Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

Purpose Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. 123I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced 123I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate 123I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with 15O-water positron emission tomography (PET). Methods We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent 123I-BMIPP single-photon emission computed tomography (SPECT) and 15O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. 123I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. 123I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. Results The numbers of segments with 123I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93±0.25, 0.86±0.21, 0.97±0.30, and 0.99±0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76±1.29, 1.84±0.74, 1.37±0.39, and 1.08±0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01±1.38, 2.20±0.95, 1.44±0.22, and 1.10±0.26, respectively. As 123I-BMIPP uptake declined, hyperemic MBF and MFR decreased. Conclusion In chronic stable angina without previous infarction, reduced 123I-BMIPP uptake implies decreased MFR

Oxygen reduction at negatively charged iron porphyrins heat-treated and bridged by alkaline-earth metal ions

金沢大学理工研究域物質化学系An ordered network of tetrasodium tetra(4-sulphonatophenyl)porphyrin iron(III) chloride (FeTPPS4Na4), which exhibited a higher catalytic activity for oxygen reduction than Co and Ir(CO)TPPS 4Na4, was fabricated by complexation with alkaline-earth metal ions. Heat treatment of these complexes enhanced their catalytic activity with the highest performance observed with Ba2+-FeTPPS4. The onset potential for oxygen reduction (Eonset) was 720mVvs. Ag|AgCl, which is almost the same as that for Pt-impregnated carbon black. The number of electrons, n, transferred during oxygen reduction at a Ba2+- FeTPPS4-coated electrode, as determined by rotating ring-disc experiments, was 3.9 and suggests that oxygen was reduced to water. A neutral solution of FeTPPS4Na4 was acidified by the addition of barium ion, and the elemental ratio Fe:S:Ba in the resulting Ba 2+-FeTPPS4 complex was approximately 1:4:2.5. This suggests the formation of a highly ordered network with Fe sites bridged with barium ions in addition to the normal salt bridges between sulphonates. Catalytic oxidation reactions with nitric oxide and nitrite ion as the intermediate at the heat-treated Ba2+-FeTPPS4 indicate the formation of Fe(IV) and Fe(IV) π-cation radicals or Fe(V). The agreement between the potential of Fe(IV) π-cation radical formation and E onset suggests that the redox cycle of the Fe(III)/Fe(IV) π-cation radical provides a sufficient driving force for the observed 4-electron reduction of oxygen at the heat-treated Ba2+-FeTPPS4 electrode. © 2010 Elsevier Ltd. All rights reserved

Automated classification of pulmonary nodules through a retrospective analysis of conventional CT and two-phase PET images in patients undergoing biopsy

Objective(s): Positron emission tomography/computed tomography (PET/CT) examination is commonly used for the evaluation of pulmonary nodules since it provides both anatomical and functional information. However, given the dependence of this evaluation on physician’s subjective judgment, the results could be variable. The purpose of this study was to develop an automated scheme for the classification of pulmonary nodules using early and delayed phase PET/ CT and conventional CT images.Methods: We analysed 36 early and delayed phase PET/CT images in patients who underwent both PET/CT scan and lung biopsy, following bronchoscopy. In addition, conventional CT images at maximal inspiration were analysed. The images consisted of 18 malignant and 18 benign nodules. For the classification scheme, 25 types of shape and functional features were first calculated from the images. The random forest algorithm, which is a machine learning technique, was used for classification.Results: The evaluation of the characteristic features and classification accuracy was accomplished using collected images. There was a significant difference between the characteristic features of benign and malignant nodules with regard to standardised uptake value and texture. In terms of classification performance, 94.4% of the malignant nodules were identified correctly assuming that 72.2% of the benign nodules were diagnosed accurately. The accuracy rate of benign nodule detection by means of CT plus two-phase PET images was 44.4% and 11.1% higher than those obtained by CT images alone and CT plus early phase PET images, respectively.Conclusion: Based on the findings, the proposed method may be useful to improve the accuracy of malignancy analysis