胍

Dr Gregg Fonarow, Eliot Corday Professor of Cardiovascular Medicine at UCLA and coauthor of this study, noted, Experimental studies suggest that metformin improves myocardial function via activation of a signaling mechanism (AMP-activated protein kinase) independent of antihyperglycemic effects.

另两位合作研究者，加州大学洛杉矶分校心血管内科教授Gregg Fonarow博士和Eliot Corday博士还提到："实验室研究提示，二甲双胍改善心肌功能是通过激活了一种不同于降糖作用的信号机制（AMP-活化的蛋白激酶）"这些研究结果共同提示，二甲双胍可能具有心脏保护作用，这一作用是通过在分子水平增强心脏功能来实现的。

On the basis of the kinetic equation of substrate reaction in the presence of urea or guanidine hydrochloride, all microscopic kinetic constants for the free enzyme and enzyme-substrate binary and ternary complexes have been determined. The results of the present studies indicate that:①In the presence of urea or guanidine hydrochloride, enzyme-substrate complexes lose their activity less rapidly than the free enzyme. Therefore, both substrates, NADPH and 7, 8-dihydrofolate, protect dihydrofolate reductase against inactivation.②The denaturation of dihydrofolate reductase by urea follows single-phase kinetics, and changes in enzyme activity and tertiary structure proceed simultaneously in the unfolding process, so it may be an"all or none"process.③The GdnHCl-induced unfolding of the dihydrofolate shows a biphasic transition, while the change in the enzyme activity is a single exponential process. The rate constant of inactivation is consistent with that of the fast conformational change. Therefore, the kinetic intermediate of protein unfolding should be a partially folded and inactive form.

我们根据在脲或盐酸胍存在下的底物反应动力学方程求得游离酶和酶底物二元、三元复合物的微观动力学常数，结果表明：①酶-底物二元、三元复合物的失活速度明显慢于游离酶，说明两个底物二氢叶酸和NADPH对酶的失活都具有一定程度的保护作用；②在脲作用下，酶的失活和构象变化均为单指数项过程，而且酶的活力丧失和三级结构变化是同时发生的，说明二氢叶酸还原酶的脲变性可能是一个"全或无"的两态过程；③在盐酸胍作用下，酶的构象变化为两相过程，而失活则是单指数项过程，酶分子构象变化的快相速度常数与失活速度常数基本一致，因此我们认为二氢叶酸还原酶的盐酸胍变性过程中存在一个没有活力、但仍具备一定空间结构的变性中间体。

Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose leel aboe preprandial alues (mean postprandial incremental area under the cure ).

相反，使用2，000-mg二甲双胍缓释片的治疗组糖化血红蛋白水平有显著下降(–1.06%)， 2，000mg二甲双胍缓释片治疗组与速效二甲双胍片治疗组比，糖化血红蛋白水平平均值相差–0.36% [98.4% CI –0.65 to –0.06]。

This review will summarize several aspects concerning the distribution of agmatine and NMDA receptors in the central nervous system, the binding sites of agmatine on NMDA receptors as well as the pharmacological functions closely associated with NMDA receptors.

本文就胍丁胺与NMDA受体在中枢神经系统的分布、胍丁胺在NMDA受体上的作用位点以及胍丁胺通过NMDA受体介导的药理作用等几个方面进行了综述。

Results The highest drug use frequency was biguanide. There was 50.9% in the oral antidiabetic drug combination. Leading the first 3 places on the list of drug combination were sulfonylureas in combination with biguanide, sulfonylureas in combination with α-Glycosidace inhibitor, biguanide in combination with α-Glycosidace inhibitor, while there was 16.1% in 3 kinds combination. When oral antidiabetic drugs were combined with other drugs, combination with antihypertensives drugs led the fist, while with antihypertensives drugs led the second.

结果 二甲双胍使用频率最高，口服降糖药联合用药的比例高达50.9%，居前3位的依次是磺脲类＋双胍类、磺脲类＋α-葡萄糖苷酶抑制剂和双胍类＋α-葡萄糖苷酶抑制剂，而3种以上口服降糖药联合用药的比例也达16.1%；口服降糖药与其他药物联合使用情况看，配合使用抗高血压药的频率最高，其次是降脂药。

Inactivation of the enzyme folioed an elhance of GndHClconcentlation. Half of the ovelall reaction activity was lost within l.5 Ininuthe in 0.54Inol/LGndHO, and 5% achvity remained at the end of inachvation.

在低浓度盐酸胍溶液中该酶的全反应活性和其中两个还原部位单独活性被同步可逆抑制，随着胍浓度增高，出现不可逆失活且程度和速度均迅速提高，在0.54mol／L胍中该酶全反应活性在1.5分钟内已有一半不可逆丧失，终态只余约5％活性。

This is a special reaction of arginine's carbamidine, which is useful in quantitating and determining the natures of protein and the amino acid.

这是由于蛋白质分子中精氨酸胍基的特征反应。许多胍的衍生物如胍乙酸、胍基丁胺等也发生此反应。

The results of its intrinsic fluorescence spectroscopy and fluorescence phase diagram showed that when the guanidine hydrochloride concentration in denaturation solution was about 1.0 mol/L, there existed a partially folded intermediate of Bacillus amyloliquefaciens a-amylase during its unfolding procedure, which followed a three-state model; the result of its fluorescence probe showed that when the guanidine hydrochloride concentration in denaturation solution was about 1.0 mol/L, there existed some stable hydrophobic regions, which could interact with a hydrophobic reagent 8-anilino-1-naphthalene sulfonic acid, in the partially folded intermediate of Bacillus amyloliquefaciens a-amylase; and the results of fluorescence quenching using acrylamide and potassium iodide as quenchers showed the distribution of Trp residues in Bacillus amyloliquefaciens a-amylase in different denaturation solution, with the maximum number (8) of tryptophan residues in a partially folded intermediate Bacillus amyloliquefaciens a-amylase molecule could be quenched by potassium iodide; and the results of their protein electrophoresis and SEC showed that no aggregate or aggregate precipitation of Bacillus amyloliquefaciens a-amylase formed during the whole unfolding procedure of Bacillus amyloliquefaciens a-amylase induced by guanidine hydrochloride.

内源荧光光谱和荧光相图结果表明，当变性液中盐酸胍浓度约为1.0 mol/L时，芽孢杆菌a-淀粉酶的去折叠过程中出现一个部分折叠中间体，其去折叠过程符合&三态模型&；荧光探针结果表明，在溶液中盐酸胍浓度约为1.0 mol/L时，中间态芽孢杆菌a-淀粉酶分子中存在着能够与探针分子1-苯胺基-8-萘磺酸结合的稳定的疏水区域；荧光猝灭研究给出了不同程度变性的淀粉液化芽孢杆菌a-淀粉酶中的Trp的分布情况，结果表明中间态芽孢杆菌a-淀粉酶分子中能够被碘化钾猝灭的位于分子表面的色氨酸残基数目达到最大的8个；蛋白电泳和体积排阻色谱结果表明，在盐酸胍诱导的芽孢杆菌a-淀粉酶分子的整个去折叠过程中，不会以共价键或非共价键形式形成芽孢杆菌a-淀粉酶分子之间的集聚体或集聚体沉淀。

The results of its fluorescence probe showed that when the guanidine hydrochloride concentration in denaturation solution was about 1.0 mol/L,there existed some stable hydrophobic regions,which could interact with a hydrophobic reagent 8-anilino-1-naphthalene sulfonic acid,in the partially folded intermediate of Bacillus amyloliquefaciensα-amylase;with the denaturation concentration increasing,the stable hydrophobic regions disappered.the results of fluorescence quenching using acrylamide and potassium iodide as quenchers showed that using acrylamide as quenchers,with the protein denaturation extent increasing,the number of Trp that can be quenched increased untill all the Trp residues were quenched;Using potassium iodide as quenchers,with the maximum number(8) of tryptophan residues in a partially folded intermediate Bacillus amyloliquefaciensα-amylase molecule could be quenched by potassium iodide;with the denaturation concentration increasing,the number of Trp that can be quenched decreased to 5.the results of their protein electrophoreses and SEC showed that no aggregate or aggregate precipitation of Bacillus amyloliquefaciensα-amylase formed during the whole unfolding/refolding procedure of Bacillus amyloliquefaciensα-amylase induced by guanidine hydrochloride or urea.

ANS外源荧光探针结果表明：盐酸胍诱导的芽孢杆菌α-淀粉酶分子去折叠过程中存在着能够与探针分子1-苯胺基-8-萘磺酸结合的稳定的疏水区域；而随着芽孢杆菌α-淀粉酶分子在盐酸胍溶液中变性程度的加深，这一疏水区域逐步被瓦解。丙烯酰胺和碘化钾猝灭结果表明：在盐酸胍溶液中，随着芽孢杆菌α-淀粉酶分子变性程度的进一步加深，其分子内能够被丙烯酰胺接近的色氨酸残基逐渐增多，直至全部被猝灭。但位于芽孢杆菌α-淀粉酶分子表面的能够被碘化钾猝灭的色氨酸残基，在中间态芽孢杆菌α-淀粉酶分子中数目达到最大的8个，而随着其分子变性程度的进一步加深，反而减少至5个。

Results:Osteoblasts has the ability of transmembrane transport of metformin. The transport of metformin could be saturable with time and drug concentration adding;a certain range of temperature and pH can promote the transport of metformin;The transport of metformin was inhibited by cimetidine and phenformin,but promoted by verapamil;Oct1 but no Oct2 was expressed extensively in cell membrane and cytoplasm of osteoblasts;The protein level of Oct1 can be up-regulated by metformin with different drug concentrations and times,but no obvious differentces from each group.

结果：二甲双胍能够在成骨细胞上进行跨膜转运，且随着转运时间和药物浓度的增加而增加，并可达到饱和；一定范围内提高温度和pH值可以促进二甲双胍的转运；西米替丁和苯乙双胍对二甲双胍转运有明显抑制作用，而维拉帕米则对转运有明显的促进作用；Oct1广泛表达在成骨细胞的胞膜及胞浆中，而Oct2无表达；二甲双胍在不同浓度及不同给药时间均能够上调Oct1的表达，但各组间无明显差别。

Breath, muscle contraction of the buttocks; arch body, as far as possible to hold his head, right leg straight towards the ceiling (peg-leg knee in order to avoid muscle tension).

呼气，收缩臀部肌肉；拱起身体，尽量抬起头来，右腿伸直朝向天花板（膝微屈，以避免肌肉紧张）。

The cost of moving grain food products was unchanged from May, but year over year are up 8%.

粮食产品的运输费用与5月份相比没有变化，但却比去年同期高8％。