本色吴晓滨

未见其人，先闻其语。敢言敢行者，非吴晓滨莫属。 在我们对惠氏中国公司公共关系总监席庆的个人采访中，他几乎拿出了一半的时间去描述惠氏中国的新进展。而惠氏中国的新进展，是在吴晓滨任职后开始的。     

14-Methoxymetopon,a very potent mu-opioid receptor-selective analgesic with an unusual pharmacological profile

14-Methoxymetopon is a potent opioid analgesic. When given systemically, it is approximately 500-fold more active than morphine. However, this enhanced potency is markedly increased with either spinal or supraspinal administration, where its analgesic activity is more than a million-fold greater than morphine. It was mu-opioid receptor selective in binding assays and its analgesia was blocked only by mu-opioid receptor-selective antagonists. Yet, it had a different selectivity profile than either morphine or morphine-6beta-glucuronide. Unlike morphine, 14-methoxymetopon was antagonized by 3-O-methylnaltrexone, it was sensitive to antisense probes targeting exons 1, 2 and 8 of the opioid receptor gene and was inactive both spinally and supraspinally in CXBK mice. Although it retarded gastrointestinal transit, it displayed a ceiling effect with no dose lowering transit by more than 65%, in contrast to the complete inhibition of transit by morphine. These finding demonstrate that 14-methoxymetopon is a highly potent mu-opioid with a pharmacological profile distinct from that of the traditional mu-opioid morphine.     

极高剂量缬沙坦对2型糖尿病患者蛋白尿的影响

目的探讨高剂量缬沙坦对降低2型糖尿病患者尿白蛋白排泄率（UAER）的疗效是否优于常规剂量的缬沙坦。方法连续人选2010年6月～2012年11月在我院内科门诊就诊的391例高血压合并2型糖尿病和蛋白尿的患者,随机分为160rag、320mg和640mg缬沙坦组。前4周所有患者均服用缬沙坦160rag。在之后的30周内,其中2组增加缬沙坦的剂量。分别采用基线、4周、16周和30周时收集的过夜尿（一式三份）来评估蛋白尿。结果在第4周时,各组的白蛋白尿均显著减少（P〈0．001）,之后,缬沙坦320mg组和640mg组的白蛋白尿出现非常显著地减少（P〈0．001）,而160mg组只有中等程度的进一步减少（P=-0．03）。至30周时,缬沙坦640mg组白蛋白尿恢复正常的患者比例是160mg组的2倍（P〈0．01）。高剂量组患者的耐受性良好．未出现与剂量增加相关的不良事件（包括低血压和高钾血症）。结论高剂量缬沙坦减少白蛋白尿的疗效优于常用剂量160mg．且明显与血压无关。因此,至少2型糖尿病患者需要较高剂量的缬沙坦,这不是为了控制血压．而是要获得最佳的组织保护。     

Something old,something new and something very old: drugs for treating type 2 diabetes

Diabetes mellitus belongs to the most rapidly increasing diseases worldwide. Approximately 90–95% of these patients suffer from type 2 diabetes mellitus, which is characterized by peripheral insulin resistance and the progressive loss of beta-cell function and mass. Considering the complications of this chronic disease, a reliable anti-diabetic treatment is indispensable. An ideal oral anti-diabetic drug should not only correct glucose homeostasis but also preserve or even augment beta-cell function and mass, ameliorate the subclinical inflammation present under insulin-resistant conditions and prevent the macro- and microvascular consequences of diabetes in order to reduce the mortality. Despite the many anti-diabetic drugs already in use, there is an ongoing research for additional drugs, guided by different concepts of the pathogenesis of type 2 diabetes. This review will briefly summarize current oral anti-diabetic drugs. In addition, emerging strategies for the treatment of diabetes will be described, among them the inhibition of glucagon action and anti-inflammatory drugs. Their suitability as ‘ideal anti-diabetic drugs’ will be discussed.     

3-Benzazocine amidinium nitronates. An unusual type of opiate antagonist

An interesting type of 3-benzazocine ring system which contains amidine functionality has been found to have significant narcotic antagonist activity. The isomeric 2-benzazocine, which incorporates similar structural features, except for the position of the ring nitrogen and adjacent phenyl substituent, is inactive. These 2- and 3-benzazocines can be synthesized in a single step from appropriately structured amidines and naphthalenes, and such syntheses may provide useful routes to new and interesting types of narcotic antagonists.     

Pinifolin, a new iridoid glucoside of unusual type from Penstemon pinifolius

From the aerial parts of PENSTEMON PINIFOLIUS Greene, a new iridoid glucoside of unusual type has been isolated and structurally elucidated by spectroscopic means. This new compound, called pinifolin, contains a Delta (4)-instead of a Delta (3)-double bond and a methyl ether function at carbon 3 of the iridoidic skeleton.     

A new type of very low-power modulated laser: soft-tissue changes induced in osteoarthritic patients revealed by sonography

Patients with symptomatic osteoarthritis of the cervical spine were studied by ultrasound examination. The region of interest was the soft connective tissue layer above the right and the left superior trapezium that revealed a significant difference in thickness between the left and right side. The aching side was treated with a new type of very low-power, modulated laser for 3 min. Immediately after application, the sonographic examination revealed a significant symmetrization of the subcutaneous tissue.     

A day at the cricket: The breath alcohol consequences of a type of very English binge drinking

Media images of violence and accidents associated with binge drinking raise concerns and the headlines and sound-bites blame heavy intoxication. However, there has been very little attention to breath alcohol concentrations (BACs) associated with bingeing. In this naturalistic study of 12 male spectators at a cricket match, alcohol consumption ranged from 8.5 to 21.7 units and at the end of play BACs ranged 0?61?µg/100?mL. The implications of these results for the definition of a “binge” are discussed.