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71.
Krystyna Piasecka Magdalena Marć Hasmik Hayrapetyan Tamara Sarkisian Bartosz Korczowski 《Pediatria polska》2012,87(3):311-313
Familial Mediterranean Fever (FMF) is a disease with an autosomal recessive inheritance affecting inhabitants of the Mediterranean Sea basin area. It is the most prevalent fever-inflammatory syndrome manifested by fever episodes, serositis and rash. The symptoms regress spontaneously and between recurrent attacks of fever the child is healthy. Amyloidosis is the most serious complication. A case of a 8 year-old boy, a son of Armenian immigrants, with recurrent pleuritis is presented. 相似文献
72.
Renata Zajączkowska Barbara Przewłocka Magdalena Kocot-Kępska Joanna Mika Wojciech Leppert Jerzy Wordliczek 《Pharmacological reports : PR》2018,70(4):812-820
Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug–drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain. 相似文献
73.
Paulina Sokołowska Anna Urbańska Kaja Biegańska Waldemar Wagner Wojciech Ciszewski Magdalena Namiecińska Jolanta B. Zawilska 《Journal of molecular neuroscience : MN》2014,52(1):48-55
Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection. 相似文献
74.
75.
Meike Stumpp Marian Y. Hu Frank Melzner Magdalena A. Gutowska Narimane Dorey Nina Himmerkus Wiebke C. Holtmann Sam T. Dupont Michael C. Thorndyke Markus Bleich 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(44):18192-18197
Calcifying echinoid larvae respond to changes in seawater carbonate chemistry with reduced growth and developmental delay. To date, no information exists on how ocean acidification acts on pH homeostasis in echinoderm larvae. Understanding acid–base regulatory capacities is important because intracellular formation and maintenance of the calcium carbonate skeleton is dependent on pH homeostasis. Using H+-selective microelectrodes and the pH-sensitive fluorescent dye BCECF, we conducted in vivo measurements of extracellular and intracellular pH (pHe and pHi) in echinoderm larvae. We exposed pluteus larvae to a range of seawater CO2 conditions and demonstrated that the extracellular compartment surrounding the calcifying primary mesenchyme cells (PMCs) conforms to the surrounding seawater with respect to pH during exposure to elevated seawater pCO2. Using FITC dextran conjugates, we demonstrate that sea urchin larvae have a leaky integument. PMCs and spicules are therefore directly exposed to strong changes in pHe whenever seawater pH changes. However, measurements of pHi demonstrated that PMCs are able to fully compensate an induced intracellular acidosis. This was highly dependent on Na+ and HCO3−, suggesting a bicarbonate buffer mechanism involving secondary active Na+-dependent membrane transport proteins. We suggest that, under ocean acidification, maintained pHi enables calcification to proceed despite decreased pHe. However, this probably causes enhanced costs. Increased costs for calcification or cellular homeostasis can be one of the main factors leading to modifications in energy partitioning, which then impacts growth and, ultimately, results in increased mortality of echinoid larvae during the pelagic life stage. 相似文献
76.
Nicoletta Sorvillo Robin B. Hartholt Esther Bloem Magdalena Sedek Anja ten Brinke Carmen van der Zwaan Floris P. van Alphen Alexander B. Meijer Jan Voorberg 《Haematologica》2016,101(3):309-318
It has been proposed that von Willebrand factor might affect factor VIII immunogenicity by reducing factor VIII uptake by antigen presenting cells. Here we investigate the interaction of recombinant von Willebrand factor with immature monocyte-derived dendritic cells using flow cytometry and confocal microscopy. Surprisingly, von Willebrand factor was not internalized by immature dendritic cells, but remained bound to the cell surface. As von Willebrand factor reduces the uptake of factor VIII, we investigated the repertoire of factor VIII presented peptides when in complex with von Willebrand factor. Interestingly, factor VIII-derived peptides were still abundantly presented on major histocompatibility complex class II molecules, even though a reduction of factor VIII uptake by immature dendritic cells was observed. Inspection of peptide profiles from 5 different donors showed that different core factor VIII peptide sequences were presented upon incubation with factor VIII/von Willebrand factor complex when compared to factor VIII alone. No von Willebrand factor peptides were detected when immature dendritic cells were pulsed with different concentrations of von Willebrand factor, confirming lack of von Willebrand factor endocytosis. Several von Willebrand factor derived peptides were recovered when cells were pulsed with von Willebrand factor/factor VIII complex, suggesting that factor VIII promotes endocytosis of small amounts of von Willebrand factor by immature dendritic cells. Taken together, our results establish that von Willebrand factor is poorly internalized by immature dendritic cells. We also show that von Willebrand factor modulates the internalization and presentation of factor VIII-derived peptides on major histocompatibility complex class II. 相似文献
77.
Yabin Cheng Jing Lu Guangdi Chen Gholamreza Safaee Ardekani Anand Rotte Magdalena Martinka Xuezhu Xu Kevin J. McElwee Guohong Zhang Youwen Zhou 《Oncotarget》2015,6(6):4180-4189
The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities. 相似文献
78.
Venkatesh Pilla Reddy Magdalena Kozielska Rik de Greef An Vermeulen Johannes H. Proost 《Journal of pharmacokinetics and pharmacodynamics》2013,40(3):377-388
High and variable placebo effect (PE) within and among clinical trials can substantially affect conclusions about the efficacy of new drugs in the treatment of schizophrenia and other neuropsychiatric disorders. In recent years, it has become increasingly difficult to prove drug efficacy against placebo, and one of the reasons is that the placebo response has increased over recent years. The increased placebo response over the years is partly explained by unidentified parallel interventions, patient factors, issues with trial designs, and regional variability or demographic differences. In addition, a nocebo effect, which is undesirable effects a subject manifests after receiving placebo, e.g. extrapyramidal side effects, in placebo arms of antipsychotic trials could also influence the PE and clinical trial outcomes. Placebo effects (PEs) are a natural phenomenon and cannot be avoided completely in clinical trials. However, accounting for the PE via mixed effects modelling approaches could reduce bias in quantifying the overall effect size of the drug treatment. This review article focuses on the PE and its impact on schizophrenia clinical trial outcomes. The authors briefly describe the factors that lead to high and variable PE. Next, pharmacometric approaches to account for the PE and dropouts in schizophrenia clinical trials are described. Finally, some points are provided that could be considered while designing and optimizing antipsychotic trials via simulation approaches. 相似文献
79.
Michael Bauer Uwe Kölsch Renate Krüger Nadine Unterwalder Karin Hameister Fabian Marc Kaiser Aglaia Vignoli Rainer Rossi Maria Pilar Botella Magdalena Budisteanu Monica Rosello Carmen Orellana Maria Isabel Tejada Sorina Mihaela Papuc Oliver Patat Sophie Julia Renaud Touraine Thusari Gomes Kirsten Wenner Xiu Xu Alexandra Afenjar Annick Toutain Nicole Philip Aleksandra Jezela-Stanek Ludwig Gortner Francisco Martinez Bernard Echenne Volker Wahn Christian Meisel Dagmar Wieczorek Salima El-Chehadeh Hilde Van Esch Horst von Bernuth 《Journal of clinical immunology》2015,35(2):168-181
80.
Yasmeen Niazi Hauke Thomsen Bozena Smolkova Ludmila Vodickova Sona Vodenkova Michal Kroupa Veronika Vymetalkova Alena Kazimirova Magdalena Barancokova Katarina Volkovova Marta Staruchova Per Hoffmann Markus M. Nöthen Maria Dušinská Ludovit Musak Pavel Vodicka Kari Hemminki Asta Försti 《Environmental and molecular mutagenesis》2019,60(1):17-28
Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10−5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17–28, 2019. © 2018 Wiley Periodicals, Inc. 相似文献