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

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): effects of lowered serum zinc level on the toxicity

Introduction. We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. Material and methods. Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1β as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. Results. Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1β, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1β-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. Conclusions. These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat

Silicosis, caused by the inhalation of crystalline silicon dioxide or silica, is one of the most severe occupational diseases. Persistent inflammation and progressive massive pulmonary fibrosis are the most common histological changes caused by silicosis. Association of epithelial-mesenchymal transition (EMT) of hyperplastic type II epithelial cells with the fibrotic events of pulmonary fibrosis has been suggested in in vitro silica-exposed cultured cell models, patients with idiopathic pulmonary fibrosis, and bleomycin-induced experimental models. Histological features of EMT, however, are not fully described in silicotic lungs in in vivo. The purpose of this study was to demonstrate EMT of hyperplastic type II epithelial cells in the developmental process of progressive massive pulmonary fibrosis in the lungs of rats exposed to silica. F344 female rats were intratracheally instilled with 20 mg of crystalline silica (Min-U-Sil-5), followed by sacrifice at 1, 3, 6, and 12 months after instillation. Fibrosis, characterized by the formation of silicotic nodules, progressive massive fibrosis, and diffuse interstitial fibrosis, was observed in the lungs of the treated rats; the effects of fibrosis intensified in a time-dependent manner. Hyperplasia of the type II epithelial cells, observed in the massive fibrotic lesions, dominated in the lungs of rats at 6 and 12 months after the treatment. Immunohistochemistry of the serial sections of the lung tissues demonstrated positive labeling for cytokeratin, vimentin, and α-smooth muscle actin in spindle cells close to the foci of hyperplasia of type II epithelial cells. Spindle cells, which exhibited features of both epithelial cells and fibroblasts, were also demonstrated with bundles of collagen fibers in the fibrotic lesions, using electron microscopy. Increased expression of TGF-β was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-β expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis