MECHANISMS BY WHICH INTRARENAL DOPAMINE AND ANP INTERACT TO REGULATE SODIUM METABOLISM

Maintenance of a normal blood pressure requires a precise and fine-tuned regulation of salt metabolism. This is accomplished by a bidirectional regulation of renal tubular sodium transporters by natriuretic and antinatriuretic hormones. Dopamine, produced in the renal proximal tubular cells, plays an important role in this interactive system. Dopamine inhibits the activity of Na⁺,K⁺ATPase as well as of many important sodium influx pathways in the nephron. These effects of dopamine are particularly pronounced in situation of sodium loading.

There is an abundance of evidence suggesting that the natriuretic effects of ANP are to a large extent mediated via renal dopamine 1 like receptors. The renal tubular dopamine 1 like receptors are, under basal conditions, mainly located intracellularly. ANP and its second messenger, cGMP, cause a rapid translocation of the dopamine 1 like receptors to the plasma membrane. This phenomenon may explain how ANP and dopamine act in concert to regulate sodium metabolism. Regulation of sodium metabolism and blood pressure is critically dependent on a normal function of the renal dopamine system. Hence, abnormalities in the interaction between dopamine and ANP may predispose to hypertension.     

ECONOMIC VALUATION OF ECOSYSTEM SERVICES: DISCUSSION AND APPLICATION

ABSTRACT

Ecosystems provide a wide range of services that improve human welfare. Changes in ecosystems imply potential changes in the generation of these ecosystem services and thus changes in welfare. In the lingo of economists, these welfare changes are measured as changes in economic values—increases in welfare being benefits and decreases in welfare being costs. For instance, individuals may benefit from, and thus value, reductions in risks to endangered species. Yet values for many changes in ecosystem services are not captured in market transactions, and thus measuring these values requires nonmarket valuation methods. This paper discusses ecosystem services and values from the viewpoint of an economist, explains what is meant by the valuation of ecosystems, and provides an overview of methods for valuation of ecosystem services. An example is presented from a recent natural resource damage assessment—the Green Bay total value equivalency study. Resources in the Lower Fox River and Green Bay in Wisconsin have been injured by polychlorinated biphenyl contamination from numerous paper mills along the river over several decades. The Green Bay study examines individuals' preferences and values for reducing ecosystem risks and improving ecosystem services and how these values are related to individuals' awareness of and use of ecosystem services in the area. The study uses methods from nonmarket valuation to scale potential restoration projects.     

Mussel oligopeptides ameliorate cognition deficit and attenuate brain senescence in d-galactose-induced aging mice

Dietary supplementation exerts beneficial effects in reducing incidence of chronic neurodegenerative diseases. The purpose of this study was to examine protective effects of mussel (Mytilus edulis) oligopeptides supplementation on brain function in d-galactose induced aging mice. Sixty female 8-month-old mice were randomly divided into five groups: vehicle control, d-galactose, and d-galactose combined with 200, 500, 1000 mg/kg mussel oligopeptides. The results showed that mussel oligopeptides could improve cognitive learning and memory ability and protect the hippocampal neurons. In addition, GSH, SOD and GSH-pX activities were increased and MDA level was significantly decreased in mice fed with mussel oligopeptides. It was also found that mussel oligopeptides supplementation prevented d-galactose-induced elevations of iNOS activity and NO production and lactate acid levels in brain. Moreover, PI3K and Akt genes were up-regulated by mussel oligopeptides supplementation. These findings suggest that mussel oligopeptides are able to enhance exercise capacity and protect against oxidative damage caused by d-galactose in aging model mice through regulating oxidation metabolism and PI3K/Akt/NOS signal pathway. Therefore, mussel oligopeptides are good materials for future development of healthcare products to combat age-related brain dysfunction and to improve healthy life span.     

Four factor prothrombin complex concentrate (human): review of the pharmacology and clinical application for vitamin K antagonist reversal

Vitamin K antagonists (VKAs) have been used for decades for the treatment and prophylaxis of thromboembolic events. Due to their wide range of therapeutic indications, they are the most prescribed oral anticoagulant worldwide. However, they are associated with bleeding complications due to their narrow therapeutic range, variability in individual dose responses and laboratory monitoring, and overdoses. Despite off-label use of 3-factor prothrombin complex concentrates and recombinant activated factor VII, until recently, vitamin K and plasma were the only recommended therapeutic options for reversing VKAs in the USA. In 2013, a 4-factor prothrombin complex concentrate (4F-PCC) was approved in the USA for VKA reversal in patients with bleeding or requiring emergency surgery and invasive procedure. Recent randomized controlled clinical trials have shown that 4F-PCC (Kcentra?) is non-inferior for hemostatic efficacy and superior for international normalized ratio correction as compared to plasma and has a similar safety profile.     

胆道梗阻肝细胞膜Na+/K+ATP酶的变化

目的动态观察在胆道梗阻和梗阻缓解过程中,肝细胞膜Na+/K+ATP酶活性变化的规律。方法对130只胆道梗阻大鼠模型的260份样本进行组织化学染色,结合免疫电镜方法,在肝细胞膜上染色定位Na+/K+ATP酶,计算机图像分析测定,半定量比较肝细胞膜Na+/K+ATP酶活性。结果Na+/K+ATP酶广泛存在于肝细胞膜上,但其活性(相对灰度比值)在肝细胞血窦面、肝细胞间面和肝细胞毛细胆管面呈不均匀分布,分别为107.60±16.64、74.40±9.37、90.30±8.04。反映了肝细胞分泌胆汁的正常极性。Na+/K+ATP酶活性在胆道梗阻和梗阻缓解过程中随着胆红素水平的升高或降低而发生变化,并且随着梗阻和缓解的时间延长而明显下降或改善。在梗阻14d时,分别降为84±10、60±7、65±15;在梗阻14 d缓解1 d时,Na+/K+ATP酶活性分别为86±14、62±6、68±19,而在缓解7 d时其活性分别恢复为96±8、65±6、85±7。结论胆道梗阻对肝细胞膜Na+/K+ATP酶活性的影响可能与胆道梗阻时肝细胞代谢胆红素障碍有关。     

慢性粒细胞白血病的生物治疗

慢性粒细胞白血病(CML)是一种造血干细胞的恶性克隆增殖性疾病,以分子生物学、免疫学为基础的生物治疗手段成为新的研究方向.生物治疗主要包括分子靶向治疗、基因治疗和过继免疫治疗.基因治疗主要通过基因转染使肿瘤细胞抗原标志过度表达而增加机体的免疫识别;或通过下调相关原癌基因表达,抑制细胞增殖,诱导细胞凋亡等方式发挥抗肿瘤作用.过继免疫治疗是将CIK、NK等免疫活性细胞注入肿瘤宿主体内的一种治疗方法.基于K562细胞系的相关研究为深入进行生物治疗研究奠定了基础,但因缺乏合适靶标等原因,生物治疗尚不能取代传统的治疗方法.     

高迁移率蛋白B1对血管平滑肌细胞迁移的影响及分子机制研究

目的：探讨高迁移率蛋白B1（HMGB1）对血管平滑肌细胞（VSMCs）迁移的影响及 TLR4依赖的 TLR4／PI3K／Akt信号通路介导的分子机制。方法体外分离培养大鼠胸主动脉VSMCs ,采用不同浓度 HMGB1（0．1～1000．0 ng ／mL）处理,分为对照组（未经任何处理）、HMGB1组、HMGB1＋ TLR4 siRNA转染组、Control siRNA转染组和磷脂酰肌醇3‐激酶（PI3K）抑制剂（LY294002）干预组,观察各组细胞活性及 HMGB1对 VSMCs 迁移的影响;实时定量 RT‐PCR与 Western blot 分别检测TLR4、Akt、p‐Akt、PI3K mRNA和蛋白的表达;ELISA测定PI3K的活性。结果 HMGB1（0．1～1000．0 ng／mL）呈剂量依赖性促进VSMCs迁移（P＜ 0．05）;经细胞活性测定,HMGB1在使用的浓度范围内对 VSMCs未造成细胞毒性作用（P＜ 0．05）;HMGB1（100 ng／mL）处理的 VSMCs细胞组 PI3K 活性及 Akt磷酸化水平明显增加（P＜ 0．05）;经 TLR4 siRNA 转染发现, HMGB1引起的VSMCs迁移明显减弱（P＜0．05）,同样在PI3k抑制剂干预组,PI3K／Akt途径活化和HMGB1介导的VSMCs迁移也被明显抑制（P＜0．05）。结论 HMGB1呈剂量依赖性促进VSMCs迁移,TLR4依赖的 TLR4／PI3K／Akt信号通路参与了此过程,提示以TLR4依赖的PI3K／Akt途径为靶点,可为阻塞性血管疾病的治疗提供新思路。     

Survivin和PI3K、AKT在寻常型银屑病皮损角质形成细胞中的表达及其相关性

目的 探讨凋亡抑制蛋白Survivin和PI3K、AKT在寻常型银屑病(PV)进行期斑块状皮损角质形成细胞(KCs)中的表达水平及作用.方法 临床上收集22例PV患者进行期斑块状皮损以及18例正常皮肤组织.采用免疫组织化学、Western blot和real-time quantitative PCR等方法检测22例PV患者进行期斑块状皮损和18例正常皮肤组织中KCs的Survivin、PI3K和AKT表达,并分析它们在PV皮损KCs中的相关性.使用小干扰RNA(siRNA)在HaCaT细胞中沉默AKT,并通过Western blot实验检测Survivin的表达水平.结果 PV皮损KCs中Survivin、PI3K和AKT的蛋白表达水平均高于正常皮肤组织.PV皮损KCs中Survivin和PI3K mRNA表达成正相关(r=0.4510;P=0.0351);PV皮损KCs中Survivin和AKT mRNA表达成正相关(r=0.4423;P=0.0393);在HaCaT细胞中,沉默AKT后可引起Survivin的表达下调.结论 凋亡抑制蛋白Survivin与PI3K/AKT信号通路可能参与了PV的发生与发展.