Imaging of Cardiomyopathy

Background: In cardiomyopathy, 99mTc-MIBI washout can reflect mitochondrial dysfunction and late gadolinium enhancement (LGE) on cardiac magnetic imaging (MRI) is associated with tissue fibrosis. We sought to determine the relationship between 99mTc-MIBI uptake, 99mTc-MIBI washout, and LGE on MRI in patients with cardiomyopathy. Methods: Twenty-one patients underwent rest myocardial perfusion scintigraphy at 45 minutes (early) and 4 hours (delayed) after intravenous 99mTc-MIBI administration and cardiac MRI. We assessed myocardial perfusion, 99mTc-MIBI washout, and LGE. We divided the left ventricle (LV) wall into 16 segments using a polar map. Then, we classified each segment into 5 groups according to 99mTc-MIBI uptake in early-rest images and washout. Additionally, we created a contingency table based on LGE presence/absence in the groups. Results: We evaluated 336 segments in 21 patients. 99mTc-MIBI uptake was decreased in 168 segments in the early-rest 99mTc-MIBI images. 99mTc-MIBI washout was observed in 108 segments with either normal perfusion or reduced perfusion in the early-rest 99mTc-MIBI images. LGE was positive in 104 segments. A contingency table analysis with Fisher’s exact test showed that LGE was observed significantly more frequently in the segments with decreased 99mTc-MIBI uptake (p < 0.001). In segments without a decreased 99mTc-MIBI uptake, there was a significant correlation between increased 99mTc-MIBI washout and the presence of LGE (p = 0.033). Conclusions: In cardiomyopathy, the mitochondrial dysfunction in the early stage is shown as 99mTc-MIBI washout, and fibrotic changes in the myocardium in advanced stages are shown as LGE on cardiac MRI. The severity of myocardial damage and the clinical stage of cardiomyopathy can be evaluated using multimodal imaging

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1 beta-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1 beta-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States（Ⅹ）

This short paper reports on the 10th overseas teaching practicum in the United States by 8 graduate students of Hiroshima University， Japan， partly organized by Hiroshima University Global Partnership School Center (GPSC). This year marks the 10-year anniversary of this project since its start. This year’s participants were students of Graduate School of Education and Graduate School for International Development and Cooperation (IDEC). They observed and conducted lessons in English in four local public schools in North Carolina. This project had the following three aims: 1) to self-develop practical instructional competence by teaching pupils with different cultural backgrounds; 2) to enhance the abilities in developing teaching materials through hands-on teaching experiences in English; and 3) to acquire the abilities to design， implement and evaluate programs for promoting global partnership. Like previous years， their teachings were very positively covered by the local newspapers and websites. Later， the project was followed by cross-cultural field study visits to NC State Capitol， Raleigh and the U.S. Capitol， Washington， D.C. It is hoped that this intensive experience will raise the prospective teachers’ global awareness and confidence in teaching

Examination of Pyridazine as a Possible Scaffold for Nucleophilic Catalysis

Pyridazines with amino groups positioned para to each aromatic ring nitrogen and fixed in six-membered rings were prepared. The representative symmetric amino <i>N</i>-Et derivative was found to slightly exceed DMAP in catalytic activity in the acetylation reaction of a tertiary alcohol in C₆D₆. Nucleophilicity eclipsing that of DMAP was established in competitive reactions using phenacyl bromide as the electrophile, and the unsymmetric <i>N</i>-Et derivative was revealed to have even higher nucleophilicity

25-ヒドロキシビタミンＤ-1α-水酸化酵素は異所性石灰化を誘導する

Vascular calcification is an important pathogenesis related to cardiovascular disease and high mortality rate in chronic kidney disease (CKD) patients. It has been well-known that hyper­phosphatemia induces osteochondrogenic transition of vascular smooth muscle cells (VSMCs) resulting ectopic calcification in aortic media, cardiac valve, and kidney. However, the detailed mechanism of the ectopic calcification has been not clarified yet. Here, we found that the co-localization of CYP27B1 with the calcified lesions of aorta and arteries in kidney of klotho mutant (kl/kl) mice, and then investigated the role of CYP27B1 in the mineralization of the VSMCs. Under high phosphate condition, overexpression of CYP27B1 induced calcification and osteocalcin mRNA expression in the VSMCs. Inversely, siRNA-CYP27B1 inhibited high phosphate-induced calcification of the VSMCs. We also found that the accumulated CYP27B1 protein was glycosylated in the kidney of kl/kl mice. Therefore, overexpression of CYP27B1-N310A and CYP27B1-T439A, which are a mutation for N-linked glycosylation site (N310A) and a mutation for O-linked glycosylation site (T439A) in CYP27B1, decreased calcium deposition and expression of RUNX2 induced by high phosphate medium in VSMCs compared with wild-type CYP27B1. These results suggest that extra-renal expression of glycosylated CYP27B1 would be required for ectopic calcification of VSMCs under hyperphosphatemia

Comparison of INTREPID® balanced and hybrid tips on anterior capsule rupture in ex vivo porcine eyes.

Phacoemulsification has emerged as the global standard for cataract surgery, and various novel methods, tools, and agents have promoted surgical efficiency and reduced complications. Conventionally, the phaco tip, which cleaves and aspirates the cataractous lens, has been mainly constructed of metal. In this study, the risk of anterior capsule rupture was evaluated under conditions of different power modes, longitudinal (Mode-L), torsional (Mode-T), or both (Mode-LT), and different aspiration powers (0 or 200 mmHg), using a traditional metal phaco tip (Group-M) or a new phaco tip with a high-strength polymer overmold on the needle edge (Group-P), which was developed to reduce the risk of capsule rupture. One hundred twenty porcine eyes were used for experiments within a setting of typical human physiological intraocular pressure. We found that Group-M showed capsule rupture with a smaller ultrasound power than did Group-P, regardless of power mode or aspiration power. In Group-M, there was no significant difference in risk of capsule rupture among power modes, however in Group-P, capsule rupture was least likely to occur with Mode-T. These results provide useful information for inexperienced ophthalmologists to improve surgical safety

Tsukamurella pulmonis central venous catheter infection mimicking proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis

A 40-year-old Japanese woman, who underwent total thyroidectomy, had suffered from repeated episodes of fever and microscopic hematuria for 3 years, which had started 3 months after central venous port catheter insertion. On admission, she had malaise and low-grade fever, and was found to have microscopic hematuria, urinary red blood cell casts, multiple pulmonary nodules, and positivity of proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA), which were suggestive to the presence of ANCA-associated small vessel vasculitis. However, her blood culture and subsequent gene analysis revealed the positivity of Tsukamurella pulmonis, and she was diagnosed with Tsukamurella pulmonis bacteremia accompanying PR3-ANCA positivity. Her condition improved after the removal of the catheter and antibiotic treatment. Tsukamurella species are categorized to the order Actinomycetales and can be misidentified as other Actinomycetales without genetic analyses. This case illustrates that chronic Tsukamurella pulmonis infection can cause ANCA production and nephritis, which mimics ANCA-associated vasculitis. Thus, it is critical to diagnose these cases correctly to avoid misdiagnosis and inappropriate treatment, such as immunosuppressive treatment