神经再生研究任重而道远——连线第五届亚太神经再生学术大会

2006年12月8日至10日，神经再生领域基础和临床研究的一次盛会——第五届亚太神经再生学术大会在上海召开。国际神经再生学术界的权威专家，包括世界知名的脊髓损伤基础和临床应用研究的先驱和领导者杨咏威教授、国际知名的脑外伤和中风领域专家美国堪萨斯大学Randolph Nudo教授、EMERY大学的Donald Stein教授、加拿大英属哥伦比亚大学脊髓损伤治疗专家John Steeves，以及国内以苏国辉院士和鞠躬院士为代表的神经再生学界学者，均出席了此次会议，并作了精彩的报告。本刊编译部分报告摘要如下。     

Regulation of microRNAs by Natural Agents: An Emerging Field in Chemoprevention and Chemotherapy Research

In recent years, microRNAs have received greater attention in cancer research. These small, non-coding RNAs could inhibit target gene expression by binding to the 3′ untranslated region of target mRNA, resulting in either mRNA degradation or inhibition of translation. miRNAs play important roles in many normal biological processes; however, studies have also shown that aberrant miRNA expression is correlated with the development and progression of cancers. The miRNAs could have oncogenic or tumor suppressor activities. Moreover, some miRNAs could regulate formation of cancer stem cells and epithelial-mesenchymal transition phenotype of cancer cells which are typically drug resistant. Furthermore, miRNAs could be used as biomarkers for diagnosis and prognosis, and thus miRNAs are becoming emerging targets for cancer therapy. Recent studies have shown that natural agents including curcumin, isoflavone, indole-3-carbinol, 3,3′-diindolylmethane, (-)-epigallocatechin-3-gallate, resveratrol, etc. could alter miRNA expression profiles, leading to the inhibition of cancer cell growth, induction of apoptosis, reversal of epithelial-mesenchymal transition, or enhancement of efficacy of conventional cancer therapeutics. These emerging results clearly suggest that specific targeting of miRNAs by natural agents could open newer avenues for complete eradication of tumors by killing the drug-resistant cells to improve survival outcome in patients diagnosed with malignancies.     

Kellersberger Memorial Lecture 1998: Nerve Damage in Leprosy: a problem for patients, doctors and scientists

There are interesting challenges in leprosy right now. The last fifteen years have seen the world-wide implementation of multidrug therapy with tangible benefits for patients and doctors. Paradoxically this success has revealed how much we still need to understand about leprosy nerve damage. For patients it is imperative that nerve damage is detected at an early stage when damage is still reversible. They need effective education to prevent the development of disability and to minimise the social and economic effects of nerve damage. For doctors and paramedical workers nerve damage needs effective treatment. We need to use current treatments effectively and also develop new treatments. This lecture looks critically at the pathology, detection and treatment of nerve damage, reviewing our present knowledge and looking to future developments.     

British Association for Psychopharmacology Max Hamilton Memorial Lecture Quantitative estimates of drug effects in psychopharmacology: what we measure and what we do not

This paper is an edited version of the Max Hamilton Memorial Lecture that was delivered at the annual meeting of the British Association for Psychopharmacology in Cambridge in July 1989. In tribute to Professor Hamilton's pioneering efforts in the field, the lecture focuses on several aspects of the measurement process in psychopharmacology. The role of enumeration in the classification of psychopathology is reviewed and its importance illustrated with an example drawn from the literature. Attention is given to the fundamental link between agreements within the field about the nature and qualities of clinical phenomena and the field's ability to construct and use multi-item rating scales to measure meaningful changes in the intensity of psychopathology. The importance of global assessment as a validation procedure is emphasized and selected hazards to reliable inference are examined.     

Antihistaminic/antiallergic activity of 2-dialkylaminoalkylthio(oxy)-1-substituted benzimidazoles: evaluation "in vitro" and "in vivo".

A new series of 2-dialkylamino-alkylthio(oxy)-1-substituted benzimidazoles synthesized in our laboratories was found to have promising antihistaminic activity. The results of pharmacological screening ("in vitro": radioreceptor binding and isolated organs; "in vivo": protection against mortality induced by histamine or by compound 48/80, passive cutaneous anaphylaxis, and prolongation of barbiturate-induced sleeping-time) gave clear-cut structure-activity relationships. This series of products has a general selectivity towards H1 receptors, weak antiallergic properties and negligible central effects. DF 10967 (1-ethoxyethyl-2-dimethyl-aminoethylthiobenzimidazole) was the most interesting compound, being very potent both "in vitro" (Ki = 3.2 +/- 0.8 nM) and "in vivo" (ID50 11 micrograms/kg, i.p. and 8 micrograms/kg, i.p. against histamine- and 48/80-induced mortality), with no central effects. The last finding is probably due to poor penetration into the brain (as confirmed by "in vivo" binding test with [3H]-mepyramine) and to lack of interaction with other central receptors.     

"ESVITAF". Survey on the vitamin status of the French: relationships between nutrient intake and biochemical indicators

The relationships between dietary data and biochemical nutritional status for vitamins B1, B2, A, E, beta-carotene, folic acid and iron have been studied using data from a survey conducted on 710 adults. Significant correlations were found between riboflavin intake and biochemical values for males only (r = -0.105, p less than or equal to 0.05), between beta-carotene intake and plasma beta-carotene (r = 0.232, for males and r = 0.292 for females, p less than or equal to 0.001), and between iron intake and plasma iron for males only (r = 0.115, p less than or equal to 0.05). Concerning nutrient densities, correlations were significant between dietary riboflavin and biochemical measure (r = 0.163, p less than or equal to 0.01 for males, r = -0.135, p less than or equal to 0.05 for females), between vitamin A intake (expressed in retinol equivalent) and beta-carotene (r = 0.212, p less than or equal to 0.001 for males, r = 0.157, p less than or equal to 0.01 for females) and for males only, between dietary iron and hemoglobin (r = 0.144, p less than or equal to 0.01). The dietary data for each nutrient were examined for their sensitivity, specificity and predictive values in identifying subjects with substandard or overstandard biochemical values. For all nutrients the positive predictive value percentage was always below 25%, the negative predictive value percentage always under 75%.     

Pharmaceutical Technology Licensing: An Analysis in the Field of Cardiovascular Disease

The technological flows and licensing across institutions plays an essential role in the process of pharmaceutical innovation by integrating the competing resources of different institutions and sharing the costs and risks, especially in the current era of open innovation. This article aims to generally describe technology licensing activities on cardiovascular drugs and, based on visualizing technology flows at different stages, to further investigate the multistage leading performers and their licensing strategies. From the IMS R&D Focus, a world-leading database in the healthcare industry, the research sample comprises 632 licensing inventions for cardiovascular drugs from 1980 to 2014. Furthermore, a network-based approach is employed to visualize the technology flows by setting nodes to represent licensing institutions and edges for licensing behavior, and further to analyze institution leaders and licensing strategies through various indicators, e.g., out-degree, in-degree, and betweenness centrality. The results show that technology licensing networks gradually transformed from sparse to dense from the preclinical to marketed stages. There is obvious synergy and complementation among universities, multinational enterprises, and mid- and small-sized enterprises. R&D organizations represented by universities denote themselves as upstream in the pharmaceutical R&D chain. As a hub, multinational enterprises play an important role as technology integrators and show the most frequent technology licensing, both in technology inflows and outflows, whereas various small firms are viewed as satellite partners around multinational enterprises. This work provides valuable insights for pharmaceutical researchers, investors, policymakers, and technology brokers not only in the field of the discovery of cardiovascular drugs but also of other therapeutic drugs.