Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury

<p>Abstract</p> <p>Background</p> <p>Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown.</p> <p>Methods</p> <p>Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double-labeling analysis of <it>in situ </it>hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086).</p> <p>Results</p> <p>RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia.</p> <p>Conclusions</p> <p>Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.</p

The role of digital rectal examination for diagnosis of acute appendicitis: A systematic review and meta-analysis

Background: Digital rectal examination (DRE) has been traditionally recommendedto evaluate acute appendicitis, although several reports indicate its lack of utility for this diagnosis. No metaanalysis has examined DRE for diagnosis of acute appendicitis. Objectives: To assess the role of DRE for diagnosis of acute appendicitis. Data Sources: Cochrane Library, PubMed, and SCOPUS from the earliest available date of indexing through November 23, 2014, with no language restrictions. Study Selection: Clinical studies assessing DRE as an index test for diagnosis of acute appendicitis. Data Extraction and Synthesis: Two independent reviewers extracted study data and assessed the quality, using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Bivariate random-effects models were used for the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) as point estimates with 95% confidence intervals (CI). Main Outcomes and Measures: The main outcome measure was the diagnostic performance of DRE for diagnosis of acute appendicitis. Results: We identified 19 studies with a total of 7511 patients. The pooled sensitivity and specificity were 0.49 (95% CI 0.42-0.56) and 0.61 (95% CI 0.53-0.67), respectively. The positive and negative likelihood ratios were 1.24 (95% CI 0.97-1.58) and 0.85 (95% CI 0.70-1.02), respectively. The DOR was 1.46 (0.95-2.26). Conclusion and Relevance: Acute appendicitis cannot be ruled in or out through the result of DRE. Reconsideration is needed for the traditional teaching that rectal examination should be performed routinely in all patients with suspected appendicitis

Synthetic studies on pterin glycosides: the first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin

L-Rhamnose was led, in a 14-step-sequence, to N2-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (23), an appropriately protected precursor for 2′-O-glycosylation, while 4,6-di-O-acetyl-2,3-di-O-(4-methoxybenzyl)-α-d-glucopyranosyl bromide (32), a novel glycosyl donor, was efficiently prepared from d-glucose in 8 steps. The first synthesis of 2′-O-(α-d-glucopyranosyl)biopterin (2a) was achieved by treatment of the key intermediate 23 with 32 in the presence of silver triflate and tetramethylurea, followed by successive removal of the protecting groups

Correlation between thermal aggregation and stability of lysozyme with salts described by molar surface tension increment: an exceptional propensity of ammonium salts as aggregation suppressor

Protein aggregation is a critical problem for biotechnology and pharmaceutical industries.Despite the fact that soluble proteins have been used for many applications, our understandingof the effect of the solution chemistry on protein aggregation still remains to be elucidated.This paper investigates the process of thermal aggregation of lysozyme in the presence ofvarious types of salts. The simple law was found; the aggregation rate of lysozyme increasedwith increasing melting temperature of the protein (Tm) governed by chemical characteristicsof additional salts. Ammonium salts were, however, ruled out; the aggregation rates oflysozyme in the presence of the ammonium salts were smaller than the ones estimatedfrom Tm. Comparing with sodium salts, ammonium salts increased the solubility of thehydrophobic amino acids, indicating that ammonium salts adsorb the hydrophobic region ofproteins, which leads to the decrease in aggregation more effectively than sodium salts. Thepositive relation between aggregation rate and Tm was described by another factor such as thesurface tension of salt solutions. Fourier transform infrared spectral analysis showed thatthe thermal aggregates were likely to form b-sheet in solutions that give high molar surfacetension increment. These results suggest that protein aggregation is attributed to the surfacefree energy of the solution

High-performance Ge/Si electro-absorption optical modulator up to 85°C and its highly efficient photodetector operation

We studied a high-speed Ge/Si electro-absorption optical modulator (EAM) evanescently coupled with a Si waveguide of a lateral p–n junction for a high-bandwidth optical interconnect over a wide range of temperatures from 25 °C to 85 °C. We demonstrated 56 Gbps high-speed operation at temperatures up to 85 °C. From the photoluminescence spectra, we confirmed that the bandgap energy dependence on temperature is relatively small, which is consistent with the shift in the operation wavelengths with increasing temperature for a Ge/Si EAM. We also demonstrated that the same device operates as a high-speed and high-efficiency Ge photodetector with the Franz-Keldysh (F-K) and avalanche-multiplication effects. These results demonstrate that the Ge/Si stacked structure is promising for both high-performance optical modulators and photodetectors integrated on Si platforms

Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia

<p>Abstract</p> <p>Background</p> <p>Honeybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV) into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK) in the generation of BV-induced pain hypersensitivity.</p> <p>Results</p> <p>We found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38) was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn.</p> <p>Conclusion</p> <p>The results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.</p

Reliable long-term operation of superconducting bus lines for the LHD

The Large Helical Device (LHD) is an experimental device for helical type fusion plasma in National Institute for Fusion Science and plasma experiments over 150,000 shots have been successfully conducted during twenty long-term plasma experimental campaigns. The LHD has two kinds of superconducting magnets and nine flexible superconducting bus lines with an average length of 55 m, which are utilized as a part of the current feeder system between the coils and the power sources. The superconducting bus lines consist of a pair of aluminum stabilized NbTi/Cu compacted stranded cable insulated electrically and coaxial five corrugated stainless steel tubes with two layers of vacuum insulations. The nominal current is 32 kA and the withstand voltage is 5 kV in 77 K gas helium. From the first experimental campaign, the superconducting bus lines have been stably operated at steady state by using automatic control. It is also confirmed that the status of the superconducting bus lines are kept good thanks to appropriate maintenances. As the results, the reliable operation of the superconducting bus lines has been achieved during the plasma experimental campaigns without any serious failure and the total operational time of the steady state cooling is approximately 58,000 hours

Effects of Subcooling on Lengths of Propagating Normal Zones in the LHD Helical Coils

Propagation of a short normal zone was observed in a helical coil of the Large Helical Device, when the coil was cooled with subcooled helium, of which the inlet and outlet temperatures are 3.2 K and below 4.0 K, respectively. The normal zone was induced at the bottom position of the coil. It propagated to only the downstream side of the current with recovery from the opposite side, and stopped after passing the outer equator of the torus. The induced balance voltage is obviously lower and the propagating time is shorter than those of propagating normal zones observed in the helical coil cooled with saturated helium at 4.4 K. According to the simulation of the propagation of a normal zone, it is considered that such a short normal zone at the current close to the minimum propagating current propagates without full transition to film boiling