《艾滋病诊疗指南第三版(2015版)》更新解读

2015年中华医学会感染病学分会艾滋病学组发布了第三版《艾滋病诊疗指南》。新版指南强调抗病毒治疗时点前移:一旦成人确诊感染人类免疫缺陷病毒(HIV), 若无禁忌宜尽早启动抗HIV治疗。对于合并机会性感染的HIV感染者, 在感染控制、病情稳定后也应及早开始抗病毒治疗。尤其强调HIV合并结核患者在CD4阳性淋巴细胞数少于200/μL的情况下, 建议抗结核两周内即开始抗病毒治疗。在抗HIV治疗用药中, 淘汰了一些毒副作用大、依从性较差的药物, 如司他夫定、去羟肌苷、茚地那韦等, 优选抗病毒效力强、服药方便的组合, 如拉米夫定、替诺福韦、依非韦伦组合。对于HIV感染的婴幼儿, 亦主张及早抗HIV治疗。对于五岁以内的幼儿, 主张确诊后即启动抗病毒治疗。对于HIV感染的孕产妇, 建议尽快予以全程、联合抗HIV治疗, 寓防于治。     

肝内胆管癌转化治疗

肝内胆管癌（ICC）可切除率低，进展期ICC的治疗有效率不高，预后很差。转化治疗在多种晚期肿瘤中有一定的疗效，是目前晚期肿瘤治疗的研究热点。随着对ICC基因组的深入了解和新的治疗药物的开发及组合，基于系统化疗的联合治疗策略，精准靶向治疗，免疫检查点抑制剂等显示出较好的疗效，使得部分进展期ICC病人能降期转化手术，获得长期生存。     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.

Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.

Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.     

Academic–Industrial Collaboration: Toward the Consilience of Two Solitudes

Current major advances in drug discovery can be traced back to pioneering contributions originating from academics over a century ago. Living in a symbiotic yet noninvasive coexistence, the academic community and the pharmaceutical industry have strived, each in their own way, to develop the modern medicines that benefit humankind today. The subject is presented from a historical and personal perspective.     

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.     

Synthesis of deramciclane* labeled with tritium in various positions

[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐³H]camphor and via [3‐³H]phenylborneol converted to [3‐³H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐³H]camphor gave an overall yield of 22%. Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐³H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐³H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐³H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [³H]NaBH₄ gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd.