Specific down-regulation of spinal μ-opioid receptor and reduced analgesic effects of morphine in mice with postherpetic pain

The analgesic effects of opioid agonists and the expression of μ-and κ-opioid receptors were compared between mice with herpetic pain and those with postherpetic pain induced by herpetic virus inoculation. Morphine inhibited herpetic pain more effectively than postherpetic pain. Intrathecal injection reduced the analgesic effects of morphine on postherpetic pain, but intracerebroventricular injection did not. The κ-opioid receptor agonist nalfurafine suppressed herpetic and postherpetic pain to similar degrees. μ-Opioid receptor-like immunoreactivities in the lumbar dorsal horn were markedly decreased at the postherpetic, but not herpetic, stage of pain. In the dorsal root ganglia, the expression of μ-opioid receptor mRNA was significantly decreased in mice with postherpetic pain, whereas the κ-opioid receptor mRNA level was not altered. These results suggest that specific down-regulation of the μ-opioid receptor in the primary sensory neurons is responsible for the reduced analgesic action of morphine on postherpetic pain. The κ-opioid receptor may be a useful target for the analgesic treatment of postherpetic neuralgia

Copper recovery and reduction of environmental loading from mine tailings by high‐pressure leaching and sx‐ew process

The flotation tailings obtained from Bor Copper Mine contain pyrite (FeS2) and chalcopyrite (CuFeS2), these sulfide minerals are known to promote acid mine drainage (AMD) which poses a serious threat to the environment and human health. This study focuses on the treatment of mine tailings to convert the AMD supporting minerals to more stable forms, while simultaneously valorizing the mine tailings. A combination of hydrometallurgical processes of high-pressure oxidative leaching (HPOL), solvent extraction (SX), and electrowinning (EW) were utilized to recover copper from mine tailings which contain about 0.3% Cu content. The HPOL process yielded a high copper leaching rate of 94.4% when water was used as a leaching medium. The copper leaching kinetics were promoted by the generation of sulfuric acid due to pyrite oxidation. It was also confirmed that a low iron concentration (1.4 g/L) and a high copper concentration (44.8 g/L) obtained in the stripped solution resulted in an improved copper electrodeposition current efficiency during copper electrowinning.Moreover, pyrite, which is primarily in the mine tailings, was converted into hematite after HPOL. A stability evaluation of the solid residue confirmed almost no elution of metal ions, confirming the reduced environmental loading of mine tailings through re-processing

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

Electrochemical behavior and in situ observation of galvanic couples of copper and silver or zinc wires in acidic copper sulfate solutions

The anodic dissolution reaction of copper in copper electro-refining was studied by considering the reaction of galvanic couples with different metals as impurities. In this study, zinc was chosen as a typical anodic impurity and silver as a cathodic impurity, and electrochemical measurements of galvanic couples with silver or zinc wires winding around a copper wire and in situ observation of the electrode surface using a stereo microscope were carried out. For comparison, copper wire with zinc or silver plating was used. As a result, even the simple method of winding silver or zinc wire around copper wire was able to capture the characteristic behavior of the galvanic reaction of silver and zinc on copper wire. It was also confirmed that zinc dissolution was accelerated by copper and copper dissolution was accelerated by silver, and that the effects were more promoted under anodic polarization. The crystallization and passivation of copper sulfate on the copper electrode surface and the dissolution behavior of silver were also observed. These results indicate that the experimental method presented in this study is an effective way to investigate the effects of impurities on the solubility and passivation of crude copper metal