中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Purpose—The aim of this guideline is to provide a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. Methods—Writing group members were nominated by th...

Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association

Lysine acetylation is a key mechanism that regulates chromatin structure; aberrant acetylation levels have been linked to the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are small interaction modules found on diverse proteins, some of which have a key role in the acetylation-dependent assembly of transcriptional regulator complexes. These complexes can then initiate transcriptional programmes that result in phenotypic changes. The recent discovery of potent and highly specific inhibitors for the BET (bromodomain and extra-terminal) family of bromodomains has stimulated intensive research activity in diverse therapeutic areas, particularly in oncology, where BET proteins regulate the expression of key oncogenes and anti-apoptotic proteins. In addition, targeting BET bromodomains could hold potential for the treatment of inflammation and viral infection. Here, we highlight recent progress in the development of bromodomain inhibitors, and their potential applications in drug discovery.

Targeting bromodomains: epigenetic readers of lysine acetylation

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jsr.12594

European guideline for the diagnosis and treatment of insomnia

Diagnostic and Statistical Manual of Mental Disorders, 4th ed

Alcohol impairs inhibitory control, and it alters implicit alcohol cognitions including attentional bias and implicit associations. These effects are seen after doses of alcohol which do not lead to global impairments in cognitive performance. We review studies which demonstrate that the effects of alcohol on inhibitory control are associated with the ability of alcohol to prime alcohol-seeking behavior. We also hypothesize that alcohol-induced changes in implicit alcohol cognitions may partially mediate alcohol-induced priming of the motivation to drink. Based on contemporary theoretical models and conceptualizations of executive function, impulsivity, and the motivational salience of alcohol-related cues, we speculate on other aspects of cognition that may underlie alcohol’s effects on alcohol seeking. Inconsistencies in existing research and priorities for future research are highlighted, including dose effects and the potential interactions between chronic heavy drinking and the acute effects of alcohol on these cognitive processes.

http://www.impliciet.eu/adapt/publications/2010%20FieldEtAlReviewAcuteAlcACER.pdf

Acute Alcohol Effects on Inhibitory Control and Implicit Cognition: Implications for Loss of Control Over Drinking

Objectives:
The literature exploring the role that cytokine functioning plays in the pathogenesis and treatment of depressive illness is reviewed. The review focuses on the influence of antidepressants on cytokines, and on how treatment response might be affected by genetic variants of cytokines.

Method:
The authors systematically reviewed the scientific literature on the subject over the last 20 years, searching PubMed, PsychInfo, and Cochrane databases.

Results:
Antidepressants modulate cytokine functioning, and these mechanisms appear to directly influence treatment outcome in depression. Antidepressants appear to normalize serum levels of major inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ). Antidepressants are postulated to modulate cytokine functioning through their effects on intracellular cyclic adenosyl monophosphate (cAMP), serotonin metabolism, the hypothalamo-pituitary-adrenocortical (HPA) axis or through a direct action on neurogenesis. Preliminary research shows that cytokine genotypes and functioning may be able to help predict antidepressant treatment response.

Conclusions:
Current literature demonstrates an association between antidepressant action and cytokine functioning in major depression. Improved understanding of the specific pharmacologic and pharmacogenetic mechanisms is needed. Such knowledge may serve to enhance our understanding of depression, leading to promising new directions in the pathology, nosology, and treatment of depression.

A psychoneuroimmunological review on cytokines involved in antidepressant treatment response.

This review discusses the methodology of the standardized on-the-road driving test and standard operation procedures to conduct the test and analyze the data. The on-the-road driving test has proven to be a sensitive and reliable method to examine driving ability after administration of central nervous system (CNS) drugs. The test is performed on a public highway in normal traffic. Subjects are instructed to drive with a steady lateral position and constant speed. Its primary parameter, the standard deviation of lateral position (SDLP), ie, an index of ‘weaving’, is a stable measure of driving performance with high test–retest reliability. SDLP differences from placebo are dose-dependent, and do not depend on the subject’s baseline driving skills (placebo SDLP). It is important that standard operation procedures are applied to conduct the test and analyze the data in order to allow comparisons between studies from different sites.

/pdf/standard-operation-procedures-for-conducting-the-on-the-road-3yv34eqq5n.pdf

Standard operation procedures for conducting the on-the-road driving test, and measurement of the standard deviation of lateral position (SDLP).

https://dspace.library.uu.nl/bitstream/handle/1874/11902/verster_04_residual_effects_of_sleep.pdf?sequence=2

Residual effects of sleep medication on driving ability

Background All antihistamines are capable of crossing the blood-brain barrier and thus may cause sedation. Most antihistamine users are ambulatory patients and therefore presumably drive a car. Objective To summarize the effects of antihistamine drugs on driving ability. Data Sources and Study Selection A literature search (MEDLINE and cross-references) was performed using the keywords driving and antihistamine . Sixteen studies using the on-the-road driving test during normal traffic were included in the review. Studies were double-blind and placebo-controlled and included a positive control. Results First-generation antihistamines (diphenhydramine, triprolidine, terfenadine, dexchlorpheniramine, clemastine) significantly impair driving performance after both one-time and repeated (daily) administration. Second-generation antihistamines (cetirizine, loratadine, ebastine, mizolastine, acrivastine, emedastine, mequitazine) may also impair driving performance, but the magnitude and extent of impairment depend on the administered dose, sex, and time between testing and treatment administration. Tolerance develops after 4 to 5 days of administration, but impairment is not absent. Third-generation antihistamines (fexofenadine and levocetirizine) have been shown to produce no driving impairment after both one-time and repeated administration. Conclusions First- and second-generation antihistamines may significantly impair driving performance. In the context of driving safety but also taking into account the cardiotoxic properties of some of the second-generation antihistamines, we advise treating patients with third-generation antihistamines such as fexofenadine and levocetirizine.

/pdf/antihistamines-and-driving-ability-evidence-from-on-the-road-2bdvfiitg4.pdf

Joris C. Verster

Papers

Acute Alcohol Effects on Inhibitory Control and Implicit Cognition: Implications for Loss of Control Over Drinking

A psychoneuroimmunological review on cytokines involved in antidepressant treatment response.

Standard operation procedures for conducting the on-the-road driving test, and measurement of the standard deviation of lateral position (SDLP).

Residual effects of sleep medication on driving ability

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.