An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125–2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125–2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process

More efficient conservation and use of vegetable genetic resources in Europe: ECPGR achievement and perspectives

The European Cooperative Programme for Plant Genetic Resources (ECPGR) is a regional network funded by the European countries and coordinated by Bioversity International. The Vegetables Network with representatives of 42 countries, is one of the crop specific ECPGR networks (http://www.ecpgr.cgiar.org/ networks/vegetables.html). It consists of six Working Groups (WGs), i.e., on Allium, Brassica, Cucurbits, Leafy Vegetables, Solanaceae and Umbellifer Crops. Sharing responsibilities for the ex situ conservation of European vegetable crops genetic resources is the highest priority of the Vegetables Network. It is foreseen that the rationalization of the collections will lead to higher cost-efficiency, and improvement of plant genetic resources documentation and quality. These efforts will be continued within the framework of the AEGIS initiative (A European Genebank Integrated System) (http://www.aegis.cgiar.org/). Challenges for the Vegetables Network include the identification of the so-called Most Appropriate Accessions (MAA) for each crop for their inclusion in the decentrally managed European Collection, and the development of agreed crop specific technical standards for conservation. Achievements of the Network in recent years include the development of European Central Crop Databases (ECCDBs), quality standards for collection man-agement of seed-propagated crops and cryopreserved material, safety duplication improvement and definition of minimum characterization descriptors. Several EU-funded projects have initiated and accelerated the activities of the WGs. Apart from further improvements within the framework of AEGIS, the Network is planning a number of other initiatives, such as improving collaboration at the global level (Allium), developing molecular characterization protocols (lettuce), filling the gaps in the conservation of wild relatives (Brassica and Umbellifer Crops), and improving the Network’s communication with the scientific community and the public at large

Preventive drugs in the last year of life of older adults with cancer: Is there room for deprescribing?

BACKGROUND: The continuation of preventive drugs among older patients with advanced cancer has come under scrutiny because these drugs are unlikely to achieve their clinical benefit during the patients' remaining lifespan. METHODS: A nationwide cohort study of older adults (those aged ≥65 years) with solid tumors who died between 2007 and 2013 was performed in Sweden, using routinely collected data with record linkage. The authors calculated the monthly use and cost of preventive drugs throughout the last year before the patients' death. RESULTS: Among 151,201 older persons who died with cancer (mean age, 81.3 years [standard deviation, 8.1 years]), the average number of drugs increased from 6.9 to 10.1 over the course of the last year before death. Preventive drugs frequently were continued until the final month of life, including antihypertensives, platelet aggregation inhibitors, anticoagulants, statins, and oral antidiabetics. Median drug costs amounted to $1482 (interquartile range [IQR],$700-$2896]) per person, including$213 (IQR, $77-$490) for preventive therapies. Compared with older adults who died with lung cancer (median drug cost, $205; IQR,$61-$523), costs for preventive drugs were higher among older adults who died with pancreatic cancer (adjusted median difference,$13; 95% confidence interval, $5-$22) or gynecological cancers (adjusted median difference, $27; 95$18-$36). There was no decrease noted with regard to the cost of preventive drugs throughout the last year of life. CONCLUSIONS: Preventive drugs commonly are prescribed during the last year of life among older adults with cancer, and often are continued until the final weeks before death. Adequate deprescribing strategies are warranted to reduce the burden of drugs with limited clinical benefit near the end of life

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (-/-) rats self-administer less cocaine (0.25, 0.125 or 0.5 mg/infusion) both under a Fixed Ratio 1 and a Progressive Ratio schedule of reinforcement compared to wild type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (-/-). When NOP (-/-) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showeda significantly lower drug intake compared to Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (-/-) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (-/-) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.Neuropsychopharmacology accepted article preview online, 26 August 2016. doi:10.1038/npp.2016.171

Selective mGluR1 Antagonist EMQMCM Inhibits the Kainate-Induced Excitotoxicity in Primary Neuronal Cultures and in the Rat Hippocampus

Abundant evidence suggests that indirect inhibitory modulation of glutamatergic transmission, via metabotropic glutamatergic receptors (mGluR), may induce neuroprotection. The present study was designed to determine whether the selective antagonist of mGluR1 (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), showed neuroprotection against the kainate (KA)-induced excitotoxicity in vitro and in vivo. In in vitro studies on mouse primary cortical and hippocampal neuronal cultures, incubation with KA (150 μM) induced strong degeneration [measured as lactate dehydrogenase (LDH) efflux] and apoptosis (measured as caspase-3 activity). EMQMCM (0.1–100 μM) added 30 min to 6 h after KA, significantly attenuated the KA-induced LDH release and prevented the increase in caspase-3 activity in the cultures. Those effects were dose- and time-dependent. In in vivo studies KA (2.5 nmol/1 μl) was unilaterally injected into the rat dorsal CA1 hippocampal region. Degeneration was calculated by counting surviving neurons in the CA pyramidal layer using stereological methods. It was found that EMQMCM (5–10 nmol/1 μl) injected into the dorsal hippocampus 30 min, 1 h, or 3 h (the higher dose only) after KA significantly prevented the KA-induced neuronal degeneration. In vivo microdialysis studies in rat hippocampus showed that EMQMCM (100 μM) significantly increased γ-aminobutyric acid (GABA) and decreased glutamate release. When perfused simultaneously with KA, EMQMCM substantially increased GABA release and prevented the KA-induced glutamate release. The obtained results indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against excitotoxicity after delayed treatment (30 min to 6 h). The role of enhanced GABAergic transmission in the neuroprotection is postulated

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

Collection of genetic resources of cultivated mushrooms growing in wild state

W pracy została przedstawiona aktualna kolekcja grzybów uprawnych dziko rosnących w Polsce, znajdujących się w Instytucie Warzywnictwa w Skierniewicach. W kolekcji banku genów znajduje się 465 obiektów reprezentujących 6 gatunków grzybów uprawnych dziko rosnących w Polsce: pieczarka szlachetna (Agaricus bitorquis) - 25 obiektów, pieczarka dwuzarodnikowa (Agaricus bisporus) - 26, pieczarka polowa (Agaricus arvensis) - 93, boczniak ostrygowaty (Pleurotus ostreatus) - 103, pierścieniak uprawny (Stropharia rugosoannulata) - 48, płomienica zimowa = zimówka aksamitnotrzonowa (Flammulina velutipes) - 170 obiektów. Przedstawiono także sposoby pozyskiwania grzybów uprawnych dziko rosnących, metody otrzymywania grzybni z zarodników, z plektenchymy oraz sposoby ich długoterminowego przechowywania.In the work the actual of genetic resources collection of cultivated mushrooms growing in wild state in Poland founding at Research Institute of Vegetable Crops - Skierniewice. Germplasm collection include 465 accessions from 6 species of cultivated mushrooms growing in wild state in Poland. Collected materials belongs to following species: Agaricus bitorquis - 25 accessions, Agaricus bisporus - 26, Agaricus arvensis - 93, Pleurotus ostreatus - 103, Flammulina velutipes - 170, Stropharia rugoso-annulata - 48. The methods wild of mushroom collecting methods of mycelium obtainment from spores, plectenchyma, and also methods of long term storage were presented either

Economy of district property and local governance

Celem artykułu jest przedstawienie organizacyjnych oraz finansowych uwarunkowań gospodarowania nieruchomościami powiatowymi oraz ich roli w rozwoju lokalnym, wiążących się z przeznaczeniem nieruchomości oraz dochodami przez nie wygenerowanymi. W artykule zaproponowano konstrukcję programu gospodarowania nieruchomościami. Tezy oparto na wynikach badań. Wykorzystano metodę analizy źródeł oraz metodę kwestionariuszową.The purpose of this article is to highlight the organisational and financial aspects of managing property at the district level, as well as the role of those aspects in local development, resulting in how property is used and the income it generates. The article contains some suggestions as to how a property-managing program should be constructed, based upon research including both source analysis and questionnaire methods