ACEI及无创呼吸机辅助治疗心衰合并OSAHS的疗效及对血清BNP水平的影响

目的:探讨血管紧张素转换酶抑制剂(Angiotensin-converting enzyme inhibitor,ACEI)联合无创呼吸机辅助治疗心衰合并阻塞性睡眠呼吸暂停低通气综合征(Obstructive sleep apnea hypopnea syndrome,OSAHS)疗效及对血清脑钠素(Brain natriuretic peptide,BNP)水平的影响。方法:抽取我院自2013年1月到2019年4月收治的98例心衰合并OSAHS患者,根据治疗方法分为对照组(49例,ACEI常规治疗)与实验组(49例,ACEI联合无创呼吸机辅助治疗),比较两组患者治疗前后红细胞生成素(Erythropoietin,EPO)、血红蛋白(hemoglobin,Hb)、红细胞计数(red blood cell,RBC)、平均红细胞蛋白含量(Mean corpuscular protein content,MCH)、血细胞比容(Hematocrit,HCT)、平均红细胞体积(Mean red blood cell volume,MCV)、夜间平均最低血氧合度(Lowest oxygen saturation,LSaO2)、睡眠呼吸暂停低通气指数(apnea hypopnea index,AHI)、血清脑钠素(Brain natriuretic peptide,BNP)水平、中心收缩压(systolic pressure,SP)及中心舒张压(diastolic pressure,DP)的变化。结果:治疗后,两组患者EPO、Hb、RBC、MCH、HCT、MCV水平均明显低于治疗前,且实验组患者的以上指标水平均显著低于对照组(P<0.05)。两组治疗后LSaO2高于明显高于治疗前,AHI水平低于治疗前,且实验组LSaO2高于对照组,AHI水平低于对照组(均P<0.05)。治疗后两组患者BNP、SP和DP明显低于治疗前(P<0.05),且实验组患者的以上指标水平低于对照组(P<0.05)。实验组患者的术后并发症发生率明显低于对照组(P<0.05)。结论:ACEI及无创呼吸机辅助治疗心衰合并OSAHS可改善患者的睡眠紊乱、睡眠呼吸障碍、心衰及高血压,具有临床推广应用的价值。     

Predictive markers of safety and immunogenicity of adjuvanted vaccines

Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/.     

Continuous health monitoring: integrating biomarkers for the management of chronic diseases

With the recent progresses of the information and communication technologies, biosensors and nanotechnologies, the access to continuing health monitoring is becoming real. The development of efficient, accurate and interactive solutions integrating biomarkers for continuing health monitoring might contribute to an improved care of some chronic diseases like hypertension, diabetes or heart failure. Continuing health monitoring might also enhance the efficiency and safety of patient’s treatments.     

Diagnostic utility of BNP,corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients

Abstract

Context: The number of patients with type 2 diabetes mellitus (T2DM) is progressively increasing, and diabetic cardiovascular complications have become a public health problem. Brain or B-type natriuretic peptide (BNP) is a cardiac hormone synthesized as a pre-pro-peptide. pro-BNP is produced by cleaving the signal peptide then two proprotein convertases, corin and furin cleave pro-BNP to form a biologically active hormone. Two corin single nucleotide polymorphisms (SNPs) have been reported to alter corin protein conformation and impair its biological activity.

Objective: We aimed to investigate the potential role of corin and furin in comparison to BNP as biomarkers for predicting cardiovascular complications in T2DM patients. The association of corin gene SNPs with corin levels was also examined.

Methods: Seventy-five subjects were recruited in this study, including 25 T2DM patients with complications, 25 T2DM patients without complications as well as 25 healthy subjects. Plasma BNP, corin and furin levels were measured using enzyme-linked immunosorbent assays. Two corin SNPs were genotyped using allele specific oligonucleotide-polymerase chain reaction.

Results: Both furin and BNP were found to be more sensitive than corin (80% versus 56%, p?=?0.008), whereas furin showed higher specificity when compared to BNP (96% versus 84%, p?=?0.041) and corin (96% versus 64%, p?<?0.0001) in predicting cardiovascular complications in T2DM patients. Corin SNPs are not associated with corin levels, neither in the entire study cohort nor in the subgroup of T2DM patients with cardiovascular complications (p?>?0.05).

Conclusions: Furin may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment in T2DM patients.     

芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床研究

目的：探讨芪苈强心胶囊辅助治疗老年慢性心力衰竭的临床疗效及其安全性。方法：选择我科2012年1月．6月收治的102例老年慢性心力衰竭患者为研究对象,并将其随机分为两组,对照组42例,给予西医常规治疗及地高辛0．125mg／d;观察组60例,在对照组基础上将地高辛用量改为O．0625mg／d,并予芪苈强心胶囊,每次4粒,每日3次12服,2个月为1个疗程,治疗3个疗程后观察和比较两组心功能的变化。结果：观察组和对照组的治疗总有效率分别为95．0．％和78．6％,观察组显著高于对照组,两组比较差异有统计学意义（P〈0．05）;观察组的平均住院时间明显短于对照组（P〈0．05）。治疗后,两组心输出量（cO）、每搏输出量（SV）、左室射血分数（LVEF）舒张晚期与舒张早期充盈速度比（～E）均较治疗前明显升高（P〈0．05）,而脑钠肽（BNP）水平较治疗前显著降低（P〈O．05）,且观察组CO、SV水平均明显高于对照组（P〈0．05）,BNP水平明显低于对照组（P〈0．05）。治疗过程中,对照组发生洋地黄中毒3例,观察组无不良事件发生。结论：芪苈强心胶囊辅助治疗老年慢性心力衰竭可有效改善其心功能,并减少地高辛用量和洋地黄中毒的发生,值得临床推广应用。     

地高辛对老年慢性心衰患者血清CA125，BNP及MMP-9 水平的影响

目的:探讨地高辛片对老年慢性心力衰竭患者血清血清糖类抗原(CA125)、心钠肽(ANP)、脑钠肽(BNP)、基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制剂(TIMP-1)水平的影响。方法:收集我院老年慢性心力衰竭患者100例,随机分为对照组和实验组,每组各50例,对照组患者给予常规治疗,实验组患者在对照组的基础上给予地高辛片。比较治疗前后两组患者血清糖类抗原(CA125)、心钠肽(ANP)、脑钠肽(BNP)、基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制剂(TIMP-1)水平。结果:与治疗前相比,两组患者血清CA125、ANP、BNP及MMP-9水平降低,TIMP-1水平升高(P0.05);治疗后与对照组相比,实验组CA125水平(34.05±4.63)较低,ANP水平较低(216.98±27.65),BNP水平较低(437.62±45.26),MMP-9水平较低(550.17±65.15),TIMP-1水平较高(182.32±21.78)(P0.05)。结论:地高辛片能够改善老年慢性心力衰竭患者心肌功能,推测其机制可能与降低血清CA125、ANP、BNP、MMP-9水平,升高TIMP-1水平有关。     

NT-pro BNP与LAVI对原发性高血压患者左心室舒张功能的评价

目的:应用左房容积指数(LAVI)与血清N末端脑钠肽原(NT-pro BNP)水平的变化情况评价原发性高血压(EH)患者左心室舒张功能。方法:选择2013年5月-2015年5月在我院接受治疗的原发性高血压患者100例。根据左房舒张功能将患者分为A组(E/A1,且Em/Am1)、B组(E/A1,且Em/Am1)、C组(E/A1,且Em/Am1)及D组(E/A2,且Em/Am1),。另选取同期在我院接受体检的健康志愿者100例作为对照组。观察并比较各组LAVI及NT-pro BNP水平,分析LAVI与及NT-pro BNP与原发性高血压患者左心室舒张功能的相关性关系。结果:原发性高血压患者E/A、LAVI及NT-pro BNP水平均显著高于对照组,而Em/Am则低于对照组,差异具有统计学意义(P0.05);原发性高血压患者中,LAVI及NT-pro BNP水平随E/A升高而递增,随Em/Am升高而递减,其中D组LAVI及NT-pro BNP水平显著高于其他三组,差异均具有统计学意义(P0.05)。根据Pearson相关性分析可知结果显示,原发性高血压患者LAVI与NT-pro BNP呈正相关关系(P0.05),但与E/A及Em/Am无明显相关关系(P0.05)。LAVI的截断值为29.040,NT-pro BNP为2.065时评价左室舒张功能存在异常的敏感度及特异度均较高(P0.05)。结论:LAVI及NT-pro BNP可较好地评价EH患者左室舒张功能情况,且:LAVI及NT-pro BNP二者之间联系紧密与原发性高血压存在一定的相关性,两者均能较为准确的评价原发性高血压患者的左心室舒张功能,值得在临床给予推广应用。     

祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及机制

目的:观察不同剂量祛痰通阳汤对慢性心衰大鼠心肌损伤的保护作用及可能机制。方法:将90只Wistar大鼠随机均分正常组、模型组、卡托普利组、祛痰通阳汤低、中、高剂量六组。为建立慢性心力衰竭模型,除正常组外的五组大鼠均以2ml/kg给予阿霉素腹腔,一周1次,共6周。注射造模成功后次日进行灌胃给予对应的不同药物,连续给药治疗四周后,应用ELISA法测定各组大鼠血浆脑尿钠肽(Brain natriuretic peptide,BNP)水平,称重计算心脏质量指数并采用投射电镜观察心肌细胞结构,通过实时荧光定量PCR法测定检测Kelch样环氧氯丙烷相关蛋白-1 (epoxy chloropro-pane Kelch sample related protein-1,Keap1)和核因子E2相关因子2(nuclearfactor erythroid-2 related factor 2,Nrf2)mRNA的表达。结果:1.电镜结果显示:正常组肌丝排列规则,肌节结构清晰,心肌细胞线粒体清晰且形态正常;细胞核发育良好,无空泡以及集块现象。模型组肌原纤维排列紊乱,心肌细胞线粒体形态异常,排列不齐,增生明显,有空泡现象形成。卡托普利组及祛痰通阳汤高剂量组电镜肌原纤维排列基本整齐,线粒体未见明显肿胀,线粒体嵴密集,优于中药低剂量组及中剂量组。2.卡托普利组、中药高剂量组大鼠血浆BNP水平较模型组显著降低(P0.01)。3.与模型组相比,中药高剂量组和卡托普利组心脏质量指数均显著降低(P0.05)。4.卡托普利组及祛痰通阳汤高剂量组心肌组织Keap1 m RNA表达与模型组相比显著降低(P0.05);卡托普利组及祛痰通阳汤高剂量组心肌组织Nrf2 m RNA表达与模型组的相比显著提高(P0.05)。结论:高剂量祛痰通阳汤可显著减轻慢性心衰大鼠的心肌损伤,可能与抑制Keap1 m RNA的表达及增强Nrf2 m RNA表达,进而抗心肌氧化损伤有关。     

Quantification of mesna and total mesna in kidney tissue by high-performance liquid chromatography with electrochemical detection

A sensitive and selective assay for the determination of mesna and total mesna in tissue was developed and validated. After a simple homogenization, extraction and deproteinization step, mesna could be measured immediately by HPLC with an electrochemical detector provided with a sensitive wall-jet gold electrode. Total mesna (i.e., free mesna and mesna present in mesna disulfides and mixed mesna disulfides) could be measured after pre-column reduction with sodium borohydride to free mesna. The lower limit of quantification of mesna and total mesna was for both compounds 10 nmol/g. The assays for mesna and total mesna in tissue were linear over the ranges of 10-3000 and 10-10000 nmol/g, respectively. The within-day and between-day precisions of both methods were better than 9%. The within-day and between-day accuracy of the mesna assay ranged from 103.7 to 113.6%, whereas the accuracies of the total mesna assay ranged from 97.8 to 106.7%. Mesna in an EDTA containing tissue homogenate or in deproteinized tissue homogenate stored at -80 degrees C was stable for at least 12 weeks. Total mesna was stable under all conditions measured. The developed assays will be applied for the determination of the distribution of mesna and total mesna in tissues of the rat after administration of mesna or BNP7787.     

B-Type and C-Type Natriuretic Peptides Modify Norepinephrine Uptake in Discrete Encephalic Nuclei of the Rat

SUMMARY 1. We previously demonstrated that atrial natriuretic factor and B- and C-type natriuretic peptides (ANF, BNP, and CNP, respectively) modified catecholamine metabolism by increasing the neuronal uptake and decreasing the neuronal release of norepinephrine in the rat hypothalamus. The aim of the present work was to study the effects of natriuretic peptides BNP and CNP on norepinephrine uptake as an index of the amine metabolism in discrete areas and nuclei of the central nervous system (CNS) of the rat.2. Experiments were carried out in vitro using the punchout technique in diverse areas and nuclei of rat CNS. Results showed that 100 nM BNP and 1 nM CNP increased norepinephrine (NE) uptake in all brain areas and nuclei studied.3. Present results permit us to conclude that BNP and CNP regulate NE metabolism independently of the encephalic area or nucleus involved. In fact, NE uptake increased in nuclei related to the regullation of cardivascular activity as well as nuclei associated with endocrine metabolism and hydrosaline homeostasis. These observations suggest that BNP and CNP may be involved in the regulation of these physiological processes in an indirect manner through modifications of noradrenergic neurotransmission. Present findings provide futher support to the hypothesis that CNP would be the main natriuretic peptide in brain. Furthermore, previous as well as present results support the role of the natriureic peptides as neuromodulators of noradrenergic transmission at the presynaptic level.