Gdańsk Medical University

About: Gdańsk Medical University is a education organization based out in Gdańsk, Poland. It is known for research contribution in the topics: Population & Cancer. The organization has 4893 authors who have published 11216 publications receiving 260523 citations.

Decreased quinolinic acid in the hippocampus of depressive patients: evidence for local anti-inflammatory and neuroprotective responses?

Abstract: Disturbances of glutamatergic neurotransmission and mononuclear phagocyte system activation have been described uni- and bipolar depression (UD/BD). Linking the glutamate and immune hypotheses of depression, quinolinic acid (QUIN) is synthesized by activated microglia and acts as an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist with neurotoxic properties. Recently, we observed an increased microglial QUIN expression in the subgenual and supracallosal, but not in the pregenual part of the anterior cingulate cortex in postmortem brains of suicide cases with severe depression. Since several hints point to a role of the hippocampus in depression, we extended our study and addressed the question whether microglial QUIN is also changed in subregions of the hippocampus (CA1 and CA2/3 areas) in these patients. Postmortem brains of 12 acutely depressed patients (UD, n = 6; BD, n = 6) and 10 neuropsychiatric healthy age- and gender-matched control subjects were analyzed using QUIN-immunohistochemistry. Hippocampal volumes were determined in order to assess possible neurotoxic or neurodegenerative aspects. Microglial QUIN expression in the whole group of depressed patients was either comparable (left CA1, right CA2/3) or decreased (right CA1: p = 0.004, left CA2/3: p = 0.044) relative to controls. Post hoc tests showed that QUIN was reduced both in UD and BD in the right CA1 field (UD, p = 0.048; BD, p = 0.031). No loss of hippocampal volume was detected. Our data indicate that UD and BD are associated with a local reduction in QUIN-immunoreactive microglia in the hippocampus and underline the importance of the NMDA-R signaling in depressive disorders.

Corticotropin‐releasing hormone induces keratinocyte differentiation in the adult human epidermis

Abstract: Previously we documented that human epidermis exclusively expresses corticotropin releasing hormone receptor 1 (CRH-R1). To define the role of CRH in the epidermis, we investigated its effects on differentiation of normal human adult epidermal keratinocytes. Thus, CRH inhibited proliferation in a dose dependent fashion and significantly decreased Ki-67 antigen expression. This effect was independent of either the presence or the absence of growth factors in the medium. Flow cytometry analysis demonstrated that CRH inhibited the transition from G0/1 to S phase of the cell cycle, which was accompanied by an increased expression of cdk inhibitor p16 (Ink4a) protein. The antiproliferative effect was attenuated by protein kinase C inhibitor (GF109203X) but not by H89 (protein kinase A inhibitor), PD98059, or SB203580 (MAP kinase inhibitors). The cell cycle withdrawal was associated with the induction of keratinocyte differentiation. Thus, CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels. It also increased cell granularity and cell size. Furthermore, CRH induced signal transduction cascade that included stimulation of inositol 1,4,5-triphosphate, which was time and dose dependent. CRH also increased activator protein-1 DNA binding activity with JunD identified as the most important element. Thus, activation of CRH-R1 induces a non-random and sequential signal transduction cascade governing both keratinocyte differentiation and the inhibition of cell proliferation through G0/1 arrest. We propose that this program, triggered by CRH interaction with CRH-R1, includes induction of a transduction pathway involving the sequential activation of phospholipase C, protein kinase C, activator protein-1 (including Jun D), and p16. © 2004 Wiley-Liss, Inc.

Atrial fibrillation after coronary artery bypass grafting without cardiopulmonary bypass.

Abstract: Objective Atrial fibrillation is the most common complication after heart surgery. It rarely has a fatal outcome but causes patient instability, prolongs hospital stay, or even is the reason for perioperative infarction. Although conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass has excellent short-term and long-term results, the number of coronary operations on a beating heart without cardiopulmonary bypass is still growing. To reduce surgical trauma, off-pump coronary artery bypass grafting via sternotomy (OPCABG) or minimally invasive direct vision coronary artery bypass grafting (MIDCABG) via small thoracotomy are performed. The aim of this study was to estimate the frequency of atrial fibrillation in patients after myocardial revascularization without cardiopulmonary bypass. Methods A retrospective analysis of 48 patients undergoing myocardial revascularization without cardiopulmonary bypass was performed. Twenty-four patients underwent OPCABG and 24 were operated using the MIDCABG technique. The incidence of cardiac arrhythmias was analyzed since operation to the fourth postoperative day. Each patient had continuous ECG monitoring with option of arrhythmia analysis during ICU stay. After discharge from ICU 24-h ECG monitor studies were carried out. Surface 12-lead ECG was accomplished once a day, and additionally each time symptoms of cardiac arrhythmia occurred. Risk factors of atrial fibrillation were estimated. Results Atrial fibrillation occurred in 25% of patients after MIDCABG, in 29% after OPCABG, and in 18% after CABG with cardiopulmonary bypass. This difference has no statistical significance. Risk factors and incidence of postoperative complications were comparable in all groups. Conclusions Atrial fibrillation is a common complication after procedures of myocardial revascularization, performed with or without cardiopulmonary bypass. The occurrence is not dependent on the type of operation.

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

Abstract: This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.