Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood-brain barrier of male rodents

There is increasing evidence that local thyroid hormone (TH) availability changes profoundly in inflammatory conditions due to altered expression of deiodinases that metabolize TH. It is largely unknown, however, how inflammation affects TH availability via the expression of TH transporters. In this study we examined the effect of bacterial lipopolysaccharide (LPS) administration on two TH transporters that are critically important for brain TH homeostasis, organic anion-transporting polypeptide 1c1 (OATP1c1) and monocarboxylate transporter 8 (MCT8). Messenger RNA levels were studied by in situ hybridization and quantitative PCR, and protein levels by immunofluorescence in both the rat and mouse forebrain. The mRNA of both transporters decreased robustly in the first 9h after LPS injection, selectively in brain blood vessels; OATP1c1 mRNA in astrocytes and MCT8 mRNA in neurons remained unchanged. At 24 and/or 48h after LPS administration, OATP1c1 and MCT8 mRNAs increased markedly above control levels in brain vessels. OATP1c1 protein decreased markedly in vessels by 24h, whereas MCT8 protein levels did not decrease significantly. These changes were highly similar in mice and rats. The data demonstrate that OATP1c1 and MCT8 expression are regulated in a parallel manner during inflammation at the blood-brain barrier of rodents. Given the indispensable role of both transporters in allowing TH access to the brain, the results suggest reduced brain TH uptake during systemic inflammation

Ethyl 4-{1-[(2,4-dinitro­phen­yl)hydrazono]eth­yl}-5-(2-naphthyl­methoxy­meth­yl)isoxazole-3-carboxyl­ate

The title compound, C26H23N5O8, was prepared and its structure investigated to further develop a working hypothesis for the essential binding pharmacophore for ligands of the System Xc- transporter [Patel et al. (2004 ▶). Neuropharmacology, 46, 273–284]. The hydrazone group displays an E geometry and the isoxazole double bond and C=N group of the hydrazone are in an s-cis relationship. The secondary amino NH group forms an intra­molecular N—H⋯O hydrogen bond to a ring nitro group. There is a dihedral angle of 44.27 (5)° between the isoxazole plane and the hydrazone group plane

Pathology and glia type specific changes of the DPP4 activity in the spinal cord contributes to the development and maintenance of hyperalgesia and shapes opioid signalling in chronic pain states

Altered pain sensations such as hyperalgesia and allodynia are characteristic features of various chronic pain states, and remain difficult to treat. We have shown previously that spinal application of dipeptidyl peptidase 4 (DPP4) enzyme inhibitors results in a strong antihyperalgesic effect during inflammatory pain states. In this study we observed a low level of mRNA for DPP4 in the rat spinal dorsal horn in physiological conditions, which did not change significantly either in carrageenan-induced inflammatory or partial nerve ligation-generated neuropathic states. Although DPP4 protein was detected in neurons, astrocytes and microglia in naïve animals its expression significantly increased in astrocytes during inflammation and in microglia in neuropathic conditions. Intrathecal application of two DPP4 inhibitors the tripeptide isoleucin-prolin-isoleucin (IPI) and the antidiabetic drug vildagliptin resulted in robust opioid-dependent antihyperalgesic effect during inflammation and an opioid-independent effect in the Seltzer model. The opioid-mediated antihyperalgesic effect of IPI was exclusively related to mu-opioid receptors, while vildagliptin affected mainly delta-receptor activity, although mu- and kappa-receptors were also involved. Our results suggest a pathology and glia type specific changes of the DPP4 activity in the spinal cord which contributes to the development and maintenance of hyperalgesia and shapes opioid signalling

Warfarin versus DOACs in the prevention of thromboembolic stroke in patients with Afib.

ABSTRACT Purpose: Preventing thromboembolic (TE) events “such as stroke” is an important part of managing patients with non-valvular atrial fibrillation (Afib). Over the last 50 years, oral anticoagulant treatment with the Vitamin K Antagonist (VKA) warfarin has played a crucial role in the secondary prevention of stroke for patients with Afib. Direct oral anticoagulant (DOACs), and their dominance over warfarin has arrived for treatment of Afib in the context of stroke prevention and research indicates DOACs are, for the most part, superior to warfarin in the secondary prevention of stroke in patients with non-valvular Afib. But what does the evidence tell us about risk versus benefits? Method: The purpose of this review of literature is to conduct a systematic review of the advantages and disadvantages of DOACs, namely dabigatran, rivaroxaban, apixaban and edoxaban compared with warfarin in patients with (non-valvular) Afib. A search was conducted with search terms of “Oral Anticoagulants”, “Anticoagulants”, “Direct Oral Anticoagulants”, “New Oral Anticoagulants”, “Warfarin”, and “secondary prevention of non-valvular Afib”, “Afib”, “Stroke prevention” and “Stroke”. Sixty articles were selected to perform this review and twenty articles were excluded after the full-text review. Among excluded articles, six were found to be in a non-English language, eight articles were reviews of studies already included in the literature review, and six other articles did not fulfill the inclusion criteria of warfarin versus DOACs in the prevention of stroke in patients with Afib. The remaining articles were then reviewed to analyze the advantages and disadvantages of DOACs versus warfarin in patients in the prevention of TE stroke in people with non-valvular atrial fibrillation. Results: Several studies have investigated the effectiveness of warfarin versus DOACs in the secondary prevention of thromboembolic stroke in patients with non-valvular Afib, but results remain controversial. There is, however, suitable evidence to suggest that DOACs are not always superior to warfarin in secondary stroke prevention. In general, this review demonstrates the advantages of DOACs compared with warfarin including, DOACs are associated with lower rates of life-threatening and intracranial bleeding, DOACs have a rapid onset with peak effect within a few hours, they have predictable dose responses, thus eliminating the need for routine monitoring; and they have few, if any, important food or drug interactions, thus simplifying management. Conclusion: The findings of this systematic literature review suggest that in the secondary prevention of stroke in patients with non-valvular Afib, DOACs, demonstrate a significant advantage and enhanced safety profile over warfarin in reducing the risk of thromboembolic stroke compared with warfarin. As such, DOACs should be considered first-line therapy in the secondary prevention of stroke in patients with non-valvular Afib

Aspergillus fumigatus által termelt extracelluláris triacetil-fuzarinin C és intracelluláris ferrikrocin szideroforok kihozatalának optimalizálása

Aspergillus fumigatus által termelt extracelluláris triacetil-fuzarinin C és intracelluláris ferrikrocin szideroforok kihozatalának optimalizálásaMSc/MABiotechnológiag

A környezet- és energiatudatos épületek

A szakdolgozatom bemutatja, mely házak tartoznak a környezet- és energiatudatos épületek közé, foglalkozik a házak belső energiájával, fontos építési normákkal. Szemlélteti az energiatakarékos építkezés, épületüzemeltetés alternatíváit, mint a napenergia, geotermikus energia hasznosítása. Kitér a zöldtetők típusaira, tulajdonságaira és létrehozásukra. Bemutatja továbbá az esővíz hasznosítás lehetőségeit, az erre vonatkozó jogszabályokat. Tartalmazza az ökologikus hőszigetelő anyagok listáját és egy példát, hogyan lehet a külső fal hőellenállását és hőátbocsátási tényezőjét kiszámolni. Bemutatja, hogyan tesznek a növények környezet- és energiatudatossá egy házat.BscBiológiag

A népi demokratikus államrend büntetőjogi védelmének főbb kérdései

INST: L_08