Antinociceptive Effects of Intrathecal Landiolol Injection in a Rat Formalin Pain Model

Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive effects. Further investigation of the antinociceptive mechanism of landiolol is required

Cadmium Induces the Expression of Grp78, an Endoplasmic Reticulum Molecular Chaperone, in LLC-PK1 Renal Epithelial Cells

To reveal the effects of cadmium exposure on the endoplasmic reticulum (ER) stress response, we examined the expression and function of 78-kDa glucose-regulated protein (Grp78), an ER-resident molecular chaperone, in LLC-PK1 cells. In cells treated with 10 μM cadmium chloride, Grp78 protein levels increased after 6 hr and remained elevated at 24 hr. When cells were incubated with 1–20 μM CdCl(2) for 6 hr, Grp78 increased in a dose-dependent manner. In addition, Grp78 mRNA levels were elevated in response to CdCl(2) exposure. After exposure to 10 μM CdCl(2), the levels of activating transcription factor 4 (ATF4) were increased at 2 hr, with a further enhancement after that; this accumulation followed the transient but marked phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) on serine 51. Although ATF4 mRNA levels increased mildly by CdCl(2) exposure, treatment with actinomycin D did not suppress CdCl(2)-induced accumulation of ATF4 protein, suggesting the involvement of posttranscriptional and, in part, transcriptional mechanisms. Compared with other heavy-metal compounds such as manganese chloride, zinc chloride, mercuric chloride, and lead chloride, CdCl(2) could increase the levels of Grp78, ATF4, and the phosphorylated form of eIF2α more markedly without definite cellular damage. The silencing of Grp78 expression using short-interference RNA enhanced CdCl(2)-induced cellular damage. These results show that cadmium induces the expression of Grp78 probably via phosphorylation of eIF2α and resultant translation of ATF4, and this ER stress response plays a role in protection against cadmium cytotoxicity in this renal epithelial cell

A Solution for Universal Classification of Species Based on Genomic DNA

Traditionally, organisms have been classified on the basis of their phenotype. Recently, genotype-based classification has become possible through the development of sequencing technology. However, it is still difficult to apply sequencing approaches to the analysis of a large number of species due to the cost and labor. In most biological fields, the analysis of complex systems comprising various species has become an important theme, demanding an effective method for handling a vast number of species. In this paper, we have demonstrated, using plants, fish, and insects, that genome profiling, a compact technology for genome analysis, can classify organisms universally. Surprisingly, in all three of the domains of organisms tested, the phylogenetic trees generated from the phenotype topologically matched completely those generated from the genotype. Furthermore, a single probe was sufficient for the genome profiling, thereby demonstrating that this methodology is universal and compact

A Panel of Serum Biomarkers Differentiates IgA Nephropathy from Other Renal Diseases

Background and Objectives: There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN. Materials and Methods: We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients. Results: Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g), compared to patients with less proteinuria. Conclusions Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases

Clinical studies on bronchial asthma induced by chironomid midges -comparison between positive and negative cases to house dust-

近年ユスリカが気管支喘息の原因抗原となり得ることが報告されている。しかし，その臨床的特徴はいまだ明らかにされていない。このユスリカ抗原の特徴を検討する目的で，気管支喘息症例163例をHD（ハウスダスト）に感作されたRAST　score2＋以上の陽性例82例とscore1＋以下の陰性例81例とに分けて比較検討を行なった。その結果皮膚反応，ヒスタミン遊離，CTT抗原を用いた特異的IgE抗体いずれの検討においても，HDに感作された症例が，よりユスリカ抗原にも感作されやすいことが明らかになった。In recent years it has been reported that chironomid migdes might be one of the causative allergens in bronchial asthma. In order to clarify the clinical characteristics of bronchial asthma induced by chironomid midges (Tokunagayusurika akamusi), 163 patients with bronchial asthma were studied. The subjects were divided into two groups ; cases with negative (0～1 + ) and positive (2 + or more) RAST score to house dust. 1. Skin reaction to midges was positive in 54 cases (33.1%) out of 163 patients with bronchial asthma. Thirty-six cases (43.9%) out of 82 asthmatics with positive RAST score to house dust showed positive skin reaction to midges, but in 81 cases with negative RAST score, only 18 cases (22.2%) showed positive skin reaction. 2. Fourteen cases out of 85 asthmatics showed a significant amount of histamine release (more than 15%).　A significant amount of histamine release was observed in 12 cases (23.5%) out of 51 cases with positive RAST score, but in only two cases (5.9%) out of 24 cases with negative RAST score. 3. Specific IgE antibodies to CTT (Chiromonus thummi thummi) was positive in 12 cases (18.2%) out of 66 asthmatics. In 41 asthmatics with positive RAST score to house dust, 12 cases (29.3%) showed positive RAST score to CTT, though in 25 cases with negative RAST score to house dust no cases showed positive RAST score to CTT. In conclusion, cases with house dust allergy were more easily sensitized by chironomid migdes than those cases without house dust allergy

Candida-induced histamine release from basophils: relationship to house dust- and anti-IgE-induced secretion

Candida albicans-induced histamine release from basophils was studied in 54 patients with bronchial asthma in comparison with the release caused by house dust and anti-IgE. The release of histamine induced by C. albicans and that induced by house dust were closely related to the serum levels of specific IgE antibodies as expressed by RAST scores. A correlation of C. albicans-induced histamine release with the release caused by anti-IgE was not generally observed. On the other hand, a close correlation was found between house dust- and anti-IgE-induced histamine release. It was suggested from these results that the differences between C. albicans- and house dust-induced histamine release might be due to the different antigenicity of the two allergens.</p

Effect of mediastinal lymph nodes sampling in patients with clinical stage I non-small cell lung cancer

Objective : Systematic nodal dissection has been recommended for patients with resectable non-small cell lung cancer because of its staging accuracy. However, in patients with clinical stage I non-small cell lung cancer whether systematic nodal dissection provides more benefits than mediastinal lymph node sampling or not is controversial. In this retrospective study, we evaluated the effect of mediastinal lymph node sampling in patients with clinical stage I NSCLC. Methods : One hundred and nineteen consecutive patients with clinical stage I NSCLC, who underwent curative operation between January 1994 and December 2000, were retrospectively reviewed (dissection group = 58 : sampling group= 61). Systematic nodal dissection was defined as complete removal of mediastinal lymph node, and mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4, and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors. Results : The total number of removed mediastinal lymph nodes in patients who underwent systematic nodal dissection was 22.1±9.7, which was significantly higher than that in patients who underwent mediastinal lymph node sampling of 11.4±7.0 (p<0.001). Postoperatively N2 disease was detected in 8 patients (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the median follow up of 79 months, the cancer specific survival rate at 5 year was 78.0% in the dissection group and 76.2% in the sampling group (p = 0.60). Conclusions : Mediastinal lymph node sampling showed the similar effect to systematic nodal dissection in patients with clinical stage I non-small cell lung cancer

Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study

BackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.MethodsWe retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.ResultsAfter PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67–7.42) for malignancy and 3.03 (95% CI: 0.77–15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23–2.97).ConclusionThe IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed

Autoantibodies associated with neuropsychiatric systemic lupus erythematosus: the quest for symptom-specific biomarkers

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs, including the central nervous system. Neuropsychiatric SLE (NPSLE) is a severe and potentially fatal condition. Several factors including autoantibodies have been implicated in the pathogenesis of NPSLE. However, definitive biomarkers of NPSLE are yet to be identified owing to the complexity of this disease. This is a major barrier to accurate and timely diagnosis of NPSLE. Studies have identified several autoantibodies associated with NPSLE; some of these autoantibodies are well investigated and regarded as symptom-specific. In this review, we discuss recent advances in our understanding of the manifestations and pathogenesis of NPSLE. In addition, we describe representative symptom-specific autoantibodies that are considered to be closely associated with the pathogenesis of NPSLE

A case of dermatomyositis complicated with pleural effusion and massive ascites

We report a patient with dermatomyositis (DM) complicated with progressive pleural effusion and ascites. A 40-year-old woman was hospitalized in our department because of severe myalgia and dysphagia, complicated with pleural effusion and massive ascites. Elevated muscle enzymes, Gottron's papules, and electromyography (EMG) confirmed the diagnosis of DM. Combined immunosuppressive treatment consisting of intravenous immunoglobulin (IV-IG), intravenous-cyclophosphamide (IV-CY) and tacrolimus resolved her myopathy and dysphagia as well as pleural effusion and massive ascites. Her clinical course and the absence of other factors that cause pleural effusion and ascites suggest that these symptoms were related to the pathophysiology of DM