Accuracy of allometrically predicted pharmacokinetic parameters in humans: role of species selection.

A general equation was derived, which directly describes the mathematical relationship between the allometrically predicted pharmacokinetic (PK) parameters in humans and the body weights of animal species (along with their corresponding measured PK parameters). It was shown, with use of the derived equation, that the predicted values in humans, based on combinations of animal species commonly used in allometry, are heavily dependent on certain species, for example, the dog. In contrast, parameter values from the rat made no contribution to the predicted human values, as long as the rat was not the smallest species used. Monte Carlo simulations were further performed to examine the species or weight dependence. The cost-effective combinations of animal species, in terms of number and species type, were theoretically examined through simulations. Finally, literature data demonstrated the species or weight dependence predicted from the equation and as illustrated through the Monte Carlo simulations. Appreciation of this species or weight dependence should guide researchers in selecting animal species and designing optimal experiments in the application of allometric scaling.     

胰岛素样生长因子-Ⅰ对软骨细胞凋亡的抑制

目的:探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)对软骨细胞增殖及白细胞介素-1(IL-1)诱导软骨细胞凋亡的影响,揭示其抗损伤作用机制,为关节软骨损伤治疗提供理论依据。方法:分离培养人胚胎关节软骨细胞,采用四氮甲基唑蓝(MTT)法测定不同含量软骨细胞增殖活性的变化,利用光镜、电镜、DNA电泳及流式细胞仪测定作为凋亡检测指标。结果:IGF-Ⅰ呈剂量依赖式促软骨细胞增殖,当IGF-Ⅰ含量达50μg/L时,促软骨细胞增殖作用达最大值。IL-1组光镜、电镜下可见典型的细胞凋亡形态学改变,琼脂糖凝胶电泳示特征性的DNA梯状条带,IGF-Ⅰ处理组未见明显凋亡征象。流式细胞仪检测发现,IGF-Ⅰ处理后软骨细胞凋亡率显著降低。结论:IGF-Ⅰ能促进软骨细胞增殖,对IL-1诱导的软骨细胞凋亡具有保护作用。     

Soluble polystyrene derivatives of metal bis(3,4-dicarboxybenzoyl)phthalocyaninates: Synthesis,thermal analysis,and sensitivity towards toxic gases

Polystyrene-bound metal [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]phthalocyaninates were synthesized by Friedel-Crafts reaction of polystyrene with the corresponding metal phthalocyaninates. Co(II) and Cu(II) [2,9 or 2,10 (or 2,16 or 2,17) bis(3,4-dicarboxybenzoyl)]-phthalocyaninate (PS-CodaPc and PS-CudaPc) contained 0,13 mmol · g^?1 (12,4 wt.-%) and 0,13 mmol · g^?1 (12,8 wt.-%) of CodaPc and CudaPc, respectively. They were soluble in N,N'-dimethylformamide, but only partially soluble in chloroform, tetrahydrofuran (THF), dimethyl sulfoxide, N-methyl-2-pyrrolidone, and pyridine. The THF extracts contained 0,12 mmol · g^?1 (11,4 wt.-%) and 0,18 mmol ? g^?1 (17,2 wt.-%) of PS-CodaPc and PS-CudaPc, respectively. The thermal stability of the polymers was studied using thermogravimetric and differential thermal analysis in nitrogen and synthetic air atmosphere. The contents of MdaPc(M: metal) in THF-extracted polymers calculated from the data of residue in thermogravimetric analysis are 0,12 mmol · g^?1 for PS-CodaPc and 0,19 mmol · g^?1 for PS-CudaPc. In addition, the sensitive properties of the polymers towards toxic gases were also investigated by quartz microbalance transducers. The results show that the quartz microbalance sensors coated with both polymers were sensitive to NO₂ and chlorinated hydrocarbons, i.e. chloroform and perchloroethylene. The sensitivity to NO₂ was 6,53 · 10^?7 m³ · mL^?1 · s^?1 for PS-CodaPc and 1,90 · 10^?6 m³ · mL^?1 · s^?1 for PS-CudaPc, and that to chloroform and perchloroethylene was 2,33 · 10^?8 and 4,60 · 10^?8 m³ · mL^?1 · s^?1, respectively, for PS-CodaPc and 4,79 · 10^?8 and 9,51 · 10^?7 m³ · mL^?1 · s^?1 for PS-CudaPc.     

甾体避孕药不增加血栓栓塞性疾病危险(病例对照研究)

本文采用1:3病例对照研究方法,对甾体避孕药的使用与血栓栓塞性疾病(急性心肌梗塞、脑栓塞、脑血栓形成和深静脉血栓形成)间的关联进行多因素分析。结果提示在我国广泛应用的甾体避孕药(主要为国产Ⅰ号避孕药)并不增加血栓栓塞性疾病的危险性。用药和停药时间的长短与血栓栓塞性疾病的发生无关,并与高血压病之间亦不存在协同作用。     

THE EFFECT OF ACUPUNCTURE ON PREVENTION AND TREATMENT OF ISCHEMIC ARRHYTHMIA AND THE RELATION BETWEEN EFFECT OF ACUPUNCTURE AND CHOLINERGIC MUSCARINE-LIKE RECEPTORS

For investigating the effect of acupuncture on ischemic arrhythmia and its mech-anism, adult albino rats with ligated anterior descending branch of coronary artery as experimentalmodel were treated with or without acupuncture, and others with imitative operation but without bothcoronary artery ligation and acupuncture treatment were used as control. It was found in acupuncturegroup that the fibrillation-liability of ischemic myocardium was efficiently decreased, the affinity ofAch-M receptors on membranes of ischemic myocardium was markedly increased, and the tolerance ofischemic myocardium to atropine was elevated in the experiment of atropine inducing fibrillation.These results indicate that acupuncture may play a therapeutic role on ischemic arrhythmia throughactivating the activity of muscarine-like receptors of cholinergic nervous system.     

穿透性角膜移植术后角膜内皮细胞之命运

地２组猴行５。５→５．０ｍｍ穿透性角膜移植术，异种组４只，同种组４只，术前用冷冻创伤＾３Ｈ－ＴｄＲ标记法标记受生角膜内皮细胞，术后１４周摘除眼球，用放射自显影法显示银颗粒的分布。     

严重肺挫伤早期肺泡灌洗液表面活性蛋白变化与肺功能及形态学改变的关系

目的探讨严重肺挫伤及缺血再灌注后早期肺泡灌洗液（BALF）中表面活性蛋白（SP）-A、B、C、D动态变化与肺功能及肺形态学改变的关系。方法75只兔随机分为对照组（A）、肺挫伤组（B）及缺血再灌注组（C）。每组均为25只。检测各组0，1，2，3，4h肺功能变化及BAIF中SP—A、B、C、D含量百分比，进行组织病理学及电镜检查。结果与A组比较，B、C组sSP—A、B、C、D含量百分比明显减少（P〈0．01）；肺功能出现明显的损害且呈持续下降（P〈0．05）；肺泡Ⅱ型细胞电镜及病理学检查呈不同程度的炎症及变性改变。结论严重肺挫伤BALF中SP—A、B、C、D动态变化与肺功能及肺组织病理学改变一致。     

Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.