Staphylococcus aureus Formyl-Methionyl Transferase Mutants Demonstrate Reduced Virulence Factor Production and Pathogenicity

Inhibitors of peptide deformylase (PDF) represent a new class of antibacterial agents with a novel mechanism of action. Mutations that inactivate formyl methionyl transferase (FMT), the enzyme that formylates initiator methionyl-tRNA, lead to an alternative initiation of protein synthesis that does not require deformylation and are the predominant cause of resistance to PDF inhibitors in Staphylococcus aureus. Here, we report that loss-of-function mutations in FMT impart pleiotropic effects that include a reduced growth rate, a nonhemolytic phenotype, and a drastic reduction in production of multiple extracellular proteins, including key virulence factors, such as α-hemolysin and Panton-Valentine leukocidin (PVL), that have been associated with S. aureus pathogenicity. Consequently, S. aureus FMT mutants are greatly attenuated in neutropenic and nonneutropenic murine pyelonephritis infection models and show very high survival rates compared with wild-type S. aureus. These newly discovered effects on extracellular virulence factor production demonstrate that FMT-null mutants have a more severe fitness cost than previously anticipated, leading to a substantial loss of pathogenicity and a restricted ability to produce an invasive infection.     

TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund’s adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol–induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol– and WS-12–induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.     

个案研讨式沙龙在老年患者护理骨干培训中的应用效果

目的探讨个案研讨式沙龙在老年患者护理骨干培训中的应用及效果。方法 2012年6-9月南方医科大学珠江医院举办护理人员老年患者护理专项进修班,从各个专科老年人的常见病、重点需要解决的问题、难点入手,通过个案研讨、统一规范的组织形式安排组织了7次个案研讨式沙龙活动。在沙龙开展前和最后一次沙龙结束时进行问卷调查,并评价培训效果。结果 33名学员中,26名(占78.8%)学员在参加本期护理沙龙前没有参加过其他形式的护理沙龙;对本期沙龙的形式及内容安排的满意率为100%,认为总体收获较大的32名(占97.0%)学员认为个案研讨式沙龙对提高临床实践能力比较有效,33名(100%)学员认为对提高全院老年患者护理整体水平和科室间合作非常重要;参加个案研讨式沙龙前后,学员的老年患者护理相关能力自评总分分别为(33.98±8.564)分、(51.87±6.668)分,差异有统计学意义(t=19.549,P<0.01),且老年患者护理相关能力13个自评项目的评分均高于参加前,差异均有统计学意义(均P<0.01)。结论个案研讨式沙龙对提高临床老年患者护理骨干临床实践能力、促进理论向实践转化起到了积极的作用,在今后的护理骨干培养中可以进一步推广并实施。     

槌果藤软膏治疗银屑病的实验研究

目的:观察槌果藤软膏对银屑病动物模型的疗效及其抗炎、止痒等作用。方法:观察计数小鼠尾部给药后鳞片表皮颗粒层形成情况;计数处于有丝分裂中期的阴道基底细胞有丝分裂数,并换算成有丝分裂指数;观察记录右旋糖苷致小鼠瘙痒次数及瘙痒持续时间;测定二甲苯致小鼠耳廓肿胀程度;测定小鼠腹腔毛细血管炎性渗出。结果:槌果藤软膏对小鼠尾部鳞片表皮颗粒层的形成具有显著的促进作用;可明显抑制小鼠阴道上皮细胞有丝分裂;能明显缓解右旋糖苷引起的小鼠瘙痒;减轻二甲苯致小鼠耳肿胀程度并抑制小鼠腹腔毛细血管通透性增高。结论:槌果藤软膏对小鼠银屑病模型有显著的治疗作用,并具有抗炎、止痒等作用。     

非典型尤文氏瘤误诊骨囊肿1例

胡某，男，23岁，未婚。因左髋部劳累后酸痛于1997年8月入院。局部曾有外伤史。患者1年前无明显诱因出现左大腿上方酸痛，劳累后加重，予消炎、镇痛药可缓解。局部无红肿及流脓，发病后两便正常，睡眠一般，胃纳可。平常素有鼻血及牙出血史(舅舅也有类似情况)，父母及一兄均健。否认有遗传病史。体格检查：营养一般，轻度贫血貌。头、面、颈无     

~(99m)锝腮腺动态显像对舍格伦综合征的诊断价值

目的 探讨＾９９ｍ锝腮腺动态显像对诊断舍格伦征的价值。方法 应用＾９９ｍ锝对临床诊断为舍格伦综合征的５２例患者进行腮腺动态显像,将所得的结果应用计算机ＲＯＩ程序进行定量分析和动态曲线分析,结果 腮腺外形较正常大者４６例（８８．４％）肿大腮腺轮廓清晰２８例（５３．８５％）轮廓模糊１８例（３４．６２％）腮腺功能正常７例（１３．４６％）轻度受损１５例（２８．８４％）中８度受损１７例（３２．６９％）,重度     

AQP4参与卵巢激素对单胺类神经递质的调节作用

目的：探讨AQP4对卵巢激素调节神经递质作用的影响。方法：应用雌性AQP4基因敲除型CD1小鼠与野生型CD1小鼠，测定AQP4基因敲除对小鼠血浆中雌孕激素水平的影响；两种基因型小鼠实施卵巢去势手术，测定纹状体和皮层中单胺类神经递质的含量。结果：AQP4基因敲除型小鼠动情后期血浆雌、孕激素水平显著低于野生型小鼠；去势后野生型小鼠纹状体多巴胺（DA）及皮层去甲肾上腺素（NE）含量明显降低，但去势不影响AQP4基因敲除型小鼠脑内相应的递质水平。结论：AQP4参与了卵巢激素对单胺类神经递质的调节。