不同时辰针刺足阳明胃经中枢效应差异脑功能磁共振成像对比研究

目的探讨不同时辰针刺足阳明胃经后引起的脑功能变化及其各功能区在脑内定位的异同和分布规律,寻找不同时辰针刺同一经络治疗效果差异的中枢原因。方法健康志愿者20名在足阳明胃经开穴和闭穴时配伍电针针刺足三里与上巨虚2个穴位后,进行磁共振脑功能成像检查。结果足阳明胃经开穴组与闭穴组脑功能磁共振成像结果显示,功能被激活信号增高和功能被抑制信号减低脑区有不同。结论脑功能磁共振成像观察到不同时辰针刺后中枢效应的差异。     

针刺治疗坐骨神经痛脑功能磁共振研究进展

针刺治疗坐骨神经痛在临床应用广泛,但其具体作用机制尚不确切.应用功能磁共振成像(Bold-fMRI)技术可以从影像学角度为针刺治疗坐骨神经疼痛提供客观理论依据,进而对针刺治疗坐骨神经痛的中枢机制进行分析与探索.本文对比针刺治疗坐骨神经痛任务态和静息态fMRI相关研究文献进行综述,发现针刺镇痛主要引起与痛觉辨识、疼痛认知...     

脑功能磁共振成像在针刺作用机制研究中的应用

<正>脑功能成像是一种日渐成熟的新兴技术,也是目前为止人类所掌握的唯一无侵入、无创伤、可以精确定位的人脑高级功能动态研究手段[1],它可以实时地反映出针刺过程中人脑功能的变化。针刺疗法作为祖国医学中重要的一部分,其作用机制并不十分明确。因此,脑功能成像技术的应用在针刺作用机制的研究中有着至关重要的意义。本文将近年来脑功能成像在针刺作用机制上的研究情况总结如下。1不同针刺穴位的脑功能成像变化     

电针刺激曲池穴在颈脊髓效应的功能磁共振成像研究

目的应用脊髓血氧浓度相依对比（BOLD）功能成像技术,观察电针刺激曲池穴在颈脊髓磁共振功能成像激活情况。方法 20例健康志愿者,电针刺激曲池穴,使用统计参数图（SPM2）软件得到健康志愿者脊髓内的激活区,观察激活区在矢状位和横断位上的功能成像激活特征。结果 20例受试者颈脊髓功能成像均可以分析出脊髓神经功能激活区,横断面上激活区域主要位于同侧（右侧）脊髓后角,同侧前角及对侧后角也有不同程度激活;矢状面上功能激活区主要位于C4-7,高位颈脊髓C1-2也有少量激活。结论电针刺激右侧曲池穴均可以引起C1-7水平脊髓的功能激活,成像发现矢状位激活区主要位于C4-7,横断位激活区主要位于同侧（右侧）脊髓后角区,激活区域与脊髓神经反射通路基本一致。C1、C2、C3及延髓功能激活区可能是电针刺激曲池穴在颈脊髓的特定后效应功能区,可能提示针灸有复杂的脊髓内神经机制与经络独特的传感通道存在。     

点按丘墟穴诱发脑卒中患者Bechterev屈曲反射的脑部激活效应

目的利用fMRI技术研究点按穴位法、常规方法诱发Bechterev屈曲反射法对脑功能重朔的影响。方法选择2014年4月~2015年9月期间,福建中医药大学附属康复医院住院和门诊符合纳入标准23例右脑脑卒中的患者,先后随机用点穴法及常规方法诱发左下肢Bechterev屈曲反射为刺激模式,采用组块设计,使用f MRI检测,利用spm8和xjview软件数据分析。结果本研究两种方法均以激活右侧大脑和左侧小脑为主;点穴方法对脑的激活主要有双侧小脑、双侧枕叶、双侧额叶、双侧颞叶,右中央旁小叶、右顶下小叶;常规方法对脑的激活主要有双侧小脑、双侧枕叶、双侧额叶,右中央旁小叶、右顶下小叶;点穴方法同常规方法比较,点穴方法激活脑区为左颞中回、右颞上回、右颞中回,常规方法未激活上述脑区,激活脑区结果差异有统计学意义(P<0.01,K>10)。结论本研究两种手法均能促进脑卒中患者脑部功能重组;点穴方法比常规手法更具有广泛激活效应,其更易激发Bechterev屈曲反射的机制可能是点穴手法促进颞叶功能区对运动功能的补偿。     

面部表情刺激脑功能磁共振成像研究进展

目的功能性磁共振在面部表情及情感疾病方面研究中的应用。方法参阅大量相关文献。结果与结论面部表情刺激脑功能磁共振成像能以最小限度认知的任务来研究自主情感反应的神经基础。     

功能磁共振成像在运动区脑胶质瘤的临床应用

目的 探讨功能磁共振成像(fMRI)在运动区脑胶质瘤的临床应用价值.方法 13例脑胶质瘤患者(治疗组)术前行常规MRI和fMRI检查,根据术前肿瘤影像学评估,分别设计手术方案切除肿瘤,并行术后随访.10例正常志愿者进行常规MRI和fMRI检查作为正常对照(对照组).结果 治疗组fMRI表现为手运动功能区被挤压、移位；对照组fMRI表现为手运动功能区显示良好.术后两周随访,治疗组患者Karnofsky评分恢复至平均95分,与术前比较有统计学差异(P＜0.05).结论 fMRI对邻近脑运动功能区胶质瘤患者手术前评价具有重要临床意义,可指导外科治疗,提高手术疗效,减少术后并发症.     

Effects of polyoxyethylene (40) stearate on the activity of P-glycoprotein and cytochrome P450

The present study was aimed to investigate the effects of polyoxyethylene (40) stearate (PS), a non-ionic surfactant, on the activity of P-glycoprotein (P-gp) and six major cytochrome P450 (CYP) isoforms. An in vitro diffusion chamber system was utilized to estimate the effects of PS concentration on the transport characteristics of Rhodamine 123 (R123) and Rhodamine 110 (R110), a standard P-gp substrate and nonsubstrate, respectively, across the excised intestinal segments of rat. Caco-2 cells were cultured to investigate the mechanisms by estimating the effects of PS on intracellular ATP levels, P-gp ATPase activity and membrane fluidity. The obtained results showed that PS inhibited P-gp mediated efflux in a concentration-dependent manner mainly by modulating substrate-stimulated P-gp ATPase activity. On the other hand, human liver microsomes were utilized to examine the inhibitive potential of PS on six major CYP isoforms. Inhibitive potential on two of these CYP2C9 and CYP2C19 was found to be clinically significant. In conclusion, PS is potentially useful as a pharmaceutical ingredient to improve the oral bioavailability of coadministered P-gp substrates and substrates for certain CYP isoforms.     

Progress in the discovery and development of small-molecule modulators of G-protein-coupled receptor 40 (GPR40/FFA1/FFAR1): an emerging target for type 2 diabetes

Background: The family of G-protein-coupled receptors (GPCRs) serves as the target for almost a third of currently marketed drugs and provides the predominant mechanism through which extracellular factors transmit signals to the cell. GPCRs have been proved to be good therapeutic targets for metabolic disorders. In recent years, a number of companies have been actively involved in the discovery of small-molecule modulators of the GPR40 (FFA1) receptor. However, to date, no critical, comprehensive review on small-molecule modulators of GPR40 (FFA1) has been published. Objective: To review the discovery and development of small-molecule GPR40 (FFA1) agonists/antagonists by different research groups and to classify them based on the key structural features. Method: Systematic search, analysis, and summary of the publication and patent literature for small-molecule modulators of the GPR40 (FFA1) receptor to June 2008. The patent information for this review is drawn from the Integrity Prous, Scifinder, Esp@cenet, and freepatentonline.com databases. Conclusion: The para-substituted phenyl propionic acid scaffold has emerged as a common structural motif found in many GPR40 (FFA1) agonists, and compounds having an aromatic ring and a group capable of releasing a cation have exhibited excellent GPR40 (FFA1) agonistic activity. Several small-molecule agonists of GPR40 (FFA1) have been discovered, which offer a great promise in the treatment of type 2 diabetes.     

Bis(acetylacetonato)-oxidovanadium(IV) inhibits isoproterenol-induced lipolysis in insulin-resistant 3T3-L1 adipocytes by reducing phosphorylation of perilipin and hormone-sensitive lipase

Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus (T2DM), and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis(acetylacetonato)-oxidovanadium (IV) (VO(acac)₂) could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO(acac)₂ were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO(acac)₂ might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.     

Developmental toxicity of perfluorooctane sulfonate (PFOS) is not dependent on expression of peroxisome proliferator activated receptor-alpha (PPARα) in the mouse

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of perfluorinated compounds. Both are environmentally persistent and found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in laboratory rodents. Exposure to these chemicals in utero delays development and reduces postnatal survival and growth. Exposure to PFOS on the last 4 days of gestation in the rat is sufficient to reduce neonatal survival. PFOS and PFOA are weak agonists of peroxisome proliferator activated receptor-alpha (PPARα). The reduced postnatal survival of neonatal mice exposed to PFOA was recently shown to depend on expression of PPARα. This study used PPARα knockout (KO) and 129S1/SvlmJ wild type (WT) mice to determine if PPARα expression is required for the developmental toxicity of PFOS. After mating overnight, the next day was designated gestation day (GD) 0. WT females were weighed and dosed orally from GD15 to 18 with 0.5% Tween-20, 4.5, 6.5, 8.5, or 10.5 mg PFOS/kg/day. KO females were dosed with 0.5% Tween-20, 8.5 or 10.5 mg PFOS/kg/day. Dams and pups were observed daily and pups were weighed on postnatal day (PND) 1 and PND15. Eye opening was recorded from PND12 to 15. Dams and pups were killed on PND15, body and liver weights recorded, and serum collected. PFOS did not affect maternal weight gain or body or liver weights of the dams on PND15. Neonatal survival (PND1–15) was significantly reduced by PFOS in both WT and KO litters at all doses. WT and KO pup birth weight and weight gain from PND1 to 15 were not significantly affected by PFOS exposure. Relative liver weight of WT and KO pups was significantly increased by the 10.5 mg/kg dose. Eye opening of PFOS-exposed pups was slightly delayed in WT and KO on PND13 or 14, respectively. Because results in WT and KO were comparable, it is concluded that PFOS-induced neonatal lethality and delayed eye opening are not dependent on activation of PPARα.     

双(α-呋喃甲酸)氧钒对胰岛素抵抗3T3-L1脂肪细胞糖摄取的影响

目的探讨新型的有机羧酸氧钒配合物双(α-呋喃甲酸)氧钒(BFOV)对正常及胰岛素抵抗的3T3-L1脂肪细胞糖摄取的影响。方法采用地塞米松诱导3T3-L1脂肪细胞建立胰岛素抵抗的细胞模型,研究双(α-呋喃甲酸)氧钒对正常及胰岛素抵抗3T3-L1脂肪细胞葡萄糖消耗的影响。结果双(α-呋喃甲酸)氧钒(2.5μmol·L-1~40μmol·L-1)对正常的3T3-L1脂肪细胞仅有增加葡萄糖消耗量的趋势,与空白对照组比较,差异无显著性;但能明显增加地塞米松诱导的胰岛素抵抗3T3-L1脂肪细胞的葡萄糖消耗量,改善模型细胞的胰岛素抵抗状态。结论双(α-呋喃甲酸)氧钒能促进胰岛素抵抗脂肪细胞的葡萄糖摄取,改善胰岛素抵抗状态。     

meso-4(4-甲基,3-磺基苯基)卟啉分光度法测定葡萄糖酸锌含量

本文研究了在碱性介质中,利用锌(Ⅱ)与-meso-4(4-甲基,3-磺基苯基)卟啉(TTPS4)的显色反应,采用分光光度法测定葡萄糖酸锌的含量.结果表明:在pH为9.80的NH3～NH4Cl缓冲液中,利用Hg(Ⅱ)作催化剂、CTMAB为辅助配位剂,在室温5 min内,TTPS4与Zn(Ⅱ)形成很稳定的Zn-TTPS4-CTMAB三元配合物,ε432＝2.0×105.Zn(Ⅱ)浓度在0～0.18 μg·ml-1范围内遵守比耳定律.应用本法直接测定补锌口服液葡萄酸锌含量,结果满意.     

3''取代吲哚类衍生物诱导HL-60细胞凋亡的实验研究

目的：研究3-吲哚乙基(3’-甲基-2’-酮)戊酰胺诱导HL-60细胞凋亡的作用机制。方法：用DNA琼脂糖凝胶电泳和流式细胞仪分析3-吲哚乙基(3’-甲基-2’-酮)戊酰胺对HL-60细胞的凋亡诱导作用,检测天冬酰胺特异酶切的半胱氨酸蛋白酶(Caspase)-8和Caspase-3活性来研究其对HL-60细胞的凋亡诱导途径,并通过间接免疫荧光技术检测其对Bcl-2表达的影响。结果：1．8％DNA琼脂糖凝胶电泳可观察到清晰的“DNA ladder”,流式细胞仪检测3-吲哚乙基(3’-甲基-2’-酮)戊酰胺对HL-60细胞具有明显的凋亡诱导作用。Caspase活性检测表明,Csapase-3活性明显升高而Caspase-8活性无明显变化。流式细胞仪分析表明Bcl-2的表达随着受试物浓度的升高而下降。结论：3-吲哚乙基(3’-甲基-2’-酮)戊酰胺可诱导HL-60细胞凋亡,其诱导凋亡与Bcl-2表达及Caspase-3活性有关。     

Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (–)-epigallocatechin-3-O-gallate

The molecular mechanism of inhibition of human catechol-O-methyltransferase (COMT) by (–)-epigallocatechin-3-O-gallate (EGCG), which is a modest substrate of COMT but an ultra-potent inhibitor of this enzyme, was studied. EGCG has an IC₅₀ value of 70 nM for inhibiting human liver COMT-mediated O-methylation of 2-hydroxyestradiol, which was 210–760 times more potent than catechin, epigallocatechin and epicatechin. Kinetic analyses showed that EGCG had a strong component of non-competitive inhibition of the O-methylation of 2-hydroxyestradiol. Computational molecular modelling studies showed that the B- and D-rings of EGCG can bind tightly to the human COMT in four different modes (i.e. D-para-OH, D-meta-OH, B-para-OH, and B-meta-OH). The binding geometry of EGCG in these binding modes was found to be less than ideal to form perfect Mg²⁺ coordination for the catalysis of its own methylation. It is concluded that the very tight binding interaction of EGCG with COMT makes it a potent non-competitive inhibitor, but its imperfect geometry makes it a poor substrate for methylation by this enzyme.     

Determination of some metal ions by flame-AAS after their preconcentration using sodium dodecyl sulfate coated alumina modified with 2-hydroxy-(3-((1-H-indol 3-yle)phenyl) methyl) 1-H-indol (2-HIYPMI)

Selective, sensitive and efficient methods for preconcentration of trace amounts of metal ions including Cr³⁺, Cu²⁺, Zn²⁺ and Ni²⁺ ions by incorporation of 2-hydroxy-(3-((1-H-indol 3-yle)phenyl) methyl) 1-H-indol (2-HIYPMI) on SDS-A has been reported. The proposed methods are based on the uptake of chelate of under study metal ions with these new ligands loaded on SDS-A. The influences of the analytical parameters including pH, ligand and SDS amount, eluting solution (type and concentrations) and sample volume on metal ions recoveries were investigated. The extraction efficiency was >95% with relative standard deviation lower than 5%. The method has been successfully applied for the extraction and determination of these ions content in some real samples.     

新型抗生素葡糖脱乙酰基酶LpxC抑制剂研究进展

革兰阴性菌耐药性已经严重威胁人类健康，亟需开发新作用机制的抗菌药物。UDP-3-O-(R-羟基十四酰)-N-乙酰氨基葡糖脱乙酰基酶(LpxC)是催化合成革兰阴性菌外膜脂多糖主要成分类脂A的关键酶，在革兰阴性菌中具有较高的同源性，与哺乳动物(包括人)的各种酶都没有共同序列。LpxC的缺失或过表达都会使某些革兰阴性致病菌死亡，这使其成为具有开发前景的抗革兰阴性菌药物的全新靶标。为此，本文综述了LpxC的结构、酶学性质、催化机理及其抑制剂等研究进展。