Search

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS.

Objective: The value of endoscopic transsphenoidal surgery of pituitary adenomas compared to the traditional microscopic technique is still discussed in the literature. Here we analyse our long-term results of both approaches in 38 consecutive cases, using patient- as well as clinician-related outcome[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Restless Legs Syndrome (RLS) is primarily treated with levodopa and dopaminergics that target the inhibitory dopamine receptor subtypes D3 and D2. The initial success of this therapy led to the idea of a hypo-dopaminergic state as the mechanistic origin underlying RLS. However, multiple lines of evidence suggest that this simplified concept of a reduced dopamine function as the basis of RLS is incomplete. Moreover, long-term medication with the D2/D3 agonists leads to a reversal of the initial benefits of dopamine agonists and augmentation, which is a worsening of symptoms under therapy. The recent findings on the state of the dopamine system in RLS that support the notion that a dysfunction in the dopamine system may in fact give rise to a hyper-dopaminergic state is summaraized. Based on this data, the concept of a dynamic nature of the dopamine effects in a circadian context, is presented. The possible interactions of cell-adhesion molecules expressed by dopaminergic systems and their possible impact on RLS and augmentation are discussed. Genome-wide association studies (GWAS) indicate a significantly increased risk for RLS in populations with genomic variants of the cell adhesion molecule receptor type protein tyrosine phosphatase D (PTPRD), and PTPRD is abundantly expressed by dopamine neurons. PTPRD may play a role in the reconfiguration of neural circuits, including shaping the interplay of G protein-coupled receptor (GPCR) homomers and heteromers that mediate dopaminergic modulation. Recent animal model data support the concept that interactions between functionally-distinct dopamine receptor subtypes can re-shape behavioral outcomes and change with normal aging. Additionally, long-term activation of one dopamine receptor subtype can increase receptor expression of a different receptor subtype with opposing modulatory actions. Such dopamine receptor interactions at both spinal and supra-spinal levels appear to play important roles in RLS. In addition, these interactions can also extend to the adenosine A2A receptor, which is also prominently expressed in the striatum. Interactions between A2A and dopamine receptors and dopaminergic cell adhesion molecules, including PTPRD, may provide new pharmacological targets in treating RLS. In summary, new treatment options for RLS that include recovery from augmentation will have to take into account dynamic changes to the dopamine system that occur during the circadian cycle, plastic changes that can develop as a function of treatment or with aging, changes to the connectome based on alterations to cell adhesion molecules, and receptor interactions that may reach beyond the dopamine system itself.

Einleitung: Aus zwei Studien in einem Zeitraum von 10 Jahren konnten retrospektive Langzeitergebnisse zum Funktionsverhalten verglichen werden. Es handelt sich um insgesamt 188 Augen. Methoden: Die Visusverläufe wurden anhand von Langzeit-Nachuntersuchungen daraufhin verglichen, ob Unterschiede[zum vollständigen Text gelangen Sie über die oben angegebene URL], 66. Tagung der Vereinigung Norddeutscher Augenärzte

Einleitung: Die äußere Abriegelung der retikulären Schisis durch thermische Koagulation in der eigenen Studie komplett zugunsten der Koagulation innerhalb der Schisisblase aufgegeben. Bei 15 Patienten konnte eine Bestätigung des geänderten Verfahrens gefunden werden. Bei 10 [for full text, please go to the a.m. URL], 65. Tagung der Vereinigung Norddeutscher Augenärzte

Dopamine is a catecholaminergic neuromodulatory transmitter that acts through five molecularly-distinct G protein-coupled receptor subtypes (D(1)-D(5)). In the mammalian spinal cord, dopaminergic axon collaterals arise predominantly from the A11 region of the dorsoposterior hypothalamus and project diffusely throughout the spinal neuraxis. Dopaminergic modulatory actions are implicated in sensory, motor and autonomic functions in the spinal cord but the expression properties of the different dopamine receptors in the spinal cord remain incomplete. Here we determined the presence and the regional distribution of all dopamine receptor subtypes in mouse spinal cord cells by means of quantitative real time polymerase chain reaction (PCR) and digoxigenin-label in situ hybridization. Real-time PCR demonstrated that all dopamine receptors are expressed in the spinal cord with strongly dominant D(2) receptor expression, including in motoneurons and in the sensory encoding superficial dorsal horn (SDH). Laser capture microdissection (LCM) corroborated the predominance of D(2) receptor expression in SDH and motoneurons. In situ hybridization of lumbar cord revealed that expression for all dopamine receptors was largely in the gray matter, including motoneurons, and distributed diffusely in labeled cell subpopulations in most or all laminae. The highest incidence of cellular labeling was observed for D(2) and D(5) receptors, while the incidence of D(1) and D(3) receptor expression was least. We conclude that the expression and extensive postsynaptic distribution of all known dopamine receptors in spinal cord correspond well with the broad descending dopaminergic projection territory supporting a widespread dopaminergic control over spinal neuronal systems. The dominant expression of D(2) receptors suggests a leading role for these receptors in dopaminergic actions on postsynaptic spinal neurons.

At the conference "Flexible Europe - Mobility as a tool for enhancing research capacity" (Tallinn, Estonia, 19 - 20 September 2002 - http://www2.archimedes.ee/mobility/) the European Commission presented a first outline of their new ‘pan-European Researcher’s Mobility Portal’. The Marie Curie Fellowship Association (MCFA) was invited to provide comments and suggestions for the development of the portal. Based on input from a large number of MCFA members, a document with recommendations was drawn up, which was discussed with representatives from DG RTD, Directorate D: ‘The Human Factor, Mobility and Marie Curie Actions’, at a meeting in Brussels in December 2002. The document addresses the following topics: I. General Set-up of the Portal II. Information on Grants, Fellowships, Job Offers and similar III. Practical Information IV. European Science and Research Policy V. Discussion Area VI. Language of the Portal VII. Securing the Quality of the Information provided on the Portal VIII. Obtaining the Information to be displayed on the Portal IX. Other Comments on the Portal X. The Mobility Centers