Glycine transporter type-1 and its inhibitors

The ionotropic glutamate receptor NMDA is allosterically modulated by glycine, a coagonist, its presence is an absolute requirement for receptor activation. The transport of glycine in glutamatergic synapse is carried out by glycine transporter-1 (GlyT1), a Na+/Cl(-)-dependent carrier molecule. The primary role of GlyT1 is to maintain glycine concentrations below saturation level at postsynaptic NMDA receptors. Several isoforms of GlyT1 (a-e) have been identified, which are expressed both in glial and neuronal cell membranes. GlyT1 operates bidirectionally: it decreases synaptic glycine concentration when operates in normal mode and releases glycine from glial cells as operates in a reverse mode. It is expected that non-transportable, non-competitive inhibitors of GlyT1 may have therapeutic value in CNS disorders characterized by hypofunctional NMDA receptor-mediated glutamatergic neurotransmission. Accordingly, GlyT1 inhibitors exhibited antipsychotic profile in a number of animal tests. The first promising in vitro and in vivo experiments with glycine itself, and its N-methyl analogue, sarcosine, had initiated the syntheses of potential GlyT1 inhibitors with more complex structures, in which, however, the glycine or sarcosine moiety had always been incorporated. Those attempts led to the development of two compounds, ALX-5407 and Org-24461 with high inhibitory potency; however, none of which is now considered as a drug candidate due, most probably, to safety and/or pharmacokinetic issues. More recently, several structurally new series of highly potent inhibitors with no aminomethylcarboxy group have also been discovered. Some of them might be expected to fulfill all requirements for clinical development. The new generation of GlyT1 inhibitors may represent a novel treatment of patients suffering from schizophrenia and/or other neuropathological conditions.     

Brain plasticity and pathology in psychiatric disease: sites of action for potential therapy

Recent advances have been made in understanding the changes in neuronal plasticity in psychiatric disease at the molecular level (changes in neurotransmission, long-term potentiation, long-term depression, glutamate receptors, synaptic strength and neurotrophic support) and the systems level (changes in hippocampal, frontal and amygdala function in health and disease and the impact of stress on the hippocampal/frontal axis), as well as in the impact of drugs and sites of action for therapeutic intervention. Drugs acting on plasticity could affect the abnormal set point in psychiatric disease, resulting in treatment of the disease rather than just the symptoms.     

肝炎后高胆红素血症18例分析

0　引言　肝炎后高胆红素血症 ,极易与肝炎伴发高胆红素血症相混淆 .该病是肝炎后遗症之一 ,临床上并不少见 .患者常以间歇性黄疸或隐性黄疸前来就诊 ,但并无先天性黄疸、肝炎、肝硬化及肝内外胆管结石的临床证据 ,多数既往有肝炎病史 ,肝炎已达治愈标准 ,虽增加活动量亦无复发 ,临床预后良好 .现将我院 1995 - 10 / 1999- 0 9肝炎后高胆红素血症 18例作一小结 .1　临床资料　男 12例 ,女 6例 ,年龄 2 2～ 5 8(平均 40岁 ) .门诊 11例 ,住院 7例 .其中 11例曾患急性病毒性乙型肝炎 ,1例曾患中毒性肝炎 ,1例曾患药物性肝炎 ,5例无明确肝炎病…     

人脑动静脉畸形中VEGF的表达变化

目的 :探讨 VEGF在脑动静脉畸形的变化。方法 :14例 AVMs行显微外科手术切除 AVMs和 AVMs周围脑组织、 8例正常脑血管和脑组织标本 ,分别提取总 RNA。 RNA狭逢斑点杂交检测 VEGF在脑 AVMs中的改变。结果 :与正常脑血管相比 ,AVMs、 AVMs周围脑组织 VEGF m RNA表达增高 ;结论 :VEGF可能与脑 AVMs的发生发展有关。     

Einsichtsrecht des Patienten in die Originalbilder

Abstrakt 1. Der Patient hat gegen den ihn behandelnden Arzt einen Anspruch auf Einsichtnahme in die von diesem gefertigten Originalr?ntgenbilder. 2. Der Patient kann insoweit die überlassung der Originalr?ntgenbilder an den von ihm bevollm?chtigten Rechtsanwalt in dessen Kanzleibetrieb zum Zwecke der Einsichtnahme verlangen. Auf eine Einsichtnahme in den Praxisr?umen des Arztes muss sich der Patient nicht verweisen lassen. (Leits?tze der Bearbeiterin)     

Zur Darlegungslast und Haftung des erstbehandelnden Zahnarztes, der behauptet, M?ngel einer Prothetik seien erst durch nachbehandelnde ?rzte verursacht worden

1. §27 Abs.6 Berufsordnung der Nordrheinischen ?rztinnen und ?rzte ist eine das Marktverhalten regelnde Vorschrift i.S. des §4 Nr.11 UWG. 2. Die Eintragung in den “Gelben Seiten” ist Werbung i.S. des §27 Berufsordnung für die Nordrheinischen ?rztinnen und ?rzte. L?sst sich ein Facharzt für Mund-, Kiefer und Gesichtschirurgie in der Kategorie “plastische Chirurgie” eintragen, ohne dass sich aus diesem Eintrag ergibt, dass der Eingetragene diese Leistungen (nur) nach eigenen Angaben, also ohne objektive Best?tigung, erbringt, liegt ein Versto? gegen §27 Abs.6 Berufsordnung für die Nordrheinischen ?rztinnen und ?rzte vor. (Leits?tze des Bearbeiters)     

Correction of misaligned slices in multi-slice cardiovascular magnetic resonance using slice-to-volume registration

A popular technique to reduce respiratory motion for cardiovascular magnetic resonance is to perform a multi-slice acquisition in which a patient holds their breath multiple times during the scan. The feasibility of rigid slice-to-volume registration to correct for misalignments of slice stacks in such images due to differing breath-hold positions is explored. Experimental results indicate that slice-to-volume registration can compensate for the typical misalignments expected. Correction of slice misalignment results in anatomically more correct images, as well as improved left ventricular volume measurements. The interstudy reproducibility has also been improved reducing the number of samples needed for cardiac MR studies.     

伴或不伴有左心室收缩功能障碍的慢性心力衰竭患者中房颤与临床事件危险度的关系：来自CHARM（坎地沙坦治疗心力衰竭-降低死亡率与发病率的评估）研究的结果

房颠是慢性心衰患者中最常见的持续性心律失常。其患病率和发病率随年龄增长及心衰加重而升高，在某些研究中上升到50％。心房收缩功能的丧失导致每搏量下降，灌注压升高及心房扩大。快速心室率及不规则心律进一步降低心脏充盈和排空。房颠影响慢性心衰预后的重要性已经在临床研究、门诊病人队列研究以及流行病学研究等多种情况下得到了验证。     

Zum Umfang des Schadensersatzes für die Geburt eines behinderten Kindes nach fehlerhafter Beratung

Ohne Zusammenfassung