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Journal Article 2015; 36(Suppl 2): 11-16 PubMed PMID: 26748521 Citation  Keywords:  Adult, Attitude of Health Personnel, Czech Republic, Female, Hospitals:standards, Humans, Middle Aged, Nursing Staff, Hospital:statistics & numerical data, Organizational Culture, Patient Safety:standards,.   

THEORETICAL BACKGROUND: Patient safety is a strategic goal of managers of all health care facilities in the Czech Republic. The development of a safety culture in the facility helps to ensure high quality health care. GOAL OF THE SURVEY was to assess the safety culture with regard to patient safety and team cooperation. A partial goal was to confirm the hypothesis that team cooperation among health care staff significantly influences patient safety.

METHODOLOGY: 772 nurses took part in a quantitative survey. The respondents were nurses working shifts in inpatient departments of hospitals in the Czech Republic.

RESULTS: Patient safety was described as excellent by 17.5% of nurses. It is described as very good by 60.2% of nurses and described as acceptable by 20.5% nurses. 78% of respondents agreed with the statement that patient safety was never neglected at the expense of increased workload. More than 10% of nurses reported that there were problems with patient safety. 19.8% of respondents were reported that efforts to prevent errors were not practiced at their clinic, and, therefore, and only chance had prevent more errors from occurring. According to 64.9% of respondents, the staff on the wards supported each other and a similar number of respondents reported that they showed respect for each other (60.2%). Respondents reported that intra-ward support increased the degree of patient safety.

CONCLUSION: Results from the survey show that team cooperation is a precondition for providing safe patient care, which cannot be underestimated and must be refined and improved through good hospital management....

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Journal Article 2015; 36(1): 59-66 PubMed PMID: 25789586 Citation  Keywords:  Anilides:pharmacology, Cells, Cultured, Human Umbilical Vein Endothelial Cells:drug effects, Humans, Hypoglycemic Agents:pharmacology, Insulin:pharmacology, PPAR gamma:agonists, Receptors, Chemokine:metabolism, Thiazolidinediones:pharmacology,.   

OBJECTIVE: This study investigated the effect of different insulin concentrations on the activity of vascular endothelial cells (VECs), and the role of PPARγ activator rosiglitazone (RGZ) on the expression of the chemerin receptor, ChemR23, in insulin-treated human umbilical vein endothelial cells (HUVECs).

METHODS: Cell viability was determined in HUVECs treated with different insulin concentrations. Immunofluorescence staining was used to detect ChemR23 expression in insulin-treated HUVECs. Western blot assays were used to evaluate ChemR23 and PPARγ protein expression in insulin-treated HUVECs after pretreatment with PPARγ activator (RGZ) or inhibitor (GW9662).

RESULTS: High insulin concentrations significantly inhibited HUVEC cell viability compared to low insulin concentrations, and this inhibition was attenuated by pretreatment with RGZ. High concentrations of insulin caused a significant upregulation of ChemR23 and a significant downregulation of PPARγ. These effects were attenuated by RGZ pretreatment, while PPARγ antagonist, GW9662 reversed this attenuation.

CONCLUSION: ChemR23 upregulation may play a role in VEC damage caused by high concentrations of insulin. The protective effect of PPARγ activation in VECs may be mediated via ChemR23 downregulation....

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Journal Article 2014; 35(8): 724-732 PubMed PMID: 25702302 Citation  Keywords:  Animals, Calcium Channels, L-Type:drug effects, Cells, Cultured, Cerebral Cortex:cytology, Estradiol:pharmacology, Female, Insulin-Like Growth Factor I:pharmacology, Ion Channel Gating:drug effects, Neurons:drug effects, Patch-Clamp Techniques, Rats.Rats.   

INTRODUCTION: Calcium transport pathways are key factors for understanding how changes in the cytoplasmic calcium concentration are associated with neuroprotection because calcium is involved in the onset of death signaling in neurons.

OBJECTIVES: This study characterized the effects of 17β-estradiol and IGF-1 on voltage-activated and stretch-activated calcium channels in rat cultured cortical neurons.

METHODS: The whole-cell patch-clamp technique, using a voltage steps protocol or by applying positive pressure into the micropipette, was used on 7-10 day cultured neurons from a Wistar rat cortex, and pharmacological characterization was performed on these neurons.

RESULTS: Both 17β-estradiol and IGF-1 inhibited the currents mediated by L-type voltage-activated calcium channels, although the IGF-1 effects were lower than those of 17β-estradiol. The effect of both hormones together was greater than the sum of the effects of the individual agents. Unlike IGF-1, 17β-estradiol decreased the current mediated by stretch-activated channels. The inhibition of the classical receptors of these hormones did not affect the results.

CONCLUSION: Both hormones regulate voltage-activated calcium channels in a synergistic way, but only 17β-estradiol has an inhibitory effect on stretch-activated calcium channels. These effects are not mediated by classical receptors and may be relevant to the neuroprotective effects of both hormones because they diminish calcium entry into the neuron and decrease the possibility for the onset of apoptotic signaling....

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Journal Article 2014; 35(Suppl 2): 175-179 PubMed PMID: 25638383 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antipsychotic Agents:pharmacology, Cells, Cultured, Clozapine:pharmacology, Inflammation:drug therapy, Interleukin-6:metabolism, Macrophages:drug effects, Mice,.   

OBJECTIVES: Clozapine is an atypical antipsychotic drug known for its impact on production of pro-inflammatory cytokines. The aim of our work was to examine the impact of clozapine on the production of interleukin 6 (IL-6) by the LPS (lipopolysaccharide) stimulated macrophage cells and to confirm or exclude that it regulates the inflammation due to its interaction with alpha 7 nicotinic receptor (nAChR). Secondly, we focused on a verification of the antioxidant effect of clozapine.

METHODS: The levels of IL-6 in cell culture media were determined by ELISA method. Antioxidant properties of clozapine were estimated based on the reduction of 2,2-diphenyl-1-picrylhydrazyl radical.

RESULTS: The IL-6 level produced by cells treated clozapine decreased significantly from IL-6 level created by clozapine-untreated cells. However, the production of IL-6 in the cells treated with clozapine and simultaneously with selective alpha 7 nAChR antagonist methyllycaconitine did not alter significantly from the IL-6 production in the cells treated just with clozapine. The free radical scavenging activity of clozapine in concentration 1.00 mM was found equivalent to 0.13 mM of standard antioxidant N-acetyl-L-cystein.

CONCLUSION: Our study confirmed, that clozapine reduces production of IL-6 in LPS-activated macrophage cells nevertheless we denied that it would be mediated through alpha 7 nAChR. Moreover antioxidant potential of clozapine was observed.

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Journal Article 2014; 35(5): 385-392 PubMed PMID: 25275260 Citation  Keywords:  Animals, Basolateral Nuclear Complex:cytology, Dopamine:metabolism, Dopamine Agents:metabolism, Dopamine Antagonists:pharmacology, Dopaminergic Neurons:physiology, Excitatory Postsynaptic Potentials:drug effects, Male, Organ Culture Techniques, Presynapti.   

OBJECTIVES: Dopaminergic signaling in the basolateral amygdala (BLA) is important for emotion-related activity. However, little is known about the influence of dopamine (DA) on excitatory synaptic transmission of pyramidal neurons in BLA at early developmental stage. Here in this study, we observed the effect of DA on excitatory neurotransmission in the pyramidal cells of BLA in acute slices.

METHODS: Acute slices from amygdala of rats at the age of 14-16 days were prepared and maintained in vitro using standard method. Whole-cell patch clamp recordings were performed to examine the evoked excitatory postsynaptic current (eEPSC), spontaneous excitatory postsynaptic current (sEPSC) and miniature excitatory postsynaptic current (mEPSC). Drugs including DA and synaptic blockers were added in recording solution due to different experimental designs.

RESULTS: We found that bath application of DA at a concentration of 100 μM significantly inhibited the amplitude of evoked EPSC. However, the amplitude and frequency of mEPSC were not affected. We also found increased pair pulse facilitation after DA application, indicating DA inhibited excitatory neurotransmission through suppression of release probability at the pre-synaptic terminals. Importantly, DA was also effective in decreasing activity induced upregulation in sEPSCs. Moreover, the DA effects were not affected by either antagonist of dopamine 1 or dopamine 2-like receptors.

CONCLUSION: We studied the effects of DA on excitatory neurotransmission and found that DA inhibited glutamatergic synaptic transmission via modulation of pre-synaptic release probability....

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Journal Article 2014; 35(3): 224-229 PubMed PMID: 24977973 Citation  Keywords:  Alzheimer Disease:genetics, Amyloid Precursor Protein Secretases:genetics, Amyloid beta-Peptides:antagonists & inhibitors, Amyloid beta-Protein Precursor:metabolism, Cells, Cultured, Gene Expression Regulation, Enzymologic:drug effects, Humans, Insulin:ph.   

OBJECTIVE: Amyloid-beta (Abeta) is a 36-43 amino acid peptide that is derived by processing of the beta-amyloid precursor protein (APP). Abeta plays a central role in the development of Alzheimer's disease (AD). Although growing evidence suggests that insulin has important functions in Abeta metabolism, the underlying mechanisms are still unknown.

METHODS: Using an SH-SY5Y cell line overexpressing human APP Swedish mutant (APPsw), we evaluated the effect of insulin on APP processing and Abeta production by using western blot analysist.

RESULTS: Our data showed that administration of insulin reduced the Abeta generation in culture media with a concomitant decreases in the levels of beta-secretase BACE1, secreted extracellular domain (sAPPbeta) and a fragment of 99 amino acids (C99) in APPsw cells. We further showed that insulin increased the levels of alpha-secretase ADAM10, a secreted extracellular domain secreted (sAPPa) and a fragment of 83 amino acids (C83) in APPsw cells.

CONCLUSION: Our present data suggest that insulin could inhibit Abeta production through modulation of APP processing by increasing cleavage at the a-secretase site and decreased cleavage at the beta-secretase sites....

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Journal Article 2013; 34(6): 529-538 PubMed PMID: 24378454 Citation  Keywords:  Animals, Antibodies, Monoclonal:pharmacology, Apoptosis:drug effects, Boron Compounds:pharmacology, Cells, Cultured, Cerebellum:cytology, Cytokine Receptor gp130:antagonists & inhibitors, Dantrolene:pharmacology, Drug Interactions, Excitatory Amino Acid A.   

OBJECTIVE: To reveal the involvement of inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR) in IL-6 prevention from neuronal apoptosis and necrosis induced by N-methyl-D-aspartate (NMDA).

METHODS: Cerebellar granule neurons (CGNs) from 8-day-old rats were exposed to IL-6 for 8 days and then stimulated with NMDA for 30 min. The 2-aminoethoxydiphenyl borate (2-APB) and dantrolene (DAN) were used to antagonize IP3R and RyR, respectively. Anti-gp130 monoclonal antibody (mAb) was employed to neutralize gp130, a 130-kDa signal-transducing β-subunit of IL-6 receptor complex. Neuronal apoptosis and necrosis were determined by TUNEL, fluorometric caspase-3 enzyme activity, annexin V-FITC/PI staining and ELISA. Western blot and real-time PCR measured IP3R1 and RyR2 expression, respectively.

RESULTS: IL-6 prevented the elevation of TUNEL-positive cells and caspase-3 expression and activity, and also suppressed the increase in annexin V-FITC/PI-positive cells and DNA- and histone-associated nucleosomes in cultured CGNs evoked by NMDA. These anti-apoptotic and anti-necrotic effects of IL-6 were larger on DAN-treated cells than on 2-APB-exposed neurons, since 2-APB treatment alone significantly inhibited the neuronal apoptosis and necrosis but DAN exposure alone did not alter the apoptosis and necrosis induced by NMDA. In support of these results, IL-6 downregulated IP3R1 but did not affect RyR2 expression. All these IL-6 effects were blocked by anti-gp130 mAb.

CONCLUSION: IL-6 prevention from NMDA-triggered Ca2+-induced Ca2+ release-mediated apoptosis and necrosis in CGNs depends on the inhibition of IP3R channel opening and expression rather than on RyR activity. IL-6 receptor-coupled gp130 signaling mediates this neuroprotection of IL-6 resistance to neuronal apoptosis and necrosis....

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Journal Article 2013; 34(4): 302-308 PubMed PMID: 23803874 Citation  Keywords:  Animals, Cells, Cultured, Chromatography, Ion Exchange, Female, GABA Agents:pharmacology, Gonadotrophs:drug effects, Gonadotropin-Releasing Hormone:pharmacology, Inositol 1,4,5-Trisphosphate:biosynthesis, Luteinizing Hormone:drug effects, Pituitary Gland,.   

OBJECTIVE: Mechanism(s) responsible for VPA-induced effects on reproductive axis activity are not fully recognized. Previously we reported that VPA suppressed only GnRH-stimulated but not the basal LH release from rat anterior pituitary (AP) cells in vitro. Since the inhibitory effect of VPA was exerted only in GnRH-activated cells, potential VPA impact on GnRH-R-coupled IP3/PKC signaling could not be excluded. In this study the effect of VPA on IPs synthesis in non-stimulated and GnRH-treated rat AP cells was examined.

MATERIAL AND METHODS: In the first experiment 5 × 105 cells/ml were incubated for 3h with VPA (10 nM-10 μM), PMA (100 nM), GnRH (100 nM), PMA (100 nM) + VPA (10 nM-10 μM), GnRH (100 nM) + VPA (10 nM-10 μM). In the second experiment cells were preincubated for 24h with 1μCi myo-[23 H]-inositol, then for 30 min with 10 mM LiCl and finally for 3hr with GnRH (100 nM) VPA (1 μM, 10 μM), GnRH (100 nM) + VPA (1 μM, 10 μM). LH concentration was measured by RIA and intracellular IPs accumulation by ion-exchange chromatography analysis.

RESULTS: VPA diminished GnRH-stimulated LH release without affecting PMA-induced LH release at any dose tested. Moreover, VPA-induced increase of IPs accumulation occurred in both non-stimulated and GnRH-treated cells and intensity of cellular response was similar in both groups.

CONCLUSION: VPA affects IP3/PKC pathway activity through its up-regulatory effect on IPs synthesis in AP cells. VPA-induced inhibition of GnRH-stimulated LH release from gonadotrope cells appears to be the result of still unrecognized cellular mechanism....

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