Investigating of the Knocking Out Properties of Moulding Sands with New Inorganic Binders Used for Castings of Non-ferrous Metal Alloys in Comparison with the Previously Used

The article presents the results of investigations, which make a fragment of the broad-scale studies carried out as a part of the projectPOIG.01.01.02-00-015/09 “Advanced materials and technologies”.One of the objectives of the introduction of new inorganic binders is to provide a good knocking out properties of moulding sands, whilemaintaining an appropriate level of strength properties.Therefore, a logical continuation of the previous studies were carried out the tests knocking out properties of moulding sands with newinorganic binders, including making moulds, pouring them by the chosen of non-ferrous metal alloys, knoking-out, and determining theknocking out work.The results of the study were related to the research results obtained by applying the moulding sand performed by existing technology

Evaluation of Reclamability of Molding Sands with New Inorganic Binders

One of the purposes of the application of chemically modified inorganic binders is to improve knocking out properties and the related reclamability with previously used in foundry inorganic binder (water glass), which allowing the use of ecological binders for casting non- ferrous metals. Good knocking out properties of the sands is directly related to the waste sands reclamability, which is a necessary condition of effective waste management. Reclamation of moulding and core sands is a fundamental and effective way to manage waste on site at the foundry, in accordance with the Environmental Guidelines. Therefore, studies of reclamation of waste moulding and core sands with new types of inorganic binders (developed within the framework of the project) were carried out. These studies allowed to determine the degree of recovery of useful, material, what the reclaimed sand is, and the degree of its use in the production process. The article presents these results of investigation. They are a part of broader research programme executed under the project POIG.01.01.02-00- 015/09 "Advanced materials and technologies"

Moulding Sands with New InorganicBinders - Ecology Assessment in the Aspect of Work Environment

The development of economy and industry introducing new technologies and materials often means the increased threat of occurrenceof factors harmful to humans and environment. Workers employed in foundries as mould pourers are the group of high professional risk.Foundry moulding sands when poured with liquid metal are a source of the emission of harmful, toxic and carcinogenic (benzene,PAHs) compounds.The paper presents the results of studies on the concentration of chemical compounds emitted in the process of casting aluminiumalloy and brass using moulding sands with the new inorganic binders. The specific values of the exposure indices were compared with thelimit values. This enabled an assessment of the impact of moulding sands on work environment. The obtained results were compared withthe values of contaminants emitted when pouring foundry moulds made from furan sands and bentonite sands with an addition of coaldust.Studies were carried out under the project POIG.01.01.02-00-015/09 "Advanced materials and technologies.

Hybrid inhibitor of peripheral cannabinoid-1 receptors and inducible nitric oxide synthase mitigates liver fibrosis

Liver fibrosis, a consequence of chronic liver injury and a way station to cirrhosis and hepatocellular carcinoma, lacks effective treatment. Endocannabinoids acting via cannabinoid-1 receptors (CB1R) induce profibrotic gene expression and promote pathologies that predispose to liver fibrosis. CB1R antagonists produce opposite effects, but their therapeutic development was halted due to neuropsychiatric side effects. Inducible nitric oxide synthase (iNOS) also promotes liver fibrosis and its underlying pathologies, but iNOS inhibitors tested to date showed limited therapeutic efficacy in inflammatory diseases. Here, we introduce a peripherally restricted, orally bioavailable CB1R antagonist, which accumulates in liver to release an iNOS inhibitory leaving group. In mouse models of fibrosis induced by CCl4 or bile duct ligation, the hybrid CB1R/iNOS antagonist surpassed the antifibrotic efficacy of the CB1R antagonist rimonabant or the iNOS inhibitor 1400W, without inducing anxiety-like behaviors or CB1R occupancy in the CNS. The hybrid inhibitor also targeted CB1R-independent, iNOS-mediated profibrotic pathways, including increased PDGF, Nlrp3/Asc3, and integrin alphavbeta6 signaling, as judged by its ability to inhibit these pathways in cnr1-/- but not in nos2-/- mice. Additionally, it was able to slow fibrosis progression and to attenuate established fibrosis. Thus, dual-target peripheral CB1R/iNOS antagonists have therapeutic potential in liver fibrosis

Új mechanizmusok az angiotenzin II élettani hatásainak szabályozásában = Novel mechanisms in the regulation of the physiological actions of angiotensin II

Az AT1 angiotenzin receptor (AT1R) egy Gq-fehérjéhez kapcsolt receptor, mely angiotenzin II (AngII) hatására a sejtekben Ca2+-jelet hoz létre. Kísérleteinkben kimutattuk, hogy az AT1R és más Gq-kapcsolt receptorok jelátviteli folyamata során keletkező diacil-glicerinből a sejtekben 2-arachidonoil-glicerin (2-AG) keletkezik, mely CB1 kannabinoid receptorok parakrin aktivációját hozhatja létre. Kimutattuk e mechanizmus jelentőségét az AngII vazokonstriktor hatásának szabályozásában, és felvetettük szerepét az AngII centrális vérnyomásemelő és gyomorvédő hatásának létrehozásában. Leírtuk, hogy az AngII mellékvesekéreg glomerulosa sejtekben fokozza a neurotrofinok családjába tartozó agyi eredetű növekedési faktor (BDNF) expresszióját. BRET módszeren alapuló bioszenzorok segítségével kimutattuk, hogy AngII hatására az endoplazmatikus retikulumban és a transz-Golgi-hálózatban is létrejöhet a Ras kis G-fehérje aktiválódása; valamint azt, hogy AngII hatására megváltozik az AT1R membrán mikrodoménekben való elhelyezkedése. Kimutattuk, hogy Ca2+-mobilizáló agonistával serkentett HEK293T sejtekben a Ca2+-válasszal párhuzamosan Mg2+-jel jön létre. Leírtuk e Mg2+-jel, valamint a p38 MAP-kináz és egy új típusú (novel) protein-kináz C enzim szerepét a mitokondriális Ca2+-felvétel és a mellékvesekéreg aldoszteron-termelésének szabályozásában. Eredményeink hozzájárulnak a magasvérnyomás és más keringési betegségek terápiájában fontos célpontot jelentő AT1R működésének jobb megértéséhez. | Angiotensin II (AngII) exerts its main biological effects via the AT1 angiotensin receptor (AT1R), which is coupled to Gq protein, and produces Ca2+ signal generation after stimulation. We have demonstrated that activation of AT1R and other Gq-coupled receptors leads to the generation of 2-arachidonoylglycerol (2-AG) from diacylglcycerol, formed during the signaling process, and 2-AG can cause paracrine activation of CB1 cannabinoid receptors. Our data show that this mechanism modulates the vasoconstrictor action of AngII, and suggest its role in the central hypertensive and gastroprotective effects of AngII. We have reported that AngII can stimulate the expression of brain-dervied neurtropic factor (BDNF), a major neurotrophin, in adrenal glomerulosa cells. We have demonstrated using BRET-based biosensors that AngII induces the activation of Ras small G protein in the endoplasmic reticulum and the trans-Golgi network, and alters the localization of AT1R in membrane microdomains. We have described that in HEK293T cells Ca2+-mobilizing agonists produce Mg2+ signal, parallel with the Ca2+ signal generation; and we have demonstrated the roles of the Mg2+ signal, p38 MAP kinase and a novel protein kinase C in the regulation of the mitochondrial Ca2+ uptake and aldosterone production of adrenal glomerulosa cells. Our results facilitate better understanding of the function of AT1R, which is a main target in the therapy of hypertension and other cardiovascular diseases

Opposite physiological and pathological mTORC1-mediated roles of the CB1 receptor in regulating renal tubular function.

Activation of the cannabinoid-1 receptor (CB1R) and the mammalian target of rapamycin complex 1 (mTORC1) in the renal proximal tubular cells (RPTCs) contributes to the development of diabetic kidney disease (DKD). However, the CB1R/mTORC1 signaling axis in the kidney has not been described yet. We show here that hyperglycemia-induced endocannabinoid/CB1R stimulation increased mTORC1 activity, enhancing the transcription of the facilitative glucose transporter 2 (GLUT2) and leading to the development of DKD in mice; this effect was ameliorated by specific RPTCs ablation of GLUT2. Conversely, CB1R maintained the normal activity of mTORC1 by preventing the cellular excess of amino acids during normoglycemia. Our findings highlight a novel molecular mechanism by which the activation of mTORC1 in RPTCs is tightly controlled by CB1R, either by enhancing the reabsorption of glucose and inducing kidney dysfunction in diabetes or by preventing amino acid uptake and maintaining normal kidney function in healthy conditions

Studies of copper trafficking in a mouse model of Alzheimer's disease by positron emission tomography: comparison of Cu-64 acetate and (64)CuGTSM

Alzheimer's disease can involve brain copper dyshomeostasis. We aimed to determine the effect of AD-like pathology on 64Cu trafficking in mice, using positron emission tomography (PET imaging), during 24 hours after intravenous administration of ionic 64Cu (Cu(II) acetate) and 64Cu-GTSM (GTSMH2 = glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6–8-month-old and 13–15 month-old TASTPM transgenic and wild-type mice, by imaging 0–30 min and 24–25 h after intravenous administration of 64Cu tracer. Regional 64Cu distribution in brains was compared by ex vivo autoradiography to that of amyloid-β plaque. 64Cu-acetate showed uptake in, and excretion through, liver and kidneys. There was minimal uptake in other tissues by 30 minutes, and little further change after 24 h. Radioactivity within brain was focussed in and around the ventricles and was significantly greater in younger mice. 64CuGTSM was taken up in all tissues by 30 min, remaining high in brain but clearing substantially from other tissues by 24 h. Distribution in brain was not localised to specific regions. TASTPM mice showed no major changes in global or regional 64Cu brain uptake compared to wildtype after administration of 64Cu acetate (unlike 64Cu-GTSM) but efflux of 64Cu from brain by 24 h was slightly greater in 6–8 month-old TASTPM mice than in wildtype controls. Changes in copper trafficking associated with Alzheimer's-like pathology after administration of ionic 64Cu are minor compared to those observed after administration of 64Cu-GTSM. PET imaging with 64Cu could help understand changes in brain copper dynamics in AD and underpin new clinical diagnostic imaging methods

Extramitochondrial OPA1 and adrenocortical function

We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial 27 Ca2+ signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 28 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the 29 enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few 30 OPA1 immunopositive spots were detected in �40% of the cells. In cell fractionation studies OPA1/COX 31 IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher 32 than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mito- 33 chondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phos- 34 phorylation of hormone-sensitive lipase (HSL), Ca2+ signaling and aldosterone secretion. In conclusion, 35 OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with 36 the cAMP – PKA – HSL mediated activation of aldosterone secretio

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex