Gas Embolism Caused by Portal Vein Gas: Case Report and Literature Review

Introduction: We describe a case of pulmonary gas embolism caused by portal vein gas (PVG) observed using echocardiography. Echography revealed gas flowing through the hepatic vein, inferior vena cava, right atrium, and right ventricle, as well as pulmonary hypertension. The patient was diagnosed as having pulmonary gas embolism caused by PVG. Objective: We consider PVG routes to pulmonary circulation, diagnosis of gas embolism caused by PVG, and treatment of gas embolism caused by PVG.Methods: We reviewed reports of eight cases of gas embolism caused by PVG and compared these cases to cases of gas embolism without PVG. Results: Mortality of gas embolism caused by PVG was 67%, positive blood culture was observed in six cases, and pulmonary edema was seen in three cases. PVG initially excites microbubble formation, which causes tissue damage in the liver and liver abscess. A large volume of PVG causes portal obstruction. As a result, portal hypertension, a portosystemic shunt or gastrointestinal congestion can occur. PVG can travel to the systemic vein through the liver or portosystemic shunt without anomaly and cause pulmonary gas embolism, followed by arterial embolism. In this environment, sepsis easily occurs. Echocardiography is useful for diagnosis of gas embolism caused by PVG, but the gas can be seen intermittently. The view of pulmonary edema is important for pulmonary gas embolism caused by PVG. Conclusion: It is important to treat the underlying disease, but PVG must be considered and treated as the gas embolism’s source

Nutritional sources of meio- and macrofauna at hydrothermal vents and adjacent areas: Natural-abundance radiocarbon and stable isotope analyses

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nomaki, H., Uejima, Y., Ogawa, N. O., Yamane, M., Watanabe, H. K., Senokuchi, R., Bernhard, J. M., Kitahashi, T., Miyairi, Y., Yokoyama, Y., Ohkouchi, N., & Shimanaga, M. Nutritional sources of meio- and macrofauna at hydrothermal vents and adjacent areas: Natural-abundance radiocarbon and stable isotope analyses. Marine Ecology Progress Series, 622, (2019): 49-65, doi:10.3354/meps13053.Deep-sea hydrothermal vents host unique marine ecosystems that rely on organic matter produced by chemoautotrophic microbes together with phytodetritus. Although meiofauna can be abundant at such vents, the small size of meiofauna limits studies on nutritional sources. Here we investigated dietary sources of meio- and macrofauna at hydrothermal vent fields in the western North Pacific using stable carbon and nitrogen isotope ratios (δ13C, δ15N) and natural-abundance radiocarbon (Δ14C). Bacterial mats and Paralvinella spp. (polychaetes) collected from hydrothermal vent chimneys were enriched in 13C (up to -10‰) and depleted in 14C (-700 to -580‰). The δ13C and Δ14C values of dirivultid copepods, endemic to hydrothermal vent chimneys, were -11‰ and -661‰, respectively, and were similar to the values in the bacterial mats and Paralvinella spp. but distinct from those of nearby non-vent sediments (δ13C: ~-24‰) and water-column plankton (Δ14C: ~40‰). In contrast, δ13C values of nematodes from vent chimneys were similar to those of non-vent sites (ca. -25‰). Results suggest that dirivultids relied on vent chimney bacterial mats as their nutritional source, whereas vent nematodes did not obtain significant nutrient amounts from the chemolithoautotrophic microbes. The Δ14C values of Neoverruca intermedia (vent barnacle) suggest they gain nutrition from chemoautotrophic microbes, but the source of inorganic carbon was diluted with bottom water much more than those of the Paralvinella habitat, reflecting Neoverruca’s more distant distribution from active venting. The combination of stable and radioisotope analyses on hydrothermal vent organisms provides valuable information on their nutritional sources and, hence, their adaptive ecology to chemosynthesis-based ecosystems.We are grateful to the crews and scientists of the R/V ‘Natsushima’ and the ROV ‘Hyper-Dolphin’ of the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) during the NT12-10, NT13-09 and NT14-06 cruises, and the R/V ‘Kaimei’ and the KM-ROV of JAMSTEC during the KM-ROV training cruise. We thank Yuki Iwadate for her help on sample preparations and 2 anonymous reviewers and the editor, who provided helpful comments on an earlier version of this manuscript. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Scientific Research C 26440246 to M.S.), the Japan Society for the Promotion of Science (Invitational fellowships for research in Japan, S14032 to J.M.B.), the WHOI Robert W. Morse Chair for Excellence in Oceanography, and The Investment in Science Fund at WHOI

Mitochondrial dysfunction and increased reactive oxygen species impair insulin secretion in sphingomyelin synthase 1-null Mice

Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic β-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic β-cells.Masato Yano, Ken Watanabe, Tadashi Yamamoto, Kazutaka Ikeda, Takafumi Senokuchi, Meihong Lu, Tsuyoshi Kadomatsu, Hiroto Tsukano, Masahito Ikawa, Masaru Okabe, Shohei Yamaoka, Toshiro Okazaki, Hisanori Umehara, Tomomi Gotoh, Wen-Jie Song, Koichi Node, Ryo Taguchi, Kazuya Yamagata, Yuichi Oike, Mitochondrial Dysfunction and Increased Reactive Oxygen Species Impair Insulin Secretion in Sphingomyelin Synthase 1-null Mice, Journal of Biological Chemistry, Volume 286, Issue 5, 2011, Pages 3992-4002, ISSN 0021-9258, https://doi.org/10.1074/jbc.M110.179176

Study Design of a Phase II Clinical Trial to Assess the Efficacy and Safety of Eperisone in Japanese Type 2 Diabetes Patients with Risk and Non-risk Alleles of CDKAL1

Genetic variation in Cdk5 Regulatory Associated Protein 1-Like 1 (CDKAL1) is associated with the development of type 2 diabetes (T2D). Dysfunction of CDKAL1 impairs the translation of proinsulin, which leads to glucose intolerance. Eperisone, an antispasmodic agent, has been shown to ameliorate glucose intolerance in Cdkal1-deficient mice. We have launched a phase II clinical study to investigate the potential anti-diabetic effect of eperisone in T2D patients carrying risk or non-risk alleles of CDKAL1. The primary endpoint is the change of hemoglobin A1c (HbA1c) levels. We also examined whether the efficacy of eperisone in T2D patients is associated with CDKAL1 activity

A pivotal role for interleuking-4 in Atorvastatin-associated neuroprotection in rat brain.

noInflammatory changes, characterized by an increase in pro-inflammatory cytokine production and up-regulation of the corresponding signaling pathways, have been described in the brains of aged rats and rats treated with the potent immune modulatory molecule lipopolysaccharide (LPS). These changes have been coupled with a deficit in long-term potentiation (LTP) in hippocampus. The evidence suggests that anti-inflammatory agents, which attenuate the LPS-induced and age-associated increase in hippocampal interleukin-1ß (IL-1ß) concentration, lead to restoration of LTP. Here we report that atorvastatin, a member of the family of agents that act as inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, exerts powerful anti-inflammatory effects in brain and that these effects are mediated by IL-4 and independent of its cholesterol-lowering actions. Treatment of rats with atorvastatin increased IL-4 concentration in hippocampal tissue prepared from LPS-treated and aged rats and abrogated the age-related and LPS-induced increases in pro-inflammatory cytokines, interferon-¿ (IFN¿) and IL-1ß, and the accompanying deficit in LTP. The effect of atorvastatin on the LPS-induced increases in IFN¿ and IL-1ß was absent in tissue prepared from IL-4¿/¿ mice. The increase in IL-1ß in LPS-treated and aged rats is associated with increased microglial activation, assessed by analysis of major histocompatibility complex II expression, and the evidence suggests that IFN¿ may trigger this activation. We propose that the primary effect of atorvastatin is to increase IL-4, which antagonizes the effects of IFN¿, the associated increase in microglial activation, and the subsequent cascade of events

Forkhead Transcription Factors (FoxOs) Promote Apoptosis of Insulin-Resistant Macrophages During Cholesterol-Induced Endoplasmic Reticulum Stress

OBJECTIVE—Endoplasmic reticulum stress increases macrophage apoptosis, contributing to the complications of atherosclerosis. Insulin-resistant macrophages are more susceptible to endoplasmic reticulum stress–associated apoptosis probably contributing to macrophage death and necrotic core formation in atherosclerotic plaques in type 2 diabetes. However, the molecular mechanisms of increased apoptosis in insulin-resistant macrophages remain unclear

DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties