Proteomic analysis of mitochondria-enriched fraction isolated from the frontal cortex and hippocampus of apolipoprotein E knockout mice treated with alda-1, an activator of mitochondrial aldehyde dehydrogenase (ALDH2)

The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer’s disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products of lipid peroxidation, such as 4-hydroxynonenal and other reactive aldehydes. The goal of our study was to apply a differential proteomics approach in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE−/−) mice upon treatment with Alda-1—a small molecular weight activator of ALDH2. Despite the lack of significant morphological changes in the brain of apoE−/− mice as compared to age-matched wild type animals, the proteomic and molecular approach revealed many changes in the expression of genes and proteins, indicating the impairment of energy metabolism, neuroplasticity, and neurogenesis in brains of apoE−/− mice. Importantly, prolonged treatment of apoE−/− mice with Alda-1 led to the beneficial changes in the expression of genes and proteins related to neuroplasticity and mitochondrial function. The pattern of alterations implies mitoprotective action of Alda-1, however, the accurate functional consequences of the revealed changes require further research

The effect of chronic tianeptine administration on the brain mitochondria : direct links with an animal model of depression

A growing body of evidence has focused on the impact of mitochondrial disturbances in the development of depression, but little data exist regarding the effects of chronic administration of antidepressant drugs on the brain’s mitochondrial protein profile. The aim of this study was to investigate the impact of chronic treatment with an atypical antidepressant drug—tianeptine—on the mitochondria-enriched subproteome profile in the hippocampus and the frontal cortex of 3-month-old male rats following a prenatal stress procedure. Rats that were exposed to a prenatal stress procedure displayed depressive- and anxiety-like disturbances based on the elevated plus-maze and Porsolt tests. Moreover, two-dimensional electrophoresis coupled with mass spectrometry showed structure-dependent mitoproteome changes in brains of prenatally stressed rats after chronic tianeptine administration. A component of 2-oxoglutarate and succinate flavoprotein subunit dehydrogenases, isocitrate subunit alpha, was upregulated in the hippocampus. In the frontal cortex, there was a striking increase in the expression of glutamate dehydrogenase and cytochrome bc1 complex subunit 2. These findings suggest that mitochondria are underappreciated targets for therapeutic interventions, and mitochondrial function may be crucial for the effective treatment of stress-related diseases

Synthesis of Novel Pyrido[1,2-c]pyrimidine Derivatives with 6-Fluoro-3-(4-piperidynyl)-1,2-benzisoxazole Moiety as Potential SSRI and 5-HT1A Receptor Ligands

Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidine (6a–i) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine (7a–i) derivatives were synthesized. The chemical structures of the new compounds were confirmed by 1H and 13C NMR spectroscopy and ESI-HRMS spectrometry. The affinities of all compounds for the 5-HT1A receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays. The test compounds demonstrated very high binding affinities for the 5-HT1A receptor of all derivatives in the series (6a–i and 7a–i) and generally low binding affinities for the SERT protein, with the exception of compounds 6a and 7g. Extended affinity tests for the receptors D2, 5-HT2A, 5-HT6 and 5-HT7 were conducted with regard to selected compounds (6a, 7g, 6d and 7i). All four compounds demonstrated very high affinities for the D2 and 5-HT2A receptors. Compounds 6a and 7g also had high affinities for 5-HT7, while 6d and 7i held moderate affinities for this receptor. Compounds 6a and 7g were also tested in vivo to identify their functional activity profiles with regard to the 5-HT1A receptor, with 6a demonstrating the activity profile of a presynaptic agonist. Metabolic stability tests were also conducted for 6a and 6d

Ostatecznie gruźlica, a nie choroba nowotworowa. Prezentacja trzech przypadków pediatrycznych

Gruźlica wieku dziecięcego należy obecnie w krajach wysoko rozwiniętych do rzadkości. W pracy zaprezentowano przypadki trojga dzieci z objawami nasuwającymi podejrzenie choroby nowotworowej, u których ostatecznie dzięki interwencji chirurgicznej rozpoznano gruźlicę (węzłowo-płucną, wielonarządową oraz ściany klatki piersiowej). Tylko u jednej pacjentki uzyskano potwierdzenie bakteriologiczne. Objawy gruźlicy wymagają różnicowania z chorobą nowotworową. Chirurg, który pobiera materiał diagnostyczny, powinien pamiętać o wykonaniu badań bakteriologicznych w kierunku gruźlicy. Forum Medycyny Rodzinnej 2010, tom 4, nr 6, 464–47

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

The influence of time perspective, values and the sense of being lucky on satisfaction with life.

Celem przeprowadzonych w tej pracy badań było sprawdzenie związków pomiędzy satysfakcją z życia jako zmienną zależną oraz czynnikami takimi, jak perspektywy postrzegania czasu, wyznawane wartości oraz poczucie posiadania fartu. Badania zostały przeprowadzone na 183 studentach hiszpańskich w wieku od 18 do 27 lat (M=21,14; SD=2,23). Do pomiaru badanych zmiennych wykorzystano: Skalę satysfakcji z życia Dienera (SWLS), Inwentarz perspektywy czasowej Zimbardo (ZTPI), Portretowy kwestionariusz wartości Schwartza (PVQ-40) oraz Kwestionariusz szczęścia-pecha Kolemby. Analiza uzyskanych wyników wykazała istotny dodatni związek pomiędzy satysfakcją z życia oraz przeszłą pozytywną perspektywą czasową, a także ujemny związek z przeszłą negatywną orientacją temporalną. Co więcej zauważono wpływ współczynnika szczęścia na poziom zadowolenia z życia oraz korelacje pomiędzy współczynnikiem szczęścia a przeszłą negatywną i pozytywną perspektywą czasową, jak i teraźniejszą hedonistyczną orientacją. Badania wykazały ciekawe relacje między postrzeganiem siebie jako farciarza a innymi czynnikami co prowokuje kolejne badania na tym polu.The purpose of this study was to check the relations between life satisfaction, time perspectives, values and feeling lucky. The research was made on 183 Spanish students the age of 18-27 (M=21,14; SD=2,23). To measure the variables were used: Satisfaction with Life Scale SWLS, Zimbardo Time Perspective Inventory ZTPI, Portrait Values Questionnaire PVQ-40 and Luck-bad luck Questionnaire. The analysis of the results has showed the important relations between life satisfaction and positive past perspective also negative correlation with negative past. What is more there has been an influence of feeling lucky on the level of life satisfaction noticed and correlations between feeling lucky and positive past, negative past and hedonistic present time perspectives. The research has proven an interesting relation between feeling lucky and other variables that provokes new study on this field

Changes in thrust force in swimmers in the annual training cycle

Study aim: Determination of changes in thrust force and effect size of training load in swimmers using four swimming strokes monitored 4 times a year

Molecular Research on Mental Disorders

Mental disorders and substance use disorders affect approximately 13% of the world’s population [...