Serial changes in anxiety levels related to corticosteroid use: A single-center prospective study.

Patients with autoimmune diseases treated with corticosteroids sometimes display feelings of anxiety regarding corticosteroid use. In this single-center prospective study, we aimed to evaluate the serial changes in anxiety levels related to corticosteroid use in 18 patients with autoimmune diseases. The degree of anxiety toward corticosteroid use was assessed using the visual analogue scale. Comprehension of drug characteristics and use was assessed using the Likert scale. To assess the patients' levels of depression and anxiety we used the State-Trait Anxiety Inventory. These surveys were conducted immediately before the initiation of corticosteroid therapy and just before discharge from the hospital. We observed a decrease in anxiety levels related to corticosteroid use and State-Trait Anxiety Inventory scores before discharge. However, we did not detect a correlation between these score changes. Additionally, we found that patients who had a poor understanding of the drugs showed little or no changes in their anxiety levels related to corticosteroid use at discharge. These results suggest that some aspects of anxiety related to corticosteroids might be groundless and substantiated by assumptions without a complete understanding of corticosteroid functioning. Patient education regarding corticosteroid use may lead to reductions in anxiety levels and improvement in quality of life of the patients.

Glomerulonephritis and Interstitial Nephritis Originating from Vasculitis of the Interlobular Arteries of the Kidney in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis. Patients often present with peripheral neuropathy and purpura, suggesting impairment of small vessels, especially capillaries. However, medium-sized vessels and small vessels with a vascular diameter larger than that of capillaries may also be impaired, causing atypical findings. We report a case of EGPA treated with corticosteroids, cyclophosphamide, and mepolizumab. Renal biopsy revealed vasculitis of the interlobular arteries as the cause of glomerulonephritis and interstitial nephritis. This case suggests the importance of considering vessels upstream of capillaries dominant EGPA as a differential diagnosis in patients with eosinophilia.

Anti-neutrophil cytoplasmic antibody-associated vasculitis complicated with diffuse alveolar haemorrhage and central nervous system vasculitis.

Diffuse alveolar haemorrhage and central nervous system vasculitis are life-threatening complications of anti-neutrophil cytoplasmic antibody-associated vasculitis. The simultaneous occurrence of diffuse alveolar haemorrhage and central nervous system vasculitis is a rare presentation of antibody-associated vasculitis. Its diagnosis by histopathology is difficult because biopsy is difficult to perform, and urgent treatment is needed. We report a case of a Japanese man with diffuse alveolar haemorrhage and central nervous system vasculitis associated with antibody-associated vasculitis. New classification criteria may be needed for diffuse alveolar haemorrhage and central nervous system vasculitis associated with systemic vasculitis. When antibiotic-resistant atypical bilateral pneumonia is noted in the acute phase of a cerebral stroke, with elements suggestive of vasculitis, clinicians should be aware that diffuse alveolar haemorrhage and central nervous system vasculitis may occur simultaneously.

Establishment of a reborn MMV-microarray technology: realization of microbiome analysis and other hitherto inaccessible technologies.

BACKGROUND: With the accelerating development of bioscience, the problem of research cost has become important. We previously devised and developed a novel concept microarray with manageable volumes (MMV) using a soft gel. It demonstrated the great potential of the MMV technology with the examples of 1024-parallel-cell culture and PCR experiments. However, its full potential failed to be expressed, owing to the nature of the material used for the MMV chip. RESULTS: In the present study, by developing plastic-based MMVs and associated technologies, we introduced novel technologies such as C2D2P (in which the cells in each well are converted from DNA to protein in 1024-parallel), NGS-non-dependent microbiome analysis, and other powerful applications. CONCLUSIONS: The reborn MMV-microarray technology has proven to be highly efficient and cost-effective (with approximately 100-fold cost reduction) and enables us to realize hitherto unattainable technologies.

Tongue muscle-derived stem cells express connexin 43 and improve cardiac remodeling and survival after myocardial infarction in mice.

BACKGROUND: Cell transplantation therapy for heart failure is hindered by poor differentiation into cardiomyocytes and arrhythmias caused by the poor expression of connexin 43 (Cx43). A new stem cell source for cardiac regeneration is needed. METHODS AND RESULTS: Tongue muscle-derived Sca-1(+) cells (TDSCs) were isolated from normal and green fluorescence protein (GFP)-transgenic mouse tongues using surface antigen Sca-1. Cardiomyogenic differentiation was confirmed by measuring the calcium transient and the expression of cardiac-specific genes. The formation of gap junctions was confirmed by the expression of Cx43 and the dye transfer method. The contraction of regenerated cells was demonstrated by the calcium transients. GFP mouse-derived TDSCs were transplanted into hearts in a model of acute myocardial infarction. Three months after transplantation, LV remodeling was attenuated and the survival rate was improved compared with the control group. CONCLUSIONS: TDSCs form gap junctions and improve cardiac function and long-term survival after myocardial infarction.

Effect of a contrast agent on long-term renal function and the efficacy of prophylactic hemodiafiltration.

BACKGROUND: There have been few studies regarding the effect of contrast agent on long-term renal function and, moreover, there are still many uncertainties regarding the efficacy of prophylactic hemodiafiltration (HDF) for contrast-induced nephropathy. METHODS AND RESULTS: Patients with heart disease and a serum creatinine level (Scr) of less than 1.2 mg/dl were classified as Group N (20 patients), those with Scr of at least 1.2 mg/dl but less than 2.0 mg/dl were classified as Group D1 (10 patients without HDF) and D2 (15 patients with HDF), respectively. For each group, a linear regression of 1/Scr was extrapolated using Scr measured more than 3 times during each period that was longer than 3 months before and after use of a contrast agent, and the slopes (constant k) thereof were compared. To remove the contrast agent, HDF was performed for 2 h. Group D1 showed a significant decrease in the k after use of the contrast agent (p<0.05). CONCLUSION: Use of a contrast agent is an independent factor that promotes chronic renal insufficiency and prophylactic HDF was found to effectively improve the long-term outcome of decreased renal function.

Pleiotropic effects of the beta-adrenoceptor blocker carvedilol on calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes.

Carvedilol is a nonselective beta-adrenoceptor blocker with multiple pleiotropic actions. A recent clinical study suggested that carvedilol may be superior to other beta-adrenoceptor blockers in the treatment of heart failure. Despite numerous investigations, the underlying mechanisms of carvedilol on improving heart failure are yet to be fully established. The purpose of this study is to clarify the pleiotropic effect of carvedilol on cytosolic and mitochondrial calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes. Carvedilol (10 microM), but not metoprolol (10 microM), reduced H2O2 (100 microM)-induced apoptosis in neonatal rat cardiomyocytes. During the process, changes in cytosolic calcium concentration ([Ca2+]i) and mitochondrial calcium concentration ([Ca2+]m) and mitochondrial membrane potential (DeltaPsim) were measured by fluorescent probes [Fluo-3/acetoxymethyl ester (AM), Rhod-2/AM, and tetramethylrhodamine ethyl ester, respectively] and imaged by laser confocal microscopy. The results showed that H2O2 caused [Ca2]m overload first, followed by [Ca2+]i overload, leading to DeltaPsim dissipation and the induction of apoptosis. Carvedilol (10 microM) significantly delayed these processes and reduced apoptosis. These effects were not observed with other beta-adrenoceptor blockers (metoprolol, atenolol, and propranolol) or with a combination of the alpha (phentolamine)- and the beta-adrenoceptor blocker. The antioxidant N-acetyl-L-cysteine (NAC, 5 mM) and the combination of NAC and propranolol (10 microM) showed an effect similar to that of carvedilol. Therefore, the effect of carvedilol on H2O2-induced changes in [Ca2+]m, [Ca2+]i, and DeltaPsi(m) is independent of alpha- and beta-adrenoceptors but is probably dependent on the antioxidant effect.

Carvedilol inhibits mitochondrial oxygen consumption and superoxide production during calcium overload in isolated heart mitochondria.

BACKGROUND: The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca(2+) overload was investigated. METHODS AND RESULTS: The mitochondrial oxygen consumption (mVO(2)) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca(2+) overload from 10 to 100 micromol/L augmented mVO(2) was from 527+/-139 to 671 +/-138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 micromol/L), but not by metoprolol (100 micromol/L). Ca(2+) overload augmented the ROS production upon complex I injury (9.7+/-1.2 to 11.4+/-1.4 nmol/mg, p<0.05). Carvedilol dose-dependently suppressed this ROS production, whereas metoprolol did not. CONCLUSIONS: Carvedilol, but not metoprolol, was thus found to inhibit the calcium-dependent augmentation of mVO(2) and ROS production upon complex I injury. This new effect of carvedilol might partly explain the beneficial effect of carvedilol for the treatment of heart failure.

NO donor-activated PKC-delta plays a pivotal role in ischemic myocardial protection through accelerated opening of mitochondrial K-ATP channels.

Nitric oxide (NO) can activate protein kinase C (PKC) and the activation of mitochondrial ATP-sensitive potassium (K-ATP) channels is cardioprotective. However, interactions among NO, PKC, and mitochondrial K-ATP channels remain vague. To clarify the cardioprotective mechanism induced by nicorandil, we compared its ability to activate PKC isoforms with that of the mitochondrial K-ATP channel opener, diazoxide. We induced myocardial infarction in rats by 30 minutes of ischemia followed by reperfusion, then assessed the infarct size 3 weeks later. We also examined the translocation of PKC isoforms in the isolated perfused rat heart. Nicorandil and diazoxide reduced infarct size, and the effect of nicorandil, but not of diazoxide attenuated by the PKC inhibitor, chelerythrine, or by the NO quencher, carboxy PTIO. Immunoblotting revealed that nicorandil translocated PKC-delta to the mitochondria, and that this was inhibited by carboxy PTIO. The protective effect of nicorandil against myocardial infarction partly depended on the translocation of PKC-delta to the mitochondria, which we attributed to the NO donor effect of nicorandil. The PKC-delta- dependent activation of mitochondrial K-ATP channel opening might be synergistic with its direct effect, making nicorandil an efficient opener of such channels.