Recruitment of striatonigral disinhibitory and nigrotectal inhibitory GABAergic pathways during the organization of defensive behavior by mice in a dangerous environment with the venomous snake Bothrops alternatus (Reptilia,Viperidae)

The neuropsychopharmacological basis of fear‐ or panic‐related behavior has been the focus of several studies. Some mesencephalic tectum (MT) structures, such as the superior colliculus (SC) and dorsal periaqueductal gray matter (dPAG), are considered to be responsible for the control of defensive responses evoked during threatening situations. Furthermore, the pars reticulata of the substantia nigra (SNpr) sends inputs to the SC that can work as a sensory channel to MT neurons fundamental for the elaboration of defensive responses. The purpose of the present study was to investigate the role of striato‐nigral GABAergic inputs in the activity of nigro‐tectal outputs during the elaboration of defensive behavior using a GABA_A receptor selective blockade in the MT of mice confronted pre‐treated with Bothrops alternatus. Mice with injections of physiological saline into the SNpr and treated with a GABA_A receptor selective antagonist in the MT displayed an increase in panic‐related behavior, expressed by an increase in the duration of freezing, frequency of nonoriented escape and frequency of total escape responses during the confrontation with the snake. However, intra‐SNpr injections of cobalt chloride followed by MT injections of bicuculline caused a significant decrease in the duration of freezing and total escape responses. In addition, intra‐SNpr injections of lidocaine followed by MT injections of bicuculline caused an increase in panic‐related behavior. The results highlight the involvement of SNpr and MT structures in the organization of defensive behaviors and suggest an inhibitory control of striatonigral‐nigrotectal pathways during the elaboration of fear‐ and panic‐related behavior. Synapse 69:299–313, 2015 . © 2015 Wiley Periodicals, Inc.     

A role for inflammatory metabolites as modulators of the glutamate N-methyl-d-aspartate receptor in depression and suicidality

BackgroundPatients with depression and suicidality suffer from low-grade neuroinflammation. Pro-inflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-d-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF).MethodsWe measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Åsberg Depression Rating Scale and the Suicide Assessment Scale.ResultsQuinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms.ConclusionsWe demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression.     

中链脂肪酸在脂肪代谢异常时的临床价值

中链脂肪酸是由6~10个碳原子组成的一类脂肪酸,具有不同于长链脂肪酸的代谢途径及特点。在胰脂肪酶或胆汁盐缺乏的情况下,中链脂肪酸仍然可以被吸收,且可直接通过门静脉血流输送到肝脏被快速代谢,不需要在肠细胞内形成乳糜微粒经淋巴系统再入血液循环。因此,对于存在脂肪代谢异常相关的疾病,如长链脂肪酸氧化障碍、脂肪营养不良、淋巴乳糜微粒转运受损等,可通过中链脂肪酸替代大部分长链脂肪酸的膳食或配方来控制或缓解病情。     

老年帕金森病患者血清同型半胱氨酸及血尿酸水平与认知功能障碍的相关性

目的探讨血清同型半胱氨酸（Hcy）和血尿酸（UA）的水平与帕金森病（PD）患者认知功能障碍的相关性。方法检测58例帕金森病患者和50例健康老人的血清同型半胱氨酸及血尿酸水平,采用简易精神状态检查（MMSE）量表对老年 PD 患者进行认知功能评分。结果老年帕金森病组的 Hcy 浓度[（25．89±3．01）μmol／L]显著高于健康老年组[（13．29±2．13）μmol／L]（P ＜0．01）;血尿酸水平显著低于健康老年组[（267．34±68．43）μmol／L 比（341．26±52．75）μmol／L,P ＜0．01],并且 PD 伴认知障碍组的 Hcy 浓度显著高于 PD 无认知障碍组[（29．54±4．35）μmol／L 比（20．78±3．17）μmol／L ,P ＜0．05],PD 伴认知障碍组的血尿酸水平显著低于 PD 无认知障碍组[（245．10±55．61）μmol／L 比（302．21±52．31）μmol／L ,P ＜0．05]。结论老年帕金森病患者会出现血清同型半胱氨酸水平升高及血尿酸水平的降低,其变化与程度认知功能障碍的发生有一定关联度。     

四种检验方法在细菌性阴道炎诊断的临床价值

目的探讨4种检验方法对细菌性阴道炎的临床诊断作用与应用价值。方法选取该院2012年7月至2014年5月80例疑似细菌性阴道炎患者,分别使用胺试验、线索细胞检查、乳酸杆菌检查、细菌性阴道炎(BV)快速检测法进行检测,并对4种方法的检测结果作比较分析。结果乳酸杆菌检测阳性率为80.0%,线索细胞检查为78.75%,传统检查法(胺试验、pH值)为62.50%与61.25%、BV快速检测法为77.50%。BV快速检测法检出阳性率显著高于传统检测法,差异有统计学意义(P0.05);传统检测法检测结果与其他3种比较,诊断结果最差。结论 BV快速检测法对细菌性阴道炎的检测速度较快且检出率较高,具有临床价值。     

Valproate in the treatment of epilepsy in girls and women of childbearing potential

This document provides guidance on the use of valproate in girls and women of childbearing age from a joint Task Force of the Commission on European Affairs of the International League Against Epilepsy (CEA‐ILAE) and the European Academy of Neurology (EAN), following strengthened warnings from the Coordination Group for Mutual Recognition and Decentralised Procedures‐Human (CMDh) of the European Medicines Agency (EMA), which highlight the risk of malformations and developmental problems in infants who are exposed to valproate in the womb. To produce these recommendations, the Task Force has considered teratogenic risks associated with use of valproate and treatment alternatives, the importance of seizure control and of patient and fetal risks with seizures, and the effectiveness of valproate and treatment alternatives in the treatment of different epilepsies. The Task Force's recommendations include the following: (1) Where possible, valproate should be avoided in women of childbearing potential. (2) The choice of treatment for girls and women of childbearing potential should be based on a shared decision between clinician and patient, and where appropriate, the patient's representatives. Discussions should include a careful risk–benefit assessment of reasonable treatment options for the patient's seizure or epilepsy type. (3) For seizure (or epilepsy) types where valproate is the most effective treatment, the risks and benefits of valproate and other treatment alternatives should be discussed. (4) Valproate should not be prescribed as a first‐line treatment for focal epilepsy. (5) Valproate may be offered as a first‐line treatment for epilepsy syndromes where it is the most effective treatment, including idiopathic (genetic) generalized syndromes associated with tonic–clonic seizures. (6) Valproate may be offered as a first‐line treatment in situations where pregnancy is highly unlikely (e.g., significant intellectual or physical disability). (7) Women and girls taking valproate require regular follow‐up for ongoing consideration of the most appropriate treatment regimen.     

Guidelines for ethical behavior relating to clinical practice issues in neuromuscular and electrodiagnostic medicine

The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed guidelines to formalize the ethical standards that neuromuscular and electrodiagnostic (EDx) physicians should observe in their clinical and scientific activities. Neuromuscular and EDx medicine is a subspecialty of medicine that focuses on evaluation, diagnosis, and comprehensive medical management, including rehabilitation of individuals with neuromuscular disorders. Physicians working in this subspecialty focus on disorders of the motor unit, including muscle, neuromuscular junction, axon, plexus, nerve root, anterior horn cell, and the peripheral nerves (motor and sensory). The neuromuscular and EDx physician's goal is to diagnose and treat these conditions to mitigate their impact and improve the patient's quality of life. The guidelines are consistent with the Principles of Medical Ethics adopted by the American Medical Association and represent a revision of previous AANEM guidelines. Muscle Nerve 52 : 1122–1129, 2015     

Phenylketonuria: brain phenylalanine concentrations relate inversely to cerebral protein synthesis

In phenylketonuria, elevated plasma phenylalanine concentrations may disturb blood-to-brain large neutral amino acid (LNAA) transport and cerebral protein synthesis (CPS). We investigated the associations between these processes, using data obtained by positron emission tomography with l-[1-¹¹C]-tyrosine (¹¹C-Tyr) as a tracer. Blood-to-brain transport of non-Phe LNAAs was modeled by the rate constant for ¹¹C-Tyr transport from arterial plasma to brain tissue (K₁), while CPS was modeled by the rate constant for ¹¹C-Tyr incorporation into cerebral protein (k₃). Brain phenylalanine concentrations were measured by magnetic resonance spectroscopy in three volumes of interest (VOIs): supraventricular brain tissue (VOI 1), ventricular brain tissue (VOI 2), and fluid-containing ventricular voxels (VOI 3). The associations between k₃ and each predictor variable were analyzed by multiple linear regression. The rate constant k₃ was inversely associated with brain phenylalanine concentrations in VOIs 2 and 3 (adjusted R²=0.826, F=19.936, P=0.021). Since brain phenylalanine concentrations in these VOIs highly correlated with each other, the specific associations of each predictor with k₃ could not be determined. The associations between k₃ and plasma phenylalanine concentration, K₁, and brain phenylalanine concentrations in VOI 1 were nonsignificant. In conclusion, our study shows an inverse association between k₃ and increased brain phenylalanine concentrations.