Oral lichenoid drug reaction with autoantibodies in peripheral blood: Case report

AbstractA 51-year-old man complained of oral roughness and pain. At the age of 49 years, he was admitted for 8 months for bipolar emotional disorder. Oral administration of lithium carbonate was started. Extensive, hemorrhagic, erythema-mixed white lace-like patches were noted on the lip, buccal mucosae, and lingual margins. On biopsy, all lesions were consistent with oral lichen planus. A drug lymphocyte stimulation test showed a positive reaction to lithium carbonate. Blood examination revealed marked increases in the peripheral blood levels of antinuclear antibodies. To relieve the symptoms, the systemic administration of prednisolone was performed while continuing the lithium carbonate

A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline.

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline

Infusion of angiotensin II reduces loss of glomerular capillary area in the early phase of anti-Thy-1.1 nephritis possibly via regulating angiogenesis-associated factors

Infusion of angiotensin II reduces loss of glomerular capillary area in the early phase of anti-Thy-1.1 nephritis possibly via regulating angiogenesis-associated factors.BackgroundAlthough angiotensin II (Ang II) is involved in the progression of renal diseases, infusion of Ang II was reported to surprisingly ameliorate the early phase of anti-Thy-1.1 nephritis (Wenzel et al,Kidney Int 61:1020, 2002). Considering the known proangiogenic effect of Ang II and that angiogenic glomerular capillary repair is required for the recovery of damaged glomeruli in rat anti-Thy-1.1 nephritis, we hypothesized that Ang II infusion starting prior to the initiation of nephritis may induce the expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), resulting in the increased glomerular capillary area in the early phase.MethodsAng II was infused (170ng/min) in rats, and 5 days later, nephritis was induced by the administration of monoclonal 1-22-3 antibodies. Ang II type 1 or type 2 receptor antagonist (AT1R or AT2R, respectively) (losartan or PD123319, respectively) was coadministered.ResultsAng II infusion affected on neither the deposition of Ig nor mesangiolysis in the initial phase, and resulted in the aggravation of creatinine clearance at day 14 and 35 after initiating anti-Thy-1.1 nephritis. Histologic alterations were ameliorated accompanied by reduced loss in rat endothelial cell antigen (RECA)-1(+) endothelial area in Ang II-infused nephritic rats on day 6 and 14 as compared to control nephritic group, and nephritic alterations were mostly resolved on day 35 in both groups. At the early stage (day 6), glomerular expression of VEGF and receptors flk-1 and flt-1 as well as Ang-1, and receptor Tie2 were increased, and glomerular monocyte infiltration and the expression of angiopoietin-2 (Ang-2), a natural antagonist of Ang-1, were reduced. Both Ang II receptors were involved in the regulation of angiogenic factors and receptors.ConclusionThese results demonstrate that infusion of exogenous Ang II starting prior to the induction of nephritis activates VEGF and Ang-1 signaling regulated via both Ang II receptors, potentially leading to the accelerated recovery of injured glomerular endothelial cells in the early phase of anti-Thy-1.1 nephritis. Increased expression of VEGF and Ang-1 on podocytes further suggests the crucial association of endothelial cells and podocytes in maintaining proper glomerular capillary structures

A Management Policy for North Japan Sea Sailfin Sandfish, Arctoscopus japonicus Stock

The fishery cooperative association of Akita Prefecture closed the sailfin sandfish Arctoscopus japonicus fisheries from 1992 to 1994 to rehabilitate the stock. Following the temporary closure, the total allowable catch (TAC) has gradually increased. The aim of this study is to evaluate the effects of the fishery moratorium and other restrictions for this stock using several scenarios involving age-structured models and ocean environmental factors. The following results were obtained: 1) stock biomass (SB) did increase during the fishing moratorium; 2) if more prefectures, including Aomori, Akita, Yamagata and Niigata had also implemented the moratorium, a greater increases in SB would have been realized; 3) if a 30% reduction in fish harvest had been implemented from 1980 to 1982 when the ocean environmental condition was relatively good, SB would have recovered; 4) SB would not have recovered if the moratorium had not been implemented; 5) if exploitation rated E[t] could be tightly controlled, a constant exploitation rate policy of E[t] - 0.4 would be a better policy compared to other policies based on Monte-Carlo simulation tests; and 6) if E[t] can not be controlled at a constant level, a short-term reduction policy of Et, for example, a 30% reduction during the 3 years when stock size was very low, would be very effective. In particular, when the ocean environmental condition is good, this policy works effectively.Keywords: age-structured model, Fisheries Economics, Theoretical and Empirical Bio-Economic Analysis, fishing moratorium, environmental factor, Arctoscopus japonicus, management policy, sailfin sandfis

Novel oestrogen receptor beta-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice

Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ER beta activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor beta-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17 beta-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERa in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ER beta-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.ArticleSCIENTIFIC REPORTS. 7:4663 (2017)journal articl

Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population

BackgroundVaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination.MethodsIn total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression.ResultsSignificant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%).ConclusionsThe candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules

Urinary biopyrrins levels are elevated in relation to severity of heart failure

AbstractObjectivesWe investigated the relationship between the urinary levels of biopyrrins and the severity of heart failure (HF).BackgroundOxidative stress is evident in heart disease and contributes to the development of ventricular dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin, have been discovered as potential markers of oxidative stress.MethodsWe measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects (30 men; mean age 65 years). Urine and blood samples were taken after admission in all subjects. Further urine samples were obtained from 40 patients after treatment of HF.ResultsThe urinary biopyrrins/creatinine levels (μmol/g creatinine) were the highest in patients in New York Heart Association (NYHA) class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range 2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant differences in urinary biopyrrins/creatinine levels among each group. The treatment of HF significantly decreased both urinary biopyrrins/creatinine levels (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class (from 2.5 ± 0.1 to 1.7 ± 0.1). Log biopyrrins/creatinine levels were positively correlated with log BNP levels (r = 0.650, p < 0.001).ConclusionsThese results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity

Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial

AbstractBackgroundAlthough the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy.PurposeThe Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD.MethodsThe study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis.ConclusionPRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population

Clinical efficacy of osimertinib for a patient with ileus due to peritoneal carcinomatosis.

We report a patient of stage IV lung adenocarcinoma who developed ileus due to peritoneal carcinomatosis. We placed an ileus tube and started an oral intake of osimertinib. Within one month, the tumor had shrunk, and the ileus was controlled

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function