Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease

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Endogén pszichózisok klinikuma, összehasonlító nozológiája, genetikai, pszichometriai szociológiai és experimentális vizsgálata, 21-33 éves követéses vizsgálatuk alapján = Clinical, sociological, psychometric, experimental, genetic research and comparative nosology, of functional psychoses based on their 21-33-year follow through investigation

A hagyományos pszichopatológiában manifeszt és látens tünetek között észlelhető "szakadék" feltöltését az úgynevezett "alaptünetek" általunk alkotott becslésskálába foglalásának és az általunk konceptualizált Morbaffin Személyiségtípusok Skáláinak az alkalmazásával mutattuk meg. A "Spontán önjellemzés" innovációt bevezetve sajátos megoszlást mutattunk ki egyfelől normálkontroll személyek vs. betegek, másfelől különböző betegcsoportok között. Egy másik innovációnk a "reliabilitás validitása" terminus bevezetése és verifikálása. Ezt a negyed évszázad időkülönbséggel felvett pontozó skálák és a vizsgáló pontozók közötti egyezések vizsgálatával verifikáltuk. Ajánljuk a rendszeresítését. A Wechsler intelligenciateszt morbospecificitásának komparatív nozológiai vizsgálata során szignifikáns deficiteket mutattunk ki a 21-33 éves kórlefolyásban. Tudomásunk szerint elsőként vizsgáltuk meg a Leonhardi nozológiai rendszer validitását hosszú távú követéses katamnesztikus felméréssel. Ezt a nozológiai osztályozást egy sor összefüggésben validnak találtuk. Megállapítottuk a hallucináció hosszú távú változásainak nozospecifikus mintáit. A témavezető tudomány-logikai elemzést írt a pszichiátriai jelenlegi kríziséről. Továbbá két határterületi kérdést elemzett: "Szellem és kórságai", "Deviancia és rendszerváltozás". Kimutattuk, hogy a szám-szimbólum teszttel mért neurokognitív deficit a betegségfolyamat intenzitásának és tartamának függvénye. Pethő Bertalan | We demonstrated the relevance of a special psychopathological dimension between the definitive symptoms on one hand and the latent disturbances on the other by using two rating scales developed by us. We have found nosospecific pattern by introducing an innovative term and method named "Spontaneous self-characterization". Based on analyses of the data of psychopathological rating scales on one hand and on analyses of ratings of independent investigators on the other we introduced the new term "of reliability". We verified it by comparison of two series of assessments of the same population followed-up after a quarter of century. Using the Wechsler Intelligence Scale we have found nosospecific patterns of deficits being manifested in the 21-33-year course of illness. To our knowledge no previous long-term studies of the Leonhardean classification of endogenous psychoses have been conducted. Our prospective study started in 1967-1976. The same population was followed-up by participation of a "blind control" psychiatrist in 1997-2002. Hebephrenias, group of normal persons, of schizophrenias and of systematic paraphrenias proved to be valid. Bipolar manic-depressive psychoses, cycloid psychoses and unipolar depression were also valid by forming "nosological families". The digit symbol coding impairment was found to represent the disease process, which ultimately results in a "defect-state". Bertalan Peth

Az otosclerosis gyógyszeres kezelési lehetőségeinek áttekintése

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Hard nut to crack: Solving the disulfide linkage pattern of the Neosartorya (Aspergillus) fischeri antifungal protein 2

As a consequence of the fast resistance spreading, a limited number of drugs are available to treat fungal infections. Therefore, there is an urgent need to develop new antifungal treatment strategies. The features of a disulfide bond-stabilized antifungal protein, NFAP2 secreted by the mold Neosartorya (Aspergillus) fischeri render it to be a promising template for future protein-based antifungal drug design, which requires knowledge about the native disulfide linkage pattern as it is one of the prerequisites for biological activity. However, in the lack of tryptic and chymotryptic proteolytic sites in the ACNCPNNCK sequence, the determination of the disulfide linkage pattern of NFAP2 is not easy with traditional mass spectrometry-based methods. According to in silico predictions working with a preliminary nuclear magnetic resonance (NMR) solution structure, two disulfide isomers of NFAP2 (abbacc and abbcac) were possible. Both were chemically synthesized; and comparative reversed-phase high-performance liquid chromatography, electronic circular dichroism and NMR spectroscopy analyses, and antifungal susceptibility and efficacy tests indicated that the abbcac is the native pattern. This knowledge allowed rational modification of NAFP2 to improve the antifungal efficacy and spectrum through the modulation of the evolutionarily conserved gamma-core region, which is responsible for the activity of several antimicrobial peptides. Disruption of the steric structure of NFAP2 upon gamma-core modification led to the conclusions that this motif may affect the formation of the biologically active three-dimensional structure, and that the gamma-core modulation is not an efficient tool to improve the antifungal efficacy or to change the antifungal spectrum of NFAP2

Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP

Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity

The impact of currently recommended antihypertensive therapy on depression and other psychometric parameters: preliminary communication.

AIMS: Current evidence on the psychological effects of antihypertensive medications is controversial. The aim of this study was to evaluate the effect of current antihypertensive medication on different psychometric parameters and on serum brain-derived neurotrophic factor (BDNF) level. METHODS: Psychometric, haemodynamic, arterial stiffness and laboratory parameters were evaluated before and 3 months after the initiation of antihypertensive medication in untreated hypertensive patients (HT, n=31), and once in healthy controls (CONT, n=22). Subjects completed the following psychometric tests: Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAM-A), Symptom Checklist 90 Revised (SCL-90), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire, Big Five Inventory, Pain Vigilance and Awareness Questionnaire and Berkeley Expressivity Questionnaire. Amlodipine and/or perindopril compounds were preferred medications. Serum BDNF was measured with ELISA. RESULTS: Brachial systolic blood pressure, as well as pulse wave velocity were significantly improved in the HT group over the 3-month follow-up (153.3+/-15.9 mmHg vs. 129.5+/-10.0 mmHg and 8.2+/-1.4 m/s vs 7.5+/-1.6 m/s, respectively). Similarly, we found improvements in BDI (0.73 points) and in several Scl-90 subscales. Serum BDNF was not different between CONT and HT and did not change for therapy. CONCLUSIONS: Our results indicate that initiation of currently recommended antihypertensive medications in newly diagnosed patients may have a significant impact on psychological well-being of patients and could influence quality of life as well

Confirmation of the Disulfide Connectivity and Strategies for Chemical Synthesis of the Four-Disulfide-Bond-Stabilized Aspergillus giganteus Antifungal Protein, AFP

Emerging fungal infections require new, more efficient antifungal agents and therapies. AFP, a protein from Aspergillus giganteus with four disulfide bonds, is a promising candidate because it selectively inhibits the growth of filamentous fungi. In this work, the reduced form of AFP was prepared using native chemical ligation. The native protein was synthesized via oxidative folding with uniform protection for cysteine thiols. AFP's biological activity depends heavily on the pattern of natural disulfide bonds. Enzymatic digestion and MS analysis provide proof for interlocking disulfide topology (abcdabcd) that was previously assumed. With this knowledge, a semi-orthogonal thiol protection method was designed. By following this strategy, out of a possible 105, only 6 disulfide isomers formed and 1 of them proved to be identical with the native protein. This approach allows the synthesis of analogs for examining structure-activity relationships and, thus, preparing AFP variants with higher antifungal activity