprotein‐associated phospholipase A2 and coronary atherosclerotic plaque and its research progress／ / 心血管康复医学杂志

Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is a kind of chronic inflammatory factor which par‐ticipates in occurrence and development of coronary atherosclerotic plaques .In recent years ,intraluminal imaging research found that Lp‐PLA2 can trigger vulnerable plaque formation , then further lead to plaque rupture and thromboembolism ,and finally cause acute cardiovascular events .The present article made a review about relation‐ship between Lp‐PLA2 and coronary atherosclerotic plaque and its research progress .

Change of lipoprotein-associated phospholipase A2 and neuron specific enolase and its significance in patients with acute cerebral infarction / 中华老年心脑血管病杂志

Objective To study the change of serum lipoprotein-associated phosphorlipase A2 (Lp-PLA2) and neuron specific enolase (NSE) and its clinical significance in patients with acute cerebral infarction (ACI).Methods Fifty-two ACI patients served as ACI group and 45 subjects undergoing physical examination served as control group.The patients in ACI group were further divided into mild ACI group (n =10),moderate ACI group (n =26) and severe ACI group (n =16) according to their NIHSS score.Relationship of serum Lp-PLA2 and NSE levels with NIHSS score in ACI patients was analyzed.Results The serum Lp-PLA2 and NSE levels were significantly higher in ACI group than in control group (289.3±19.4 μg/L vs 123.4±28.4 μg/L,22.1±2.8 μg/L vs 7.2±1.9 tμg/L,P＜0.05),and in moderate and severe ACI group than in mild ACI group (P＜0.05).The serum Lp-PLA2 and NSE levels and NIHSS score were significantly higher on days 2-7 than on day 1 after treatment (P＜0.05) and significantly lower on days 6 and 7 than on day 5 after treatment (P＜0.05).Pearson correlation analysis showed that serum Lp-PLA2 and NSE level were positively related with NIHSS score in ACI group (r =0.788,P =0.035;r=0.950,P=0.001).Conclusion Lp-PLA2 and NSE play an important role in the occurrence and progression of ACI,and are closely related with the severity and outcome of ACI,which can thus provide reference for the treatment,outcome and assessment of ACI.

Predictive value of serum lipoprotein-associated phospholipase A 2for the outcome in patients with large atherosclerotic stroke / 国际脑血管病杂志

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2) for the outcomes in patients with large atherosclerotic stroke (LAA). Methods Patients with LAA admitted to the Second People's Hospital of Lianyungang from March 2015 to January 2018 were enrolled retrospectively. The outcomes were evaluated by the modified Rankin Scale at 90 d after onset, 0-2 was defined as good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for poor outcome. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of Lp-PLA2for outcomes. Results A total of 121 patients with LAA were enrolled, including 64 males (52.9%) and 57 females (47.1%), aged 63.5 ±9.5 years; 72 (59.5%) had good outcome and 49 (40.5%) had poor outcome. The differences were statistically significant in the proportion of diabetic patients (26.4% vs.65.3%; χ2=18.110, P<0.001) and glycated hemoglobin ( 6.39% ±2.33% vs. 7.58% ±3.12%; t=1.663, P=0.041), baseline National Institutes of Health Stroke Scale (NIHSS) score (5 [3-6] vs.10[7 -14]; Z= -7.498, P< 0.001), and Lp-PLA2(194.7 ±84.3 μg/L vs.291.4 ± 82.6 μg/L; t= -5.447, P<0.001) between the good outcome group and the poor outcome group. Multivariate logistic regression analysis showed that diabetes ( odds ratio [ OR] 1.215, 95% confidence interval [CI] 1.102-1.601; P=0.046), glycosylated hemoglobin ( OR 2.275, 95% CI 1.065-4.865; P=0.037), baseline NIHSS score ( OR 2.113, 95% CI 1.585-2.734; P=0.015), and Lp-PLA2(OR 5.183, 95% CI 3.203-8.134; P<0.001) were the independent risk factors for poor outcomes in patients with LAA. ROC analysis showed that the area under the curve of Lp-PLA2predicting poor outcome was 0 .792 (95% CI 0.713-0.872); the optimal cut-off value was 260.5 μg/L, the sensitivity for predicting poor outcome was 79.6%, and the specificity was 84.7%. Conclusion The higher serum Lp-PLA2level is an independent predictive factor for poor outcome in patients with LAA. It has a higher predictive value for poor outcome.

Alpha-type phospholipase A2 inhibitors from snake blood

Abstract It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA2 toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA2s. The present study aimed to review the currently available literature on PLA2 and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A2 and myotoxins, complementing the conventional serum therapy.

Efecto citotóxico de fosfolipasas A2 del veneno de Crotalus durissus cumanensis de Colombia / Cytotoxic effect of A2 phospholipases of the venom of Crotalus durissus cumanensis from Colombia / Efeito citotóxico da fosfolipase A2 do veneno de Crotalus durissus cumanensis da Colômbia

Introducción. Los venenos de serpientes representan una fuente importante de proteínas y péptidos, los cuales exhiben diversas actividades biológicas, tales como antibacterianas, antiparasitarias, antivi-rales, antitumorales, antifúngicas y contra la agregación plaquetaria, entre otras.Las fosfolipasas A2 presentes en los venenos de serpientes son las proteínas más estudiadas en estos modelos. Se ha demostrado que las fosfolipasas A2, activas e inactivas, poseen actividad catalítica contra células tumorales. Objetivo. Aislar, purificar y caracterizar la fosfolipasa A2 del veneno de Crotalus durissus cumanensis para evaluar su actividad antitumoral in vitro. Materiales y métodos. El aislamiento, la purificación y la identificación de la crotoxina B se hizo mediante la cromatografía de exclusión molecular, la cromatografía líquida de alto rendimiento de fase inversa (Reversed Phase High-Performance Liquid Chromatography, RP-HPLC) y la espectrometría de masas. El efecto citotóxico sobre células tumorales (K562) y células normales (células mononucleares de sangre periférica) se determinó utilizando la técnica de MTT. Resultados. La separación y posterior identificación de la crotoxina B del veneno de C. d. cumanensis de Colombia, permitieron evidenciar que esta fosfolipasa A2 posee efecto citotóxico sobre las células mononucleares de sangre periférica con una dosis de 18,23 ± 0,57 µg/ml, mientras que, para las células K562, fue de 2,34 ± 0,199 µg/ml. Conclusiones. Los resultados sugieren la posibilidad de utilizar la crotoxina B aislada del veneno de C. d. cumanensis como un posible recurso terapéutico para su aplicación en humanos.

Introduction. Snake venoms are an important source of proteins and peptides, which display various biological activities such as antibacterial, antiparasitic, antiviral, antitumor, antifungal and against platelet aggregation, among others.Phospholipases A2 present in snake venoms are the most studied proteins in these models. Active and inactive A2 phospholipases have been shown to possess catalytic activity against tumor cells. Objective. To isolate, purify and characterize the phospholipase A2 of the venom of Crotalus durissus cumanensis to evaluate its in vitro antitumor activity. Materials and methods. Isolation, purification and identification of crotoxin B was done with Size Exclusion Chromatography, Reversed Phase High-Performance Liquid Chromatography, RP-HPLC, and Mass Spectrometry. The cytotoxic effect on tumor cells (K562) and normal cells (peripheral blood mononuclear cells) was determined using the MTT technique. Results. The separation and subsequent identification of crotoxin B, found in the venom of C. d. cumanensis from Colombia, showed that this phospholipase A2 has a cytotoxic effect on peripheral blood mononuclear cells at a dose of 18.23 ± 0.57 µg / ml, whereas for K562 cells, it was 2.34 ± 0.199 µg/ml Conclusions. The results suggest the use of crotoxin B, isolated from the venom of C. d. cumanensis, as a possible therapeutic resource for human application.

Introdução. Os venenos da serpentes constituem uma importante fonte de proteínas e péptidos, os quais exibem várias actividades biológicas, tais como agentes antibacterianos, antiparasitárias, antivi-rais, antitumorais, antifúngicas e contra a agregação de plaquetas, entre outros. As fosfolipases A2 presentes no veneno da serpentes são as proteínas mais estudadas nestes modelos. Tem sido demostrado que as fosfolipases A2, activas e inactivas, possuem actividade catalítica contra células tumorais. Objetivo. Isolar, purificar e caracterizar a fosfolipase A2 do veneno da Crotalus durissus cumanensis para avaliar a sua actividade anti-umoral in vitro. Materiais e métodos. O isolamento, a purificação e identificação da crotoxina B foi realizada por cromatografia de exclusão molecular, cromatografia líquida de alta eficiência de fase reversa (Reversed Phase High-Performance Liquid Chromatography, RP-HPLC) e espectrometria de massa. O efeito cito-tóxico sobre células tumorais (K562) e células normais (células mononucleares do sangue periférico) foi determinada usando a técnica de MTT. Resultados. A Separação e subsequente identificação da crotoxina B do veneno da C. d. cumanensis da Colômbia, permitiu constatar que esta fosfolipase A2 tem um efeito citotóxico em células mono-nucleares de sangue periférico, com uma dose de 18,23 ± 0,57 µg/ ml, enquanto que para as células K562, foi 2,34 ± 0,199 ug/ml. Conclusões. Os resultados sugerem a possibilidade de utilizar crotoxina B isolada a partir do veneno da C. d. cumanensis como recurso para o potencial uso terapêutico em humanos.

Alpha-type phospholipase A2 inhibitors from snake blood

It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA2 toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA2s. The present study aimed to review the currently available literature on PLA2 and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A2 and myotoxins, complementing the conventional serum therapy.(AU)

The influence of probucol combined with atorvastatin on plasma levels of oxidative low density lipoprotein and lipoprotein-associated phospholipase A2 in patients with acute coronary syndrome after percutaneous coronary intervention / 天津医药

Objective To evaluate the effects of probucol combined with atorvastatin medication on blood levels of oxidized low-density lipoprotein (ox-LDL), lipoprotein-associated phospholipase A2 (Lp-PLA2), and the correlation of their changes in patients with acute coronary syndrome (ACS) undergoing percutaneous poronary intervention (PCI). Methods A total of 97 patients with ACS and undergoing PCI were randomly divided into two groups according to the date of admission:single medication group (n=42),the patients were taken atorvastatin 20 mg/d; and combined medication group (n=55),the patients were taken atorvastatin 20 mg/d with probucol 500 mg/d. The plasma levels of ox-LDL and Lp-PLA2 were measured in both groups before and 6-8 weeks after the medication. Then the results were compared and analyzed between two groups. Results (1) Before treatment there were no significant differences in levels of ox-LDL and Lp-PLA2 between two groups (P>0.05). After the treatment, the ox-LDL level was significantly decreased in combined medication group (P<0.01). After the treatment, the levels of Lp-PLA2 were significantly decreased than those before treatment in both groups (P<0.01). Compared with single medication group, levels of ox-LDL and Lp-PLA2 were significantly lower in combined medication group (P < 0.01). (2) After treatment, the absolute value of Lp-PLA2 decline (ΔLp-PLA2) was positively correlated with the absolute value of ox-LDL decline (Δox-LDL) in combined medication group (r=0.314, P=0.020). Conclusion Probucol combined with statin therapy can reduce ox-LDL and Lp-PLA2 levels, and with a positive correlation between them. Probucol can further decrease the level of Lp-PLA2 by inhibiting ox-LDL production, which may be one of the mechanisms of its anti-atherosclerosis.

The clinical application value of serum hs-CRP, IL-1β and Lp-PLA2 in ACS / 中国医师杂志

Objective To investigate the serum levels of high sensitivity C-reactive protein (hsCRP),interleukin-1β (IL-1β) and lipoprotein-associated phospholipase A2 (Lp-PLA2),and investigate their clinical diagnostic value in acute coronary syndrome (ACS) patients.Methods Fifty three clinical serum samples of patients specifically diagnosed with acute coronary syndrome were collected.A total of 21 healthy subjects were enrolled as healthy controls.Serum IL-1β and Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay.The concentration of hs-CRP was tested by immunoturbidimetry method.Results Compared to the healthy controls,the levels of serum hs-CRP,IL-1βand Lp-PLA2 were significantly higher in ACS and ACS subgroups (P ＜ 0.05),respectively.The level of Lp-PLA2 was gradually increased among healthy controls,angina pectoris (AP),ST-segment elevation myocardial infarction (STE-MI),non-ST-segment elevation myocardial infarction (NSTEMI) groups.The best cut-off value of hs-CRP,IL-1β and Lp-PLA2 was 7.44 mg/L,90.88 ng/L and 219.92 μg/L,respectively.The parallel test had better sensitivity (94.3％) and specificity (100％).Conclusions Serum hs-CRP,IL-1β and Lp-PLA2 play an important role in classifying the clinical types and monitoring the conditions of patients with ACS.Combination of hs-CRP,IL-1β and Lp-PLA2 is expected to be a new biomarker for ACS.

Ação cardiovascular da peçonha de Bothrops atrox em ratos anestesiados / Cardiovascular response to Bothrops atrox snake venom in anesthetized rats

Bothrops atrox (jararaca-do-norte) é a principal causa de envenenamento ofídico na região amazônica. Vários estudos têm investigado a bioquímica desta peçonha, bem como os efeitos locais (dor, edema, hemorragia e mionecrose) que ela causa. Por outro lado, os efeitos sistêmicos têm sido menos estudados. Neste trabalho, investigamos as alterações hemodinâmicas causadas por esta peçonha em ratos anestesiados bem como os possíveis mediadores envolvidas nestas respostas. Métodos: Ratos machos Wistar (300-400 g) anestesiados com isoflurano foram canulados para o registro da pressão arterial (carótida) e para a administração intravenosa (i.v.) de diferentes substâncias (peçonha, antagonistas e inibidores) (veia femoral esquerda). Em alguns experimentos, houve administração intramuscular (i.m.) de peçonha. A frequência respiratória foi determinada manualmente e o ECG foi monitorado via eletrodos introduzidos nas patas dianteiras e traseira. Em intervalos pré-estabelecidos, foram coletadas amostras de sangue arterial para análise bioquímica e determinação da cinética da peçonha. Ao término dos experimentos, foram coletados tecidos (rim, pulmão, coração, fígado e músculo) para análise histológica. A capacidade do antiveneno botrópico comercial em neutralizar algumas atividades enzimáticas e as alterações hemodinâmicas foi avaliada pré-incubando-se a peçonha com antiveneno antes de testar a atividade residual. A peçonha também foi fracionada por gel filtração e os picos testados quanto à sua atividade sobre a pressão arterial. Resultados: A peçonha (0,4 mg/kg, i.v.) causou hipotensão imediata (máxima aos 5 min) seguida por recuperação nos 20 min seguintes; não houve alteração na frequência cardíaca, ECG ou frequência respiratória, e não houve mortes (sobrevida até o final do experimento: 120 min). Uma dose maior (0,7 mg/kg, i.v.) causou hipotensão progressiva, bradicardia e falência respiratória, com morte de todos os ratos (n=6) em 20±4 min. A administração intramuscular (músculo gastrocnêmio) de peçonha (4 mg/kg) mostrou um perfil hemodinâmico semelhante àquele observado com a dose menor i.v. A análise histológica mostrou que a dose menor i.v. causou trombose e hemorragia pulmonares, além de dano renal (descamação epitelial, deposição proteica e microaneurismos); houve proteinúria e hemoglobinúria em urina coletada no final do experimento. Não houve alteração histológica nos outros tecidos examinados (fígado, coração)...(AU)

Bothrops atrox (jararaca-do-norte) is the main cause of snakebite in the Amazon region. Various studies have examined the biochemical aspects of this venom, as well as local effects such as pain, edema, hemorrhage and myonecrosis that this species causes. In contrast, the systemic effects caused by this venom have been less studied. In this work, we investigated the hemodynamic alterations caused by B. atrox venom in anesthetized rats, as well as the possible mediators involved in this response. Methods: Male Wistar rats (300-400 g) anesthetized with isoflurane were cannulated for arterial blood pressure measurements (carotid artery) and for the intravenous (i.v., femoral vein) administration of test substances (venom, antagonists and inhibitors). In some experiments, venom was injected intramuscularly (i.m.). Respiratory rate was determined manually and ECG was monitored using conventional electrodes. At pre-established intervals, arterial blood was drawn for biochemical analyses and determination of venom kinetics. At the end of the experiments, tissue samples were collected from heart, liver, lung and muscle for histological analysis. The ability of commercial bothropic antivenom to neutralize selected venom enzymatic activities and the venom-induced hemodynamic alterations was assessed by preincubating venom with antivenom prior to testing for residual activity. Venom was also fractionated by gel filtration and the resulting peaks were screened for their activity on blood pressure. Results: Venom (0.4 mg/kg, i.v.) caused immediate hypotension (maximal at 5 min) followed by recovery over 20 min; there were no changes in heart rate, ECG or respiratory rate and no deaths (survival for up to 120 min post-venom). A higher dose of venom (0.7 mg/kg, i.v.) caused progressive hypotension, bradycardia and respiratory failure, with all rats (n=6) dying in 20±4 min. A similar hemodynamic profile to the lower dose of venom i.v. was seen with venom (4 mg/kg) given i.m. (gastrocnemius muscle). Venom given i.v. (lower dose) caused pulmonary thrombosis and hemorrhage, in addition to renal damage (epithelial desquamation, deposition of protein and microaneurysms); proteinuria and hemoglobinúria were observed in urine collected at the end of the experiment. Venom given i.m. or i.v. (higher dose) caused only pulmonary thrombosis. Renal damage (epithelial desquamation, proteinuria and hemoglobinuria) was seen with venom i.v. (0.4 mg/kg); venom given i.m. caused local hemorrhage and necrosis, and proteinuria. There were no histological alterations in the other tissues examined (heart, liver)... (AU)

Effects of loading dose of atorvastatin on inflammatory cytokines in acute myocardial infarction patients undergoing emergency percutaneous coronary intervention / 天津医药

Objective To investigate the effects of high loading dose of atorvastatin on lipoprotein-associated phospho?lipase A2 (Lp-PLA2) and inflammatory cytokines in patients with acute myocardial infarction (AMI), who underwent emergen?cy percutaneous coronary intervention (PCI). Methods A total of 65 cases with AMI who underwent emergency PCI be?tween October 2011 and August 2013 were randomly divided into two groups:control group (n=32, atorvastatin 20 mg/24 h) and high dose atorvastatin group (n=33, atorvastatin 40 mg/24 h). Two groups of patients were given the same basic treat?ment. Blood samples were obtained before treatment and 72 h after PCI in two groups. Levels of Lp-PLA2, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), alanine transaminase (ALT) and aspartate transaminase (AST) were detected in two groups. The adverse drug reactions were observed. Results There were no significant differences in Lp-PLA2, IL-6, TNF-α, ALT and AST levels between two groups (P>0.05). After PCI, the levels of Lp-PLA2, IL-6 and TNF-αwere significantly increased compared with those of baseline in two groups, and they were more notable in control group than those of high dose atorvastatin group (P0.05). Conclusion The high loading dose of atorvastatin in AMI patients underwent emergency PCI can de?crease the inflammation and stabilize the plaques in acute stage, and which is safe.

Effect of perioperative Atorvastatin treatment on lipoprotein-associated phospholipase A2 level and heart function in elderly patients with acute ST-segment elevation myocardial infarction and type 2 diabetes / 中华老年医学杂志

Objective To investigate the effects of perioperative high loading dose of Atorvastatin treatment on lipoprotein associated phospholipase A2 (Lp-PLA2) and heart function in patients with acute ST-segment elevation myocardial infarction and type 2 diabetes who underwent emergency percutaneous coronary intervention (PCI).Methods Totally 83 cases with acute ST segment elevation myocardial infarction and type 2 diabetes who underwent emergency PCI from September 2012 and August 2014 were randomly divided into two groups.In control group (n=42)patients took Atorvastatin 20 mg daily before and after emergency PCI,and in intensive group (n=41) patients took atorvastatin 40 mg daily before and after emergency PCI.Each group was given the same basic treatment according to the guideline.Blood samples were obtained from all the patients before PCI and at 3,7 days after PCI,and levels of Lp-PLA2 and brain natriuretic peptide (BNP)were detected.And the left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured at 1 day and 1 month after PCI.Results The levels of Lp-PLA2 and BNP at 3 days after PCI were obviously increased in the two groups versus baseline [(297.8± 53.4) mg/L vs.(194.7±39.1) mg/L,(270.3±47.0) mag/L vs.(205.6±27.5) mg/L,both P＜0.05],and decreased in intensive versus control group [(270.3±47.0) mg/L vs.(297.8±53.4)mg/L and (353.8±76.3) mg/L vs.(375.4±57.0) mg/L,P＜0.05].And levels of Lp-PLA2 and BNP at 7 days after PCI were improved more in intensive than in control group [(227.2±33.3)mg/L vs.(249.3±42.3) mg/L,(206.0±48.2)mg/L vs.(267.6±50.8) mg/L,P＜0.05].There were no significant differences in LVEDD and LVEF between the two groups 1 day after PCI.Meanwhile,the LVEDD was decreased and the LVEF was increased in the two groups 1 month after PCI as compared with 1 day after PCI (both P＜0.05).Conclusions Perioperative high loading dose of Atorvastatin treatment may stabilize the plaques and improve heart function in acute stage in patients with acute ST-segment elevated myocardial infarction and type 2 diabetes after emergency PCI.

The influence of chronic Helicobacter pylori infection in serum lipoprotein associated phospholipase A2 level and stability of atherosclerotic plaques in patients with carotid atherosclerosis / 中国医师杂志

Objective To explore the influence of Helicobacter pylori (Hp) infection in serum lipoprotein associated phospholipase A2 (Lp-PLA2), carotid intima-media thickness and stability of atherosclerotic plaques in atherosclerosis patients.Methods A total of 393 cases of patients with carotid artery arteriosclerosis confirmed by carotid color uhrasonography, who are informed consent, was selected as objects.The14C urea breath test was used to determine the infection situation of selected objects of helicobacter pylori.Meanwhile, enzyme-linked immunosorbent assay (ELISA) was used to determine the level of serum lipoprotein associated phospholipase A2 (Lp-PLA2).Results Serum Lp-PLA2 levels and carotid intimamedia thickness (IMT) of patients with carotid artery atherosclerosis in Hp infection group were higher than that of Hp non-infection group, and with the degree of Hp infection aggravating in the patients of carotid artery atherosclerosis, their serum Lp-PLA2 levels and carotid IMT were also increased accordingly.F test showed that the differences of serum Lp-PLA2 levels and carotid IMT in different degree of carotid artery atherosclerosis group were statistically significant (P ＜0.01).The incidence of unstable plaque of Hp infection group was obviously higher than that of the Hp non-infection group in the carotid atherosclerosis with plaques with statistical significance (chi square value =4.744, P =0.029).Multivariate linear regression analysis showed that the possibility of complication of unstable plaques in Hp infection group of carotid artery atherosclerosis was 1.82 times than that of non-infection group.With serum Lp-PLA2 every increasing 1 μg/L, the possibility of instability plaque increased by 2％.Conclusions Hp infection may promote the occurrence and development of carotid artery atherosclerosis by increasing serum level of Lp-PLA2 and changing the stability of atherosclerotic plaques.

Relationship among ABI, baPWV, plasma Lp-PLA2 level and coronary heart disease / 心血管康复医学杂志

Objective:To explore the relationship among plasma level of lipoprotein‐associated phospholipase A2 (Lp‐PLA2) ,ankle brachial index (ABI) ,brachial‐ankle pulse wave velocity (baPWV) and coronary heart disease (CHD) .Methods :According to results of coronary angiography ,a total of 120 patients with suspected or diagnosed CHD were divided into CHD group (n=90) and non‐CHD group (n=30) .CHD group was further divided into sin‐gle vessel coronary disease group (single vessel group ,n=30) ,double‐vessel coronary disease group (double‐vessel group ,n=30) and multi‐vessel coronary disease group (multi‐vessel group ,n= 30) .Plasma Lp‐PLA2 level ,ABI and baPWV were measured and compared among all groups .Results:Compared with non‐CHD group ,there were significant rise in plasma Lp‐PLA2 level [ (23.60 ± 13.33)μg/L vs .(36.65 ± 17.24)μg/L] and baPWV [ (1244.27 ± 127.85) cm/s vs .(1753.08 ± 284.32) cm/s] in CHD group ,P<0.01 both .In CHD group ,compared with single vessel group ,plasma Lp‐PLA2 level significantly rose [ (25.81 ± 8.97)μg/L vs .(35.03 ± 9.80)μg/L vs .(49.13 ± 21.22)μg/L] in double‐vessel group and multi‐vessel group ,and that of multi‐vessel group was significantly higher than that of double‐vessel group ( P<0.05 or <0.01 );baPWV significantly rose [ (1579.77 ± 178.05 ) cm/s vs . (1808.07 ± 272.11) cm/s ,(1871.40 ± 306.03) cm/s] in double‐vessel group and multi‐vessel group , P<0.01 both . ABI of single vessel group and double‐vessel group were significantly higher than that of multi‐vessle group [ (1.19 ± 0.08) ,(1.17 ± 0.07) vs .(1.11 ± 0.15)] ,P<0.01 or <0.05 .Conclusion:Plasma Lp‐PLA2 level ,ABI and baP‐WV are related to CHD and its lesion degree ,combined measurement of these three indexes can predict CHD and its severity more accurately ,then preventing and treating CHD should be more effective .

Correlation betw een lipoprotein-associated phospholipase A2 gene R92H polymorphism and ischemic stroke and its subtype in a Chinese Han population of Shandong province / 国际脑血管病杂志

Objective To investigate the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2) gene R92H polymorphism and ischemic stroke and its subtype in a Chinese Han population of Shandong province. Methods A total of 386 patients w ith first-ever ischemic stroke and 368 healthy controls in China Shandong region w ere enrol ed. According to the TOAST criteria, the patients w ere further divided into large artery atherosclerosis (LAA) and smal artery occlusion (SAO). Enzyme linked immunosorbent assay w as used to detect the serum Lp-PLA2 level. Polymerase chain reaction and directly sequencing w ere used to detect R92H gene polymorphism. Results The serum Lp-PLA2 levels in the ischemic stroke group, LAA group and SAO group w ere higher than that in the control group, and there w ere significant differences (al P<0.01). The distribution frequencies of GA (P=0.006), AA (P=0.020), AA+AG (P=0.009), and A al ele (P=0.001) in the ischemic stroke group w ere significant higher than those in the control group. There w ere also significant differences in distribution frequencies of GA+AA genotype (P=0.007) and A al ele (P<0.001) betw een the LAA group and the control group, w hile the SAO group w as not the case. Multivariate logistic regression analysis showed that GA+ AA genotype (odds ratio [OR] 1.43, 95%confidence interval [CI] 1.02-2.00; P=0.029), GA genotype (OR 1.42, 95%CI 1.01-2.00; P=0.037), and A alele (OR 1.44, 95%CI 1.11-2.18; P=0.028) were the independent risk factors for ischemic stroke. GA+AA genotype (OR 1.73, 95%CI 1.18-2.55; P<0.001) and GA genotype (OR 1.67, 95%CI 1.13-2.48; P<0.001) w ere the independent risk factors for LAA, and they w ere not significantly independent correlated w ith SAO. Conclusions The serum Lp-PLA2 levels increased in patients w ith ischemic stroke, and they increased most significantly in the LAA group. The R92H gene polymorphism might be associated w ith the susceptibility of ischemic stroke in a Chinese Han population of Shandong province.