The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice

Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice

Inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>It has been reported that immunoglobulin G4-related systemic disease can spread to nearly every organ, and often presents as an inflammatory mass or masses at those sites. In the kidney, this disease is often diagnosed after a radical or partial nephrectomy following the discovery of an inflammatory mass which is often suspected to be a malignant tumor. Here, we present a rare case of inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease, which were diagnosed by computed tomography-guided biopsies.</p> <p>Case presentation</p> <p>A 54-year-old Japanese man was referred to our hospital with suspected bilateral renal cancer, multiple lung metastases and autoimmune pancreatitis. His serum immunoglobulin G4 level was high. We used computed tomography-guided biopsies and histopathological examinations of the biopsied specimens to diagnose the tumors as immunoglobulin G4-related bilateral renal and lung inflammatory pseudotumors. Our patient was treated with oral prednisolone, and after one month of treatment, contrast-enhanced computed tomography demonstrated a general improvement, as noted by a reduction in size of the masses.</p> <p>Conclusion</p> <p>Renal masses that are formed due to immunoglobulin G4-related disease require comprehensive diagnosis to prevent unnecessary surgical resections from being performed. Further consideration should be paid to immunoglobulin G4-related diseases in the future.</p

99mTc-DTPA腎摂取率法を用いたGFR測定による分腎機能評価

金沢大学大学院医学系研究

腎摂取率法を用いたGFR,ERPF,FF,算出による分腎機能評価

金沢大学大学院医学系研究

Feasibility of classical secondary hormonal therapies prior to docetaxel therapy in Japanese patients with castration-resistant prostate cancer: Multicenter retrospective study

BackgroundWe retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy.MethodsThe cases of 73 CRPC patients who underwent docetaxel therapy in 2005–2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate.ResultsOf the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053).ConclusionThe induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases

Mixed alkali-ion transport and storage in atomic-disordered honeycomb layered NaKNi2TeO6

Honeycomb layered oxides constitute an emerging class of materials that show interesting physicochemical and electrochemical properties. However, the development of these materials is still limited. Here, we report the combined use of alkali atoms (Na and K) to produce a mixed-alkali honeycomb layered oxide material, namely, NaKNi2TeO6. Via transmission electron microscopy measurements, we reveal the local atomic structural disorders characterised by aperiodic stacking and incoherency in the alternating arrangement of Na and K atoms. We also investigate the possibility of mixed electrochemical transport and storage of Na+ and K+ ions in NaKNi2TeO6. In particular, we report an average discharge cell voltage of about 4 V and a specific capacity of around 80 mAh g–1 at low specific currents (i.e., &lt; 10 mA g–1) when a NaKNi2TeO6-based positive electrode is combined with a room-temperature NaK liquid alloy negative electrode using an ionic liquid-based electrolyte solution. These results represent a step towards the use of tailored cathode active materials for “dendrite-free” electrochemical energy storage systems exploiting room-temperature liquid alkali metal alloy materials

The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice

Curcumin is a naturally occurring p300-histone acetyltransferase (p300-HAT) inhibitor that suppresses cardiomyocyte hypertrophy and the development of heart failure in experimental animal models. To enhance the therapeutic potential of curcumin against heart failure, we produced a series of synthetic curcumin analogues and investigated their inhibitory activity against p300-HAT. The compound with the strongest activity was further evaluated to determine its effects on cardiomyocyte hypertrophy and pressure overload-induced heart failure in mice. We synthesised five synthetic curcumin analogues and found that a compound we have named GO-Y030 most strongly inhibited p300-HAT activity. Furthermore, 1 μM GO-Y030, in a manner equivalent to 10 µM curcumin, suppressed phenylephrine-induced hypertrophic responses in cultured cardiomyocytes. In mice undergoing transverse aortic constriction surgery, administration of GO-Y030 at a mere 1% of an equivalently-effective dose of curcumin significantly attenuated cardiac hypertrophy and systolic dysfunction. In addition, this low dose of GO-Y030 almost completely blocked histone H3K9 acetylation and eliminated left ventricular fibrosis. A low dose of the synthetic curcumin analogue GO-Y030 effectively inhibits p300-HAT activity and markedly suppresses the development of heart failure in mice

Pulmonary MR angiography and perfusion imaging—A review of methods and applications

The pulmonary vasculature and its role in perfusion and gas exchange is an important consideration in many conditions of the lung and heart. Currently the mainstay of imaging of the vasculature and perfusion of the lungs lies with CT and nuclear medicine perfusion scans, both of which require ionizing radiation exposure. Improvements in MRI techniques have increased the use of MRI in pulmonary vascular imaging. Here we review MRI methods for imaging the pulmonary vasculature and pulmonary perfusion, both using contrast enhanced and non-contrast enhanced methodology. In many centres pulmonary MR angiography and dynamic contrast enhanced perfusion MRI are now well established in the routine workflow of patients particularly with pulmonary hypertension and thromboembolic disease. However, these imaging modalities offer exciting new directions for future research and clinical use in other respiratory diseases where consideration of pulmonary perfusion and gas exchange can provide insight in to pathophysiology