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31.
Beáta Flachner Tünde Tömöri István Hajdú Krisztina Dobi Zsolt Lőrincz Sándor Cseh György Dormán 《Medicinal chemistry research》2014,23(3):1234-1247
Target-focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds’ databases if structures of active compounds are available. In the present study, a multi-step virtual and in vitro screening cascade is used to select melanin-concentrating hormone receptor-1 antagonists. The 2D similarity search combined with physico-chemical parameter filtering is suitable for selecting candidates from multimillion compounds’ repository. The seeds of the first round of virtual screening were collected from literature commercial databases, whereas the seeds of the second round were the hits the first round of biological testing In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9 %), applying a strict requirement for hit selection, and also this cascade-like screening method was appropriate for selecting several compounds reaching efficacies even below 10 nM. 相似文献
32.
Ferenc Ruzsnavszky Bence Hegyi Kornél Kistamás Krisztina Váczi Balázs Horváth Norbert Szentandrássy Tamás Bányász Péter P. Nánási János Magyar 《Naunyn-Schmiedeberg's archives of pharmacology》2014,387(5):457-467
Adrenergic activation of L-type Ca2+ and various K+ currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca2+ and K+ currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I Ca, I Ks, and I Kr, while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I Ca and I Ks and moderate stimulation of I Kr. The ISO-induced plateau shift and I Ca increase developed faster than the shortening of APD and stimulation of I Ks and I Kr. Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I Ca is turned on faster than the stimulation of I Ks and I Kr in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization. 相似文献
33.
Orsolya Balogh Valentin Brodszky László Gulácsi Emese Herédi Krisztina Herszényi Hajnalka Jókai Sarolta Kárpáti Petra Baji Éva Remenyik Andrea Szegedi Péter Holló 《The European journal of health economics》2014,15(1):101-109
Background
Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies.Objectives
To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary.Methods
Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures.Results
Two-hundred patients were involved (females 32 %) with a mean age of 51 (SD 13) years, 103 (52 %) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86 %. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups.Conclusions
Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.34.
Prof. Dr. Phil. Teodóra Tomcsányi Viola Sallay Tünde Szabó Edit A. Kiri Krisztina Csáky-Pallavicini Prof. Dr. Katalin Horváth-Szabó Tamás Martos PhD. 《Zeitschrift für Psychodrama und Soziometrie》2014,13(1):27-50
The relationships of Hungarian psychotherapists and their praxis to spirituality are examined in a comprehensive qualitative research based on Grounded Theory. The study demonstrates what surplus originates according to the experience of psychotherapists from the means of psychodrama in psychotherapy applied to cases involving spiritual content. 相似文献
35.
Eszter Banki Krisztina Kovacs Daniel Nagy Tamas Juhasz Peter Degrell Katalin Csanaky Peter Kiss Gabor Jancso Gabor Toth Andrea Tamas Dora Reglodi 《Journal of molecular neuroscience : MN》2014,54(3):300-309
Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30–40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect. 相似文献
36.
Arjan J. Kwakernaak Rob W. van der Pluijm Neelke C. van der Weerd Lianne Koens Wytske M. Westra Krisztina B. Gecse Ankie Kleinjan 《Clinical Case Reports》2022,10(4)
We report a case of intestinal lesions in a patient with a history of lupus nephritis and renal transplantation. Biopsy revealed an EBV‐driven post‐transplant lymphoproliferative disease (PTLD). An EBV‐driven PTLD is a major complication after renal transplantation and is an important differential diagnostic consideration in the follow‐up of renal transplant recipients. 相似文献
37.
Alinda Dalma Varnai Magdolna Bollmann Agnes Bankfalvi Krisztina Kovacs Hildegard Heller Christoph Schmitt Jan Volek Marianna Szendy Reinhard Bollmann Ralf Hildenbrand 《Journal of oral pathology & medicine》2009,38(2):181-187
Background: Evidence is accumulating for the aetiological role of human papillomavirus (HPV) in the pathogenesis of potentially malignant oral mucosal lesions and squamous cell carcinomas.
Methods: Paraffin tissue sections from 49 patients with 'white patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH).
Results: Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ≥ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed.
Conclusions: The high prevalence of HPV infection in hyperplastic 'white patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions – flat, exophytic, wart-like or papillary proliferations – could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis. 相似文献
Methods: Paraffin tissue sections from 49 patients with 'white patches' of the oral mucosa were investigated histologically, by broad-spectrum PCR followed by genotyping and chromogenic in situ hybridisation (CISH).
Results: Histologically, 33 flat hyperplasias and 16 papillary hyperplasias were diagnosed. Twenty-two of 28 samples studied (78.6%) were positive for HPV DNA by PCR and six were negative. The following HPV types were detected in decreasing order of prevalence: HPV 35, HPV 6, HPV16, HPV 53, HPV 18, HPV 51 and HPV 55. Seventeen samples (60.7%) contained high-risk HPV DNA. Using CISH, ≥ 1 HPV signals were detected at least in a few epithelial cells in 95% of cases studied. All but one case were positive with the high-risk HPV probe and all HPV infections contained low viral load. Concordant positive results both by PCR and CISH were detected in 14 of 19 cases (73.7%) analysed.
Conclusions: The high prevalence of HPV infection in hyperplastic 'white patches' of the oral mucosa supports the putative role of HPV at an early stage of oral carcinogenesis. These results further indicate that the majority of white oral mucosal lesions – flat, exophytic, wart-like or papillary proliferations – could be considered as the clinical manifestations of oral HPV infection. This finding has clinical relevance regarding therapy and patient management and may help in elucidating the role of HPV infection in oral carcinogenesis. 相似文献
38.
Balazs Antus Imre Barta Krisztina Czebe Ildiko Horvath Eszter Csiszer 《Inflammation research》2010,59(1):83-86
Introduction
Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this pilot study we tested the cytokine pattern of EBC of lung transplant patients with and without clinical evidence of bronchiolitis obliterans syndrome (BOS). 相似文献39.
40.
Gyimesiné FK 《Acta pharmaceutica Hungarica》2002,72(3):205-212
The separation and quantitation of the enantiomers and also the determination of the enantiomeric purity are all current and indispensable tasks for the pharmaceutical analysis. The aim of this work was to study the sorption properties of the alpha 1-acid glycoprotein (AGP) based stationary phase, which may have crucial importance for the enantioselectivity. New binding data are presented for the mechanism of the chromatographic separation, which has not clarified in the literature yet. On the basis of these new findings the composition of the mobile phase for a given analytical separation can be designed, including the preparative separation, as well. Binding data for dioxane, known as a solvent with low dielectric constant, are determined at first time. It was found that the sorption of both acetonitrile and dioxane is pH-dependent: as at pH 7.2 the binding can be characterized by a saturation curve, while at pH 4.0 by a twostep, monotone curve. The pH-dependence of the adsorption has been explained by conformational changes of the selector, which were confirmed by CD-spectroscopic and fluorescence quenching study of the native AGP. In accordance with the binding study by increasing the acetonitrile percentage at pH 4.0 a tipical alpha-helical peak was observed in the CD-spectrum. Opposite that at pH 7.2 the increase in the acetonitrile content does not result in any changes in the spectra. Effective dynamic quenching constants of AGP have been determined at given acetonitrile concentrations using 2,2,2-trichloroethanol as fluorescence quencher. In agreement with the results of the CD measurements at pH 4.0 it was found that the degree of quenching enhanced by increasing the amount of the acetonitrile, that can be explained by enhanced exposure of the buried tryptophan residues. Taking these results into account, new optimized and validated HPLC methods have been developed for compendial control in testing the enantiomeric purity of an acidic (ibuprophen), a basic (propranolol) and a neutral (norgestrel) drug molecule. 相似文献