FK228抑制EPO介导的人红系前体细胞的增殖与分化

目的:探讨组蛋白脱乙酰化酶抑制剂FK228在红细胞生成素(EPO)介导的人红系前体细胞增殖与分化中的调节作用。方法:从经粒细胞集落刺激因子动员的肿瘤患者外周血单核细胞中分离CD34 细胞,用含干细胞生长因子(SCF)、EPO或SCF IL-3及不同浓度FK228的无血清培养基培养7d,分别用抗GPA及抗CD36单克隆抗体(mAb)染色并行流式细胞术检测;将CD34 细胞用含SCF IL-3的无血清培养基培养7d,分离CD36 GPA-细胞,将细胞用含有EPO FK228的无血清培养基培养7d,并行细胞计数;将CD36 GPAlow/-细胞用含EPO加或不加FK228的无血清培养基培养,并进行annexin V和PI染色。结果:FK228以一种剂量依赖方式抑制CD36 GPAhigh、CD36 GPAlow和CD36 GPA-细胞的产生;FK228可诱导CD36 GPAhigh和CD36 GPAlow/-细胞在含EPO的培养基中发生细胞凋亡。结论:FK228可抑制EPO介导的人红系前体细胞的增殖与分化。     

血脂康与烟酸肌醇酯调脂疗效比较

目的：探讨血脂康的调脂疗效。方法：对８４例原发性高脂血症患随机分为血脂康组和烟酸肌醇酯组,。服用血脂康组４４例,酸肌醇酯组４０例,观察用药８周（ｗｋ）后血脂变化,并对二进行比较。结果：显示血脂康有较好的调脂（降ＴＣ、ＴＧ、ＴＣ－ＨＤＬ－ｃｈ／ＨＤＬ－ｃｈ及升ＨＤＬ－ｃｈ）作用,且优于烟酸肌醇酯。结论：提示血脂康调脂职效确切,服用方便,副作用少,可作为较好的临床调脂药物推广使用。     

槲皮素,异鼠李素对Cu^2＋介导的LDL氧化修饰的抑制作用

目的：观察槲皮素（Ｑｕｅ）、异鼠李素（Ｉｓｏ）对Ｃｕ＾２＋介导的低密脂蛋白（ＬＤＬ）氧化修饰的影响。方法：采用一次性密度梯度离心法分离正常人血浆脂蛋白,用Ｃｕ＾２＋进行体外氧化修饰,温育前加不同浓度的Ｑｕｅ及Ｉｓｏ。检测脂蛋白中脂质过氧化物（ＬＰＯ）、维生素Ｅ（ＶｉｔＥ）含量及超氧化物歧化酶（ＳＯＤ）活性。结果：在Ｃｕ＾２＋与ＬＤＬ温育前加入Ｑｕｅ、Ｉｓｏ可使ＬＤＬ中ＬＰＯ生成减少,明显延缓 ,Ｖ     

Hydrophobic Bombyx mori Silk Fibroin: Routes to Functionalization with Alkyl Chains

Bombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid- and solid-phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop-casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid-state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features.     

Polyether Synthesis through Reductive Etherification Reaction Strategy

The reductive etherification reaction (RER) of carbonyl groups (aldehydes or ketones) through silane as a reducing agent together with Bronsted or Lewis acid affords the synthesis of symmetrical and unsymmetrical ethers. This strategy is applied at the macromolecular level for the first time in 1993, and isophthalaldehyde is self-polymerized in the presence of triethylsilane (Et₃SiH)/ tritylperchlorate (TrClO₄) to yield polyethers with low to moderate molecular weights. Next, the polyethers with alternating structures are achieved by reacting isophthalaldehyde with bis(trimethylsilyl) ethers or diols as comonomers using reducing agent silane and Lewis acid. Moreover, in recent years, it is shown that polyether synthesis and post-polymerization modification (PPM) of polymers proceeds smoothly and effectively with the RER strategy in the presence of chlorodimethylsilane (CDMS), which acts as both a reducing agent and a Lewis acid.     

磷改性层柱交联累托石催化剂的积炭性能

采用有机磷化合物对层柱交联累托石催化剂进行了改性研究。考察了有机磷化合物的加入对催化剂轻瓦斯油裂化活性和积炭性能的影响。结果表明：含有适量磷化合物的层柱交联累托催化剂,焦炭产率可降低３０％,轻瓦斯油在层柱交联累托石催化剂上的裂化反应和积炭反应是并行的,而裂化活性仍保持不变。磷化合物的加入使层柱交联累托石催化剂的Ｂ酸强度增加,但积炭反应主要不是由Ｂ酸强度决定,而是与强弱Ｂ酸中心数目的比例以及Ｂ酸和Ｌ     

Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat

This study examined the effect of a pharmacologically induced rightward shift in the partial pressure of oxygen at which 50% of hemoglobin is saturated (P50) on outcome from transient focal cerebral ischemia in the rat. Halothane anesthetized rats (n=20 per group) were given saline or a single 15-min infusion of 150 mg/kg RSR13 (2-[4-[[3,5-dimethylanilino) carbonyl]methyl]phenoxy]-2-methylproprionic acid) intravenously before or 30 min after onset of 75 min of middle cerebral artery filament occlusion (MCAO). Seven days later, severity of hemiparesis and cerebral infarct size were examined. RSR13 alone did not significantly improve outcome. Conscious normothermic rats (n=12 per group) were also given RSR13 (150 mg/kg) or 0.9% NaCl intravenously and subjected to 75 min of MCAO with 7 days of recovery. Again, RSR13 alone did not significantly reduce infarct size or improve neurologic score. A dose-response curve for dizocilpine (MK-801) was then constructed in conscious normothermic rats subjected to 75 min of MCAO. Dizocilpine (0.5 mg/kg i.v.) caused a 90% reduction in mean infarct size while 0.25 mg/kg reduced infarct size by 48%. Other rats were then subjected to 75 min of MCAO after being given dizocilpine (0.25 mg/kg i.v.; n=18) or RSR13 (150 mg/kg i.v. )+dizocilpine (0.25 mg/kg i.v.; n=15). RSR13+dizocilpine resulted in smaller cortical infarct volume (8+/-14 mm3 vs. 34+/-37 mm3, p<0.02) and total cerebral infarct volume (46+/-28 mm3 vs. 81+/-60 mm3, p<0. 05) compared to dizocilpine alone, respectively. We conclude that a pre-ischemic peak increase in P50 of approximately 25 mmHg alone is insufficient to reduce focal ischemic injury, but may be advantageous when used in conjunction with other neuroprotective agents.     

反义寡核苷酸的化学修饰

反义技术是近20年来发展的一种全新的药物设计方法。本文就近几年来反义寡核苷酸在化学修饰方面，包括骨架修饰、糖环修饰、碱基修饰等的最新发展进行了综述。     

A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels.

Toxins from cone snail (Conus species) venoms are multiple disulfide bonded peptides. Based on their pharmacological target (ion channels, receptors) and their disulfide pattern, they have been classified into several toxin families and superfamilies. Here, we report a new conotoxin, which is the first member of a structurally new superfamily of Conus peptides and the first conotoxin affecting vertebrate K+ channels. The new toxin, designated conotoxin ViTx, has been isolated from the venom of Conus virgo and comprises a single chain of 35 amino acids cross-linked by four disulfide bridges. Its amino acid sequence (SRCFPPGIYCTSYLPCCWGICCSTCRNVCHLRIGK) was partially determined by Edman degradation and deduced from the nucleotide sequence of the toxin cDNA. Nucleic acid sequencing also revealed a prepropeptide comprising 67 amino acid residues and demonstrated a posttranslational modification of the protein by releasing a six-residue peptide from the C-terminal. Voltage clamp studies on various ion channels indicated that the toxin inhibits the vertebrate K+ channels Kv1.1 and Kv1.3 but not Kv1.2. The chemically synthesized product exhibited the same physiological activity and identical molecular mass (3933.7 Da) as the native toxin.