溪黄草口服液制备工艺研究

目的：制备质量稳定,澄清的溪黄草口服液。方法：以口服液中总黄酮含量为指标,用正交试验优选撮提取工艺,用甲壳质与乙醇作澄清工艺比较优选澄清工艺。结果：溪黄草加水１５倍,提取３次,每次１ｈ,用３５０ｐｐｍ浓度甲壳质吸附澄清,总黄酮含量高、稳定性好。结论：用水提聚、甲壳质吸附澄制备的口服液质量稳定、澄明度好。     

Tyrosinase gene (TYR) mutations in Chinese patients with oculocutaneous albinism type 1

Background: To identify the sequence variants of the tyrosinase (TYR) gene in Chinese families with oculocutaneous albinism. Methods: Three families with oculocutaneous albinism type 1 and 95 unrelated healthy Chinese individuals with normal pigmentation were screened for mutations in the TYR gene by direct sequencing. Computational algorithms were used to characterize the biological significance of the mutants. Results: Four previously reported mutations (R299C, R299H, W400L and frame‐shift c.930insC) and one novel mutation (F214del) were identified, and probands had homozygous or compound heterozygous TYR mutant alleles. None of the mutants were identified among the 95 normal control subjects. Computational analysis predicted that the R299C mutant inactivates the tyrosinase enzyme by misfolding of protein tertiary structure and/or retention of the misfolded tyrosinase within the endoplasmic reticulum, and F214del causes dysfunction of tyrosine enzyme by affecting the copper binding sites and altering substrate orientation and electronic transfers during catalytic reactions for melanosynthesis. Conclusion: We have identified five different TYR mutations, including one novel mutation, which caused oculocutaneous albinism type 1 in Chinese. Further analysis of the patients will be useful to determine the effects of these mutations on the tyrosinase activities.     

K-Ⅱ和U-50488H对κ阿片受体亲和力的比较

3,4-二氯-N-甲基-N-[反式-2-(1-△³-吡咯啉基)环己基]苯乙酰胺(K-Ⅱ)是新合成的U-50488H类似物,其对小鼠的镇痛效应和对离体兔输精管的抑制作用均比U-50488H强。本文用放射受体结合试验方法对这两种化合物在富含x阿片受体的豚鼠小脑和大脑皮层前叶上的亲和力进行了比较,并求出这两种化合物的Ki值.结果表明K-Ⅱ对k阿片受体的亲和力比U-50488H强6～42倍。K-Ⅱ对阿片受体亚型选择性比较研究正在进行中。     

7-酰氨基-3-(1,2,3-三唑甲基)头孢菌素衍生物的合成及其抗菌活性

本文以青霉素G扩环而得的7-苯乙酰氨基-3-甲基-3-头孢烯-4-羧酸(Ⅰ)为原料,合成了12个C₃位上有1,2,3-三唑甲基取代的新头孢菌素衍生物(Ⅷ_1～12),并经分析确证了各化合物的结构。体外抑菌试验结果表明,其中6个化合物,即Ⅶ_2～4,9～11,不仅对革兰氏阳性菌有较高的抑制作用。而且对革兰氏阴性菌也有高度敏感性。     

A common intracellular allosteric binding site for antagonists of the CXCR2 receptor

Background and purpose:

We have previously shown that SB265610 (1-(2-bromo-phenyl)-3-(7-cyano-3H-benzotriazol-4-yl)-urea) behaves as an allosteric, inverse agonist at the C-X-C chemokine (CXCR)2 receptor. The aim of this study was to determine whether SB265610, in addition to two other known antagonists, bind to either of the two putative, topographically distinct, allosteric binding sites previously reported in the Literature.

Experimental approach:

Ten single point mutations were introduced into the CXCR2 receptor using site-directed mutagenesis. Three CXCR2 antagonists were investigated, SB265610, Pteridone-1 (2-(2,3 difluoro-benzylsulphanyl)-4-((R)-2-hydroxy-1-methyl-ethylamino)-8H-pteridin-7-one) and Sch527123 (2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5-methyl-furan-2-yl)-propyl]amino]-3,4-dioxo-cyclobut-1enylamino}-benzamide), and the effect of these mutations on their binding affinity and ability to inhibit interleukin-8-stimulated binding of [³⁵S]GTPγS was examined.

Key results:

Seven of the nine mutations introduced into the C-terminal domain and intracellular loops of the receptor produced a significant reduction in affinity at least one of the antagonists tested. Of those seven mutations, three produced a significant reduction in the affinity of all three antagonists, namely K320A, Y314A and D84N. In all but one mutation, the changes observed on antagonist affinity were matched with effects on inhibition of interleukin-8-stimulated [³⁵S]GTPγS binding.

Conclusions and implications:

These antagonists bind to a common intracellular, allosteric, binding site of the CXCR2 receptor, which has been further delineated. As many of these mutations are close to the site of G protein coupling or to a region of the receptor that is responsible for the transduction of the activation signal, our results suggest a molecular mechanism for the inhibition of receptor activation.     

Minimally Invasive Surgery Future Perspectives

Following the advances in diagnostic endoscopy in the 1970＇s, therapeutic endoscopy in the 1980＇s and laparoscopic surgery in the 1990＇s the next break-through in endoscopic treatment is likely to be in the form of endoscopic surgery through natural orifices （NOTES）. The development of endoscopic mucosal resection （EMR） of early cancers may be considered the first step in this direction.     

Asperger's Disorder,Criminal Responsibility and Criminal Culpability

In the seminal 2002 case of Atkins v. Virginia, the United States Supreme Court held that executing the mentally retarded violates the Eighth Amendment's ban on cruel and unusual punishment. The Court did not set forth guidelines for defining mentally retarded and instead left it to the states to define the issue individually. State definitions for mental retardation or intellectual disability were examined, including documentation of procedures for Atkins claims. Results indicated significant differences between states in definitions and procedures. Not all states had a statutory ban on executing the mentally retarded, and while most states subscribed to a three-pronged definition modeled after clinical psychiatric definitions, most failed to operationalize the prongs. Additionally, states differed on the burden of proof required to show mental retardation, which party bears that burden, the timing of the showing, who makes the determination of mental retardation, and the standard used to review the determination. In addition to documenting definitions of mental retardation and criminal procedures for Atkins claims in states with the death penalty, this study sought to identify an ideal definition for intellectual disability in capital cases. While aspirational, a single definition would better satisfy the mandate of the Atkins decision by providing consistent protection to criminal defendants across states.