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101.
Joanna Mika Katarzyna Popiolek-Barczyk Ewelina Rojewska Wioletta Makuch Katarzyna Starowicz Barbara Przewlocka 《PloS one》2014,9(8)
The analgesic effect of delta-opioid receptor (DOR) ligands in neuropathic pain is not diminished in contrast to other opioid receptor ligands, which lose their effectiveness as analgesics. In this study, we examine whether this effect is related to nerve injury-induced microglial activation. We therefore investigated the influence of minocycline-induced inhibition of microglial activation on the analgesic effects of opioid receptor agonists: morphine, DAMGO, U50,488H, DPDPE, Deltorphin II and SNC80 after chronic constriction injury (CCI) to the sciatic nerve in rats. Pre-emptive and repeated administration of minocycline (30 mg/kg, i.p.) over 7 days significantly reduced allodynia and hyperalgesia as measured on day 7 after CCI. The antiallodynic and antihyperalgesic effects of intrathecally (i.t.) administered morphine (10–20 µg), DAMGO (1–2 µg) and U50,488H (25–50 µg) were significantly potentiated in rats after minocycline, but no such changes were observed after DPDPE (10–20 µg), deltorphin II (1.5–15 µg) and SNC80 (10–20 µg) administration. Additionally, nerve injury-induced down-regulation of all types of opioid receptors in the spinal cord and dorsal root ganglia was not influenced by minocycline, which indicates that the effects of opioid ligands are dependent on other changes, presumably neuroimmune interactions. Our study of rat primary microglial cell culture using qRT-PCR, Western blotting and immunocytochemistry confirmed the presence of mu-opioid receptors (MOR) and kappa-opioid receptors (KOR), further we provide the first evidence for the lack of DOR on microglial cells. In summary, DOR analgesia is different from analgesia induced by MOR and KOR receptors because it does not dependent on injury-induced microglial activation. DOR agonists appear to be the best candidates for new drugs to treat neuropathic pain. 相似文献
102.
Synowiec E Szaflik J Chmielewska M Wozniak K Sklodowska A Waszczyk M Dorecka M Blasiak J Szaflik JP 《Molecular biology reports》2012,39(3):2081-2087
Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the
other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1
(HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress.
In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited
in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase
chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and
the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the
other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD. 相似文献
103.
Blasiak J Synowiec E Tarnawska J Czarny P Poplawski T Reiter RJ 《Molecular biology reports》2012,39(7):7487-7496
Methacrylate monomers used in dentistry have been shown to induce DNA double strand breaks (DSBs), one of the most serious DNA damage. In the present work we show that a model dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) at concentrations up to 0.25 mM Bis-GMA induced oxidative DNA in cultured primary human gingival fibroblasts (HGFs) as evaluated by the comet assay and probed with human 8-hydroxyguanine DNA-glycosylase 1. HEMA/Bis-GMA induced DSBs in HGFs as assessed by the neutral comet assay and phosphorylation of the H2AX histone and sodium ascorbate or melatonin (5-methoxy-N-acetyltryptamine) both at 50 μM reduced the DSBs, they also inhibited apoptosis induced by HEMA/Bis-GMA. The adhesive slowed the kinetics of the repair of DNA damage induced by hydrogen peroxide in HGFs, while sodium ascorbate or melatonin improved the efficacy of H(2)O(2)-induced damage in the presence of the methacrylates. The adhesive induced a rise in the G2/M cell population, accompanied by a reduction in the S cell population and an increase in G0/G1 cell population. Sodium ascorbate or melatonin elevated the S population and reduced the G2/M population. In conclusion, HEMA/Bis-GMA induce DSBs through, at least in part, oxidative mechanisms, and these compounds may interfere with DSBs repair. Vitamin C or melatonin may reduce the detrimental effects induced by methacrylates applied in dentistry. 相似文献
104.
1-O-(indole-3-acetyl)-β-d-glucose: sugar indoleacetyl transferase (1-O-IAGlc-SugAc) is a novel enzyme catalyzing the transfer of the indoleacetyl (IA) moiety from 1-O-(indole-3-acetyl)-β-d-glucose to several saccharides to form ester-linked IAA conjugates. 1-O-IAGlc-SugAc was purified from liquid endosperm of Zea mays by fractionation with ammonium sulphate, anion-exchange, Blue Sepharose chromatography, affinity chromatography on Concanavalin
A-Sepharose, adsorption on hydroxylapatite and preparative PAGE. The obtained enzyme preparation indicates only one band of
R
f 0.67 on 8% non-denaturing PAGE consisting of two polypeptides of 42 and 17 kDa in SDS/PAGE. Highly purified 1-O-IAGlc-SugAc shows maximum transferase activity with monosaccharides (mannose, glucose, and galactose), lower activity with
disaccharides (melibiose, gentobiose) and trisaccharide (raffinose) and minimal enzymatic activity with oligosaccharides from
the raffinose family as well. The novel acyltransferase exhibits, besides its primary indoleacetylation of sugar, minor hydrolytic
and disproportionation activities producing free IAA and supposedly 1,2-di-O-(indole-3-acetyl)-β-glucose, respectively. Presumably, 1-O-IAGlc-SugAc, like 1-O-indole-3-acetyl-β-d-glucose-dependent myo-inositol acyltransferase (1-O-IAGlc-InsAc), is another member of the serine carboxypeptidase-like (SCPL) acyltransferase family. 相似文献
105.
Ewelina Król Zbigniew Krejpcio S?awomir Michalak Rafa? W. Wójciak Pawe? Bogdański 《Biological trace element research》2012,150(1-3):350-359
Insulin resistance is the first step in glucose intolerance and the development of type 2 diabetes mellitus, thus effective prevention strategies should also include dietary interventions to enhance insulin sensitivity. Nutrients, such as microelement chromium(III) and thiamine, play regulatory roles in carbohydrate metabolism. The objective of this study was to evaluate the insulin-sensitizing potential of the combined supplementary chromium(III) propionate complex (CrProp) and thiamine in insulin resistance animal model (rats fed a high-fructose diet). The experiment was carried out on 40 nine-week-old male Wistar rats divided into five groups (eight animals each). Animals were fed ad libitum: the control diet (AIN-93?M) and high-fructose diets with and without a combination of two levels of CrProp (0.1 and 1?mg Cr/kg body mass/day) and two levels of thiamine (0.5 and 10?mg/kg body mass/day) for 8?weeks. At the end of the experiment rats were sacrificed to collect blood and internal organs for analyses of blood biochemical and hematologic indices as well as tissular microelement levels that were measured using appropriate methods. It was found that both supplementary CrProp and thiamine (given alone) have significant insulin-sensitizing and moderate blood-lipid-lowering properties, while the combined supplementation with these agents does not give synergistic effects in insulin-resistant rats. CrProp given separately increased kidney Cu and Cr levels, while thiamine alone increased hepatic Cu contents and decreased renal Zn and Cu contents. 相似文献
106.
The preferred treatment for hypothyroidism is oral levothyroxine (LT4) ingestion, in doses that ensure a sustained state of hormonal balance. Many different factors may significantly influence the absorption of LT4, including: interval between the ingestion of the drug and the last meal, eating habits, and different functional and organic pathologies of the gastro-intestinal tract. The main purpose of this paper is to review and systematise the available literature on the subject of the influence of different malabsorption syndromes on the effectiveness of LT4 preparations. The need to use high LT4 doses in the substitutional treatment of hypothyroidism is often the very first sign of one of the pathologies that are connected with malabsorption syndrome, which might have been asymptomatic and undiagnosed previously. Patients who require more than 2 μg/kg body weight of LT4 per day, with constantly increased thyrotropin level, should be diagnosed with the suspicion of pseudomalabsorption or real absorption disorder. An LT4 absorption test, using high doses of LT4, may be useful in the diagnosis of pseudomalabsorption. After excluding non-compliance, the differential diagnosis should include such disorders as lactose intolerance, coeliac disease, atrophic gastritis, Helicobacter pylori infection, bowel resection, inflammatory bowel disease, and parasite infection. Where there is a diagnosis of lactose intolerance, both a low lactose diet and a lactose-free LT4 preparation should be administered to restore euthyroidism or make it possible to decrease the dose of the LT4 preparation. In coeliac disease, a gluten-free diet usually allows a normalisation of the need for LT4, as do eradication of the H. pylori infection or parasite colonisation. In cases of atrophic gastritis or inflammatory bowel disease, treating the underlying diseases and regaining the state of remission may improve the absorption of LT4. In patients after gastro-intestinal tract surgery, a dose of LT4 higher than that typically used is needed to restore euthyroidism. 相似文献
107.
Yan TC Dudley JA Weir RK Grabowska EM Peña-Oliver Y Ripley TL Hunt SP Stephens DN Stanford SC 《PloS one》2011,6(3):e17586
Background
The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon.Methods and Results
The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning.Conclusion
In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies. 相似文献108.
Ewelina Adamska Jan Barciszewski Wojciech T. Markiewicz 《Nucleosides, nucleotides & nucleic acids》2013,32(12):861-871
Convenient and efficient methods of the synthesis of N6- and N4-substituted derivatives of adenine and cytosine and their 2′-deoxyribosides were developed. The reactions of either unprotected nucleobases (adenine, cytosine) or unprotected 2′-deoxyribosides with aryl or alkyl aldehydes give corresponding Schiff bases that can be reduced to the target title compounds with high overall yields. In the case of aryl aldehydes the imine derivatives are obtained in the presence of methoxides in methanol and reduced with sodium borohydride. The corresponding reactions with alkyl aldehydes require the use of acetic acid and borane dimethyl sulfide complex instead. 相似文献
109.
Dariusz Zapała Piotr Francuz Ewelina Zapała Natalia Kopiś Piotr Wierzgała Paweł Augustynowicz Andrzej Majkowski Marcin Kołodziej 《Applied psychophysiology and biofeedback》2018,43(1):23-35
The challenges of research into brain–computer interfaces (BCI) include significant individual differences in learning pace and in the effective operation of BCI devices. The use of neurofeedback training is a popular method of improving the effectiveness BCI operation. The purpose of the present study was to determine to what extent it is possible to improve the effectiveness of operation of sensorimotor rhythm-based brain–computer interfaces (SMR-BCI) by supplementing user training with elements modifying the characteristics of visual feedback. Four experimental groups had training designed to reinforce BCI control by: visual feedback in the form of dummy faces expressing emotions (Group 1); flashing the principal elements of visual feedback (Group 2) and giving both visual feedbacks in one condition (Group 3). The fourth group participated in training with no modifications (Group 4). Training consisted of a series of trials where the subjects directed a ball into a basket located to the right or left side of the screen. In Group 1 a schematic image a face, placed on the controlled object, showed various emotions, depending on the accuracy of control. In Group 2, the cue and targets were flashed with different frequency (4 Hz) than the remaining elements visible on the monitor. Both modifications were also used simultaneously in Group 3. SMR activity during the task was recorded before and after the training. In Group 3 there was a significant improvement in SMR control, compared to subjects in Group 2 and 4 (control). Differences between subjects in Groups 1, 2 and 4 (control) were insignificant. This means that relatively small changes in the training procedure may significantly impact the effectiveness of BCI control. Analysis of behavioural data acquired from all participants at training showed greater effectiveness in directing the object towards the right side of the screen. Subjects with the greatest improvement in SMR control showed a significantly lower difference in the accuracy of rightward and leftward movement than others. 相似文献
110.
The aim of this study was to determine if the loss of germinability and viability of beech (Fagus sylvatica L.) seeds stored at different variants of temperature (4, 20, and 30 °C) and relative humidity (RH: 45 and 75 %) is associated
with a loss of membrane integrity and changes in lipid composition. Beech seeds stored for 9 weeks gradually lost viability
at a rate dependent on temperature and humidity. The harmful effect of temperature increased with growing humidity. The loss
of seed viability was strongly correlated with an increase in membrane permeability and with production of lipid hydroxyperoxides
(LHPO), which was regarded as an indicator of peroxidation of unsaturated fatty acids. The condition of membranes was assessed
on the basis of their permeability and the state of lipid components: phospholipids and fatty acids. During seed storage we
observed a decline in concentration of individual phospholipids and fatty acids, proportional to the loss of seeds viability.
We also detected a decrease in concentrations of α-tocopherol and sterols, which play an important role in protection of membranes
against the harmful influence of the environment. Our results show that the germinability of beech seeds declines rapidly
at temperature above 0 °C and growing humidity. This is due mainly to the loss of membrane integrity, caused by peroxidation
of unsaturated fatty acids. 相似文献