Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation

Pain after disease/damage of the nervous system is predominantly treated with opioids, but without exploration of the long-term consequences. We demonstrate that a short course of morphine after nerve injury doubles the duration of neuropathic pain. Using genetic and pharmacological interventions, and innovative Designer Receptor Exclusively Activated by Designer Drugs disruption of microglia reactivity, we demonstrate that opioid-prolonged neuropathic pain arises from spinal microglia and NOD-like receptor protein 3 inflammasome formation/activation. Inhibiting these processes permanently resets amplified pain to basal levels, an effect not previously reported. These data support the “two-hit hypothesis” of amplification of microglial activation—nerve injury being the first “hit,” morphine the second. The implications of such potent microglial “priming” has fundamental clinical implications for pain and may extend to many chronic neurological disorders

Salvinorin A analogues PR-37 and PR-38 attenuate compound 48/80-induced itch responses in mice: Salvinorin A analogues PR-37 and PR-38 in pruritus

The opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR-37 and PR-38, exhibit antipruritic properties in mice

Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration

Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over-expressed. A conserved short isoform of Oxr1 is also sufficient to confer this neuroprotective property both in vitro and in vivo. In addition, biochemical assays indicate that Oxr1 itself is susceptible to cysteine-mediated oxidation. Finally we show up-regulation of Oxr1 in both human and pre-symptomatic mouse models of amyotrophic lateral sclerosis, indicating that Oxr1 is potentially a novel neuroprotective factor in neurodegenerative disease

Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells

BACKGROUND: Lung fluid balance in the healthy lung is dependent upon finely regulated vectorial transport of ions across the alveolar epithelium. Classically, the cellular locus of the major ion transport processes has been widely accepted to be the alveolar type II cell. Although evidence is now emerging to suggest that the alveolar type I cell might significantly contribute to the overall ion and fluid homeostasis of the lung, direct assessment of functional ion channels in type I cells has remained elusive. METHODS: Here we describe a development of a lung slice preparation that has allowed positive identification of alveolar type I cells within an intact and viable alveolar epithelium using living cell immunohistochemistry. RESULTS: This technique has allowed, for the first time, single ion channels of identified alveolar type I cells to be recorded using the cell-attached configuration of the patch-clamp technique. CONCLUSION: This exciting new development should facilitate the ascription of function to alveolar type I cells and allow us to integrate this cell type into the general model of alveolar ion and fluid balance in health and disease

Proteomic and Physiological Responses of Kineococcus radiotolerans to Copper

Copper is a highly reactive, toxic metal; consequently, transport of this metal within the cell is tightly regulated. Intriguingly, the actinobacterium Kineococcus radiotolerans has been shown to not only accumulate soluble copper to high levels within the cytoplasm, but the phenotype also correlated with enhanced cell growth during chronic exposure to ionizing radiation. This study offers a first glimpse into the physiological and proteomic responses of K. radiotolerans to copper at increasing concentration and distinct growth phases. Aerobic growth rates and biomass yields were similar over a range of Cu(II) concentrations (0–1.5 mM) in complex medium. Copper uptake coincided with active cell growth and intracellular accumulation was positively correlated with Cu(II) concentration in the growth medium (R2 = 0.7). Approximately 40% of protein coding ORFs on the K. radiotolerans genome were differentially expressed in response to the copper treatments imposed. Copper accumulation coincided with increased abundance of proteins involved in oxidative stress and defense, DNA stabilization and repair, and protein turnover. Interestingly, the specific activity of superoxide dismutase was repressed by low to moderate concentrations of copper during exponential growth, and activity was unresponsive to perturbation with paraquot. The biochemical response pathways invoked by sub-lethal copper concentrations are exceptionally complex; though integral cellular functions are preserved, in part, through the coordination of defense enzymes, chaperones, antioxidants and protective osmolytes that likely help maintain cellular redox. This study extends our understanding of the ecology and physiology of this unique actinobacterium that could potentially inspire new biotechnologies in metal recovery and sequestration, and environmental restoration

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3

Ocena cech jakościowych nasion rzepaku w zależności od nawożenia i obsady roślin

The aim of this paper has been to evaluate yields and seed quality of winter oilseed rape depending on the plant density, foliar fertilisation with magnesium, sulphur, boron and Asahi growth biostimulant combined with constant NPK fertilisation. The research was performed in 2006-2008 as a two-factor field experiment. The first factor involved plant density (A – 20, B – 30, C – 40 plants per 1 m2) and the second one comprised fertilisation treatments (n = 7). Foliar fertilisation was applied once or twice. In rape seeds, the following were determined: the content of total nitrogen, content of fat and its fractions. The results show that the concentrations of total nitrogen and fat in rape seeds were significantly dependent on both the plant density and fertilisation. Significantly the highest content of those nutrients occurred after a double application of magnesium sulphate (VI), Solubor and Asahi biostimulant at the plant density of 40 and 30 plants m2, respectively. The composition of fatty acids extracted from seeds of the hybrid oilseed rape cultivar Nelson significantly depended only on fertilisation. The highest content of oleic acid and its increase, as compared with the control, was identified after a single application of magnesium sulphate (VI), Solubor and Asahi biostimulant. The fertilisation significantly decreased the value of the sum of polienic acids C18:2 and C18:3 in rape seeds against the control. It was only after a double application of magnesium sulphate (VI), microelement fertiliser (Solubor) and Asahi biostimulant that the accumulation of these fatty acids remained at the level of concentration reported in the control seeds.Celem badań była ocena plonowania i jakości nasion rzepaku ozimego w zależności od obsady roślin, nawożenia dolistnego magnezem, siarką, boronem i biostymulantem wzrostu Ashai w połączeniu ze stałym nawożeniem NPK. Badania przeprowadzono w latach 2006- -2008 jako dwuczynnikowe doświadczenie polowe. Pierwszy czynnik to gęstość obsady roślin (A – 20, B – 30, C – 40 roślin na 1 m2), drugi – to warianty nawożenia (n = 7). Nawożenie dolistne zastosowano jedno- lub dwukrotnie. W nasionach rzepaku określono zawartość całkowitą azotu, zawartość tłuszczu oraz jego frakcji. Wyniki badań wskazują, że zawartość całkowita azotu oraz zawartość tłuszczu zależały istotnie od gęstości obsady roślin oraz nawożenia. Istotnie najwyższą zawartość wymienionych składników stwierdzono po podwójnym zastosowaniu siarczanu magnezu (VI) lub biostymulantu Ashai Solubor przy obsadzie roślin odpowiednio 40 oraz 30 roślin na m2. Skład kwasów tłuszczowych ekstrahowanych z nasion mieszańcowej odmiany rzepaku ozimego Nelson był istotnie zależny od nawożenia. Istotnie najwyższą zawartość kwasu olejowego oraz wzrost jego zawartości, w porównaniu z kontrolą, określono po pojedynczym zastosowaniu siarczanu magnezu (VI) oraz Soluboru i Ashai. Nawożenie istotnie obniżyło wartość sumy wielonienasyconych kwasów tłuszczowych C18:2 i C18:3 w nasionach rzepaku w porównaniu z kontrolą. Jedynie po zastosowaniu dwukrotnie siarczanu magnezu (VI), nawozu mikropierwiastkowego Solubor i biostymulantu Ashai akumulacja tych kwasów tłuszczowych utrzymała się na poziomie odpowiadającym zawartościom określonym w nasionach kontrolnych

Application of method for multi-criteria diagnostic analysis of patient with osteoarthritis of the hip

Artykuł przedstawia wielokryterialną procedurę postępowania przy kwalifikacji pacjentów do zabiegu wymiany stawu biodrowego w procesie leczenia. Zastosowano metodę Electre Tri w hybrydowym systemie DSS 3.0. Artykuł składa się z opisu kompetencji ekspertów, drzewa decyzyjnego oraz modelowania rankingów i klasyfikacji podjętego problemu. Przykładem badawczym są pacjenci z różnym zaawansowaniem choroby zwyrodnieniowej, których stan określono w trakcie leczenia szpitalnego.Advanced degenerative changes causing disturbances in biomechanics, disability and social isolation. A multitude of conditions of varying severity of the patient causes problem with determining the optimal timing of treatment. The classification of patients for surgery is complex. Published studies show a variety of parameters, variants and classification of evaluable patients with osteoarthritis of the hip. It notes the lack of proposals for assessing the performance in the field of biomechanics in one system, and with the classification of a sick patient. The paper presents the problem of the methodology for specific decision problems. The aim of the article was to develop (and verify) test procedure for the evaluation of osteoarthritis of the hip. Verified appropriate method of multi-criteria Electre Tri, which allowed to established patient qualifications for surgery or hip replacement program of physiotherapy or pharmacotherapy