Ioncsatornák, modulációs mechanizmusok és szinaptikus kapcsolatok jelentősége a patkány nucleus cochlearis jelfeldolgozó működésében = Roles of ion channels, modulatory mechanisms and synaptic connections in the signal processing of the rat cochlear nucleus

A projekt célja a nucleus cochlearis jelfeldolgozó tevékenységében jelentős ioncsatornák, modulációs mechanizmusok és szinaptikus kapcsolatok elemzése volt. A munka legfontosabb eredményei a következők: (a) Azonosítottuk a nucleus cochlearisban expresszált HCN-csatornaalegységeket. Feltártuk a h-áram jelentőségét az óriássejtek elektromos sajátságaiban és szinaptikus kapcsolataik finomhangolásában. (b) Leírtuk a kolinerg ingerlés hatását az óriássejtek elektrofiziológiai sajátságaira és a rajtuk kialakuló posztszinaptikus áramokra. Azonosítottuk a hatást közvetítő receptor-altípusokat. (c) Elemeztük a szemcsesejtek aktivitásfüggő intracelluláris kalciumkoncentráció-változásait. Kifejlesztettünk egy olyan félautomatikus kiértékelési eljárást, ami alkalmas a neuronális kalciumtranziensek felismerésére és analízisére. (d) Feltártuk egyes muszkarinerg receptorok szerepét sejttenyészeti körülmények között fenntartott astrocyták intracelluláris kalciumkoncentráció-változásaiban. (e) Képalkotó és elektrofiziológiai módszereket alkalmazva leírtuk a nucleus cochlearisban található Purkinje-szerű neuronok sajátságait. (f) Kvantitatív morfometriai analízis segítségével azonosítottuk a pyramis- és az óriássejtek elkülönítésére legalkalmasabb paramétereket. (f) Leírtuk a tacrolimus hatását a pyramis-sejteken kialakuló posztszinaptikus áramok tulajdonságaira. (g) Feltártuk a protein-foszfatáz-1M és a Rho-kináz szerepét a bushy-sejtek és az acusticus rostok közötti szinapszis működésében. | Our aim was to assess the roles of ionic channels, modulatory mechanisms, and synaptic connections in regulating the activity of the cochlear nucleus (CN). The most important results are as follows. (a) We identified all HCN channel subunits expressed in the CN. We revealed the significance of the h-current in shaping the electrical properties and fine-tunig the synaptic connections of the giant cells. (b) We described the effects of cholinergic stimulation on the membrane properties and postsynaptic currents of the giant cells along with the identification of the receptor subtypes mediating the effects. (c) We investigated activity-related cytoplasmic calcium concentration changes of the granule neurones, and developed a semiautomatic method for the identification and evaluation of neuronal calcium transients. (d) We assessed the involvement of various muscarinergic receptors in the regulation of intracellular calcium concentration changes of cultured astrocytes. (e) Using imaging and electrophysiological techniques, we described the properties of Purkinje-like cells of the CN. (f) We identified morphological parameters that are suitable for the unambiguous discrimination between pyramidal and giant neurones. (f) We documented the effects of tacrolimus on the postsynaptic currents recorded from pyramidal neurones. (g) We revealed and described the roles of the protein-phosphatase-1M and Rho-kinase in the synaptic transmission between the bushy cells and acoustic fibers

Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis

The aim of the present study was to investigate the expression of Fas in periarticular tenocytes of patients with osteoarthritis (OA) and to study their susceptibility to Fas ligand-mediated apoptosis. Tendon samples were obtained from the quadriceps femoris muscle of patients with knee OA and used for histological evaluation, for immunohistochemical detection of Fas, and to establish tenocyte cultures. The expression of Fas mRNA was determined by quantitative PCR. Levels of soluble Fas and soluble tumour necrosis factor (TNF) receptor I were measured using ELISA. Apoptosis was induced with recombinant human Fas ligand and measured by a histone fragmentation assay and flow cytometry. The effects of TNF-α were studied by stimulation with TNF-α alone or 24 hours before the induction of apoptosis. Tendon samples from non-OA patients were used as controls. Histological evaluation revealed degenerative changes in the tendons of all OA patients but not in the controls. Fas was detected by immunohistochemistry in all specimens, but quantitative PCR revealed significantly higher levels of Fas mRNA in OA tenocytes. In contrast, lower levels of soluble Fas were found in OA tenocytes by ELISA. OA tenocytes were significantly more susceptible to Fas ligand induced apoptosis than were control cells. TNF-α reduced the Fas ligand induced apoptosis in OA tenocytes but had no effects on control tenocytes. These data suggest that knee OA is associated with higher susceptibility of periarticular tenocytes to Fas ligand induced apoptosis because of higher expression of Fas but lower levels of apoptosis-inhibiting soluble Fas. These changes may contribute to decreased cellularity in degenerative tendons and promote their rupturing. The antiapoptotic effects of TNF-α in OA tenocytes most likely reflect regenerative attempts and must be taken into account when anti-TNF strategies are considered for OA

Osteoclast-independent bone resorption by fibroblast-like cells

To date, mesenchymal cells have only been associated with bone resorption indirectly, and it has been hypothesized that the degradation of bone is associated exclusively with specific functions of osteoclasts. Here we show, in aseptic prosthesis loosening, that aggressive fibroblasts at the bone surface actively contribute to bone resorption and that this is independent of osteoclasts. In two separate models (a severe combined immunodeficient mouse coimplantation model and a dentin pit formation assay), these cells produce signs of bone resorption that are similar to those in early osteoclastic resorption. In an animal model of aseptic prosthesis loosening (i.e. intracranially self-stimulated rats), it is shown that these fibroblasts acquire their ability to degrade bone early on in their differentiation. Upon stimulation, such fibroblasts readily release acidic components that lower the pH of their pericellular milieu. Through the use of specific inhibitors, pericellular acidification is shown to involve the action of vacuolar type ATPases. Although fibroblasts, as mesenchymal derived cells, are thought to be incapable of resorbing bone, the present study provides the first evidence to challenge this widely held belief. It is demonstrated that fibroblast-like cells, under pathological conditions, may not only enhance but also actively contribute to bone resorption. These cells should therefore be considered novel therapeutic targets in the treatment of bone destructive disorders

MORFOMETRIAI KUTATÁSOK AZ EMBERI ARC TÖRTÉNETI EMBERTANI, IGAZSÁGÜGYI, ÉS GYÓGYÁSZATI CÉLÚ 3D REKONSTRUKCIÓJÁNAK FEJLESZTÉSÉHEZ = MORPHOMETRIC RESEARCH FOR DEVELOPING THE 3D FACIAL RECONSTRUCTION METHOD FROM THE PURPOSE OF HISTORIC- AND FORENSIC ANTHROPOLOGY, AND MEDICINE

Létrehoztuk a FACE-R 3D koponya és- arc kutatói adatbázist, amely 425 élő vizsgálati személy és 5 kadáver fej adatait tartalmazza. Mysql adatbázisban tároljuk az adatállományokat, valamint a feldolgozás során nyert plusz információkat. Az adatbázis nemzetközi viszonylatban is egyedülálló, mert az illesztett 3D koponya CT-és arc modellek létrehozásával kiküszöböltük a fekvő helyzetben készülő gravitációs elmozdulást a CT-felvételeken. Előzetes elemzést végeztünk 60 egyén adatain 3D virtuális antropológiai és geometrikus morfometriai módszerekkel. Szignifikáns alaki összefüggéseket találtunk a koponya és az arc között. 20 egyén koponyáján feltáró EFA (Elliptic Fourier Analysis) elemzést végeztünk. Statisztikai módszerrel hiányzó adatpótlást végeztünk Szt. László király állkapocs rekonstrukciójához. A fekvő és- ülő helyzetű arcmodellek közti eltérés statisztikai vizsgálatára 3D biometriai elemzést végeztünk. Az arc matematikai modellezéséhez szükséges módszertani fejlesztések során standardizáltuk a 3D modelleket és programot írtunk a 3D felületi változékonyság jellemzésére, a min-max görbületi görbesereg meghatározására. Kidolgoztuk a koponya és az arc 3D „karakterisztikus geometriai modelljének” koncepcióját. Kísérleteket végeztünk a 3D külső orr rekonstrukció matematikai modelljének létrehozása. Elasztikus regisztrációs eljárást alkalmaztunk az arc modellezéséhez szükséges kiindulási adatok (3D template-ek) létrehozására. | We created the „FACE-R” 3D skull- and face research database, that is contain 425 living individuals’ and 5 cadavers’ head data. We stored the data files and the additional information in Mysql database. Thanks to the aligned 3D skull- and face models, we were able to eliminate the gravitational shift on CT-scans — recorded in supine position —, the database is unique in international relations as well. In the framework of the pilot study the virtual anthropological data collection and geometric morphometric analysis was performed on 60 persons’ data. We uncovered significant shape correlations between the skulls- and the faces. We performed exploratory EFA (Elliptic Fourier Analysis) on 20 persons’ skulls. Missing data complementation was accomplished applying statistical method for virtual mandible reconstruction of St. Laszlo, the Hungarian king. We carried on biometric analysis to uncover differences between the supine- and upright positioned 3D face models. In the framework of methodological development necessary for mathematical modelling the face, we standardized the 3D models than programmed an application for determine the min-max. curvature on the 3D skull- and face model surfaces. We worked out the concept of the „3D Characteristic Geometric Model” of the skulls and faces. We made some attempts to create a mathematical model for the 3D external nose reconstruction. We produced the 3D input templates for modelling the face applying „elastic registration” method

Massive rotator cuff tears: functional outcome after debridement or arthroscopic partial repair

Background The surgical treatment of massive rotator cuff tears (RCT) is still controversial and can be based on a variety of different surgical repair methods. This study investigated the effectiveness of arthroscopic debridement or arthroscopic partial repair in patients with massive RCT. Materials and methods This prospective, randomized study involved forty-two patients with massive RCT (fatty infiltration stage 3 or 4) treated with either arthroscopic partial repair or arthroscopic debridement were selected to detect possible differences in functional outcome. Both groups were matched according to age and gender. Patients were examined before, and 16 ± 3 and 24 ± 2 months after surgery. The status of the rotator cuff repair was determined using ultrasonographic evaluation. Results Regardless of the treatment group, postoperative results demonstrated highly significant improvements compared with preoperative values in most parameters. The overall Constant score in the partial repair group was superior to the outcome in the debridement group (P \ 0.01, F = 8.561), according to better results in abductio