Activation of trace amine-associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice.

Alcohol dependence is characterized by the abnormal release of dopamine in the brain reward-related areas. Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that negatively regulates dopamine neurotransmission and thus is a promising target in the treatment of drug addiction. However, the role of TAAR1 in the regulation of alcohol abuse remains understudied. Here, we assessed the effect of TAAR1 activation on alcohol drinking behaviours of C57Bl/6J female mice housed in IntelliCages. The animals were administered with either vehicle or TAAR1 full selective agonist, RO5256390, and tested for alcohol consumption, alcohol preference and motivation for alcohol seeking. We found that mice with the highest preference for alcohol (high drinkers) in the RO5256390 group consumed less alcohol and had lower alcohol preference in comparison with high drinkers in the vehicle group, during 20 h of free alcohol access (FAA). We also found decreased alcohol consumption and alcohol preference comparing all animals in the RO5256390 to all animals in the vehicle group, during 20 h of FAA performed after the abstinence. These effects of RO5256390 lasted for the first 24 h after administration that roughly corresponded to the compound level in the brain, measured by mass spectrometry. Finally, we found that administration of RO5256390 may attenuate motivation for alcohol seeking. Taken together, our findings reveal that activation of TAAR1 may transiently reduce alcohol drinking; thus, TAAR1 is a promising target for the treatment of alcohol abuse and relapse.

Label-Free Mass Spectrometry-Based Quantitative Proteomics to Evaluate the Effects of the Calcium-Sensing Receptor Agonist Cinacalcet on Protein Expression in Rat Brains and Livers.

BACKGROUND Cinacalcet is a calcium-sensing receptor agonist that is clinically approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and hypercalcemia in patients with parathyroid carcinoma. This study aimed to use quantitative mass spectrometry-based label-free proteomics to evaluate the effects of cinacalcet on protein expression in rat brains and livers. MATERIAL AND METHODS We randomly assigned 18 Wistar rats to 2 groups: an untreated control group (n=6) and a group treated with cinacalcet at a dose corresponding to the maximum dose used in humans (2 mg/kg/body weight, 5 days/week) divided into 7-day (n=6) and 21-day (n=6) treatment subgroups. A mass-spectrometry-based label-free quantitative proteomics approach using peptides peak area calculation was used to evaluate the changes in protein expression in examined tissues. Bioinformatics analysis of quantitative proteomics data was done using MaxQuant and Perseus environment. RESULTS No changes in protein expression were revealed in the 7-day treatment subgroup. We detected 10 upregulated and 3 downregulated proteins in the liver and 1 upregulated protein in the brain in the 21-day treatment subgroup compared to the control group. Based on Gene Ontology classification, all identified differentially expressed proteins were indicated as molecular functions involved in the enzyme regulator activity (36%), binding (31%), and catalytic activity (19%). CONCLUSIONS These findings indicate that long-term cinacalcet therapy can impair phase II of enzymatic detoxication and can cause disturbances in blood hemostasis, lipid metabolism, and inflammatory mediators or contribute to the acceleration of cognitive dysfunction; therefore, appropriate patient monitoring should be considered.

Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue.

In many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg-1/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.

Clinical Correlates of the NR3C1 Gene Methylation at Various Stages of Psychosis.

BACKGROUND: Dysregulation of epigenetic processes might account for alterations of the hypothalamic-pituitary-adrenal axis observed in patients with schizophrenia. Therefore, in this study, we aimed to investigate methylation of the glucocorticoid receptor (NR3C1) gene in patients with schizophrenia-spectrum disorders, individuals at familial high risk of schizophrenia (FHR-P), and healthy controls with respect to clinical manifestation and a history of psychosocial stressors. METHODS: We recruited 40 first-episode psychosis patients, 45 acutely relapsed schizophrenia (SCZ-AR) patients, 39 FHR-P individuals, and 56 healthy controls. The level of methylation at 9 CpG sites of the NR3C1 gene was determined using pyrosequencing. RESULTS: The level of NR3C1 methylation was significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients compared with other subgroups of participants. Individuals with FHR-P and healthy controls had similar levels of NR3C1 methylation. A history of adverse childhood experiences was associated with significantly lower NR3C1 methylation in all subgroups of participants. Higher methylation of the NR3C1 gene was related to worse performance of attention and immediate memory as well as lower level of general functioning in patients with psychosis. CONCLUSIONS: Patients with schizophrenia-spectrum disorders show altered levels of NR3C1 methylation that are significantly lower in first-episode psychosis patients and significantly higher in SCZ-AR patients. Higher methylation of the NR3C1 gene might be related to cognitive impairment observed in this clinical population. The association between a history of adverse childhood experiences and lower NR3C1 methylation is not specific to patients with psychosis. Longitudinal studies are needed to establish causal mechanisms underlying these observations.

ERp57 is protective against mutant SOD1-induced cellular pathology in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and mutations in superoxide dismutase 1 (SOD1) account for 20% of familial ALS cases. The aetiology of ALS remains unclear, but protein misfolding, endoplasmic reticulum (ER) stress and neuronal apoptosis are implicated. We previously established that protein disulphide isomerase (PDIA1) is protective against ER stress and apoptosis in neuronal cells expressing mutant SOD1, and recently mutations in PDIA1 and related PDI family member endoplasmic reticulum protein 57 (ERp57/PDIA3), were associated with ALS. Here, we examined whether ERp57 is also protective against mutant SOD1 or whether distinct specificity exists amongst individual PDI family members. Neuronal cells co-expressing SOD1 and ERp57 were examined for inclusion formation, ER stress, ubiquitin proteasome system (UPS) dysfunction and apoptosis. Over-expression of ERp57 inhibited inclusion formation, ER stress, UPS dysfunction and apoptosis, whereas silencing of ERp57 expression enhanced mutant SOD1 inclusion formation, ER stress and toxicity, indicating a protective role for ERp57 against SOD1 misfolding. ERp57 also inhibited the formation of mutant SOD1 inclusions and apoptosis in primary cortical neurons, thus confirming results obtained from cell lines. ERp57 partially co-localized with TAR DNA-binding protein-43 (TDP-43)-positive inclusions in spinal cords from sporadic ALS patients, thus linking ERp57 to protein misfolding in human sporadic disease. Our results therefore imply that ERp57 has a protective role against pathological events induced by mutant SOD1 and they link ERp57 to the misfolding of TDP-43. This study therefore has implications for the design of novel therapeutics based on the activities of the PDI family of proteins.

Design and synthesis of selective and blood-brain barrier-permeable hydroxamate-based gelatinase inhibitors.

Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases involved in the degradation of the extracellular matrix, make a major contribution to the progression of a vast number of diseases, such cancer or epilepsy. Although several MMP inhibitors (MMPi) have been developed to date for the treatment of cancer, they have all failed in clinical trials due to lack of efficacy and, most importantly, the presence of severe side effects. The latter can be explained by their lack of selectivity of these inhibitors. In this regard, MMPs' family members have a high structural homology, which challenge the development of selective inhibitors for a specific MMP. Here, we have used in silico calculations and in vitro data to design MMPi that selectively target gelatinases (MMP-2 and MMP-9) and have the capacity to cross the blood-brain barrier. Following this approach, we obtained compound 40 that shows high proteolytic stability and low cytotoxicity. This compound may be of particular interest for the treatment of central nervous diseases such epilepsy or Alzheimer's disease, where gelatinase activity is increased. Our data show the specificity of compound 40 for recombinant MMP-9 and MMP-2 and endogenous MMP-9 from rat hippocampal cell cultures, and reveals its permeability across the blood-brain barrier in vivo.

Searching for Low Molecular Weight Seleno-Compounds in Sprouts by Mass Spectrometry.

A fit for purpose analytical protocol was designed towards searching for low molecular weight seleno-compounds in sprouts. Complementary analytical techniques were used to collect information enabling the characterization of selenium speciation. Conceiving the overall characterization of the behavior of selenium, inductively plasma optical mass spectrometry (ICP-MS) was used to determine the total selenium content in entire sprouts as well as in selected extracts or chromatographic fractions. Then, high-performance liquid chromatography combined with ICP-MS (HPLC-ICP-MS) was used to evaluate the presence of inorganic and organic seleno-compounds, with the advantages of being very sensitive towards selenium, but limited by available selenium standard compounds. Finally, ultra-high performance liquid chromatography electrospray ionization triple quadrupole mass spectrometry (UHPLC-ESI-QqQ-MS/MS) and UHPLC-ESI-Orbitrap-MS/MS were used for the confirmation of the identity of selected compounds and identification of several unknown compounds of selenium in vegetable sprouts (sunflower, onion, radish), respectively. Cultivation of plants was designed to supplement sprouts with selenium by using solutions of selenium (IV) at the concentration of 10, 20, 40, and 60 mg/L. The applied methodology allowed to justify that vegetable sprouts metabolize inorganic selenium to a number of organic derivatives, such as seleno-methylselenocysteine (SeMetSeCys), selenomethionine (SeMet), 5'-seleno-adenosine, 2,3-DHP-selenolanthionine, Se-S conjugate of cysteine-selenoglutathione, 2,3-DHP-selenocysteine-cysteine, 2,3-DHP-selenocysteine-cysteinealanine, glutathione-2,3-DHP-selenocysteine, gamma-Glu-MetSeCys or glutamyl-glycinyl-N-2,3-DHP-selenocysteine.

Neuronal TDP-43 depletion affects activity-dependent plasticity.

TAR DNA-binding protein 43 (TDP-43) is a hallmark of some neurodegenerative disorders, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43-related pathology is characterized by its abnormally phosphorylated and ubiquitinated aggregates. It is involved in many aspects of RNA processing, including mRNA splicing, transport, and translation. However, its exact physiological function and role in mechanisms that lead to neuronal degeneration remain elusive. Transgenic rats that were characterized by TDP-43 depletion in neurons exhibited enhancement of the acquisition of fear memory. At the cellular level, TDP-43-depleted neurons exhibited a decrease in the short-term plasticity of intrinsic neuronal excitability. The induction of long-term potentiation in the CA3-CA1 areas of the hippocampus resulted in more stable synaptic enhancement. At the molecular level, the protein levels of an unedited (R) FLOP variant of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR1 and GluR2/3 subunits decreased in the hippocampus. Alterations of FLOP/FLIP subunit composition affected AMPAR kinetics, reflected by cyclothiazide-dependent slowing of the decay time of AMPAR-mediated miniature excitatory postsynaptic currents. These findings suggest that TDP-43 may regulate activity-dependent neuronal plasticity, possibly by regulating the splicing of genes that are responsible for fast synaptic transmission and membrane potential.

The DNA damage response (DDR) is induced by the C9orf72 repeat expansion in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in a non-coding region of C9orf72 are the major cause of familial ALS and frontotemporal dementia (FTD) worldwide. The C9orf72 repeat expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide repeat proteins (DRPs), including poly(GR) and poly(PR). Whilst it remains unclear how mutations in C9orf72 lead to neurodegeneration in ALS/FTD, dysfunction to the nucleolus and R loop formation are implicated as pathogenic mechanisms. These events can damage DNA and hence genome integrity. Cells activate the DNA damage response (DDR) with the aim of repairing this damage. However, if the damage cannot be repaired, apoptosis is triggered. In lumbar motor neurons from C9orf72-positive ALS patients, we demonstrate significant up-regulation of markers of the DDR compared to controls: phosphorylated histone 2AX (γ-H2AX), phosphorylated ataxia telangiectasia mutated (p-ATM), cleaved poly (ADP-Ribose) polymerase 1 (PARP-1) and tumour suppressor p53-binding protein (53BP1). Similarly, significant up-regulation of γ-H2AX and p-ATM was detected in neuronal cells expressing poly(GR)100 and poly(PR)100 compared to controls, revealing that DNA damage is triggered by the DRPs. Nucleophosmin (NPM1) is a histone chaperone induced during the DDR, which interacts with APE1 to enhance DNA repair. We also demonstrate that more NPM1 precipitates with APE1 in C9orf72 patients compared to controls. Furthermore, overexpression of NPM1 inhibits apoptosis in cells expressing poly(GR)100 and poly(PR)100. This study therefore demonstrates that DNA damage is activated by the C9orf72 repeat expansion in ALS.

Organic Hydroxy Acids as Highly Oxygenated Molecular (HOM) Tracers for Aged Isoprene Aerosol.

Highly oxygenated molecules (HOMs) are a class of compounds associated with secondary organic aerosols exhibiting high oxygen to carbon (O:C) ratios and often originating from the oxidation of biogenic compounds. Here, the photooxidation and ozonolysis of isoprene were examined under a range of conditions to identify HOM tracers for aged isoprene aerosol. The HOM tracers were identified as silylated derivatives by gas chromatography-mass spectrometry and by detecting their parent compounds by liquid chromatography-high resolution mass spectrometry. In addition to the previously observed methyltetrols and 2-methylglyceric acid, seven tracer compounds were identified, including 2-methyltartronic acid (MTtA), 2-methylerythronic acid (2MeTrA), 3-methylerythronic acid (3MeTrA), 2-methylthreonic acid (2MTrA), 3-methylthreonic acid (3MTrA), erythro-methyltartaric acid (e-MTA), and threo-methyltartaric acid (t-MTA). The molecular structures were confirmed with authentic standards synthesized in the laboratory. The presence of some of these HOMs in the gas and particle phases simultaneously provides evidence of their gas/particle partitioning. To determine the contributions of aged isoprene products to ambient aerosols, we analyzed ambient PM2.5 samples collected in the southeastern United States in summer 2003 and at two European monitoring stations located in Zielonka and Godów (Poland). Our findings show that methyltartaric acids (MTA) and 2- and 3-methylthreonic acids (and their stereoisomers) are representative of aged isoprene aerosol because they occur both in the laboratory chamber aerosol obtained and in ambient PM2.5. On the basis of gas chromatography-mass spectrometry (GC-MS) analysis, their concentrations were found to range from 0.04 ng for 3-methylthreonic acid to 6.3 ng m-3 for methyltartaric acid at the southeast site in Duke Forest, NC, USA.

Detection of ALDH3B2 in Human Placenta.

Aldehyde dehydrogenase 3B2 (ALDH3B2) gene contains a premature termination codon, which can be skipped or suppressed resulting in full-length protein expression. Alternatively, the longest putative open reading frame starting with the second in-frame start codon would encode short isoform. No unequivocal evidence of ALDH3B2 expression in healthy human tissues is available. The aim of this study was to confirm its expression in human placenta characterized by the highest ALDH3B2 mRNA abundance. ALDH3B2 DNA and mRNA were sequenced. The expression was investigated using western blot. The identity of the protein was confirmed using mass spectrometry (MS). The predicted tertiary and quaternary structures, subcellular localization, and phosphorylation sites were assessed using bioinformatic analyses. All DNA and mRNA isolates contained the premature stop codon. In western blot analyses, bands corresponding to the mass of full-length protein were detected. MS analysis led to the identification of two unique peptides, one of which is encoded by the nucleotide sequence located upstream the second start codon. Bioinformatic analyses suggest cytoplasmic localization and several phosphorylation sites. Despite premature stop codon in DNA and mRNA sequences, full-length ALDH3B2 was found. It can be formed as a result of premature stop codon readthrough, complex phenomenon enabling stop codon circumvention.

Single-step synthesis of Er3+ and Yb3+ ions doped molybdate/Gd2O3 core-shell nanoparticles for biomedical imaging.

Nanostructures as color-tunable luminescent markers have become major, promising tools for bioimaging and biosensing. In this paper separated molybdate/Gd2O3 doped rare earth ions (erbium, Er3+ and ytterbium, Yb3+) core-shell nanoparticles (NPs), were fabricated by a one-step homogeneous precipitation process. Emission properties were studied by cathodo- and photoluminescence. Scanning electron and transmission electron microscopes were used to visualize and determine the size and shape of the NPs. Spherical NPs were obtained. Their core-shell structures were confirmed by x-ray diffraction and energy-dispersive x-ray spectroscopy measurements. We postulated that the molybdate rich core is formed due to high segregation coefficient of the Mo ion during the precipitation. The calcination process resulted in crystallization of δ/ξ (core/shell) NP doped Er and Yb ions, where δ-gadolinium molybdates and ξ-molybdates or gadolinium oxide. We confirmed two different upconversion mechanisms. In the presence of molybdenum ions, in the core of the NPs, Yb3+-[Formula: see text] (∣2F7/2, 3T2〉) dimers were formed. As a result of a two 980 nm photon absorption by the dimer, we observed enhanced green luminescence in the upconversion process. However, for the shell formed by the Gd2O3:Er, Yb NPs (without the Mo ions), the typical energy transfer upconversion takes place, which results in red luminescence. We demonstrated that the NPs were transported into cytosol of the HeLa and astrocytes cells by endocytosis. The core-shell NPs are sensitive sensors for the environment prevailing inside (shorter luminescence decay) and outside (longer luminescence decay) of the tested cells. The toxicity of the NPs was examined using MTT assay.

The Emerging Role of DNA Damage in the Pathogenesis of the C9orf72 Repeat Expansion in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressing neurodegenerative disease affecting motor neurons, and frontotemporal dementia (FTD) is a behavioural disorder resulting in early-onset dementia. Hexanucleotide (G4C2) repeat expansions in the gene encoding chromosome 9 open reading frame 72 (C9orf72) are the major cause of familial forms of both ALS (~40%) and FTD (~20%) worldwide. The C9orf72 repeat expansion is known to form abnormal nuclei acid structures, such as hairpins, G-quadruplexes, and R-loops, which are increasingly associated with human diseases involving microsatellite repeats. These configurations form during normal cellular processes, but if they persist they also damage DNA, and hence are a serious threat to genome integrity. It is unclear how the repeat expansion in C9orf72 causes ALS, but recent evidence implicates DNA damage in neurodegeneration. This may arise from abnormal nucleic acid structures, the greatly expanded C9orf72 RNA, or by repeat-associated non-ATG (RAN) translation, which generates toxic dipeptide repeat proteins. In this review, we detail recent advances implicating DNA damage in C9orf72-ALS. Furthermore, we also discuss increasing evidence that targeting these aberrant C9orf72 confirmations may have therapeutic value for ALS, thus revealing new avenues for drug discovery for this disorder.

Genetic and psychosocial factors for benzodiazepine addiction. An analysis based on the results of the authors' own research conducted in a group of benzodiazepine addicted and non-addicted individuals.

PURPOSE: In spite of the fact that the addictive potential of benzodiazepine (BDZ) drugs has been known for a long time, benzodiazepine addiction remains a common problem for psychiatry to deal with. The etiology of benzodiazepine addiction is very complex. Among the risk factors, the course of the treatment, demographic status and psychological features of a patient seem to play an important role. The aim of this study was to investigate both psychological and genetic factors differentiating benzodiazepine addicts from non-addicted users. METHODS: We analysed a cohort of 120 individuals treated with benzodiazepines divided into two groups: benzodiazepine addicts and non-addicted benzodiazepine users (the control group). In both groups we measured genetic polymorphisms of GABA A2 and MAOA. In both groups some psychometric measurements were performed - we investigated the level of depression, anxiety as a state and as a trait, personality features and the dominant coping style using the Beck Depression Scale, Hamilton Anxiety Scale, Five-Factor Personality Inventory NEO-FFI and the Coping Inventory for Stressful Situations [4,10,17,36,41,44]. RESULTS: There are some psychological and situational risk factors for benzodiazepine addiction such as high neuroticism, introversion and lack of the ability to release tension through interpersonal contacts, dominance of emotional coping style and high accumulation of critical life events during both childhood and adulthood. The genetic background still remains a field for further exploration.

CD44 regulates dendrite morphogenesis through Src tyrosine kinase-dependent positioning of the Golgi.

The acquisition of proper dendrite morphology is a crucial aspect of neuronal development towards the formation of a functional network. The role of the extracellular matrix and its cellular receptors in this process has remained enigmatic. We report that the CD44 adhesion molecule, the main hyaluronan receptor, is localized in dendrites and plays a crucial inhibitory role in dendritic tree arborization in vitro and in vivo. This novel function is exerted by the activation of Src tyrosine kinase, leading to the alteration of Golgi morphology. The mechanism operates during normal brain development, but its inhibition might have a protective influence on dendritic trees under toxic conditions, during which the silencing of CD44 expression prevents dendritic shortening induced by glutamate exposure. Overall, our results indicate a novel role for CD44 as an essential regulator of dendritic arbor complexity in both health and disease.

DNA Damage and Chromatin Rearrangement Work Together to Promote Neurodegeneration.

Neurodegenerative diseases have a complex origin and are composed of genetic and environmental factors. Both DNA damage and chromatin rearrangement are important processes that occur under pathological conditions and in neurons functioning properly. While numerous studies have demonstrated the inseparable relationship between DNA damage and chromatin organization, understanding of this relationship, especially in neurodegenerative diseases, requires further study. Interestingly, recent studies revealed that known hallmark proteins involved in neurodegenerative diseases function in both DNA damage and chromatin reorganization, and this review discusses the current knowledge of this relationship. This review focused on hallmark proteins involved in various neurodegenerative diseases, such as the microtubule-associated protein tau, TAR DNA/RNA binding protein 43 (TDP-43), superoxide dismutase 1 (SOD1), fused in sarcoma (FUS), huntingtin (HTT), α-synuclein, and ß-amyloid precursor protein (APP). Hence, DNA damage and chromatin rearrangement are associated with disease mechanisms in distinct neurodegenerative diseases. Targeting common modulators of DNA repair and chromatin reorganization may lead to promising therapies for treating neurodegeneration.

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome.

UNLABELLED: Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions. MATERIALS AND METHODS: In 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed>50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries. RESULTS: In all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9 ± 346 pg/ml, p<0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p<0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p<0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p<0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p<0.05). CONCLUSIONS: In acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

Autoimmune encephalitis as a possible reason for psychiatric hospitalisation in the teenage population. / Autoimmunologiczne zapalenie mózgu jako mozliwa przyczyna hospitalizacji psychiatrycznej nastolatków.

Autoimmune encephalitis (AE) is a rare disease manifested by rapidly progressive short-term memory loss and other cognitive impairment accompanied by multiple disorders related to the limbic system involvement. The initial symptoms of autoimmune encephalitis may imitate other psychiatric disorders and delay the implementation of an appropriate treatment. The case description of a 15-year-old patient with an initial diagnosis of psychotic disorder has been presented. Because of atypical course of an illness and an ineffective treatment with psychotropic drugs, additional tests were made including serological tests, a cerebrospinal fluid (CSF) analysis and magnetic resonance imaging. Due to the entire clinical picture an autoimmune encephalitis was suspected. The implemented treatment included steroid therapy, intravenous immunoglobulins (IVIG) and plasmapheresis. The treatment regimen was repeated until remission was achieved.