Judit Soós

Widespread increased expression of the DNA repair enzyme PARP in brain in ALS.

Expression of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) is a known response to oxidative damage of DNA. In ALS brain, PARP expression by western analyses was increased in the motor cortex, parietal cortex, and cerebellum. PARP immunostaining in the motor cortex was increased in ALS neurons and subcortical glia and macrophages. Importantly, there was widespread increased PARP expression in neurons in the parietal cortex and cerebellum, regions that are typically clinically unaffected in ALS, suggesting widespread oxidative stress.

Subcellular localization of IgG from the sera of ALS patients in the nervous system

Immunoglobulin G (IgG) samples isolated from the sera of amyotrophic lateral sclerosis (ALS) and control patients were injected intraperitoneally into mice. After 24 h the mice were processed for immune electron microscopic immunohistochemistry to localize IgG in their nervous system. The injected ALS IgG was observed in the axon terminals of the lower motor neurons (MNs), localized to the microtubules and enriched in the rough endoplasmic reticulum (RER). In post‐mortem spinal cord samples from ALS patients, IgG was similarly detected in the vicinity of the microtubules and in the RER of the MNs. IgG was neither found in the corresponding structures of MNs of mice injected with the control human IgG nor in post‐mortem human control spinal cord samples. The data suggest that multiple antibodies directing to different structures of the MNs may play a role in their degeneration in ALS.

Comparative study of nanosized cross-linked sodium-, linear sodium- and zinc-hyaluronate as potential ocular mucoadhesive drug delivery systems

Hyaluronic acid (HA) and its derivatives play important roles in many fields of therapy, such as arthritis treatment, plastic surgery, dermatology, otology, ophthalmology, etc. With a view to increase the beneficial properties of HA in ocular drug delivery, many types of chemical structural modifications have been performed. In the course of our research work, we characterized nanosized cross-linked - (CLNaHA), linear sodium hyaluronate (NaHA) and zinc-hyaluronate (ZnHA), as potential ocular drug delivery systems. The aim was to determine the influence of the structure on biocompatibility, mucoadhesion and drug release. The structure was characterized by means of rheology. The cytotoxicity of the samples was determined on rabbit corneal epithelial cells (RCE) by the MTT test. Mucoadhesion measurements were made by a rheological method in vitro and by tensile tests in vitro and ex vivo. The release of sodium diclofenac, a frequently used non-steroidal anti-inflammatory drug with low bioavailability, from the gels was determined with a vertical Franz diffusion cell. The results demonstrated that all three derivatives have adequate mucoadhesive properties and their rapid drug release profiles are beneficial in ocular therapy. Thanks to these properties, the bioavailability of the ophthalmic preparations can be increased, especially with the application of CLNaHA.

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N′,N′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.

Mucoadhesive Cyclodextrin-Modified Thiolated Poly(aspartic acid) as a Potential Ophthalmic Drug Delivery System

Thiolated poly(aspartic acid) is known as a good mucoadhesive polymer in aqueous ophthalmic formulations. In this paper, cyclodextrin-modified thiolated poly(aspartic acid) was synthesized for the incorporation of prednisolone, a lipophilic ophthalmic drug, in an aqueous in situ gellable mucoadhesive solution. This polymer combines the advantages of cyclodextrins and thiolated polymers. The formation of the cyclodextrin-drug complex in the gels was analyzed by X-ray powder diffraction. The ocular applicability of the polymer was characterized by means of physicochemical, rheological and drug diffusion tests. It was established that the chemical bonding of the cyclodextrin molecule did not affect the complexation of prednisolone, while the polymer solution preserved its in situ gellable and good mucoadhesive characteristics. The chemical immobilization of cyclodextrin modified the diffusion profile of prednisolone and prolonged drug release was observed. The combination of free and immobilized cyclodextrins provided the best release profile because the free complex can diffuse rapidly, while the bonded complex ensures a prolonged action.

Acetazolamid orális alkalmazása mellett jelentkező chorioidealeválás két esete: ismert idioszinkráziás hatás szokatlan megjelenési formája?

Absztrakt: A szulfonamidszarmazekok („sulpha drugs”) szeles korben es valtozatos indikacioval alkalmazott gyogyszerek hatoanyagat kepezik. Az elmult nehany evtizedben szamos kozlemeny jelent meg a fenti szerek, kulonosen az acetazolamid altalanos alkalmazasa mellett, szemeszeti idioszinkrazias hataskent jelentkező sugartest- es erhartyalevalasrol, amit minden publikalt esetben tranzitorikus myopia es/vagy akut szemnyomas-emelkedes megjelenese kapcsan diagnosztizaltak. Jelen kozlemenyben ket olyan esetet ismertetunk, ahol a gyogyszermellekhataskent jelentkező chorioidealevalas veletlen lelet volt, es ahhoz sem a refrakcio valtozasa, sem a szemnyomas kiugrasa nem tarsult. Tudomasunk szerint ez az első kozlemeny, amely az acetazolamid okozta chorioideaablatio ezen specialis, „nema” formajarol szamol be. Tekintve, hogy az erhartya erintettsege valtozo mertekű lehet, es – eseteink alapjan – nem feltetlenul jar egyutt akut glaucomaval es rovidlatassal, feltetelezzuk, hogy az acetazolamid szemeszeti mellekhatasa...