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Abstract Background Marfan syndrome is a genetic disease, presenting with dysfunction of connective tissues leading to lesions in the cardiovascular and skeletal muscle system. Within these symptoms, the most typical is weakness of the connective tissue in the aorta, manifesting as aortic dilatation (aneurysm). This could, in turn, become annuloaortic ectasia, or life-threatening dissection. As a result, life-saving and preventative cardiac surgical interventions are frequent among Marfan syndrome patients. Aortic aneurysm could turn into annuloaortic ectasia or life-threatening dissection, thus life-saving and preventive cardiac surgical interventions are frequent among patients with Marfan syndrome. We hypothesized that patients with Marfan syndrome have different level of anxiety, depression and satisfaction with life compared to that of the non-clinical patient population. Methods Patients diagnosed with Marfan syndrome were divided into 3 groups: those scheduled for prophylactic surgery, those needing acute surgery, and those without need for surgery (n = 9, 19, 17, respectively). To examine the psychological features of the patients, Spielberger’s anxiety (STAI) test, Beck’s Depression questionnaire (BDI), the Berne Questionnaire of Subjective Well-being, and the Satisfaction with Life scale were applied. Results A significant difference was found in trait anxiety between healthy individuals and patients with Marfan syndrome after acute life-saving surgery (p 0.1). Finally, a significant, medium size effect was found between patient groups on the Joy in Living scale (F (2.39) = 3.51, p = 0.040, η2 = 0.15). Conclusions Involving psychiatric and mental-health care, in addition to existing surgical treatment interventions, is essential for more successful recovery of patients with Marfan syndrome.

The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic and eukaryotic organisms. The chemical nature of these polysulfides is not fully understood, however, because of their reactive or complicated redox-active properties. In our study here, we determined that tyrosine and a hydroxyphenyl-containing derivative, β-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), had potent stabilizing effects on diverse polysulfide residues formed in CysSSH-related low-molecular-weight species, e.g., glutathione polysulfides (oxidized glutathione trisulfide and oxidized glutathione tetrasulfide). The protective effect against degradation was likely caused by the inhibitory activity of hydroxyphenyl residues of tyrosine and HPE-IAM against alkaline hydrolysis of polysulfides. This hydrolysis occurred via heterolytic scission triggered by the hydroxyl anion acting on polysulfides that are cleaved into thiolates and sulfenic acids, with the hydrolysis being enhanced by alkylating reagents (e.g. IAM) and dimedone. Moreover, tyrosine prevented electrophilic degradation occurring in alkaline pH. The polysulfide stabilization induced by tyrosine or the hydroxyphenyl moiety of HPE-IAM will greatly improve our understanding of the chemical properties of polysulfides and may benefit the sulfur metabolomics analysis if it can be applied successfully to any kind of biological samples, including clinical specimens. Keywords: Reactive sulfur species, β-(4-Hydroxyphenyl)ethyl iodoacetamide, Tyrosine, Reactive sulfur metabolomics analysis, Reactive sulfur signaling, Redox signaling

UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy, endocytosis and DNA damage repair, but how its loss contributes to colorectal cancer is poorly understood. Here, we show that UVRAG deficiency in Drosophila intestinal stem cells leads to uncontrolled proliferation and impaired differentiation without preventing autophagy. As a result, affected animals suffer from gut dysfunction and short lifespan. Dysplasia upon loss of UVRAG is characterized by the accumulation of endocytosed ligands and sustained activation of STAT and JNK signaling, and attenuation of these pathways suppresses stem cell hyperproliferation. Importantly, the inhibition of early (dynamin-dependent) or late (Rab7-dependent) steps of endocytosis in intestinal stem cells also induces hyperproliferation and dysplasia. Our data raise the possibility that endocytic, but not autophagic, defects contribute to UVRAG-deficient colorectal cancer development in humans.

The review will discuss in detail the effects of polyphenols on breast cancer, including both the advantages and disadvantages of the applications of these natural compounds. First, we focus on the characterization of the main classes of polyphenols and then on in vitro and in vivo experiments carried out in breast cancer models. Since the therapeutic effects of the administration of a single type of polyphenol might be limited because of the reduced bioavailability of these drugs, investigations on combination of several polyphenols or polyphenols with conventional therapy will also be discussed. In addition, we present recent data focusing on clinical trials with polyphenols and new approaches with nanoparticles in breast cancer. Besides the clinical and translational findings this review systematically summarizes our current knowledge about the molecular mechanisms of anti-cancer effects of polyphenols, which are related to apoptosis, cell cycle regulation, plasma membrane receptors, signaling pathways and epigenetic mechanisms. At the same time the effects of polyphenols on primary tumor, metastasis and angiogenesis in breast cancer are discussed. The increasing enthusiasm regarding the combination of polyphenols and conventional therapy in breast cancer might lead to additional efforts to motivate further research in this field.

Accumulation of damaged or misfolded proteins resulted from oxidative protein modification induces endoplasmic reticulum (ER) stress by activating the pathways of unfolded protein response. In pathologic hemolytic conditions, extracellular free hemoglobin is submitted to rapid oxidation causing heme release. Resident cells of atherosclerotic lesions, after intraplaque hemorrhage, are exposed to heme leading to oxidative injury. Therefore, we raised the question whether heme can also provoke ER stress. Smooth muscle cells are one of the key players of atherogenesis; thus, human aortic smooth muscle cells (HAoSMCs) were selected as a model cell to reveal the possible link between heme and ER stress. Using immunoblotting, quantitative polymerase chain reaction and immunocytochemistry, we quantitated the markers of ER stress. These were: phosphorylated eIF2α, Activating transcription factor-4 (ATF4), DNA-damage-inducible transcript 3 (also known as C/EBP homology protein, termed CHOP), X-box binding protein-1 (XBP1), Activating transcription factor-6 (ATF6), GRP78 (glucose-regulated protein, 78kDa) and heme responsive genes heme oxygenase-1 and ferritin. In addition, immunohistochemistry was performed on human carotid artery specimens from patients who had undergone carotid endarterectomy. We demonstrate that heme increases the phosphorylation of eiF2α in HAoSMCs and the expression of ATF4. Heme also enhances the splicing of XBP1 and the proteolytic cleavage of ATF6. Consequently, there is up-regulation of target genes increasing both mRNA and protein levels of CHOP and GRP78. However, TGFβ and collagen type I decreased. When the heme binding proteins, alpha-1-microglobulin (A1M) and hemopexin (Hpx) are present in cell media, the ER stress provoked by heme is inhibited. ER stress pathways are also retarded by the antioxidant N-acetyl cysteine (NAC) indicating that reactive oxygen species are involved in heme-induced ER stress. Consistent with these findings, elevated expression of the ER stress marker GRP78 and CHOP were observed in smooth muscle cells of complicated lesions with hemorrhage compared to either atheromas or healthy arteries. In conclusion, heme triggers ER stress in a time- and dose-dependent manner in HAoSMCs. A1M and Hpx as well as NAC effectively hamper heme-induced ER stress, supporting their use as a potential therapeutic approach to reverse such a deleterious effects of heme toxicity.

Jelen könyv a Médiatudományi Könyvtár 27. kötete. A szerzõ egyrészt azt tûzte ki célul, hogy áttekintést ad arról, milyen elméleti problémák vetõdnek vagy vetõdhetnek fel a szólásszabadságnak a méltóság, illetve a becsület védelme érdekében történõ, kriminális jellegû korlátozásai során, másrészt hogy vázolja, vajon e problémákra milyen válaszok születtek és születnek az ilyen jellegû korlátozásokat alkalmazó, jellemzõen európai országokban, ezen belül is elsõsorban Magyarországon. Harmadikként végül azt a célt fogalmazta meg, hogy ismerteti és elemzi az Emberi Jogok Európai Bíróságának vonatkozó gyakorlatát.

Background: Pulse wave transit time (PWTT) is widely used to characterize the dynamic properties of the arteries. PWTT is most often calculated as the time interval from the R peak in the electrocardiogram (start of the pulse wave) to the rise in the finger photoplethysmogram (arrival of the pulse wave). This is the PWTTHF. The aim of this study was to analyse the effect of cuff occlusion on PWTT, and using this information to improve the reliability of cuff-based indirect blood pressure (BP) measurement. Methods: PWTT was measured with a home health monitoring device that inflates and deflates the cuff slowly (6 mmHg/s). The change in the arterial wall rigidity caused by cuff occlusion is different in the parts of the arterial section proximal and distal to the cuff. Accordingly, PWTT was divided into two parts: PWTT from the heart to the cuff (PWTTHC) and PWTT from the cuff to the fingertip (PWTTCF). Seven patients with various cardiovascular diseases (55–66 years old), seven healthy senior subjects (55–65 years old) and seven healthy young subjects (22–26 years old) were included in the research. Results: Changes in PWTT characterise appropriately the effect of cuff occlusion on BP measurement. Cuff occlusion affected PWTTHC and PWTTCF differently; it increased the former and decreased the latter. Increased PWTTHC reflects a less rigid arterial wall, resulting in an underestimation of BP. The changes in PWTT values are person-specific and not group-specific (patient, healthy senior, and healthy youth). Conclusion: Occlusion with the cuff is an excitation to the cardiovascular system, causing a temporary change in the dynamic properties of the arteries from the heart to the cuff. The change influences the result of indirect BP measurement. Arterial rigidity in the part proximal to the cuff can be characterized by PWTTHC, which provides different information about the arteries than the widely used PWTTHF.

Communication of molecular species through dynamic association and/or dissociation at various cellular sites governs biological functions. Understanding these physiological processes require delineation of molecular events occurring at the level of individual complexes in a living cell. Among the few non-invasive approaches with nanometer resolution are methods based on Förster Resonance Energy Transfer (FRET). FRET is effective at a distance of 1–10 nm which is equivalent to the size of macromolecules, thus providing an unprecedented level of detail on molecular interactions. The emergence of fluorescent proteins and SNAP- and CLIP- tag proteins provided FRET with the capability to monitor changes in a molecular complex in real-time making it possible to establish the functional significance of the studied molecules in a native environment. Now, FRET is widely used in biological sciences, including the field of proteomics, signal transduction, diagnostics and drug development to address questions almost unimaginable with biochemical methods and conventional microscopies. However, the underlying physics of FRET often scares biologists. Therefore, in this review, our goal is to introduce FRET to non-physicists in a lucid manner. We will also discuss our contributions to various FRET methodologies based on microscopy and flow cytometry, while describing its application for determining the molecular heterogeneity of the plasma membrane in various cell types.

BACKGROUND AND AIMS:Ductular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis-ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models. METHODS:Liver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration. The effect of thioacetamide was modulated by treatment with imatinib and erlotinib. The extent of ductular reaction and fibrosis was measured by morphometry following cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively. The proliferative activity of hepatocytes and ductular reaction was evaluated by BrdU incorporation. The temporal distribution of the parameters was followed and compared within and between different experimental groups. RESULTS:There was a strong significant correlation between the extent of fibrosis and ductular reaction in each experimental group. Although imatinib and erlotinib temporarily decreased fibrosis this effect later disappeared. We could not observe negative correlation between the proliferation of hepatocytes and ductular reaction in any of the investigated models. CONCLUSIONS:The stringent connection between ductular reaction and fibrosis, which cannot be influenced by any of our treatment regimens, suggests that there is a close mutual interaction between them instead of a unidirectional causal relationship. Our results confirm a close connection between DR and fibrogenesis. However, since the two parameters changed together we could not establish a causal relationship and were unable to reveal which was the primary event. The lack of inverse correlation between the proliferation of hepatocytes and ductular reaction questions that ductular reaction can compensate for the failing regenerative activity of hepatocytes. No evidences support the persistent antifibrotic property of imatinib or erlotinib.

Sulfide salts are known to promote the release of nitric oxide (NO) from S-nitrosothiols and potentiate their vasorelaxant activity, but much of the cross-talk between hydrogen sulfide and NO is believed to occur via functional interactions of cell regulatory elements such as phosphodiesterases. Using RFL-6 cells as an NO reporter system we sought to investigate whether sulfide can also modulate nitrosothiol-mediated soluble guanylyl cyclase (sGC) activation following direct chemical interaction. We find a U-shaped dose response relationship where low sulfide concentrations attenuate sGC stimulation by S-nitrosopenicillamine (SNAP) and cyclic GMP levels are restored at equimolar ratios. Similar results are observed when intracellular sulfide levels are raised by pre-incubation with the sulfide donor, GYY4137. The outcome of direct sulfide/nitrosothiol interactions also critically depends on molar reactant ratios and is accompanied by oxygen consumption. With sulfide in excess, a ‘yellow compound’ accumulates that is indistinguishable from the product of solid-phase transnitrosation of either hydrosulfide or hydrodisulfide and assigned to be nitrosopersulfide (perthionitrite, SSNO−; λmax 412 nm in aqueous buffers, pH 7.4; 448 nm in DMF). Time-resolved chemiluminescence and UV–visible spectroscopy analyses suggest that its generation is preceded by formation of the short-lived NO-donor, thionitrite (SNO−). In contrast to the latter, SSNO− is rather stable at physiological pH and generates both NO and polysulfides on decomposition, resulting in sustained potentiation of SNAP-induced sGC stimulation. Thus, sulfide reacts with nitrosothiols to form multiple bioactive products; SSNO− rather than SNO− may account for some of the longer-lived effects of nitrosothiols and contribute to sulfide and NO signaling.

Lethal effects of neem derived pesticides (neem leaf extract (NLE) and NeemAzal-T/S (NA)) were examined on different entomopathogenic (EPN) and slug-parasitic (SPN) nematodes. In our recent study, neem derived pesticides were tested against Phasmarhabditis hermaphrodita for the first time under in vitro conditions. Laboratory experiments were set up in 96-well microplates with different concentrations of NLE (0.1%, 0.3%, 0.6%, and 1%) and NA (0.001%, 0.003%, 0.006%, and 0.01%) and Milli-Q water as the control. After 24-h exposure time, mortality of individual nematodes was observed and recorded. Considering LC10 values, 0.1% of NLE could be used safely in combination with all the EPNs and SPNs tested in recent study. A concentration of NA three times higher than the recommended dosage did not harm either EPN or SPN species. In conclusion, NeemAzal-T/S might be applied with EPNs and the SPN Ph. hermaphrodita simultaneously, while the compatibility of neem leaf extract and beneficial nematode products needs further evaluation.

Prostate cancer is the one of the most frequently diagnosed cancers among men over the age of 50. Several lines of evidence support the observation that polyphenols have preventive and therapeutic effects in prostate cancer. Moreover, prostate cancer is ideal for chemoprevention due to its long latency. We propose here an equilibrated lifestyle with a diet rich in polyphenols as prophylactic attempts to slow down the progression of localized prostate cancer or prevent the occurrence of the disease. In this review, we will first summarize the molecular mechanisms of polyphenols in prostate cancer with a focus on the antioxidant and pro-oxidant effects, androgen receptors (AR), key molecules involved in AR signaling and their transactivation pathways, cell cycle, apoptosis, angiogenesis, metastasis, genetic aspects, and epigenetic mechanisms. The relevance of the molecular mechanisms is discussed in light of current bioavailability data regarding the activity of polyphenols in prostate cancer. We also highlight strategies for improving the bioavailability of polyphenols. We hope that this review will lead to further research regarding the bioavailability and the role of polyphenols in prostate cancer prevention and treatment.

This study investigated the effects of different groundcover materials on soil and plant nutrition. Trees of apple cv. ‘Idared’/MM.106 (Malus domestica Borkh.) were planted into lowland chernozem soil in the spring of 1999. Applied treatments can be divided into two groups: different livestock manures and mulches. Soil strips of 150 cm width were covered either with straw, different livestock manure, black plastic foil, pine bark mulch or were without cover i.e. clean cultivation as a check. Leaf and soil samples were collected for chemical analysis. It was found that all groundcover treatments induced an increase in leaf nitrogen, sulphur and calcium. Leaf magnesium was not affected so obviously by different groundcover treatments. Leaf potassium was not affected by applying different livestock manures, except horse manure but lower in mulch treatments compared to the control. Leaf phosphorous was decreased by treatments except using horse manure. Examination of ratios of nutrients showed that there were disharmonies in the available nutrients supply of soil. The best results were obtained by applying horse manure.

Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in transendothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-β-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-β-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation.

Exosomes are emerging targets for biomedical research. However, suitable methods for the isolation of blood plasma-derived exosomes without impurities have not yet been described.Therefore, we investigated the efficiency and purity of exosomes isolated with potentially suitable methods; differential ultracentrifugation (UC) and size exclusion chromatography (SEC).Exosomes were isolated from rat and human blood plasma by various UC and SEC conditions. Efficiency was investigated at serial UC of the supernatant, while in case of SEC by comparing the content of exosomal markers of various fractions. Purity was assessed based on the presence of albumin. We found that the diameter of the majority of isolated particles fell into the size range of exosomes, however, albumin was also present in the preparations, when 1h UC at 4°C was applied. Furthermore, with this method only a minor fraction of total exosomes could be isolated from blood as deduced from the constant amount of exosomal markers CD63 and TSG101 detected after serial UC of rat blood plasma samples. By using UC for longer time or with shorter sedimentation distance at 4°C, or UC performed at 37°C, exosomal yield increased, but albumin impurity was still observed in the isolates, as assessed by transmission electron microscopy, dynamic light scattering and immunoblotting against CD63, TSG101 and albumin. Efficiency and purity were not different in case of using further diluted samples. By using SEC with different columns, we have found that although a minor fraction of exosomes can be isolated without significant albumin content on Sepharose CL-4B or Sephacryl S-400 columns, but not on Sepharose 2B columns, the majority of exosomes co-eluted with albumin.Here we show that it is feasible to isolate exosomes from blood plasma by SEC without significant albumin contamination albeit with low vesicle yield.

Macronutrient contents of soil and apple leaves were investigated in an organic apple orchard in Eastern Hungary in 2002-2004. Soil samples were taken from 0-20 cm depth in April and October. The macronutrient content of leaves was measured on cvs. Jonagold, Mutsu, Idared, Red Elstar, Egri Piros, Reka, and Remo at six assessment dates (from April to September). The macronutrient contents of N, P, K, S, Ca and Mg were measured in both soil and leaf samples, then macronutrient ratios were calculated from the obtained results. The results showed that younger leaves contained more N and P than older ones. K and Ca contents of leaves decreased until July, then increased slightly, and decreased again. A continuous decrease of the S content of leaves was observed until August. The Mg content of leaves increased until June, then decreased in July and then increased again. Macronutrient values were dependent on cultivar. Calculated macronutrient ratios showed that the nutrient supply of soil was not optimal in the orchard.

Few epidemiologic studies have investigated predictors of uncomplicated peptic ulcer disease (PUD) separately from predictors of complicated PUD.To analyze risk factors associated with uncomplicated PUD and medication use after diagnosis.Patients diagnosed with uncomplicated PUD (n = 3,914) were identified from The Health Improvement Network database among individuals aged 40-84 years during 1997-2005, with no previous history of PUD. Prescription records for the year after the date of diagnosis were reviewed and a nested case-control analysis was performed to calculate the odds ratios for the association of potential risk factors with PUD.Medications associated with developing uncomplicated PUD included current use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, selective serotonin reuptake inhibitors, antidepressants, antihypertensives or acid suppressants. Uncomplicated PUD was significantly associated with being a current or former smoker and having had a score of at least 3 on the Townsend deprivation index. Approximately 50% of patients who were users of ASA (19% of patients) or chronic users of NSAIDs (7% of patients) at diagnosis did not receive another prescription of the medication in the 60 days after diagnosis, and 30% were not represcribed therapy within a year. Among patients who were current users of ASA or chronic NSAIDs at the time of the PUD diagnosis and received a subsequent prescription for their ASA or NSAID during the following year, the vast majority (80-90%) also received a proton pump inhibitor coprescription.Our results indicate that several risk factors for upper gastrointestinal bleeding are also predictors of uncomplicated PUD, and that some patients do not restart therapy with ASA or NSAIDs after a diagnosis of uncomplicated PUD. Further investigation is needed regarding the consequences for these patients in terms of increased cardiovascular burden due to discontinuation of antiplatelet therapy.

Autophagy, a lysosomal self-degradation and recycling pathway, plays dual roles in tumorigenesis. Autophagy deficiency predisposes to cancer, at least in part, through accumulation of the selective autophagy cargo p62, leading to activation of antioxidant responses and tumor formation. While cell growth and autophagy are inversely regulated in most cells, elevated levels of autophagy are observed in many established tumors, presumably mediating survival of cancer cells. Still, the relationship of autophagy and oncogenic signaling is poorly characterized. Here we show that the evolutionarily conserved transcription factor Myc (dm), a proto-oncogene involved in cell growth and proliferation, is also a physiological regulator of autophagy in Drosophila melanogaster. Loss of Myc activity in null mutants or in somatic clones of cells inhibits autophagy. Forced expression of Myc results in cell-autonomous increases in cell growth, autophagy induction, and p62 (Ref2P)-mediated activation of Nrf2 (cnc), a transcription factor promoting antioxidant responses. Mechanistically, Myc overexpression increases unfolded protein response (UPR), which leads to PERK-dependent autophagy induction and may be responsible for p62 accumulation. Genetic or pharmacological inhibition of UPR, autophagy or p62/Nrf2 signaling prevents Myc-induced overgrowth, while these pathways are dispensable for proper growth of control cells. In addition, we show that the autophagy and antioxidant pathways are required in parallel for excess cell growth driven by Myc. Deregulated expression of Myc drives tumor progression in most human cancers, and UPR and autophagy have been implicated in the survival of Myc-dependent cancer cells. Our data obtained in a complete animal show that UPR, autophagy and p62/Nrf2 signaling are required for Myc-dependent cell growth. These novel results give additional support for finding future approaches to specifically inhibit the growth of cancer cells addicted to oncogenic Myc.

Substance P, encoded by the Tac1 gene, is involved in neurogenic inflammation and hyperalgesia via neurokinin 1 (NK1) receptor activation. Its non-neuronal counterpart, hemokinin-1, which is derived from the Tac4 gene, is also a potent NK1 agonist. Although hemokinin-1 has been described as a tachykinin of distinct origin and function compared to SP, its role in inflammatory and pain processes has not yet been elucidated in such detail. In this study, we analysed the involvement of tachykinins derived from the Tac1 and Tac4 genes, as well as the NK1 receptor in chronic arthritis of the mouse.Complete Freund's Adjuvant was injected intraplantarly and into the tail of Tac1(-/-), Tac4(-/-), Tacr1(-/-) (NK1 receptor deficient) and Tac1(-/-/)Tac4(-/-) mice. Paw volume was measured by plethysmometry and mechanosensitivity using dynamic plantar aesthesiometry over a time period of 21 days. Semiquantitative histopathological scoring and ELISA measurement of IL-1β concentrations of the tibiotarsal joints were performed.Mechanical hyperalgesia was significantly reduced from day 11 in Tac4(-/-) and Tacr1(-/-) animals, while paw swelling was not altered in any strain. Inflammatory histopathological alterations (synovial swelling, leukocyte infiltration, cartilage destruction, bone damage) and IL-1β concentration in the joint homogenates were significantly smaller in Tac4(-/-) and Tac1(-/-/)Tac4(-/-) mice.Hemokinin-1, but not substance P increases inflammation and hyperalgesia in the late phase of adjuvant-induced arthritis. While NK1 receptors mediate its antihyperalgesic actions, the involvement of another receptor in histopathological changes and IL-1β production is suggested.

Recenzió: Horváth Sándor: Két emelet boldogság - mindennapi szociálpolitika a Kádár-korban Napvilág Kiadó, Budapest, 2012 (266 oldal)

Malignant melanoma represents the third common cause of brain metastasis, having the highest propensity to metastasize to the brain of all primary neoplasms in adults. Since the central nervous system lacks a lymphatic system, the only possibility for melanoma cells to reach the brain is via the blood stream and the blood-brain barrier. Despite the great clinical importance, mechanisms of transmigration of melanoma cells through the blood-brain barrier are incompletely understood. In order to investigate this question we have used an in vitro experimental setup based on the culture of cerebral endothelial cells (CECs) and the A2058 and B16/F10 melanoma cell lines, respectively. Melanoma cells were able to adhere to confluent brain endothelial cells, a process followed by elimination of protrusions and transmigration from the luminal to the basolateral side of the endothelial monolayers. The transmigration process of certain cells was accelerated when they were able to use the routes preformed by previously transmigrated melanoma cells. After migrating through the endothelial monolayer several melanoma cells continued their movement beneath the endothelial cell layer. Melanoma cells coming in contact with brain endothelial cells disrupted the tight and adherens junctions of CECs and used (at least partially) the paracellular transmigration pathway. During this process melanoma cells produced and released large amounts of proteolytic enzymes, mainly gelatinolytic serine proteases, including seprase. The serine protease inhibitor Pefabloc® was able to decrease to 44-55% the number of melanoma cells migrating through CECs. Our results suggest that release of serine proteases by melanoma cells and disintegration of the interendothelial junctional complex are main steps in the formation of brain metastases in malignant melanoma.

It has been recently demonstrated [M. P. Blodgett and P. B. Nagy, J. Nondestruct. Eval.23, 107 (2004)] that eddy current conductivity measurements can be exploited for near-surface residual stress assessment in surface-treated nickel-base superalloy components. To quantitatively assess the prevailing residual stress from eddy current conductivity measurements, the piezoresistivity coefficients of the material must be first determined using known external applied stresses. These calibration measurements are usually conducted on a reference specimen of the same material using cyclic uniaxial loads between 0.1 and 10Hz, which is fast enough to produce adiabatic conditions. Therefore, the question arises whether dynamic calibration measurements can be used or not for accurately assessing the sensitivity of the eddy current method for static residual stress. It is demonstrated in this paper that such dynamic calibration measurements should be corrected for the thermoelastic effect, which is always positive, i.e., it increases the conductivity in tension, when the material cools down, and reduces it in compression, when the material heats up. For low-conductivity titanium and nickel-base engine alloys the thermoelastic corrections are relatively modest at ≈5–10%, but for high-conductivity aluminum alloys the difference between the adiabatic and isothermal properties could be as high as 50%. [ABSTRACT FROM AUTHOR]

Nowadays the main task of scientists is to find natural ways of improving plant productivity that lead to environmentally friendly agriculture. Biofertilizers have a great potential to achieve this aim but unfortunately there is little information about its application in fruit growing mostly in Hungary. For this reason, a foliar nutrition experiment was conducted to investigate the effect of two biofertilizers (an algae product and a biostimulator, containing amino acids) on leaf nutrient concentration and quality parameters of apple (Malus domestica Borkh.) fruits. The study was conducted in 2014 at Újfehértó in East Hungary in a 14 year-old organic apple plantation on cv. ’Remo’. Treatments (application time and doses) were adjusted to the phenological phases of apple. Effect of treatments was monitored by soil and leaf analysis, apple quality measurements and field observations. Usage of biofertilizers resulted greener and healthier leaves. Treatments had no significant effect on leaf N, P, Mg and micronutrients but using algae suspension increased leaf K and Ca content significantly.

Vitrification of matured oocytes is widely adopted in human clinics and animal research laboratories. Cryopreservation of immature oocytes, particularly those at metaphase I (MI), remains a challenge. In the present work, mouse MI oocytes denuded of cumulus cells were vitrified and warmed (V/W) either prior to (V/W-BEFORE-IVM, n = 562) or after (V/W-AFTER-IVM, n = 664) in vitro maturation (IVM). Derivative metaphase II (MII) oocytes were then used for intracytoplasmic sperm injection (ICSI). In the control groups, in vivo matured MII oocytes were used freshly (FRESH-MII, n = 517) or after V/W (MII-V/W, n = 617). In vitro and in vivo developmental competencies were compared among groups. Satisfactory blastocyst rates were achieved in V/W-BEFORE-IVM (27.5%) and V/W-AFTER-IVM (32.4%) groups, albeit as expected still lower than those from fresh-MII (56.1%) or MII-V/W (45.6%) oocytes. Similarly, the term development rates from V/W-BEFORE-IVM and V/W-AFTER-IVM were 12.4% and 16.7% respectively, acceptable but lower than those of the fresh-MII (41.2%) and MII-V/W (23.3%) groups. These data demonstrate that oocytes collected at MI stage are amenable to V/W, which can be performed before or after IVM with acceptable development rates including production of healthy pups. These findings provide useful knowledge to researchers and clinical practitioners for preservation and use of the otherwise discarded MI oocytes.

Higher demands of food production for human consumption increased uses of fertilizers and other chemicals that arise in a major public problem and heavy-metal pollution. Levels of Aluminum and Nickel which affect mankind health in exact doses, were determined in fresh and dried samples of �Jumbo Cot�, �Tom Cot�, �Gold Strike�, �Gold Bar�, Bergeron�, �Bergarouge�, �Sweet Cot�, �Yellow cot� and �Zebra� apricot cultivars to assess possible health risk of apricot (Prunus armeniaca L.) consumption. Highest content of Al and Ni among all cultivars, where 9.71 and 2.14 mg/kg of dehydrated apricot samples. Fresh fruit samples maximally contain 2.9 and 0.425 mg/kg of Aluminum and Nickel respectively. Data analysis showed significant differences between cultivars for Al and Ni. Furthermore, to reveal the health-risk possibility of dried and fresh fruit consumption daily intake of elements and health-risk index were calculated and compared.