A Multidimenzionális Észlelt Társas Támogatás Kérdőív magyar nyelvű validálása = Validation of the Hungarian version of Multidimensional Scale of Perceived Social Support

Elméleti háttér A társas beágyazottság az optimális funkcionálás, a jóllét egyik komponense. Emellett hazai és nemzetközi eredmények szerint is a lelki és testi egészség megőrzésének kulcstényezője – elsősorban stresszhelyzetekben. A Multidimenzionális Észlelt Társas Támogatás Kérdőívet (Multidimensional Scale of Perceived Social Support; MSPSS) 1988-ban fejlesztették ki Zimet és munkatársai, és azóta több európai és ázsiai nyelvre is lefordították. A kérdőív pszichometriai jellemzői a legtöbb esetben kiválóak. Cél: Mivel magyar nyelven jelenleg egyetlen validált, a Caldwell-féle, társas támogatást mérő kérdőív érhető el, amelynek a kiértékelése nehezen számszerűsíthető, tanulmányunk célja, hogy bemutassuk a MSPSS kérdőív magyar nyelvű validálását felnőtt mintán (n = 1073; 72,9% nő). Módszerek A feltáró faktoranalízis mellett megerősítő eljárást is alkalmaztunk. A konvergens és divergens validitás vizsgálatára a következő mérőeszközöket használtuk fel: Társas Támogatás Erőssége Kérdőív, Caldwell-féle Társas Támogatás Kérdőív, Általános Énhatékonyság Skála, Big Five Kérdőív Extraverzió és Barátságosság skálái és a Családi Szocializáció Kérdőív. Eredmények A feltáró és megerősítő faktorelemzés eredményei alapján a végső kérdőívben 10 tétel maradt. Ebből 4 állítás a Család alfaktorához, 3 állítás a Barátok alfaktorához és 3 állítás a Jelentős mások alfaktorához tartozik. Az egyes faktorok belső megbízhatósága (Család: Cronbach-α = 0,91; Barátok: Cronbach-α = 0,93; Jelentős mások: Cronbach-α = 0,87) és az egész kérdőív reliabilitása (Cronbach-α = 0,91) megfelelőnek bizonyult. A kérdőív illeszkedési mutatói az elfogadható vagy a jó tartományba estek (CMIN/DF = 5,876; CFI = 0,974; RMSEA = 0,08; GFI = 0,949; TLI = 0,963). Következtetések Az MSPSS magyar változata egy érvényes és megbízható mérőeszköz, amely egyrészt mutat összefüggést más, széles körben használt sztenderd kérdőívekkel, másrészt van az észlelt társas támogatás pszichológiai kérdéskörének több olyan szelete, amelyet a korábbi eszközök nem fedtek le, így indokolt az új kérdőív bevezetése. | Background One of the most important factors of well-being is social embeddedness. Moreover, social embededness is the most determining predictor of physical and mental health mainly in stress situations, according to Hungarian and international studies. Multidimensional Scale of Perceived Social Support (MSPSS) was developed by Zimet et al. in 1988, and since then it has been translated to other Caucasian and Asian languages. Psychometrical characteristics of the scale seem to be excellent. Aims The aim of our study was to validate the Hungarian MSPSS with a sample of adults (N = 1073, 72.9% women). In Hungary only the Support Dimension Scale is available, that evaluation is not easily quantifiable. Methods Both exploratory and confirmatory factor analyses were conducted on the sample data. Convergent and divergent validity was measured with the following scales: Caldwell Support dimensions Scale, General Self-efficacy Scale, Big Five Inventory, and Family Socialisation Questionnaire. Results After factor analyses the final version of the measure consists of 10 items. 4 items related to Family subfactor, 3 items related to Significant Others subfactor, and 3 items to Friends subfactor. The computed psychometric properties suggest that each factor has a good level of reliabilty and validity (Family: Cronbach’s α = .91; Friends: Cronbach’s α = .93; Significant Others: Cronbach’s α = .87, MSPSS Total: Cronbach’s α = .91). The goodness of fit results of the scale were appropriate or good (CMIN/DF = 5.876, CFI = 0.974, RMSEA = 0.08, GFI = 0.949, TLI = 0.963). Conclusions The Hungarian version of MSPSS is a valid and reliable measurement that on the one hand shows correlations with other, widely used standardized questionnaires. On the other hand there are several pieces studying the psychological factors of perceived social support, which are not covered entirely by previous questionnaires. Therefore, developing the Hungarian version of MSPSS is justified

Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes

Several studies have reported that statins occasionally cause impairment of liver functions characterized by elevated serum bilirubin levels, which might be due to altered function of the multidrug resistanceassociated proteins (Mrp2/3). We aimed to study the modulation of the hepatobiliary transport of bilirubin by four statin derivatives, atorvastatin, fluvastatin, pravastatin, and rosuvastatin in sandwichcultured rat hepatocytes. All statins except pravastatin significantly inhibited the uptake of bilirubin. The biliary efflux of bilirubin conjugates was increased by pravastatin and rosuvastatin concentration dependently. Rosuvastatin stimulated not only the Mrp2 mediated biliary, but the Mrp3 mediated sinusoidal elimination, resulting in decreased intracellular bilirubin accumulation. The significantly induced Mrp2/3 protein levels (ranging from 1.5 to 1.8-fold) accounted for the elevated efflux. Cell polarization, the formation of biliary network was also significantly increased by fluvastatin, pravastatin and rosuvastatin (151%, 216% and 275% of the control, respectively). The simultaneous inhibition of the uptake and the stimulation of the sinusoidal and canalicular elimination may explain, at least in part, the clinical observation of elevated serum bilirubin levels. In conclusion, our results suggest that in spite of the elevated serum bilirubin levels, the altered Mrp2 and Mrp3 functions by statins is probably not associated with hepatotoxic effects

Ligand-Specific Regulation of the Endogenous Mu-Opioid Receptor by Chronic Treatment with Mu-Opioid Peptide Agonist

Since the discovery of the endomorphins (EM), the postulated endogenous peptide agonists of the mu-opioid receptors, several analogues have been synthesized to improve their binding and pharmacological profiles. We have shown previously that a new analogue, cis-1S,2R-aminocyclohexanecarboxylic acid2-endomorphin-2 (ACHC-EM2), had elevated mu-receptor affinity, selectivity, and proteolytic stability over the parent compound. In the present work, we have studied its antinociceptive effects and receptor regulatory processes. ACHC-EM2 displayed a somewhat higher (60%) acute antinociceptive response than the parent peptide, EM2 (45%), which peaked at 10 min after intracerebroventricular (icv) administration in the rat tail-flick test. Analgesic tolerance developed to the antinociceptive effect of ACHC-EM2 upon its repeated icv injection that was complete by a 10-day treatment. This was accompanied by attenuated coupling of mu-sites to G-proteins in subcellular fractions of rat brain. Also, the density of mu-receptors was upregulated by about 40% in the light membrane fraction, with no detectable changes in surface binding. Distinct receptor regulatory processes were noted in subcellular fractions of rat brains made tolerant by the prototypic full mu-agonist peptide, DAMGO, and its chloromethyl ketone derivative, DAMCK. These results are discussed in light of the recently discovered phenomenon, that is, the “so-called biased agonism” or “functional selectivity

Glutamate Uptake Triggers Transporter-Mediated GABA Release from Astrocytes

Background: Glutamate (Glu) and c-aminobutyric acid (GABA) transporters play important roles in regulating neuronal activity. Glu is removed from the extracellular space dominantly by glial transporters. In contrast, GABA is mainly taken up by neurons. However, the glial GABA transporter subtypes share their localization with the Glu transporters and their expression is confined to the same subpopulation of astrocytes, raising the possibility of cooperation between Glu and GABA transport processes. Methodology/Principal Findings: Here we used diverse biological models both in vitro and in vivo to explore the interplay between these processes. We found that removal of Glu by astrocytic transporters triggers an elevation in the extracellular level of GABA. This coupling between excitatory and inhibitory signaling was found to be independent of Glu receptor-mediated depolarization, external presence of Ca2+ and glutamate decarboxylase activity. It was abolished in the presence of non-transportable blockers of glial Glu or GABA transporters, suggesting that the concerted action of these transporters underlies the process. Conclusions/Significance: Our results suggest that activation of Glu transporters results in GABA release through reversal of glial GABA transporters. This transporter-mediated interplay represents a direct link between inhibitory and excitatory neurotransmission and may function as a negative feedback combating intense excitation in pathological conditions such as epilepsy or ischemia

Astrocytes convert network excitation to tonic inhibition of neurons

<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na⁺concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg²⁺] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p

Lack of Regulatory Changes of mu-Opioid Receptors by 14-Methoxymetopon Treatment in Rat Brain. Further Evidence for Functional Selectivity.

Here we have studied regulatory changes of mu-opioid receptors accompanying in vivo 14-methoxymetopon treatments of rats. Previously, this ligand has been shown to be an extremely potent, centrally acting mu-opioid specific analgesic with low physical dependence, tolerance, respiratory depression, constipation and other side effects. Our work shows that it is a highly potent full agonist of mu-opioid receptor coupled G-protein signaling in vitro, alike the well-known opioid agonist, etorphine. However, unlike etorphine, which desensitized and down-regulated the endogenous mu-opioid receptors, 14-methoxymetopon, given to rats intraperitoneally (i.p.) either acutely or chronically, did not change the binding or G-protein signaling of mu-opioid receptors in rat brain subcellular membranes. Thereby, these data provide further evidence that there is no direct relationship between the efficacy of the ligand in signaling and its ability to internalize or desensitize the receptor. Viewed collectively with published work, it is discussed that mu-opioid receptors display functional selectivity, also called 'biased agonism'. This concept implies that each ligand may induce unique, ligand-specific receptor conformation that can result in distinct agonist-directed trafficking and/or signal transduction pathways associated with the receptor. Ligand-specific signaling may open up new directions for designing potent analgesics that do not interact with unwanted signaling pathways, which mediate undesired side-effects, such as tolerance and dependence

Intracoronary endothelin-1 infusion combined with systemic isoproterenol treatment: antagonistic arrhythmogenic effects

Endothelin-1 secretion and sympathetic activation may play important role in cardiovascular pathophysiology. In vivo interactions between these systems are not defined. We aimed to study the electrophysiological and haemodynamic effects of simultaneous intracoronary endothelin-1 and intravenous isoproterenol infusions. 18 anaesthetised open chest dogs were studied after AV-ablation. Mean arterial blood pressure, coronary blood flow, left ventricular contractility, standard electrocardiograms, right and left ventricular epi- and endocardial monophasic action potential (MAP) signals were recorded. Intracoronary endothelin-1 (30 pmol/min) was given to Group ET (n=6), intravenous isoproterenol (0.2 microg/kg/min) to Group ISO (n=6), both endothelin-1 and isoproterenol to Group ET+ISO (n=6) for 30 min. MAP duration increased in all studied regions of Group ET, decreased in all studied regions of Group ISO and ET+ISO (control vs. maximal changes of left ventricular epicardial MAP 90% duration, Group ET: 296+/-22 vs 369+/-20 ms, p<0.05, Group ISO: 298+/-18 vs 230+/-27 ms, p<0.01, Group ET+ISO: 302+/-18 vs 231+/-10 ms, p<0.01). In Group ET, early after depolarisations (3/6), polymorphic non-sustained ventricular tachycardias (6/6), and ventricular fibrillation (3/6) could be observed. In Group ISO, monomorphic non-sustained ventricular tachycardias (5/6) and atrial fibrillation (3/6) appeared. In Group ET+ISO, mono- and polymorphic non-sustained ventricular tachycardias occurred (5/6), neither ventricular fibrillation nor atrial fibrillation developed. An additive effect of endothelin-1 and isoproterenol on left ventricular contractility was observed. Isoproterenol treatment showed antagonistic effect against endothelin-1 induced MAP duration prolongation, early after depolarisation and ventricular fibrillation formation, while endothelin-1 showed protective effect against the development of isoproterenol induced atrial fibrillation

Straightforward and effective synthesis of gamma-aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes.

Supply of major metabolites such as gamma-aminobutyric acid (GABA), beta-alanine and taurine is an essential instrument that shapes signalling, proper cell functioning and survival in the brain and peripheral organs. This background motivates the synthesis of novel classes of compounds regulating their selective transport through various fluid-organ barriers via the low-affinity gamma-aminobutyric acid (GABA) transporter subtype 2 (GAT2). Natural and synthetic spirocyclic compounds or therapeutics with a range of structures and biological activity are increasingly recognised in this regard. Based on pre-validated GABA transport activity, straightforward and efficient synthesis method was developed to provide an azaspiro[4.5]decane scaffold, holding a variety of charge, substituent and 3D constrain of spirocyclic amine. Investigation of the azaspiro[4.5]decane scaffold in cell lines expressing the four GABA transporter subtypes led to the discovery of a subclass of a GAT2-selective compounds with acyl-substituted azaspiro[4.5]decane core