Blood oxygen regulation via P2Y12R expressed in the carotid body.

BACKGROUND: Peripheral blood oxygen monitoring via chemoreceptors in the carotid body (CB) is an integral function of the autonomic cardiorespiratory regulation. The presence of the purinergic P2Y12 receptor (P2Y12R) has been implicated in CB; however, the exact role of the receptor in O2 sensing and signal transduction is unknown. METHODS: The presence of P2Y12R was established by immunoblotting, RT qPCR and immunohistochemistry. Primary glomus cells were used to assess P2Y12R function during hypoxia and hypercapnia, where monoamines were measured by HPLC; calcium signal was recorded utilizing OGB-1 and N-STORM Super-Resolution System. Ingravescent hypoxia model was tested in anaesthetized mice of mixed gender and cardiorespiratory parameters were recorded in control and receptor-deficient or drug-treated experimental animals. RESULTS: Initially, the expression of P2Y12R in adult murine CB was confirmed. Hypoxia induced a P2Y12R-dependent release of monoamine transmitters from isolated CB cells. Receptor activation with the endogenous ligand ADP promoted release of neurotransmitters under normoxic conditions, while blockade disrupted the amplitude and duration of the intracellular calcium concentration. In anaesthetised mice, blockade of P2Y12R expressed in the CB abrogated the initiation of compensatory cardiorespiratory changes in hypoxic environment, while centrally inhibited receptors (i.e. microglial receptors) or receptor-deficiency induced by platelet depletion had limited influence on the physiological adjustment to hypoxia. CONCLUSIONS: Peripheral P2Y12R inhibition interfere with the complex mechanisms of acute oxygen sensing by influencing the calcium signalling and the release of neurotransmitter molecules to evoke compensatory response to hypoxia. Prospectively, the irreversible blockade of glomic receptors by anti-platelet drugs targeting P2Y12Rs, propose a potential, formerly unrecognized side-effect to anti-platelet medications in patients with pulmonary morbidities.

The antidepressant effect of short- and long-term zinc exposition is partly mediated by P2X7 receptors in male mice.

Background: As a member of the purinergic receptor family, divalent cation-regulated ionotropic P2X7 (P2rx7) plays a role in the pathophysiology of psychiatric disorders. This study aimed to investigate whether the effects of acute zinc administration and long-term zinc deprivation on depression-like behaviors in mice are mediated by P2X7 receptors. Methods: The antidepressant-like effect of elevated zinc level was studied using a single acute intraperitoneal injection in C57BL6/J wild-type and P2rx7 gene-deficient (P2rx7 -/-) young adult and elderly animals in the tail suspension test (TST) and the forced swim test (FST). In the long-term experiments, depression-like behavior caused by zinc deficiency was investigated with the continuous administration of zinc-reduced and control diets for 8 weeks, followed by the same behavioral tests. The actual change in zinc levels owing to the treatments was examined by assaying serum zinc levels. Changes in monoamine and brain-derived neurotrophic factor (BDNF) levels were measured from the hippocampus and prefrontal cortex brain areas by enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Results: A single acute zinc treatment increased the serum zinc level evoked antidepressant-like effect in both genotypes and age groups, except TST in elderly P2rx7 -/- animals, where no significant effect was detected. Likewise, the pro-depressant effect of zinc deprivation was observed in young adult mice in the FST and TST, which was alleviated in the case of the TST in the absence of functional P2X7 receptors. Among elderly mice, no pro-depressant effect was observed in P2rx7 -/- mice in either tests. Treatment and genotype changes in monoamine and BDNF levels were also detected in the hippocampi. Conclusion: Changes in zinc intake were associated with age-related changes in behavior in the TST and FST. The antidepressant-like effect of zinc is partially mediated by the P2X7 receptor.

Stress and Anxiety among High School Adolescents: Correlations between Physiological and Psychological Indicators in a Longitudinal Follow-Up Study.

Mental and psychological disorders are serious health problems worldwide. Anxiety among high school students can affect school performance, relationships, and family life. OBJECTIVE: Our aim is to understand the anxiety levels and associated factors among high school students and compare the results of psychological tests measuring anxiety with the cortisol levels obtained from biological sampling. METHOD: In our longitudinal follow-up study, we involved 125 individuals in May 2019. Validated measurement tools were used during questionnaire data collection, including the State-Trait Anxiety Inventory, Clear Communication Scale, Multiple Social Perceived Support Scale, and related HBSC questions. As objective data, we collected hair samples for cortisol level measurement. RESULTS: At the end of the school year, the anxiety levels measured by psychological tests were significantly higher (p = 0.001) compared to the anxiety levels at the beginning of the next school year. Anxiety levels were higher among girls and were influenced by the type of school and parental expectations. Both state anxiety and trait anxiety showed a strong correlation with psychosomatic symptoms (p < 0.001) and anxiety arising from school expectations (p < 0.05). The changes in cortisol levels did not follow the changes in psychological tests. Cortisol level increased (p = 0.01) in the second sample.

P2X7 purinergic receptor modulates dentate gyrus excitatory neurotransmission and alleviates schizophrenia-like symptoms in mouse.

ATP-gated P2X7 receptors (P2X7Rs) play a crucial role in brain disorders. However, how they affect normal and pathological synaptic transmission is still largely unclear. Here, by using whole-cell patch-clamp technique to record AMPA- and NMDA receptor-mediated excitatory postsynaptic currents (s/mEPSCs) in dentate gyrus granule cells (DG GCs), we revealed a modulation by P2X7Rs of presynaptic sites, especially originated from entorhinal cortex (EC)-GC path but not the mossy cell (MC)-GC path. The involvement of P2X7Rs was confirmed using a pharmacological approach. Additionally, the acute activation of P2X7Rs directly elevated calcium influx from EC-GC terminals. In postnatal phencyclidine (PCP)-induced mouse model of schizophrenia, we observed that P2X7R deficiency restored the EC-GC synapse alteration and alleviated PCP-induced symptoms. To summarize, P2X7Rs participate in the modulation of GC excitatory neurotransmission in the DG via EC-GC pathway, contributing to pathological alterations of neuronal functions leading to neurodevelopmental disorders.

The dualistic role of the purinergic P2Y12-receptor in an in vivo model of Parkinson's disease: Signalling pathway and novel therapeutic targets.

Parkinson's disease (PD) is a chronic, progressive neurodegenerative condition; characterized with the degeneration of the nigrostriatal dopaminergic pathway and neuroinflammation. During PD progression, microglia, the resident immune cells in the central nervous system (CNS) display altered activity, but their role in maintaining PD development has remained unclear to date. The purinergic P2Y12-receptor (P2Y12R), which is expressed on the microglia in the CNS has been shown to regulate microglial activity and responses; however, the function of the P2Y12R in PD is unknown. Here we show that MPTP-induced PD symptoms in mice are associated with marked neuroinflammatory changes and P2Y12R contribute to the activation of microglia and progression of the disease. Surprisingly, while pharmacological or genetic targeting of the P2Y12R augments acute mortality in MPTP-treated mice, these interventions protect against the neurodegenerative cell loss and the development of neuroinflammation in vivo. Pharmacological inhibition of receptors during disease development reverses the symptoms of PD and halts disease progression. We found that P2Y12R regulates ROCK and p38 MAPK activity and control cytokine production. Our principal finding is that the receptor has a dualistic role in PD: functional P2Y12Rs are essential to initiate a protective inflammatory response, since the lack of the receptor leads to reduced survival; however, at later stages of neurodegeneration, P2Y12Rs are apparently responsible for maintaining the activated state of microglia and stimulating pro-inflammatory cytokine response. Understanding protective and detrimental P2Y12R-mediated actions in the CNS may reveal novel approaches to control neuroinflammation and modify disease progression in PD.

Accumulation of selected metals and concentration of macroelements in liver and kidney tissues of sympatric golden jackal (Canis aureus) and red fox (Vulpes vulpes) in Somogy County, Hungary.

This study examined the concentrations of Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn in the liver and kidney samples of golden jackals (n = 163) and red foxes (n = 64). Additionally, we studied how sex affected element concentration in both species, and in the case of golden jackals, how concentration levels were affected by age.Liver was the most important storage organ for Cu, Fe, Mn, and Zn, while kidney for Cd and Na in jackals and foxes.We found no sex-related differences in concentration of any of the selected elements in fox samples. In jackals, the mean concentrations of Al, Mn, and Zn were significantly higher in kidneys of males, while Zn and Cu had higher concentrations in female livers. Our results suggest bioaccumulation processes do not occur in mesocarnivores.Lead and Cd concentrations fell within ranges accepted as normal for canine species and were below toxic levels in the organs of the examined species. Concentrations of Cr, Cu, Fe, Mn, and Zn were far below the toxic levels in both organs of both species, with a slight sign of deficiency of Fe, Mn, and Zn in jackal and fox kidneys. In comparison with toxicity levels and results from other European study sites, the current study demonstrated that species living in the examined area of Somogy County, Hungary, are generally exposed to low levels of environmental contamination.

Preparation of cubic-shaped sorafenib-loaded nanocomposite using well-defined poly(vinyl alcohol alt-propenylene) copolymer.

Vinyl alcohol (VA) copolymers having fine tunable polarities are emerging materials in drug delivery applications. VA copolymers rendering well-defined molecular architecture (C/OH ratio = 2, 4, 5 and 8) were used as carriers for model drug compound, fluorescein, which exhibited significantly different release characteristics depending on the polarity of the polymers. Based on the preliminary drug release tests the well-defined VA copolymer having C/OH = 5 ratio, poly(vinyl alcohol alt-propenylene) copolymer (PVA-5) was selected for nanocomposite synthesis. Sorafenib anticancer drug was embedded into PVA-5 (C/OH = 5 ratio) nanoparticles by nanoprecipitation resulting in nanoparticles exhibiting unusual cubic shape. The sorafenib-loaded nanocomposites showed continuous release during a day and concentration-dependant cytotoxicity on HT-29 cancer cells. This might be interpreted by the sustained release of the drug.

Long-term ecological effects of the red mud disaster in Hungary: Regeneration of red mud flooded areas in a contaminated industrial region.

As one of the most severe ecological disasters ever to take place in Europe, the 2010 red mud accident has left behind long-term environmental impact, prompting the need for monitoring of soil biodiversity. Red mud (wet storage solution) can be regarded as a complex mixture of contaminants due to its extreme alkalinity and the presence of potentially toxic trace elements. After-effect investigations on soil properties and soil microarthropods were carried out in three distinct habitat types (agricultural land, grassland, woodland) in the red mud affected area. Soils in the red mud affected area were moderately to strongly alkaline (pH 7.5 to 8.5). Total content of trace metals Cd, Ni, Cr exceeded threshold concentrations for soil. Acari and Collembola were by far the most abundant taxa, while important groups like Pauropoda, Protura and Symphyla were completely absent from the samples of red mud affected plots. These observations were also reflected by the low values of the soil biological quality (QBS-ar) index. Independently of habitat types, total collembolan abundance tended to be lower in the contaminated area when compared with nearby control samples. Typical species distribution of Collembola communities in the contaminated area generally included one or two very common and abundant species and more, relatively rare species of low abundance. In the red mud affected open habitats, a distinct eudominance of Brachystomella parvula and Parisotoma notabilis was observed; whereas in contaminated woodland Parisotoma notabilis formed the bulk of the community with Sphaeridia pumilis, Folsomia manolachei and F. quadrioculata being subdominant. Species sensitive to alkalinity and red mud components (e.g. Hypogastrura vernalis, Lepidocyrtus tomosvaryi) were completely absent or were present only in limited numbers in the contaminated samples.

Accumulation of Metals in Liver Tissues of Sympatric Golden Jackal (Canis aureus) and Red Fox (Vulpes vulpes) in the Southern Part of Romania.

Several previous study results have already demonstrated that golden jackal and red fox may serve as biological indicators of trace elements and heavy metal concentrations in the various regions they inhabit. The aim of this study was to evaluate accumulation patterns of targeted elements (Al, Ca, Cr, Cu, Fe, Mg, Mn, Ni and Pb) in liver samples of red foxes and golden jackals collected during the same period in the southern part of Romania. The accumulation patterns of trace elements in the livers of sympatric golden jackal and red fox were practically the same. To date, separate studies of the species individually in different habitats have shown that either of the species can be used for ecotoxicological and biomonitoring studies. Moreover, in general gender related studies, no significant differences in the concentrations of the investigated elements were found in either jackals or foxes. Also, average metal concentrations in liver samples do not show significant differences between groups under and above 12 months of age.

Different work schedules of nurses in Hungary and their effects on health.

BACKGROUND AND PURPOSE: The shift work is burdensome for nurses and may lead to health problems. Aims - The purpose of the study was to examine the nursing shift system types and to analyse the effects on nutritional status, subjective state of physical and mental health in case of different shift schedules. METHODS: In the first phase of the research 326 nurses working in changing shifts filled out the Bergen Shift Work Questionnaire after adaptation into Hungarian. 518 nurses participated in our second study in hospitals of the South-Danubian Region, in clinics of University of Pécs and at trainings organized by the Faculty of Health Sciences of the University of Pécs. RESULTS: Based on the psychometric characteristics of Bergen Shift Work Questionnaire technically it is suitable for the examination of sleeping disorders associated with shift work. Sleeping quality is worse in those working in irregular work shifts compared to those working in regular and flexible work schedules (p<0.001). The irregular work schedule is worse than the regular work schedule according to 76.6% of the nurses. According to 63.8% of the respondents the following regular work schedule is the best: after one 12-hour day shift one 12-hour night shift, followed by two days of rest. The average Body Mass Index (BMI) is 26.16 kg/m2. Since the nurses work in shift work 47.7% of them reported weight gain. Among the psychosomatic symptoms the most frequent is back pain (78.4%) related elevated BMI (p=0.013). The nurses' sense of coherence on average is 61.76 points. In case of full-time employees the sense of coherence is better than those who work in shifts (t=2.933, p=0.004). The nurses working irregular shift work asses their health worst (mean rank: 166.61; p=0.019), and their sense of coherence is lower (p=0.04). CONCLUSION: The irregularity of work schedules is stressful for nurses. Due to the health of nurses it would be useful to establish the least exhausting work schedules.

[Vitamin D supply among healthy blood donors in Vas County, Hungary]. / D-vitamin-ellátottság felmérése Vas megye egészséges véradói körében.

INTRODUCTION: There is growing evidence showing the importance of adequate vitamin D supply for preserving health. AIM: The aim of the study was to evaluate the vitamin D supply among healthy blood donors and healthy elderly subjects in County Vas, Hungary. METHODS: Serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium and albumin (Cobas, Modular, Roche), as well as serum alfa-2-globulin concentrations (Gelelfo, Interlab) were determined in 178 serum samples (68 men, 110 women, 41 were taking oral contraceptives). The results were analysed according to sex and age (younger and older than 43 years), and the impact of oral contraceptive use was also taken into consideration. RESULTS: Deficiency and insufficiency in vitamin D levels were detected in 9.6% and 32% of the studied subjects, respectively, whereas sufficient vitamin D levels were present in 58.4% of the subjects. 63% of the older and 41.2% of the younger group had suboptimal vitamin-D supply (p < 0.01). In women taking oral contraceptives serum 25-hydroxyvitamin D and alfa-2-globulin levels were significantly higher, whereas serum albumin and calcium levels were lower than in the control group. There was no difference in serum intact parathyroid hormone concentration between oral contraceptive users and non-users. CONCLUSIONS: The occurrence of suboptimal vitamin D supply is significant, although less frequent than that in literature reports. In women taking oral contraceptives, serum 25-hydroxyvitamin D levels were higher, but serum intact parathyroid hormone concentrations were not decreased suggesting that the increased 25-hydroxyvitamin D levels may be the consequence of oestrogen-induced alterations of serum protein fractions.