Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Hydrophilic statin suppresses vein graft intimal hyperplasia via endothelial cell-tropic Rho-kinase inhibition

BackgroundRecent studies suggest that statins can protect the vasculature in a manner that is independent of their lipid-lowering activity through inhibition of the small guanosine triphosphate-binding protein, Rho, and Rho-associated kinase. Little information is available on the inhibitory effect of statins on vein graft intimal hyperplasia, the main cause of late graft failure after bypass grafting. We therefore examined the effects of a hydrophilic statin on vein graft intimal hyperplasia in vivo and Rho-kinase activity in vitro.MethodsIn the first experiment, rabbits were randomized to a control group (n = 7) that was fed regular rabbit chow or to a pravastatin group (n = 7) that was fed regular rabbit chow supplemented with 10 mg/kg pravastatin sodium. The branches of the jugular vein were ligated and an approximately 3-cm segment of the jugular vein was taken for an autologous reversed-vein graft. The carotid artery was cut and replaced with the harvested autologous jugular vein. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. In the second experiment, human umbilical vein endothelial cells and vascular smooth muscle cells were cultured and then treated with 1 μmol/L and 30 μmol/L pravastatin for 24 hours and harvested. Immunoblotting was performed on the resulting precipitates. Quantitative evaluation of phosphorylated myosin binding subunit and endothelial nitric oxide synthase was performed by densitometric analysis.ResultsWe demonstrated that oral administration of the hydrophilic statin pravastatin to normocholesterolemic rabbits inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (pravastatin group, 39.5 ± 3.5 μm vs control group, 64.0 ± 7.1 μm; n = 7; P < .05) and suppressed cell proliferation and apoptosis in the neointima 2 weeks after implantation. In addition, we found that pravastatin inhibited Rho-kinase activity and accelerated endothelial nitric oxide synthase expression in human umbilical vein endothelial cells but did not inhibit Rho-kinase activity in vascular smooth muscle cells.ConclusionsThese novel findings clearly demonstrate that a hydrophilic statin can suppress intimal hyperplasia of the vein graft in vivo and also show endothelial cell-tropic inhibition of Rho-kinase in vitro. Furthermore, these results strongly support the clinical use of hydrophilic statins to prevent intimal hyperplasia of the vein graft after bypass grafting.Clinical RelevanceLate graft failure caused by neointimal hyperplasia limits the efficacy of vein grafting. Various treatments were examined to reduce neointimal hyperplasia, but a standard clinical treatment has not yet been established. We report here the inhibitory effect of pravastatin on the development of vein graft intimal hyperplasia. In addition, we demonstrate that pravastatin showed endothelial cell-tropic benefits through both the inhibition of Rho-kinase activity and acceleration of eNOS expression in vitro. Because the clinical benefits and safety of pravastatin have been established to a certain extent through long-term clinical usage, pravastatin may soon become standard treatment after vein bypass grafting

Oseltamivir (Tamiflu®)-induced pneumonia

SummaryWe report the first case of oseltamivir-induced pneumonia. A 50-year-old man was diagnosed with influenza and prescribed oseltamivir. He had a persistent high fever, and developed a productive cough with peripheral blood eosinophilia and his chest radiograph showed ground glass opacity. Bronchoalveolar lavage fluid and histological findings obtained from transbronchial lung biopsy suggested eosinophilic pneumonia with component of cryptogenic organizing pneumonia. Drug lymphocyte stimulation test against oseltamivir was positive. In spite of discontinuation of oseltamivir, his condition did not ameliorate. He was treated with prednisolone for oseltamivir-induced lung injury and the symptoms improved immediately. We should recognize oseltamivir-induced pneumonia as a differential diagnosis in the case of developing pneumonia following treatment with oseltamivir

Spicule Dynamics over Plage Region

We studied spicular jets over a plage area and derived their dynamic characteristics using Hinode Solar Optical Telescope (SOT) high-resolution images. The target plage region was near the west limb of the solar disk. This location permitted us to study the dynamics of spicular jets without the overlapping effect of spicular structures along the line of sight. In this work, to increase the ease with which we can identify spicules on the disk, we applied the image processing method `MadMax' developed by Koutchmy et al. (1989). It enhances fine, slender structures (like jets), over a diffuse background. We identified 169 spicules over the target plage. This sample permits us to derive statistically reliable results regarding spicular dynamics. The properties of plage spicules can be summarized as follows: (1) In a plage area, we clearly identified spicular jet features. (2) They were shorter in length than the quiet region limb spicules, and followed ballistic motion under constant deceleration. (3) The majority (80%) of the plage spicules showed the cycle of rise and retreat, while 10% of them faded out without a complete retreat phase. (4) The deceleration of the spicule was proportional to the velocity of ejection (i.e. the initial velocity).Comment: 12 pages, 9 figures, accepted for publication in PAS

Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data

SummaryCellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data