The roles of Na+/H+exchanger regulatory factor 1 and Aquaporin-1 in the pathomechanism of experimental acute pancreatitis

Introduction: Pancreatic ductal epithelial cells (PDEC) secrete an alkaline HCO_3^- rich isotonic fluid. The secretion of HCO_3^- across the apical membrane of PDEC is mediated by cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) and solute carrier family 26 (SLC26) anion exchangers. Na+/H+ exchanger regulatory factor isoform 1 (NHERF 1) is a cytosolic adaptor protein, which binds CFTR on the apical membrane of epithelial cells. Aquaporins (AQPs) facilitate the transepithelial water flow involved in epithelial fluid secretion in numerous tissues. Acute pancreatitis (AP) is a serious disorder in which specific treatment is still not possible. Accumulating evidence indicate that decreased pancreatic ductal fluid secretion plays an essential role in AP. The role of NHERF-1 in the pancreas has not yet been investigated despite the fact that CFTR, a key regulator of epithelial function, is controlled by this scaffolding protein Also the functions of AQPs in the pancreas are less characterized. Our aim was to characterize the function of NHERF-1 and AQP1 in AP. Methods: We used 12 16 week old WT, NHERF 1 knock-out (KO) and AQP1 KO male mice. In the AP groups, mice were injected 7 or 10 times hourly, intraperitoneally (i.p.) with 50 µg/kg cerulein. In another AP model, 4 % Na taurocholate was administered i.d. via the punctured duodenum. Control animals were injected i.p. or i.d. with PS instead of cerulein or Na taurocholate (n=6-8). Animals were sacrificed at 12 hours in case of the cerulein model or 24 hours in the Na taurocholate experiment. Laboratory [serum amylase or, pancreatic myeloperoxidase (MPO) activity, pancreatic IL 1β concentrations] and histological parameters (pancreatic necrosis, edema, inflammatory cell infiltration) were measured to evaluate disease severity. Expression of HSP 72, IκB α, and IκB β contents were determined by Western blot analysis. Our results showed that the induction of AP was successful in both models and also in both strains. The injection of mice with cerulein or Na taurocholate increased the measured laboratory and histological parameters vs. the control groups. The measured laboratory (serum amylase, HSP72) and histological parameters (necrosis, apoptosis) were significantly elevated in AP mice injected with cerulein vs. control mice. In accord with the measured pancreatic MPO , trypsinogen activity, IκB α, IκB β, or pancreatic IL 1β concentrations were not significantly altered in the NHERF 1 KO group vs. the WT AP groups. In case of the Na taurocholate-induced AP, pancreatic necrosis, hemorrhage and MPO activity were significantly increased in the NHERF 1 KO group vs. the WT AP group. However, the pancreatic edema, leukocyte infiltration, IL 1β concentrations and serum amylase activity were significantly elevated in the WT or NHERF 1 KO AP vs. respective control groups but not in the NHERF 1 KO vs WT AP groups. The pancreatic leukocyte infiltration, edema, necrosis or serum amylase activity were significantly increased in cerulein-treated vs. control groups. In accord with the histological results, only necrosis and serum amylase activity were increased significantly in the AQP1 KO vs. WT AP groups. In conclusion, after complete evaluation of the data, we can say that the AP in both NHERF 1 or AQP1 KO groups were more severe. These results may be due the reduced HCO_3^- and fluid secretion

Micropropagation of Leuce-poplars and evaluation of their development under sandy site conditions in Hungary

AbstractLeuce-poplars are a native stand-forming tree species throughout Hungary. Several species or selections of them are used as ornamental plants in parks or to line streets and highways. They cover approximately 4.0 per cent of the total forested area in Hungary (70000 ha). The white (grey) poplar belongs to the Leuce poplars and plays a significant role in sand fixation, regional forestation, and nature conservation. The National Agricultural Research and Innovation Centre, Forest Research Institute or NARIC-FRI (formerly known as the Forest Research Institute) is involved in long-term breeding work for the selection of fast-growing white poplar trees under dry conditions. In vitro multiplication of trees is applied mainly to fruit growing trees in Hungary; in forestry research it is used primarily for selective breeding. This paper presents a short overview of the most important issues concerning the biotechnology of different Populus species, the related research on micropropagation trials, and the results of field investigations of micropropagated Leuce-poplar clone experiments.</jats:p

Efficient biotransformation of non-steroid anti-inflammatory drugs by endophytic and epiphytic fungi from dried leaves of a medicinal plant, Plantago lanceolata L.

In the current study, decomposition of diclofenac, diflunisal, ibuprofen, mefenamic acid and piroxicam was tested using nine identified strains of endophytic and epiphytic fungi (from Ascomycota) adapted to natural products resembling the pharmaceuticals. The strains were isolated from a medicinal plant, Plantago lanceolata leaves. Metabolites were tentatively identified by liquid chromatography - tandem mass spectrometry (LC-MS3). Eighteen of the 45 combinations resulted in significant decrease of the concentration of the NSAIDs in model solutions. The most active strains were Aspergillus nidulans and Bipolaris tetramera, while Epicoccum nigrum and Aspergillus niger showed somewhat less potency. Piroxicam and diclofenac were most resistant to biotransformation, while ibuprofen and mefenamic acid were efficiently metabolized by most strains. Ten metabolites could be tentatively identified, including hydroxy-metabolites of all tested NSAIDs, and a dihydroxy-metabolite of piroxicam. This biotransformation is likely to modify the toxicity and bioaccumulation potential of these pharmaceuticals. The results highlight the applicability of polyphenol-rich dried medicinal plant materials as an excellent source of fungi with high biotransforming potential. The results also suggest more in-depth testing of these fungi for biodegradation processes

Gyulladásos és neuropátiás fájdalom farmakológiai befolyásolása primér szenzoros neuronokon ható szerekkel = Pharmacological modulation of inflammatory and neuropathic pain by agents acting on primary sensory neurones

A kapszaicin-érzékeny, VR1/TRPV1 receptort expresszáló primér szenzoros neuronok afferens működésükön kívül lokális és szisztémás efferens funkciókkal is rendelkeznek. A belőlük felszabaduló calcitonin gén-rokon peptid (CGRP) és tachykininek (pl. P-anyag) neurogén gyulladást váltanak ki az innervációs területen, míg a szomatosztatin gyulladásgátló és antinociceptív hatásokkal rendelkezik az sst4 receptorokon keresztül. Ezen neuronok jelentős szerepet játszanak gyulladásos (ízületi, légúti) és neuropátiás állapotok patomechanizmusában. A neurogén gyulladás és a neuropátiás fájdalom kezelésére jelenleg nincs megfelelő terápiás lehetőség. Kísérleteinkben a TRPV1 kapszaicin receptor, az sst4 szomatosztatin receptor, a hipofízis adenilát cikláz aktiváló polipeptid (PACAP-38), valamint az endomorphin-1 szerepét és ezeken ható vegyületek hatásait vizsgáltuk különféle akut és krónikus gyulladás, valamint neuropátia modellekben. Bár bizonyos gyulladásos folyamatokban a TRPV1, a neurokinin és CGRP receptorok blokkolása, valamint a PACAP és az endomorphin-1 anti-inflammációs és anti-nociceptív hatásokat fejtett ki, az sst4 receptor bizonyult minden modellünkben a legígéretesebb célpontnak. Eredményeink alapján ezen az érzőideg végződéseken és gyulladásos sejteken egyaránt expresszálódó receptoron ható stabil, per os is hatékony szelektív agonisták egy teljesen új hatásmechanizmusú gyulladáscsökkentő és fájdalomcsillapító gyógyszercsoport kifejlesztésére adhatnak lehetőséget. | Capsaicin-sensitive, VR1/TRPV1 receptor-expressing primary sensory neurons have local and systemic efferent functions besides their afferent role. Calcitonin gene-related peptide and tachykinins (e.g. substance P) induce neurogenic inflammation in the innervated area, somatostatin exerts anti-inflammatory and anti-nociceptive actions via sst4 receptor activation. Therefore, these neurons play an important role in the pathological mechanisms of several inflammatory (arthritis, asthma) and neuropathic conditions. At present there is no appropriate pharmacological treatment for the neurogenic component of inflammatory reactions and neuropathic pain. In the present series of experiments the roles of TRPV1 capsaicin receptors, sst4 somatostatin receptors, the effects of pituitary adenylate-cyclase activating polypeptide (PACAP-38) and endomorphin-1 as well as agents acting at these targets were investigated in different acute and chronic inflammation and neuropathy models. Although in certain inflammatory processes the blockade of TRPV1, neurokinin and CGRP receptors, and also PACAP and endomorphin-1 exerted anti-inflammatory and anti-nociceptive actions, the sst4 receptor proved to be the most promising target. On the basis of our results stable, orally active, selective sst4 agonist acting on both sensory nerve terminals and several inflammatory and immune cells could provide perspectives for the development of a completely novel type of anti-inflammatory and analgesic drugs

Postconditioning in major vascular surgery: prevention of renal failure

This study investigates teachers in the Swedish ten-year compulsory school who use ICT(Information and communication technology) in their classroom practice. It poses andgives answers to questions about what is contributing most to explain why they choose touse computers and information technology in their work with students/pupils and usesmultiple regression analysis in order to investigate the best pattern of predictive variables.A significant model emerged suggesting that teachers using ICT with students wereinterested in changing their classroom practice. They also felt self-efficacious in usingcomputers in education and they have positive attitudes toward using ICT in education.The present investigation differs from other studies in that it examines teachers whoalready are using technology in their classroom practice and it could be seen as a buildingblock in the development of knowledge about how teachers can become more competentand confident in using ICT in their pedagogical work in classroom practice

Impaired Immunosuppressive Effect of Bronchoalveolar Mesenchymal Stem Cells in Hypersensitivity Pneumonitis: preliminary findings

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