Polypharmacy in the management of patients with schizophrenia on risperidone in a tertiary-care hospital in Malaysia

The present study was conducted primarily to determine the occurrence of polypharmacy in patients with schizophrenia on risperidone. The secondary aim was to ascertain the incidence of inappropriate prescribing with anticholinergics. A retrospective review of the medical records of all patients who were being followed up at the out-patient clinic of a tertiary-care hospital in Malaysia was conducted. Only patients who were being prescribed risperidone between 1 June 2008 and 31 December 2008 were included in the study. Demographic data such as patient’s age, gender and race were obtained from the patient’s medical records. In total, 113 patients met the selection criteria. Polypharmacy was found to occur in 34 patients (30.09%), with the majority (76.47%) being on two antipsychotics. In total, 27 patients (34.18%) on monotherapy with risperidone were prescribed an anticholinergic on scheduled dosing, while 19 patients (24.05%) were prescribed it on an as-needed basis. Of the patients on polypharmacy, 26 (76.47%) were on scheduled dosing of anticholinergics, while three (8.82%) were taking the medication on an as-needed basis. Polypharmacy should be avoided, and the use of anticholinergics should be closely reviewed. By adopting more efficient prescribing practices, costs can be reduced and financial resources can instead be channelled towards more beneficial areas for the patients.     

以疏勒河流域为例的“山水林田湖草”生态修复多尺度耦合框架及方法

为解决过去保护修复工程只考虑单要素、单一类型生态系统的问题，我国于2016年开展了“山水林田湖草”生态修复工程，旨在通过整体、系统、综合的方法对各类生态系统进行统筹治理。然而，目前的工程治理中仍然存在对系统内部及系统间耦合概念理解不充分、系统耦合机制不明晰、对“尺度”的关注不足、缺少科学的分析方法等问题，制约了保护修复的成效。对此，首先将多个尺度下的耦合研究方法进行归纳总结，并以国家重点冰川水源涵养区及生物多样性保护优先区——疏勒河流域为例，将耦合方法用于分析要素间、自然生态系统间的耦合关系，最后基于该实例研究，提出多尺度耦合分析框架与“升尺度”保护修复模式，以期帮助相关决策者明晰“山水工程”中要素、系统间的耦合关系，增强治理的科学性与有效性，进而推进我国社会与环境的可持续发展。     

In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine

Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral cells of sheep susceptible-to or suffering-from Scrapie were characterized by an altered cholesterol homeostasis, and that drugs affecting cholesterol ester pool were endowed with selective anti-prion activity in N2a cell lines infected with the 22L and RML prion strains. In these prion-infected N2a cell lines, we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors. Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. In addition, comparative lipid analyses in prion-infected vs. uninfected N2a cells, demonstrated a derangement of type and distribution of cholesterol ester, free cholesterol, and triglyceride pools in the infected cells. Single-drug treatments differently affected synthesis of the various lipid forms, whereas combined drug treatments appeared to restore a lipid profile similar to that of the untreated-uninfected cells. We conclude that the anti-prion synergistic effects of cholesterol ester modulators associated with the cholesterol-interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish lipid homeostasis in the prion-infected cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets.     

“山水林田湖草沙生命共同体”耦合框架、模型与展望

“山水林田湖草沙生命共同体”系统保护与修复是我国生态文明建设的重要内容。明确生命共同体的耦合机制，是科学地进行生态保护和修复工作的关键。针对当前生命共同体耦合机制不清、理论和方法不健全的问题，从耦合的视角出发，在小流域尺度上单一生态系统内部生态要素的耦合、流域尺度上不同生态系统之间的耦合、区域尺度上人与自然的耦合三个方面进行整合，在此基础上探讨了多尺度山水林田湖草沙耦合理论，提出了一般性的山水林田湖草沙耦合理论框架。梳理并比较了当前主要的生态系统模型、景观模型、统计学模型以及复合生态系统的多模型耦合方法，综合提出了一个适用于"山水林田湖草沙生命共同体"耦合研究方法。对进一步完善山水林田湖草沙一体化保护修复提出了建议，包括：一是构建多源信息数据库，推进定量化耦合机制研究；二是开展全生命周期监测与评估，探索适应性治理路径；三是强化多元主体参与，完善协同保护机制。     

Regulation of osteoblast and osteoclast functions by FGF‐6

Fibroblast growth factor‐6 (FGF‐6) is known to be the key ligand for fibroblast growth factor receptor 4 (FGFR4) during muscle regeneration but its role in bone has yet to be verified. FGFR signaling is known to be important in the initiation and regulation of osteogenesis, so in this study the actions of FGF‐6 on human osteoblasts and osteoclasts were investigated. Human primary osteoblasts (hOB) were used to study the effect of FGF‐6 on proliferation (by ATP quantification), signal transduction (by ERK and AKT phosphorylation), differentiation (by alkaline phosphatase activity, APA), and mineralization (by calcein staining). To study FGF‐6 activity on osteoclast differentiation, human bone marrow cells were used and tartrate‐resistant acid phosphatase (TRAP) multinucleated cells together with actin filaments arrangements were quantified. Human primary mature osteoclasts were used to evaluate the effect of FGF‐6 on osteoclast reabsorbing activity by reabsorbed pit measurements. FGF‐6 >10⁻⁹ M as FGF‐2 10⁻⁷ M induced hOB proliferation mediated by pERK together with a reduction in APA and reduced mineralization of the treated cells. Moreover FGF‐6 increased the formation of TRAP‐positive multinucleated cells in a dose‐dependent manner (maximal effect at 10⁻⁸ M). FGF‐6‐treated cells showed also a greater percentage of cells that formed typical osteoclast sealing zones. Mature osteoclasts cultured on dentine slice increased the area of reabsorption with a maximal effect of FGF‐6 at 10⁻¹² M. FGF‐6 may be considered a regulator of bone metabolism as shown by its activity on both osteoblasts and osteoclasts. J. Cell. Physiol. 225: 466–471, 2010. © 2010 Wiley‐Liss, Inc.