Baicalin-loaded PEGylated lipid nanoparticles: characterization,pharmacokinetics, and protective effects on acute myocardial ischemia in rats

Context: Baicalin has many pharmacological activities, including protective function against myocardial ischemia by antioxidant effects and free radical scavenging activity. However, its rapid elimination half-life in plasma and poor water solubility limits its clinical efficacy.

Objective: Novel baicalin-loaded PEGylated nanostructured lipid carriers (BN-PEG-NLC) were developed to improve bioavailability of BN, to prolong retention time in vivo and to enhance its protective effect.

Methods: In this study, BN-PEG-NLC were prepared by the emulsion-evaporation and low temperature-solidification method using a mixture of glycerol monostearate and polyethylene glycol monostearate as solid lipids, and oleic acid as the liquid lipid. The physicochemical properties of NLC were characterized. The pharmacokinetic and pharmacodynamic behaviors of BN-PEG-NLC or BN-NLC were evaluated in acute MI rats.

Results and discussion: The particle size, zeta potential, and entrapment efficiency for BN-PEG-NLC were observed as 83.9?nm, ?32.1?mV, and 83.5%, respectively. The release profiles of BN from both BN-PEG-NLC and BN-NLC were fitted to the Ritger–Peppas modal, which presented burst release initially and prolonged release afterwards. Pharmacokinetics results indicated that BN-PEG-NLC exhibited a 7.2-fold increase in AUC in comparison to BN solution, while a 3-fold increase in comparison to BN-NLC. Biodistribution results revealed that BN-PEG-NLC exhibited higher heart drug concentration compared with BN-NLC as well as BN solution. In the present study, BN-PEG-NLC significantly ameliorated infarct size.

Conclusion: The results of the present study imply that PEG-NLC could be the biocompatible carriers for heart-targeted drug delivery to improve myocardial ischemia.     

乙型肝炎与肝癌关系的流行病学研究—广西HBsAg携带者及肝损害者的分布及发生肝癌的前瞻性研究

本文对20岁以上22830人按HBsAg状况和肝损害表现分队列进行随访,平均追踪6.8年,在肝癌高发区和低发区均以HBsAg携带者并有重度肝损害者(肝大+肝功能异常)的肝癌死亡率和相对危险性最高,相对危险性分别为37.3和22.5倍。以无肝大和肝功能异常的非携带者最低,肝癌的发生和肝损害的程度呈平行关系。HBsAg携带者发生肝癌死亡的相对危险性高于非携带者7倍,并发现HBsAg携带并有重度肝损害的肝癌死亡的平均年龄显著提前。认为肝癌高发区人群中HBV的持续感染和肝损害的广泛存在是导致肝癌高发和早发的重要因素。     

羟基磷灰石义眼台作为药物缓释载体减轻术后反应的临床观察

目的评价羟基磷灰石（HA）义眼台作为药物缓释载体减轻眼球摘除义眼台植入术后反应的效果。方法植入HA义眼台前，用地塞米松5mg，庆大霉素8万u，透明质酸酶1500U混合液浸泡HA义眼台15—20min后植入，手术步骤按常规。结果观察术后1周反应情况，52例中51例（98．07％）无疼痛或仅有轻度疼痛；44例（84．62％）结膜无水肿；36例（69．23％）无恶心；16例（30．77％）轻中度恶心；48例（92．31％）无呕吐。与对照组（43例）比较，术后疼痛、结膜水肿、恶心呕吐均较轻，其差别均有统计学意义（P〈0．001）。结论HA义眼台作为药物缓释载体植入眼球肌膜囊内能有效地控制术后反应，减轻患者痛苦。     

Dermatitis from hexavalent chromate in the accelerator of an epoxy sealant (PR1422) used in the aircraft industry

4 aircraft construction workers developed allergic contact dermatitis of the hands and forearms. The allergen was hexavalent chromate in the accelerating solution of an epoxy-based sealant (PR1422). Although chromate dermatitis from an epoxy resin has been described, epoxy system accelerators are a hitherto unrecognized source of occupational chromate dermatitis.     

以胆酸为载体的肝靶向疗法

通过肝靶向给药技术将化学治疗药物选择性地投放于肝脏,能够减轻或避免其全身的毒副作用.胆酸是唯一的口服有效的小分子肝靶向载体,以胆酸为载体的肝靶向疗法为肝病及肝脏代谢性疾病提供了新的疗法.如胆酸-一氧化氮供体靶向偶合物能够选择性地将一氧化氮投放于肝脏,产生治疗肝硬化的作用;胆酸-脂肪酸靶向偶合物能够选择性地调节肝脏的脂代谢,具有治疗胆结石、脂肪肝和动脉粥样硬化的作用;胆酸-米非司酮偶合物能够选择性地作用于肝脏,产生特异性的降糖作用,而没有全身副作用.     

The hyperpolarisation-activated current,I f,is not required for pacemaking in single cells from the rabbit atrioventricular node

Using electrophysiological and radiotracer studies in parallel, we have investigated the characteristics of the endogenous Na⁺-dependent amino acid transporter (system B^0,+) in Xenopus oocytes with regard to ion dependence, voltage dependence and transport stoichiometry. In voltage-clamped oocytes (–60 mV) superfusion with saturating concentrations of amino acids (1 mM) in 100 mM NaCl resulted in reversible, inward currents (mean±SEM): alanine, 1.83±0.09 nA (n=21); arginine, 2.54±0.18 nA (n=17); glutamine, 1.73±0.10 nA (n=19). Only arginine evoked a current in choline medium (0.50±0.13 nA, n=10), whereas Cl^– replacement had no effect on evoked currents. The glutamine-evoked current was saturable (I _max=1.73 nA, glutamine K _m=0.12 mM) and linearly dependent upon voltage between –90 and –30 mV. Using direct and indirect (activation) methods, we found that transport can proceed with Na⁺/amino acid coupling stoichiometry of either 11 or 21, but coupling was the same for each amino acid tested (alanine, arginine and glutamine) within a batch of oocytes (i.e. from a single toad). Despite the net single positive charge on arginine, the magnitude of the net transmembrane charge movement during Na⁺-coupled arginine transport was identical to that for the zwitterionic neutral amino acids glutamine and alanine; this may be explained by a concomitant stimulation of K⁺ efflux during arginine transport with a putative coupling of 1 K⁺1 arginine.     

抗骨肉瘤药物纳米载体的研究进展

骨肉痛是最常见的恶性骨肿瘤,病死率较高。而生物医用纳米材料是纳米材料和生物材料交叉的一个全新领域,在生物医学上有着十分诱人的、广泛的应用前景。本文对纳米无机生物材料、纳米高分子生物材料、纳米复合生物材料作为抗骨肉瘤药物载体的研究进展作了较全面的综述。     

Hepatitis B virus DNA in serum of healthy black African adults positive for hepatitis B surface antibody alone: possible association with recombination between genotypes A and D

In some patients with chronic liver disease induced by hepatitis B virus, viral DNA is known to persist in low concentration in serum after seroconversion to hepatitis B surface antibody-positivity. This phenomenon has, however, not been documented in asymptomatic black African carriers of hepatitis B virus. Using nested amplification by the polymerase chain reaction, we detected low concentrations of hepatitis B virus DNA in the serum of 6 of 23 (26%) healthy black African adults with normal liver function and with hepatitis B virus surface antibody as the only serological marker of the virus. This finding offers one explanation for the earlier observation of integrated hepatitis B virus DNA in hepatocellular carcinomas in black Africans whose serum was positive for surface antibody alone. A number of genetic changes were found in the six isolates that might be responsible for evasion of the immune response and persistence of the virus. Isolated mutations were detected in the "a" determinant of the surface gene and in the encapsidation signal. In all five isolates sequenced in the core promoter, mutations were present in the upstream regulatory region. Recombination between genotypes A and D was present in three of the isolates, including both of those in which the entire genome was sequenced. This change in genotype also overlapped the amino end of the polymerase domain and may result in sufficiently low levels of replication to allow viral persistence. Topoisomerase 1 specific trinucleotides were concentrated in the vicinity of the recombination breakpoints.     

125I-白蛋白-黄芪多糖毫微粒在小鼠体内分布的研究

用乳液固化方法制备了１２５Ｉ－牛血清白蛋白－黄芪多糖毫微粒,透射电子显微镜测得粒径为（１６８±６２）ｎｍ,小鼠口服毫微粒（１４８×１０８Ｂｑ／只）后,主要分布在肝、脾、肺中,而心、脑组织中有少量分布。微观放射自显影实验结果表明,毫微粒分布在肝脏的Ｋｕｆｅｒｓ细胞和肝实质细胞中,以及在肺和脾脏的吞噬细胞中。实验数据用３Ｐ８７程序处理,按血管外给药开放二室模型计算得代谢动力参数,Ｔｍａｘ为２．１１ｈ,Ｃｍａｘ为２．４３×１０７Ｂｑ,ｔ１／２为９．３３ｈ,曲线下面积为３．７×１０９Ｂｑ。     

Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo

Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 M. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers.