: As a potent free radical scavenger and antioxidant, melatonin protects brain tissue against ischemia–reperfusion injury, partly via suppression of ischemia‐induced production of nitric oxide, when ...given before ischemia–reperfusion or within 2 hr of onset of ischemia. In this study, we examined the neuroprotective effect of melatonin in an in vitro model of ischemia. Primary cultured astrocytes were subjected to 4 or 8 hr of oxygen–glucose deprivation (OGD), and cultured SHSY5Y human neuronal cells were exposed to 1 hr of OGD. Melatonin was added to the medium at the commencement of OGD to achieve different final concentrations, and cell death was quantified using the measurement of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) at 24 hr after reversion of OGD. Treatment with melatonin did not affect the astrocytic cell death following 4 or 8 hr of OGD. The relative MTT values of the neuronal cells were (as mean ± S.E.M.) 59.1 ± 2.4% in the vehicle‐treated OGD group and 80.1 ± 2.7%, 82.5 ± 2.9%, 74.1 ± 2.3%, 64.2 ± 2.3%, 62.7 ± 2.8%, and 61.0 ± 3.9% in the OGD groups treated with melatonin at 10−3, 10−4, 10−5, 10−6, 10−7, and 10−8 m, respectively. Reduction in cell death was significant following treatment with melatonin at 10−3, 10−4, or 10−5 m. Reverse transcription‐polymerase chain reaction showed that human mt1 and MT2 membrane receptors were not expressed in the cultured neuronal cells. Our results show that melatonin co‐treatment protects cultured neuronal cells but not astrocytes against OGD‐induced cell death in a dose‐dependent manner and that the neuroprotection is independent of its known membrane receptors.
Melatonin is a potent scavenger of free radicals and an indirect antioxidant. Recent studies have shown that melatonin possesses beneficial effects in experimental models of brain trauma and global ...cerebral ischemia. The effects of pretreatment with melatonin on volume of cerebral infarction were investigated in the present study. Adult male Sprague–Dawley rats were anesthetized with sodium pentobarbital to undergo right‐sided endovascular middle cerebral artery occlusion (MCAO) for 3 hr. A single dose of melatonin (1.5, 5, 15, or 50 mg/kg in 1 mL normal saline) or its vehicle was given via an intraperitoneal injection at 0.5 hr before MCAO. Relative infarction volumes on day 3 after MCAO were significantly reduced in the groups treated with melatonin at 5 (mean ± S.E.M., 15.7 ± 2.5%) or 15 (21.4 ± 3.1%) mg/kg but not at 1.5 (30.6 ± 3.5%) or 50 (26.7 ± 2.8%) mg/kg when compared with the vehicle group (33.9 ± 3.5%). There was no significant difference in the arterial blood pressure (BP), heart rate (HR) and relative cerebral blood flow among the experimental groups. These results indicate that pretreatment with melatonin at a dose between 5 and 15 mg/kg protects against focal cerebral ischemia.
Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. Optimization of the ...high-throughput screening lead 6 led to the discovery of 25 (ABT-341), a highly potent, selective, and orally bioavailable DPP4 inhibitor. When dosed orally, 25 dose-dependently reduced glucose excursion in ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo tests and may represent a new therapeutic agent for the treatment of type 2 diabetes.
Plasmid pAcLEneo which bears neomycin gene derived by the baculovirus IE1 promotor was digested and the gene was harvested. A transfer vector pAc34DZ2 in which the polyhedrin envelope gene has been ...inactivated by insertion of expression cassette of PIE1/neo was constructed by inserting the neo cassette into the SacI site of plasmid pAc34DZ1. We have constructed the polyhedrin positive recombinant virus (I) vAcPhBtT which was able to express Bt truncated endotoxin gene. In order to improve the insecticide efficiency of recombinant virus (I), an anti-neomycin recombinant virus (II) vAcPhBtTPE- was obtained by second co-transfection into the Sf9 cells with pAc34DZ2 and recombinant virus (I) DNA. Southern blot and SDS-PAGE analysis indicated that the recombinant virus (II) was still able to express the 80 kD Bt truncated delta-endotoxin, but did not express the 34 kD polyhedrin envelope protein. The recombinant virus (II) without envelope released virion faster than recombinant virus (I) after alkaline lysis. Bio
Sustained (noninactivating) outward-rectifying K+ channel currents have been identified in a variety of plant cell types and species. Here, in Arabidopsis thaliana guard cells, in addition to these ...sustained K+ currents, an inactivating outward-rectifying K+ current was characterized (plant A-type current:I(AP)). I(AP) activated rapidly with a time constant of 165 ms and inactivated slowly with a time constant of 7.2 sec at +40 mV. I(AP) was enhanced by increasing the duration (from 0 to 20 sec) and degree (from +20 to -100 mV) of prepulse hyperpolarization. Ionic substitution and relaxation (tail) current recordings showed that outward I(AP) was mainly carried by K+ ions. In contrast to the sustained outward-rectifying K+ currents, cytosolic alkaline pH pH was found to inhibit I(AP) and extracellular K+ was required for I(AP) activity. Furthermore, increasing cytosolic free Ca2+ in the physiological range strongly inhibited I(AP) activity with a half inhibitory concentration of approximately 94 nM. We present a detailed characterization of an inactivating K+ current in a higher plant cell. Regulation of I(AP) by diverse factors including membrane potential, cytosolic Ca2+ and pH, and extracellular K+ and Ca2+ implies that the inactivating I(AP) described here may have important functions during transient depolarizations found in guard cells, and in integrated transduction processes during stomatal movement
Simply the best: Dynamic combinatorial chemistry coupled to enzyme catalysis was used to identify enzyme substrates in a library constructed from a series of thioesters and thiols by ...transesterification. The library was directly coupled to the catalytic action of acetylcholinesterase, which selectively hydrolyzed the best substrate candidates (see schematic representation). The process allowed rapid identification of discrete substrates.
In this paper, we present for the first time a high-directive patch antenna based on all-dielectric near-zero-index metamaterial (NZIM) superstrates. Dielectric disks with high permittivity arranged ...periodically yield low refraction index around 9.25 GHz. We used a two-layer all-dielectric
NZIM as the cover of a path antenna, both the simulation and experiment results show that the all-dielectric NZIM can focus the radiation energy, and the gain of the antenna with metamaterial is greatly enhanced.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Developments of the Hospital Plate Washer and its control system are introduced in the paper, and the application of the ultrasound technotology in the plate washer is described too.
Abstract EphB2/ephrinBs has been recently demonstrated to regulate cell proliferation in the neurogenic subventricular zone (SVZ). However, little is known about the role of EphB2 in adult ...neurogenesis following cerebral infarction. In the present study, we investigated the role of EphB2 in proliferation and differentiation of precursor cells within the SVZ, as well as the neurological function recovery after permanent middle cerebral artery occlusion (MCAO) in hypertensive rats. Bromodeoxyuridine (BrdU) was given twice per day starting from 24h after MCAO for 6-consecutive days. Recombinant EphB2-Fc or IgG-Fc was preclustered by incubation with anti-human Fcγ and then intraventricularly administrated at 24h after MCAO. The neurological function was evaluated before operation and at 7, 14 and 21 days after MCAO respectively. The infarct size and immunoreactivities of BrdU, Nestin, DCX, GFAP and NeuN were measured at 7, 14 and 21 days after MCAO respectively. Treatment with EphB2-Fc markedly improved the neurological function recovery within 3 weeks after MCAO. In parallel, EphB2-Fc significantly increased the number of BrdU-labeled cells and led to marked increases in BrdU+ /DCX+ and BrdU+ /Nestin+ cells within the ipsilateral SVZ for 2 weeks after MCAO respectively (all p < 0.05). The BrdU+ /NeuN+ cells in the peri-infarct area and neighboring ipsilateral striatum were significantly increased following EphB2-Fc infusion within 3 weeks after MCAO (all p < 0.05). Our data suggest that administration of exogenous clustered EphB2-Fc at 24h can enhance the endogenous neurogenesis and concomitantly improve neurological recovery after cerebral infarction.
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