Stereopsychopharmacology: past, present and future

Stereoisomers have been used for more than a century to study the role of three-dimensional (spatial) features in biological processes. Configuration and conformation are spatial features of primary interest for effects of drugs. The role of configuration has been studied mainly by comparing effects of optical isomers (enantiomers), whereas the role of conformation has been investigated primarily using geometrical isomers and semi-rigid molecules. Spatial features have been shown to play a role in many effects of stereoisomers on noradrenergic, dopaminergic, serotonergic, cholinergic, opioid and GABAergic mechanisms. Further information on psychopharmacological effects of stereoisomers may lead to a better understanding of mental disorders and to improvements in drugs used to treat them.     

帕金森病的昨天、今天和明天

帕金森病（Parkinson disease，PD）日益成为公共卫生关注的焦点，在我国，它影响了近1．7％的65岁以上的老年人。回顾PD的历史，有几个里程碑需要铭记。1817年Parkinson首次详述了PD的典型临床表征。1895年Brissaud从病理上提出中脑可能是PD的解剖基础。1912年Lewy发现黑质内嗜伊红包涵体，即Lewy小体是PD的重要病理特征。1960年Ehringer和Homykiewicz发现纹状体多巴胺（dopamine，DA）神经递质水平下降是产生PD运动症状的主要因素。1961年Birkmayer和Hornykiewicz首次应用左旋多巴治疗PD，但最终将其成功推向临床的要归功于Cotzias。     

Friedreich's ataxia: past, present and future

Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterized by progressive gait and limb ataxia, dysarthria, areflexia, loss of vibratory and position sense, and a progressive motor weakness of central origin. Additional features include hypertrophic cardiomyopathy and diabetes. Large GAA repeat expansions in the first intron of the FXN gene are the most common mutation underlying FRDA. Patients show severely reduced levels of a FXN-encoded mitochondrial protein called frataxin. Frataxin deficiency is associated with abnormalities of iron metabolism: decreased iron-sulfur cluster (ISC) biogenesis, accumulation of iron in mitochondria and depletion in the cytosol, enhanced cellular iron uptake. Some models have also shown reduced heme synthesis. Evidence for oxidative stress has been reported. Respiratory chain dysfunction aggravates oxidative stress by increasing leakage of electrons and the formation of superoxide. In vitro studies have demonstrated that Frataxin deficient cells not only generate more free radicals, but also show a reduced capacity to mobilize antioxidant defenses. The search for experimental drugs increasing the amount of frataxin is a very active and timely area of investigation. In cellular and in animal model systems, the replacement of frataxin function seems to alleviate the symptoms or even completely reverse the phenotype. Therefore, drugs increasing the amount of frataxin are attractive candidates for novel therapies. This review will discuss recent findings on FRDA pathogenesis, frataxin function, new treatments, as well as recent animal and cellular models. Controversial aspects are also discussed.     

Brain-machine interfaces: past, present and future

Since the original demonstration that electrical activity generated by ensembles of cortical neurons can be employed directly to control a robotic manipulator, research on brain-machine interfaces (BMIs) has experienced an impressive growth. Today BMIs designed for both experimental and clinical studies can translate raw neuronal signals into motor commands that reproduce arm reaching and hand grasping movements in artificial actuators. Clearly, these developments hold promise for the restoration of limb mobility in paralyzed subjects. However, as we review here, before this goal can be reached several bottlenecks have to be passed. These include designing a fully implantable biocompatible recording device, further developing real-time computational algorithms, introducing a method for providing the brain with sensory feedback from the actuators, and designing and building artificial prostheses that can be controlled directly by brain-derived signals. By reaching these milestones, future BMIs will be able to drive and control revolutionary prostheses that feel and act like the human arm.     

Suicide prevention: past, present and future

Efforts to prevent suicide are reviewed. Recent studies have shown that suicide prevention centers may be effective in preventing suicide, at least among females. However, in recent years, more attention has been directed toward the possibility that restricting access to methods for suicide may be an effective way for preventing suicide. In addition, there is a growing body of research on which medications and which techniques of psychotherapy may be most effective in decreasing the risk of suicide in depressed patients.     

Italian neurology: past, present and future

This short history of the Italian Society of Neurology focuses on its founders and leading personalities. The article also considers the present and the future of Italian neurology, emphasising in particular the scientific impact of Italian neurological research on the main international journals and the activities undertaken to increase the role of neurologists.     

Anxiolytics: past,present, and future agents

Although anxiety disorders were classified as neurotic disorders and not systematically studied before DSM-III, researchers and clinicians have been searching for effective, safe agents to treat anxiety symptoms and disorders for over a century. In that time, barbiturates, benzodiazepines, and many classes of antidepressants have been used as anxiolytics, all with side effect profiles that made them less than optimal treatments for anxiety. The recognition of the role of GABA in anxiety disorders has led researchers to develop anxiolytics that target GABA. The long-sought-after class of anxiolytics that are both effective and safe may be found in the new research being conducted with agents that selectively target GABA receptors and their subtypes.     

Simple schizophrenia: past, present, and future

The diagnostic category called simple schizophrenia has disappeared from official American nosology but has been retained in ICD-9. The diagnosis has a long history, was one of the traditional schizophrenic subtypes identified by Bleuler, and was later accepted by Kraepelin. The authors provide a historical overview of the concept, review its modern successors, and provide recommendations for its inclusion in DSM-IV as a proposed diagnostic category needing further study.     

Clinical linguistics: its past, present and future

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the results of a survey of articles published in Clinical Linguistics & Phonetics between 1987 and 2008 which shows, for example, a consistent primary focus on phonetics and phonology at the expense of grammar, semantics and pragmatics. I also trace the gradual broadening of the discipline from its roots in structural linguistics to its current reciprocal relationship with speech and language pathology and a range of other academic disciplines. Finally, I consider the scope of clinical linguistic research in 2011 and assess how the discipline seems likely develop in the future.     

Immunotherapy of neuroblastoma: present, past and future

Neuroblastoma is a neuroectodermal tumor of childhood with poor prognosis and low survival in patients with advanced-stage disease who respond to conventional therapies but unfortunately, often present relapse. Therefore, the search for novel therapeutic strategies is warranted and represents the objective of many investigators. Among the new, innovative approaches, immunotherapy has attracted much interest. However, until recently, little information was available about the immunogenicity of human neuroblastoma.     

Clinical linguistics: Its past,present and future

Historiography is a growing area of research within the discipline of linguistics, but so far the subfield of clinical linguistics has received virtually no systematic attention. This article attempts to rectify this by tracing the development of the discipline from its pre-scientific days up to the present time. As part of this, I include the results of a survey of articles published in Clinical Linguistics & Phonetics between 1987 and 2008 which shows, for example, a consistent primary focus on phonetics and phonology at the expense of grammar, semantics and pragmatics. I also trace the gradual broadening of the discipline from its roots in structural linguistics to its current reciprocal relationship with speech and language pathology and a range of other academic disciplines. Finally, I consider the scope of clinical linguistic research in 2011 and assess how the discipline seems likely develop in the future.     

Dementia in Taiwan: past, present, and future

The percentage of Taiwanese aged 65 years and older has been increasing over the past 27 years, from 4.1% in 1980 to 10.2% in 2007. Studies on the Taiwan population have shown that the prevalence of dementia is approximately 1.7 - 4.3% among aged people, and that the most common cause of dementia is Alzheimer's disease (AD). However, compared to Western countries, this is a low prevalence rate, which might be due to the simple lifestyle led by aged Taiwanese, a selective higher mortality rate in Taiwanese, and a low prevalence of the APOE4 allele in Taiwanese. The current evaluation of dementia in Taiwan derives from several reliable and valid cognitive and behavioral assessment tools originally developed in Western countries. These tools are not only useful for clinical evaluation, but also have offered a method for possible cross-cultural assessment. Behavioral and psychiatric symptoms of dementia in Taiwan have been shown to be similar to other ethnic groups, except for a relative high prevalence of apathy. Although three cholinesterase inhibitors and one glutamate NMDA receptor antagonist are available in Taiwan to treat dementia, their insurance reimbursement is strictly regulated and only a small proportion of patients with AD receive medical treatment. A local consensus of and guideline for diagnosis and treatment of dementia is needed in Taiwan.