Cephalic tetanus

Neurocritical Care -     

Why would laser acupuncture improve menopausal symptoms?

O'Brien KA, Varigos E, Black C, Komesaroff PA. Laser acupuncture does not improve menopausal symptoms. Menopause 2010; 17: 636–41.     

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.     

Challenges of Francisella classification exemplified by an atypical clinical isolate

The accumulation of sequenced Francisella strains has made it increasingly apparent that the 16S rRNA gene alone is not enough to stratify the Francisella genus into precise and clinically useful classifications. Continued whole-genome sequencing of isolates will provide a larger base of knowledge for targeted approaches with broad applicability. Additionally, examination of genomic information on a case-by-case basis will help resolve outstanding questions regarding strain stratification. We report the complete genome sequence of a clinical isolate, designated here as F. novicida-like strain TCH2015, acquired from the lymph node of a 6-year-old male. Two features were atypical for F. novicida: exhibition of functional oxidase activity and additional gene content, including proposed virulence determinants. These differences, which could potentially impact virulence and clinical diagnosis, emphasize the need for more comprehensive methods to profile Francisella isolates. This study highlights the value of whole-genome sequencing, which will lead to a more robust database of environmental and clinical genomes and inform strategies to improve detection and classification of Francisella strains.     

老年冠心病患者抑郁与肿瘤坏死因子-α水平有相关性

目的: 调查住院老年冠心病患者的抑郁情绪；初步探讨老年冠心病患者肿瘤坏死因子（TNF）的改变及抑郁对TNF的影响。方法: 连续收集2008年8月～11月住院的老年冠心病患者214例。根据中国精神疾病分类与诊断标准第三版（CCMD-3），将纳入患者分为冠心病并发抑郁组54例，冠心病不伴抑郁组160例。测量各生化指标，ZUNG抑郁自评量表得分和TNF值，观察各组血清TNF水平及血清TNF水平与抑郁得分的相关性。结果: 冠心病并发抑郁症组TNF值高于冠心病非抑郁组（P<0.05）；TNF与抑郁得分呈正相关（r=0.424，P<0.01）。控制白细胞计数与C-反应蛋白后，TNF仍与抑郁得分呈正相关（r=0.344，P=0.000）。结论: 老年冠心病并发抑郁患者TNF水平增高。