Less subclinical atherosclerosis in Japanese men in Japan than in white men in the United States in the post World-War-II birth cohort

PubMed Central

Sekikawa, Akira; Ueshima, Hirotsugu; Kadowaki, Takashi; El-Saed, Aiman; Okamura, Tomonori; Takamiya, Tomoko; Kashiwagi, Atsunori; Edmundowicz, Daniel; Murata, Kiyoshi; Sutton-Tyrrell, Kim; Maegawa, Hiroshi; Evans, Rhobert W.; Kita, Yoshikuni; Kuller, Lewis H.

2013-01-01

Coronary heart disease (CHD) incidence and mortality remain very low in Japan despite major dietary changes and increases in CHD risk factors that should have resulted in substantial increase in CHD rates (Japanese paradox). Primary genetic effects are unlikely, given the substantial increase in CHD in migrant Japanese to the U.S. For men aged 40–49, levels of total cholesterol and blood pressure have been similar in Japan and the U.S. throughout their lifetime. The authors tested the hypothesis that levels of subclinical atherosclerosis, coronary artery calcification and intima-media thickness of the carotid artery (IMT), in men aged 40–49 are similar in Japan and the U.S. The authors conducted a population-based study of 493 randomly-selected men: 250 men in Kusatsu, Shiga, Japan, and 243 white men in Allegheny County, Pennsylvania, U.S. in 2002–2005. The Japanese had a less favorable profile of many risk factors than the whites. Prevalence ratio for the presence of coronary calcium score ≥10 in the Japanese compared to the whites was 0.52 (95% CI, 0.35, 0.76). Mean (SE) IMT was significantly lower in the Japanese (0.616 (0.005) versus 0.672 (0.005) mm, p<0.01). Both associations remained significant after adjusting for risk factors. The findings warrant further investigations. PMID:17244636

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition).

PubMed

Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Kanamoto, Naotetsu; Otani, Hajime; Furukawa, Yasushi; Teramukai, Satoshi; Akamizu, Takashi

2016-12-30

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline.

PubMed

Yamashita, Yasuyuki; Murayama, Sadayuki; Okada, Masahiro; Watanabe, Yoshiyuki; Kataoka, Masako; Kaji, Yasushi; Imamura, Keiko; Takehara, Yasuo; Hayashi, Hiromitsu; Ohno, Kazuko; Awai, Kazuo; Hirai, Toshinori; Kojima, Kazuyuki; Sakai, Shuji; Matsunaga, Naofumi; Murakami, Takamichi; Yoshimitsu, Kengo; Gabata, Toshifumi; Matsuzaki, Kenji; Tohno, Eriko; Kawahara, Yasuhiro; Nakayama, Takeo; Monzawa, Shuichi; Takahashi, Satoru

2016-01-01

Diagnostic imaging is undoubtedly important in modern medicine, and final clinical decisions are often made based on it. Fortunately, Japan has the highest numbers of diagnostic imaging instruments, such as CT and MRI devices, and boasts easy access to them as well as a high level of diagnostic accuracy. In consequence, a very large number of imaging examinations are performed, but diagnostic instruments are installed in so many medical facilities that expert management of these examinations tends to be insufficient. Particularly, in order to avoid risks, clinicians have recently become indifferent to indications of imaging modalities and tend to rely on CT or MRI resulting in increasing the number of imaging examinations in Japan. This is a serious problem from the viewpoints of avoidance of unnecessary exposure and medical economy. Under these circumstances, the Japan Radiological Society and Japanese College of Radiology jointly initiated the preparation of new guidelines for diagnostic imaging. However, the field of diagnostic imaging is extremely wide, and it is impossible to cover all diseases. Therefore, in drafting the guidelines, we selected important diseases and focused on "showing evidence and suggestions in the form of clinical questions (CQs)" concerning clinically encountered questions and "describing routine imaging techniques presently considered to be standards to guarantee the quality of imaging examinations". In so doing, we adhered to the basic principles of assuming the readers to be "radiologists specializing in diagnostic imaging", "simultaneously respecting the global standards and attending to the situation in Japan", and "making the guidelines consistent with those of other scientific societies related to imaging". As a result, the guidelines became the largest ever, consisting of 152 CQs, nine areas of imaging techniques, and seven reviews, but no other guidelines in the world summarize problems concerning diagnostic imaging in the form

Constructing Advantage in the Knowledge Society: Roles of Universities Reconsidered--The Case of Japan

ERIC Educational Resources Information Center

Kitagawa, Fumi

2005-01-01

Based on an analysis of policy contexts in several OECD countries, this article examines the rapidly changing policy environment in Japan exemplified by the 2004 transformation of national universities into "incorporated" entities. The role of universities in the knowledge society is examined in light of the emergence of new research and…

Civil Society, State, and Institutions for Young Children in Modern Japan: The Initial Years

ERIC Educational Resources Information Center

Uno, Kathleen

2009-01-01

Research on the history of children and childhood in modern Japan (1868-1945) reveals that issues related to civil society, state, and the establishment of institutions for young children can be explored beyond the transatlantic world. In this essay, after briefly surveying historiography, a few basic terms, and earlier patterns of state and…

Activities for the Promotion of Gender Equality in Japan—Physical Society of Japan

NASA Astrophysics Data System (ADS)

Agui, Akane; Tanida, Kiyoshi; Torikai, Eiko

2005-10-01

The Gender Equality Promotion Committee of the Physical Society of Japan (JPS) was established as a result of the First International IUPAP Conference on Women in Physics (Paris, 2002). It is a gender-balanced team of 12 full members and a group of net-commentators. The former chairperson of the committee, Masako Bando, was selected to be the president of JPS between September 2006 and August 2007. Based on the survey on the present status of the gender equality and the research environment of the JPS members in 2001, JPS advanced two recommendations to the governmental authorities, academic institutes, and organizations: for flexible childcare supports and for improved research granting systems for post-doctoral fellows and part-time researchers in August 2003. Now these activities have become nationwide with the establishment in October 2002 of the Japan Inter-Society Liaison Association Committee for Promoting Equal Participation of Men and Women in Science and Engineering (EPMEWSE). It has 44 member societies, including 19 observers, from various academic fields. An extended survey was carried out by EPMEWSE in November 2003; 20,000 respondents revealed diverse visions of scientists and engineers. These activities effectively help foster public understanding and awareness of the state of women in physics, especially among policy-making authorities. In 2005 the Cabinet is drawing up two Basic Plans for 2006-2010: the Science and Technology Basic Plan for the third term and the Basic Plan for the Gender-Equal Society for the second term. To attract girls into science and engineering, JPS is organizing the Girls Science Summer School to be held in August 2005 in collaboration with the National Women Education Center and EPMEWSE.

[Recommendations of the European Society of Cardiology and the European Atherosclerosis Society on Cardiovascular Disease Prevention and Management of Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment (2016): Basic S.G.

PubMed

Bubnova, M G; Kukharchuk, V V

2017-03-01

This review summarizes the main provisions of the new, issued in 2016, recommendations of the European Society of Cardiology and Atherosclerosis Society in cooperation with the European Association on Cardiovascular Prevention and Rehabilitation on Cardiovascular disease prevention and Management of dyslipidemia. In these recommendations, the following trends can be traced distinctly: priority in primary prevention is given to non-drug methods of influence; targets of hypolipidemic therapy are identified not only for low density lipoprotein (LDL) cholesterol (CH), but also for non-high density lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In the field of therapy, in which statins remain the main tool of correction of hyperlipidemia, it is recommended to more widely resort to the use of combination therapy, especially in cases of familial hypercholesterolemia or intolerance to statins; introduction of a new class of drugs- inhibitors of proprotein convertase subtilisin/kexin type 9 makes it possible to further reduce the level of LDLCH, lipoprotein(a) more than 60%. Regarding the wider application of these drugs there are issues related to the relatively limited experience of their use and the lack of data on long-term results and the incidence of side effects. Much attention is paid to more active correction of dyslipidemia in elderly patients, patients with chronic renal failure, diabetes, and several other diseases. The emergence of new European recommendations will undoubtedly serve as a stimulus to the revision of the Russian recommendations, which remain unchanged from 2012.

Opportunistic bilateral salpingectomy during benign gynecological surgery for ovarian cancer prevention: a survey of Gynecologic Oncology Committee of Japan Society of Obstetrics and Gynecology.

PubMed

Mikami, Mikio; Nagase, Satoru; Yamagami, Wataru; Ushijma, Kimio; Tashiro, Hironori; Katabuchi, Hidetaka

2017-07-01

Recent evidence has supported the concept that epithelial ovarian cancer (EOC) arises from the cells of the fallopian tube or endometrium. This study investigated current practice in Japan with respect to performing opportunistic bilateral salpingectomy (OBS) during gynecological surgery for benign disease for Ovarian Cancer Prevention. We mailed a questionnaire to 767 hospitals and clinics, comprising 628 accredited training institutions of the Japan Society of Obstetrics and Gynecology (JSOG), Japan Society of Gynecologic Oncology (JSGO), or Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) and 139 private institutions with at least one JSGOE-certified licensed gynecologic laparoscopist. Among the 767 institutions, 444 (57.9%) provided responses, including 91 (20.6%) that were both JSGOE and JSGO accredited, 71 (16.0%) that were only JSGO accredited, 88 (19.8%) that were only JSGOE accredited, and 194 (43.7%) that were unaccredited. It was found that awareness and performance of OBS largely depended on the JSGO and/or JSGOE accreditation status. OBS was only performed at 54.0% of responding institutions and just 6.8% of the institutions were willing to participate in randomized controlled trials to validate this method for reducing the incidence of ovarian cancer. The JSOG Gynecologic Tumor Committee will announce its opinion on salpingectomy for ovarian cancer prevention to all JSOG members and will develop a system for monitoring the number of OBS procedures in Japan. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Atherosclerosis in ancient Egyptian mummies: the Horus study.

PubMed

Allam, Adel H; Thompson, Randall C; Wann, L Samuel; Miyamoto, Michael I; Nur El-Din, Abd El-Halim; El-Maksoud, Gomaa Abd; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; El-Rahman Amer, Hany Abd; Sutherland, M Linda; Sutherland, James D; Thomas, Gregory S

2011-04-01

The purpose of this study was to determine whether ancient Egyptians had atherosclerosis. The worldwide burden of atherosclerotic disease continues to rise and parallels the spread of diet, lifestyles, and environmental risk factors associated with the developed world. It is tempting to conclude that atherosclerotic cardiovascular disease is exclusively a disease of modern society and did not affect our ancient ancestors. We performed whole body, multislice computed tomography scanning on 52 ancient Egyptian mummies from the Middle Kingdom to the Greco-Roman period to identify cardiovascular structures and arterial calcifications. We interpreted images by consensus reading of 7 imaging physicians, and collected demographic data from historical and museum records. We estimated age at the time of death from the computed tomography skeletal evaluation. Forty-four of 52 mummies had identifiable cardiovascular (CV) structures, and 20 of these had either definite atherosclerosis (defined as calcification within the wall of an identifiable artery, n = 12) or probable atherosclerosis (defined as calcifications along the expected course of an artery, n = 8). Calcifications were found in the aorta as well as the coronary, carotid, iliac, femoral, and peripheral leg arteries. The 20 mummies with definite or probable atherosclerosis were older at time of death (mean age 45.1 ± 9.2 years) than the mummies with CV tissue but no atherosclerosis (mean age 34.5 ± 11.8 years, p < 0.002). Two mummies had evidence of severe arterial atherosclerosis with calcifications in virtually every arterial bed. Definite coronary atherosclerosis was present in 2 mummies, including a princess who lived between 1550 and 1580 BCE. This finding represents the earliest documentation of coronary atherosclerosis in a human. Definite or probable atherosclerosis was present in mummies who lived during virtually every era of ancient Egypt represented in this study, a time span of >2,000 years

Toward a tobacco-free society in Japan.

PubMed

Tokunaga, H

2001-08-01

Tobacco is one of the major preventable causes of death and disability. This is widely known in both Japan and the USA, and although the smoking rate in the USA is decreasing, that in Japan remains high. The tobacco histories of these two countries, which provide the background to this difference, are herein compared. The antismoking movement is becoming more vociferous in both countries. Publicity regarding of the dangers of smoking, warning signs on tobacco packages, the introduction of antismoking devices, a ban on commercials for tobacco-related products on TV and the radio, no-smoking seats on airplanes, and litigation against the tobacco industry have all been introduced. However, major differences remain between these two countries. The tobacco industry in the USA has been a private company since it was first established. Courts have ordered the tobacco industry to pay compensation for damage to health resulting from tobacco. Smoking is strictly restricted inside buildings. Advertisements for nicotine gum and nicotine patches and reports on the dangers of smoking are regularly broadcast. In the case of Japan, the government at first nationalized the tobacco industry, and then made it a private company, although the government still holds two-thirds of its stock. Moreover, it established the Tobacco Business Law to support the company. The main purpose of antismoking campaigns in Japan is a partial ban on smoking. On the basis of these differences between the two countries regarding the history of tobacco, the antismoking movement in Japan has yet to choose which path to take.

[Homozygous familial hypercholesterolaemia: Spanish adaptation of the position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Consensus document of the Spanish Society of Arteriosclerosis (SEA) and Familial Hypercholesterolaemia Foundation (FHF)].

PubMed

Ascaso, Juan F; Mata, Pedro; Arbona, Cristina; Civeira, Fernando; Valdivielso, Pedro; Masana, Luis

2015-01-01

Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening disease characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). The Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) has recently published a clinical guide to diagnose and manage HoFH (Eur Heart J. 2014;35:2146-57). Both the Spanish Society of Atherosclerosis (SEA) and Familial Hypercholesterolaemia Foundation (FHF) consider this European Consensus document of great value and utility. However, there are particularities in our country which advise to have a Spanish adaptation of the European HoFH document in order to approximate this clinical guide to our environment. In Spain, chronic treatment with statins, ezetimibe and resins (colesevelam) has a reduced contribution in the National Health System (NHS) and is one of the few European countries where LDL apheresis is included in the Basic Service Portfolio coverage. This Spanish document also includes clinical experience in the management of these patients in our country. The Drafting Committee emphasizes the need for early identification of HoFH patients, prompt referral to specialized units, and an early and appropriate treatment. These recommendations will provide a guidance for HoFH patient management in Spain. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer.

PubMed

Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

2017-01-01

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Japan: Super-Aging Society Preparing for the Future

ERIC Educational Resources Information Center

Muramatsu, Naoko; Akiyama, Hiroko

2011-01-01

Japan has the highest proportion of older adults in the world. Aging is not only an immediate personal issue but also a salient factor in crucial public policies, such as pensions, health, and long-term care. The Great East Japan Earthquake, tsunami, and nuclear power plant disaster of March 2011 has highlighted current and emerging issues of a…

Resveratrol, Wine, and Atherosclerosis

PubMed Central

Prasad, Kailash

2012-01-01

This review emphasizes the effects of resveratrol on factors involved in the mechanism of atherosclerosis and risk factors for atherosclerosis. The effects of wine and resveratrol on atherosclerosis are also discussed. Resveratrol is a potent antioxidant and an anti-inflammatory agent. It reduces the expression of cell adhesion molecules, monocyte colony stimulating factors, matrix metalloproteinases, and growth factors; and inhibits platelet aggregation and vascular smooth muscle cell proliferation. It reduces the serum levels of total cholesterol, triglycerides (TG), and raises high-density lipoprotein cholesterol, inhibits expression of C-reactive protein and lowers the levels of advanced glycation end products and its receptor in the vascular tissue. It lowers the risk factors for plaque rupture. Epidemiological data show that moderate consumption of alcohol has an inverse association with carotid atherosclerosis while high consumption has a positive association with carotid atherosclerosis. Wine reduces the extent of atherosclerosis in animal model. The antiatherosclerotic effect of wine is mainly due to it resveratrol content. Resveratrol reduces the extent of atherosclerosis in animal model of atherosclerosis (apolipoprotein [Apo] E-deficient and Apo E−/−/low-density lipoprotein receptor-deficient mice and macrophage). In rabbit model of atherosclerosis, both reduction and acceleration of atherosclerosis have been reported with resveratrol. There are no data for regression and slowing of progression of atherosclerosis. Robust clinical trials for suppression of atherosclerosis are lacking. In conclusion, resveratrol has potential but experimental studies in depth and robust clinical trials are lacking for this agent to be of any value in the primary and secondary prevention of coronary and peripheral artery disease. PMID:23450206

Status of diabetes treatment in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

PubMed

Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

2014-01-01

The Japan Diabetes Society (JDS) has recommended target levels of glycemic control based on guidelines for the management of diabetes mellitus (DM). The Japan Society of Ningen Dock created a database of subjects receiving annual health examinations nationwide. Using this database, we evaluated the efficacy of current treatment for patients with DM based on the JDS recommendations. This multicenter, retrospective study was conducted using data obtained from 21 institutions across Japan. In order to assess the level of glycemic control in the Japanese population, we analyzed previously obtained measurements of HbA1c in 7,180 patients 20 to 79 years of age (mean age: 57.9 ± 8.7 years, 6,007 men and 1,173 women) taking DM medications. According to the JDS guidelines, 44.7% of the patients fell into the good glycemic control group, with an HbA1c level of <7.0% while 22.4% were classified into the poor glycemic control group, with an HbA1c level of ≥ 8.0%. The control of other arteriosclerosis risk factors deteriorated as the glycemic control deteriorated. Lifestyle factors were strongly found to be associated with glycemic control in the patients receiving DM treatment. Aggressive lifestyle modification is needed to improve glycemic control in patients with DM.

Analysis of gender-based differences among surgeons in Japan: results of a survey conducted by the Japan Surgical Society. Part 1: Working style.

PubMed

Kawase, Kazumi; Nomura, Kyoko; Tominaga, Ryuji; Iwase, Hirotaka; Ogawa, Tomoko; Shibasaki, Ikuko; Shimada, Mitsuo; Taguchi, Tomoaki; Takeshita, Emiko; Tomizawa, Yasuko; Nomura, Sachiyo; Hanazaki, Kazuhiro; Hanashi, Tomoko; Yamashita, Hiroko; Kokudo, Norihiro; Maeda, Kotaro

2018-01-01

To assess the working styles of men and women working as surgeons in Japan. In July, 2014, the Japan Surgical Society invited all their members (n = 29,861), through an internet campaign, to participate in a nationwide survey of surgeons. The items investigated in this descriptive study included demographic information and working styles, based on a questionnaire. In total, 6211 surgeons participated (response rate 20.8%, 5586 men and 625 women). The largest age stratum was 40-49 years for men and 30-39 years for women. Overall, respondents identified their labor contract, including salary and work hours, as the highest priority for improvement. Women with children were more likely to be part-time employees, work fewer hours, and take fewer house calls/on-calls than their male counterparts. Moreover, women of all ages earned a lower annual income than men, irrespective of whether they had children. Perception scores for discrimination related to work and promotion were significantly higher among women than men (p < 0.01 and p = 0.011, respectively). A significant difference in working style was observed between men and women working as surgeons in Japan.

Learning from Each Other. The Official Proceedings of the International Symposium of Japan-America Societies (1st, Honolulu, Hawaii, June 18-21, 1995).

ERIC Educational Resources Information Center

Correa, E. Shan, Ed.

This book provides a compilation of addresses and panel presentations from the 1995 International Symposium of Japan-America Societies. Twenty-nine eminent speakers and presenters, authorities on topics ranging from economics to education, shared dialogue with delegates who gathered for the first-ever meeting of members of Japan-America Societies…

Public Outreach Program of the Planetary society of Japan

NASA Astrophysics Data System (ADS)

Iyori, Tasuku

2002-01-01

The Planetary Society of Japan, TPS/J, was founded on October 6, 1999 as the first international wing of The Planetary Society. The Society's objectives are to support exploration of the solar system and search for extraterrestrial life at the grass-roots level in terms of enhancing Japanese people's concern and interest in them. With close-knit relationships with the Institute of Space and Astronautical Science, ISAS, and The Planetary Society, TPS/J has been trying to fulfil its goal. Introduced below are major public outreach programs. Planetary Report in Japanese The key vehicle that reaches members. The publication is offered to members together with the English issue every two months. Reprint of Major Texts from The Planetary Report for Science Magazine Major texts from The Planetary Report are reprinted in Nature Science, the science magazine with monthly circulation of 20,000. The science monthly has been published with an aim to provide an easier access to science. Website: http://www.planetary.or.jp A mainstay of the vehicle to reach science-minded people. It covers planetary news on a weekly basis, basics of the solar system and space exploring missions. In order to obtain support of many more people, the weekly email magazine is also provided. It has been enjoying outstanding popularity among subscribers thanks to inspiring commentaries by Dr. Yasunori Matogawa, the professor of ISAS. Public Outreach Events TPS/J's first activity of this kind was its participation in the renowned open-house event at ISAS last August. The one-day event has attracted 20,000 visitors every summer. TPS/J joined the one-day event with the Red Rover, Red Rover project for children, exhibition of winning entries of the international space art contest and introduction of SETI@home. TPS/J also participated in a couple of other planetary events, sponsored by local authorities. TPS/J will continue to have an opportunity to get involved in these public events Tie-up with the

Atherosclerosis (image)

MedlinePlus

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities.

PubMed

Pircher, Andreas; Treps, Lucas; Bodrug, Natalia; Carmeliet, Peter

2016-10-01

Atherosclerosis is a leading cause of morbidity and mortality in Western society. Despite improved insight into disease pathogenesis and therapeutic options, additional treatment strategies are required. Emerging evidence highlights the relevance of endothelial cell (EC) metabolism for angiogenesis, and indicates that EC metabolism is perturbed when ECs become dysfunctional to promote atherogenesis. In this review, we overview the latest insights on EC metabolism and discuss current knowledge on how atherosclerosis deregulates EC metabolism, and how maladaptation of deregulated EC metabolism can contribute to atherosclerosis progression. We will also highlight possible therapeutic avenues, based on targeting EC metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Japan as the front-runner of super-aged societies: Perspectives from medicine and medical care in Japan.

PubMed

Arai, Hidenori; Ouchi, Yasuyoshi; Toba, Kenji; Endo, Tamao; Shimokado, Kentaro; Tsubota, Kazuo; Matsuo, Seiichi; Mori, Hidezo; Yumura, Wako; Yokode, Masayuki; Rakugi, Hiromi; Ohshima, Shinichi

2015-06-01

The demographic structure of a country changes dramatically with increasing trends toward general population aging and declining birth rates. In Japan, the percentage of the elderly population (aged ≥65 years) reached 25% in 2013; it is expected to exceed 30% in 2025 and reach 39.9% in 2060. The national total population has been decreasing steadily since its peak reached in 2008, and it is expected to fall to the order of 80 million in 2060. Of the total population, those aged ≥75 years accounted for 12.3% as of 2013, and this is expected to reach 26.9% in 2060. As the demographic structure changes, the disease structure changes, and therefore the medical care demand changes. To accommodate the medical care demand changes, it is necessary to secure a system for providing medical care. Japan has thus far attained remarkable achievements in medical care, seeking a better prognosis for survival; however, its medical care demand is anticipated to change both qualitatively and quantitatively. As diseases in the elderly, particularly in the old-old population, are often intractable, conventional medical care must be upgraded to one suitable for an aged society. What is required to this end is a shift from "cure-seeking medical care" focusing on disease treatment on an organ-specific basis to "cure and support-seeking medical care" with treatments reprioritized to maximize the quality of life (QOL) for the patient, or a change from "hospital-centered medical care" to "community-oriented medical care" in correlation with nursing care and welfare. (1)  Necessity for a paradigm shift to "cure-and-support seeking medical care" In addition to the process of aging with functional deterioration of multiple organs, the elderly often suffer from systemically disordering diseases, such as lifestyle-related diseases, as well as geriatric syndrome and daily activity dysfunction; therefore, integrated and comprehensive medical care is required. In addition, with regard to

Japan's funding supremo

NASA Astrophysics Data System (ADS)

Durrani, Matin

2018-02-01

Yasuhiro Iye, a condensed-matter physicist who is executive director of the Japan Society for the Promotion of Science, talks to Matin Durrani about the pressures and challenges facing Japan's biggest funding agency

Nomenclature of primary amenorrhea: A proposal document of the Japan Society of Obstetrics and Gynecology committee for the redefinition of primary amenorrhea.

PubMed

Shozu, Makio; Ishikawa, Hiroshi; Horikawa, Reiko; Sakakibara, Hideya; Izumi, Shun-Ichiro; Ohba, Takashi; Hirota, Yasushi; Ogata, Tsutomu; Osuga, Yutaka; Kugu, Koji

2017-11-01

The aim of this study was to provide medical terms to describe the condition of a girl who should be evaluated for primary amenorrhea in order to facilitate intervention at an appropriate time. We performed a literature and clinical guidelines search for recent practices with regard to menarche and discussed relevant cases that had been experienced by committee members. Additionally, we theoretically reviewed medical terms defined in the Glossary Book of Obstetrics and Gynecology in Japan (Japan Society of Obstetrics and Gynecology, 3rd edition). The committee for the redefinition of primary amenorrhea proposed the introduction of two terms and the deletion of one term that had been defined by the Japan Society of Obstetrics and Gynecology, instead of changing the age definition of primary amenorrhea. 'Delayed menarche' was introduced to describe a condition in which a girl has never experienced cyclic menstruation (menarche) by 15-17 years of age. 'Late menarche' was also introduced to describe a condition in which a girl has experienced menarche at 15 years of age or older. 'Delayed menstruation,' which was defined as a condition in which a girl experiences menarche at 15-18 years of age, was deleted. The new terms 'delayed menarche' and 'late menarche' were introduced, and the term 'delayed menstruation' was deleted. The new system might help in the early detection and appropriate treatment of primary amenorrhea. © 2017 Japan Society of Obstetrics and Gynecology.

[Biochemical markers and physiological tests of atherosclerosis--changes and usefulness of markers in anti-atherosclerotic therapy].

PubMed

Kanoh, Yuhsaku

2011-01-01

As a result of the aging of the Japanese population and westernization of the diet, atherosclerotic diseases such as ischemic heart diseases and cerebrovascular disorders are now the leading causes (2nd and 3rd, respectively) of death in Japan. Furthermore, advances in medical technology have made Japanese some of the longest-lived citizens in the world, and increasing health care costs have become an object of public concern. Therefore, the prevention and treatment of atherosclerosis that causes these ischemic organ dysfunctions is indispensable. In Japan, diagnostic criteria were established for metabolic syndrome as one of the health care cost-containment policies, and the importance of controlling the blood lipid and glucose levels and blood pressure was defined in 2005. Furthermore, persons enrolled in the health insurance system aged between 40 and 74 years have been obliged to receive a specified health check for the prevention of metabolic syndrome since April 2008. The health check includes: a medical interview; anthropometry (height, body weight, BMI, and abdominal circumference); physical examination; blood pressure; and 8 laboratory tests (neutral fat, HDL-cholesterol, LDL-cholesterol, AST, ALT, gamma-GT, fasting blood glucose [or HbAlc], and urinary protein and glucose). In fact, the specified health check is becoming one of the enlightening activities concerning the maintenance and promotion of health for staff of Kitasato University Hospital. Recently, on the other hand, the mechanism in which inflammatory reactions are involved in atherosclerosis has been elucidated, and atherosclerosis is thought to be a chronic inflammatory disease. Furthermore, the advances in laboratory test methods have made the measurement of various sensitive markers for inflammation possible. In this presentation, we would like to explain the efficient application of biochemical markers and rapid physiological tests for the pathological diagnosis of atherosclerosis. We would

Activities of the Japan Society of Applied Physics Committee for Diversity Promotion in Science and Technology (abstract)

NASA Astrophysics Data System (ADS)

Nishitani-Gamo, Mikka

2009-04-01

Since 2001, the Japan Society of Applied Physics (JSAP) Committee for Diversity Promotion in Science and Technology has worked to promote gender equality, both within and between academic societies, and in society as a whole. Main activities of the Committee are: (1) organizing symposia and informal meetings during domestic JSAP conferences to stimulate discussion and raise awareness; (2) encouraging young researchers in pursuit of their careers through the newly designed "career-explorer mark;" (3) offering childcare at biannual JSAP conferences; and (4) helping future scientists and engineers prepare to lead the fields of science and technology on a global level with the creation of an educational roadmap. In this presentation, recent activities of the JSAP Committee are introduced and reviewed.

Analysis of gender-based differences among surgeons in Japan: results of a survey conducted by the Japan Surgical Society. Part. 2: personal life.

PubMed

Kawase, Kazumi; Nomura, Kyoko; Tominaga, Ryuji; Iwase, Hirotaka; Ogawa, Tomoko; Shibasaki, Ikuko; Shimada, Mitsuo; Taguchi, Tomoaki; Takeshita, Emiko; Tomizawa, Yasuko; Nomura, Sachiyo; Hanazaki, Kazuhiro; Hanashi, Tomoko; Yamashita, Hiroko; Kokudo, Norihiro; Maeda, Kotaro

2018-03-01

To assess the true conditions and perceptions of the personal lives of men and women working as surgeons in Japan. In 2014, all e-mail subscribed members of the Japan Surgical Society (JSS, n = 29,861) were invited to complete a web-based survey. The questions covered demographic information, work environment, and personal life (including marital status, childcare, and nursing care for adult family members). In total, 6211 surgeons (5586 men and 625 women) returned the questionnaires, representing a response rate of 20.8%. Based on the questionnaire responses, surgeons generally prioritize work and spend most of their time at work, although women with children prioritize their family over work; men spend significantly fewer hours on domestic work/childcare than do their female counterparts (men 0.76 h/day vs. women 2.93 h/day, p < 0.01); and both men and women surgeons, regardless of their age or whether they have children, place more importance on the role of women in the family. The personal lives of Japanese surgeons differed significantly according to gender and whether they have children. The conservative idea that women should bear primary responsibility for the family still pertains for both men and women working as surgeons in Japan.

Contested embryonic culture in Japan--public discussion, and human embryonic stem cell research in an aging welfare society.

PubMed

Sleeboom-Faulkner, Margaret

2010-01-01

This article explores the reasons for the lack of a broad discussion on bioethical regulation of human embryonic stem cell research (hESR) in Japan and asks why scientists experience difficulties accessing resources for hESR despite the acclaimed indifference of dominant Japanese culture to embryo research. The article shows how various social actors express their views on the embryo and oocyte donation in terms of dominant Japanese culture, foiled against what is regarded as Western culture. Second, it shows how the lack of concern with hESR should be understood in the context of public health policies and communications and bioethics decision making in Japan. Finally, it interprets the meaning of the embryo in the context of Japan as an aging modern welfare society, explaining how policymakers have come to emphasize the urgency of infertility problems over issues around abortion and embryonic life.

Ageing induced vascular smooth muscle cell senescence in atherosclerosis.

PubMed

Uryga, Anna K; Bennett, Martin R

2016-04-15

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Assisted reproductive technology in Japan: a summary report for 2015 by The Ethics Committee of The Japan Society of Obstetrics and Gynecology.

PubMed

Saito, Hidekazu; Jwa, Seung Chik; Kuwahara, Akira; Saito, Kazuki; Ishikawa, Tomonori; Ishihara, Osamu; Kugu, Koji; Sawa, Rintaro; Banno, Kouji; Irahara, Minoru

2018-01-01

The Japan Society of Obstetrics and Gynecology (JSOG) implemented an assisted reproductive technology (ART) registry system in 1986. Here are reported the characteristics and treatment outcomes of ART cycles that were registered in 2015. JSOG has requested all participating ART facilities to register cycle-specific information for all ART cycles since 2007. A descriptive analysis was performed by using the registry database for 2015. In total, 424 151 cycles and 51 001 neonates (1 in 19.7 neonates born in Japan) were registered in 2015. The patients' mean age was 38.2 years (standard deviation = 4.5). Among the fresh cycles, 94 158 of 244 718 (38.5%) egg retrieval cycles were cycles with freeze-all embryos or oocytes, while fresh embryo transfer (ET) was performed in 70 254 cycles, signaling a decrease from 2014. There were 169 898 frozen-thawed ET cycles, resulting in 56 355 pregnancies and 40 599 neonates. Single ET was performed at a rate of 79.7% for fresh and 81.8% for frozen cycles and the singleton pregnancy/live birth rates were 96.9%/96.5% and 96.8%/96.4% for the respective cycles. The total ART cycles and live births resulting from ART has been increasing in Japan. Single ET was performed at a rate of almost 80% and ET cycles have shifted from fresh to frozen cycles.

Migraine and subclinical atherosclerosis in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Goulart, Alessandra C; Santos, Itamar S; Bittencourt, Márcio S; Lotufo, Paulo A; Benseñor, Isabela M

2016-08-01

The relationship between migraine and coronary heart disease (CHD) remains controversial. We aimed to investigate the association of subclinical atherosclerosis and migraine with or without aura compared to a non-migraine subgroup (reference) in a large Brazilian multicentric cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Migraine diagnostic was based on International Headache Society criteria, and aura symptoms were validated by a medical doctor in a sub-sample of the ELSA-Brasil, who also underwent coronary artery calcium score (CAC) and carotid intima-media thickness (C-IMT) evaluations. Subclinical atherosclerosis indexes (CAC and C-IMT) were analyzed as dependent variables and migraine (all, with aura, without aura) as an independent variable in the linear and multinomial logistic regression models adjusted for possible confounders. Of 3217 ELSA participants free from CVD at baseline, we found a migraine frequency of 11.9% (5.1% with aura and 6.8% without aura). Overall, migraineurs were mostly women, younger and had lower frequency of CV risk factors, such as hypertension, diabetes and low HDL-cholesterol, compared to non-migraineurs. The strongest inverse correlation between migraine and subclinical atherosclerosis was verified with CAC score. However, all associations lost their significance after multivariate adjustment. In this cross-sectional evaluation of the ELSA study, migraine was not associated with subclinical atherosclerosis, regardless of aura symptoms. © International Headache Society 2015.

BAFF Neutralization Aggravates Atherosclerosis.

PubMed

Tsiantoulas, Dimitrios; Sage, Andrew P; Göderle, Laura; Ozsvar-Kozma, Maria; Murphy, Deirdre; Porsch, Florentina; Pasterkamp, Gerard; Menche, Jörg; Schneider, Pascal; Mallat, Ziad; Binder, Christoph J

2018-06-01

Background -Atherosclerotic cardiovascular disease (heart attacks and strokes) is the major cause of death globally and is caused by the buildup of a plaque in the arterial wall. Genomic data showed that the B cell activating factor receptor (BAFFR) pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells), is a key driver of coronary heart disease. Deletion or antibody-mediated blockade of BAFFR ablates B-2 cells and decreases experimental atherosclerosis. Anti-BAFF immunotherapy is approved for treatment of autoimmune systemic lupus erythematosus and can therefore be expected to limit their associated cardiovascular risk. However, direct effects of anti-BAFF immunotherapy on atherosclerosis remain unknown. Methods -To investigate the effect of BAFF neutralization in atherosclerosis, we treated Apoe -/- and Ldlr -/- mice with a well-characterized blocking anti-BAFF antibody. Moreover, to investigate the mechanism by which BAFF impacts atherosclerosis, we studied atherosclerosis-prone mice that lack the alternative receptor for BAFF, transmembrane activator and CAML interactor (TACI). Results -We demonstrate here that anti-BAFF antibody treatment increased atherosclerosis in mice, despite efficient depletion of mature B-2 cells, suggesting a unique mechanism of action. Indeed, myeloid cell specific deletion TACI, also results in increased atherosclerosis, while B cell-specific TACI deletion had no effect. Mechanistically, BAFF-TACI signaling represses macrophage IRF7-dependent (but not NF-kB dependent) TLR9 responses including proatherogenic CXCL10 production. Conclusions -These data identify a novel B cell independent anti-inflammatory role for BAFF in atherosclerosis and may have important clinical implications.

Historical Development of Media Systems. I. Japan. Communication and Society 1.

ERIC Educational Resources Information Center

Ito, Shinichi; And Others

This report presents an insight into indigenous media forms and the introduction of modern media in Japan, and follows media development through the war and occupation to the present day. The report discusses (1) the birth of the newspaper in Japan, (2) control laws and regulations, (3) press policy under the allied forces' occupation of Japan,…

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

PubMed

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

2016-08-26

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

[Epigenetics in atherosclerosis].

PubMed

Guardiola, Montse; Vallvé, Joan C; Zaina, Silvio; Ribalta, Josep

2016-01-01

The association studies based on candidate genes carried on for decades have helped in visualizing the influence of the genetic component in complex diseases such as atherosclerosis, also showing the interaction between different genes and environmental factors. Even with all the knowledge accumulated, there is still some way to go to decipher the individual predisposition to disease, and if we consider the great influence that environmental factors play in the development and progression of atherosclerosis, epigenetics is presented as a key element in trying to expand our knowledge on individual predisposition to atherosclerosis and cardiovascular disease. Epigenetics can be described as the discipline that studies the mechanisms of transcriptional regulation, independent of changes in the sequence of DNA, and mostly induced by environmental factors. This review aims to describe what epigenetics is and how epigenetic mechanisms are involved in atherosclerosis. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Strokes Associated With Pregnancy and Puerperium: A Nationwide Study by the Japan Stroke Society.

PubMed

Yoshida, Kazumichi; Takahashi, Jun C; Takenobu, Yohei; Suzuki, Norihiro; Ogawa, Akira; Miyamoto, Susumu

2017-02-01

The incidence and cause of strokes associated with pregnancy and the puerperium are still not fully understood. The aim of this study was to characterize pregnancy-related strokes in Japan using a large-scale survey with current imaging techniques. A retrospective analysis was conducted based on clinical chart reviews in 736 stroke teaching hospitals certified by the Japan Stroke Society between 2012 and 2013, using a web-based questionnaire requesting the detailed clinical course without any personally identifying information. The collection rate of this questionnaire was 70.5%, with 151 pregnancy-associated strokes extracted. Hemorrhagic strokes were observed in 111 cases (73.5%), ischemic strokes in 37 (24.5%), and mixed type in 3 cases (2.0%). The estimated incidence of pregnancy-associated stroke was 10.2 per 100 000 deliveries. Major causes of hemorrhage were aneurysm (19.8%), arteriovenous malformation (17.1%), pregnancy-induced hypertension (11.7%), and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) (8.1%). Preexisting cerebrovascular diseases responsible for hemorrhage were detected in 59 cases (53.1%). Among the ischemic strokes, 28 (75.7%) were arterial and 9 (24.3%) were venous infarctions. The most frequent cause of arterial infarctions was reversible cerebral vasoconstriction syndrome. Hemorrhagic stroke showed much poorer prognosis than ischemic stroke. The incidence of pregnancy-associated stroke in Japan did not seem higher than that in other Asian and Western countries. The proportion of hemorrhagic stroke among Japanese women was much higher than that in white women. Preexisting cerebrovascular diseases and reversible cerebral vasoconstriction syndrome play a key role in hemorrhagic and ischemic stroke, respectively. © 2016 American Heart Association, Inc.

Configuration of Materially Retained Carbon in Our Society: A WIO-MFA-Based Approach for Japan.

PubMed

Ohno, Hajime; Sato, Hirokazu; Fukushima, Yasuhiro

2018-04-03

To achieve the goals of Paris Agreement, global society is directing much effort in substantially reducing greenhouse gas (GHG) emissions. In addition to energy-related efforts, prevention of carbon release into the atmosphere with carbon capture and storage (CCS) and/or utilization of biomass resources is considered indispensable to achieving the global objective. In this study, considering carbon-containing goods as carbon reservoirs in our society similar to forests and reservoirs enabling CCS, the flow of materially utilized carbon was quantified by input-output-based material flow analysis (IO-MFA). As a result, in 2011, 6.3 Mt-C of petroleum-derived carbon and 7.9 Mt-C of wood-derived carbon were introduced to the Japanese society as end-use products (e.g., automobiles and constructions) in various forms (e.g., plastics and synthetic rubbers). The total amount (14.2 Mt-C) corresponded to 4.1% (52.1 Mt-CO 2 ) of annual CO 2 emission in Japan in 2011. Subsequently, by referring to the technology that can treat carbon in the target forms in end-of-life products, the recoverability of carbon as a material has been discussed with respect to each form and end-use of carbon. By numerically showing the necessity and potential of implementing appropriate technologies, this study provides scientific direction for policymakers to establish a quality carbon cycle in our society.

Japan Society of Gynecologic Oncology guidelines 2013 for the treatment of uterine body neoplasms.

PubMed

Ebina, Yasuhiko; Katabuchi, Hidetaka; Mikami, Mikio; Nagase, Satoru; Yaegashi, Nobuo; Udagawa, Yasuhiro; Kato, Hidenori; Kubushiro, Kaneyuki; Takamatsu, Kiyoshi; Ino, Kazuhiko; Yoshikawa, Hiroyuki

2016-06-01

The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Current developments and clinical applications of bubble technology in Japan: a report from 85th Annual Scientific Meeting of The Japan Society of Ultrasonic in Medicine, Tokyo, 25-27 May, 2012.

PubMed

Achmad, Arifudin; Taketomi-Takahashi, Ayako; Tsushima, Yoshito

2013-06-01

The potentials of bubble technology in ultrasound has been investigated thoroughly in the last decade. Japan has entered as one of the leaders in bubble technology in ultrasound since Sonazoid (Daiichi Sankyo & GE Healthcare) was marketed in 2007. The 85th Annual Scientific Meeting of The Japan Society of Ultrasonics in Medicine held in Tokyo from May 25 to 27, 2012 is where researchers and clinicians from all over Japan presented recent advances and new developments in ultrasound in both the medical and the engineering aspects of this science. Even though bubble technology was originally developed simply to improve the conventional ultrasound imaging, recent discoveries have opened up powerful emerging applications. Bubble technology is the particular topic to be reviewed in this report, including its mechanical advances for molecular imaging, drug/gene delivery device and sonoporation up to its current clinical application for liver cancers and other liver, gastrointestinal, kidney and breast diseases.

Assessing the effect of guideline introduction on clinical practice and outcome in patients with endometrial cancer in Japan: a project of the Japan Society of Gynecologic Oncology (JSGO) guideline evaluation committee.

PubMed

Shigeta, Shogo; Nagase, Satoru; Mikami, Mikio; Ikeda, Masae; Shida, Masako; Sakaguchi, Isao; Ushioda, Norichika; Takahashi, Fumiaki; Yamagami, Wataru; Yaegashi, Nobuo; Udagawa, Yasuhiro; Katabuchi, Hidetaka

2017-11-01

The Japan Society of Gynecologic Oncology (JSGO) published the first practice guideline for endometrial cancer in 2006. The JSGO guideline evaluation committee assessed the effect of this guideline introduction on clinical practice and patient outcome using data provided by the Japan Society of Obstetrics and Gynecology (JSOG) cancer registration system. Data of patients with endometrial cancer registered between 2000 and 2012 were analyzed, and epidemiological and clinical trends were assessed. The influence of guideline introduction on survival was determined by analyzing data of patients registered between 2004 and 2009 using competing risk model. In total, 65,241 cases of endometrial cancer were registered. Total number of patients registered each year increased about 3 times in the analyzed period, and the proportion of older patients with type II endometrial cancer rapidly increased. The frequency of lymphadenectomy had decreased not only among the low-recurrence risk group but also among the intermediate- or high-recurrence risk group. Adjuvant therapy was integrated into chemotherapy (p<0.001). Overall survival did not significantly differ before and after the guideline introduction (hazard ratio [HR]=0.891; p=0.160). Additional analyses revealed patients receiving adjuvant chemotherapy showed better prognosis than those receiving adjuvant radiation therapy when limited to stage I or II (HR= 0.598; p=0.003). It was suggested that guideline introduction influenced the management of endometrial cancer at several aspects. Better organized information and continuous evaluation are necessary to understand the causal relationship between the guideline and patient outcome. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Japan as a Prototype of the "Degreeocracy" Society?

ERIC Educational Resources Information Center

Okada, Akito

2001-01-01

In Japan, the necessity of a prestigious academic degree for advancement has led to extreme educational credentialism ("degreeocracy"). Despite the assumption that educational opportunities are open to all and advancement is thus meritocratic, social class inequalities do influence access to opportunities and educational attainment.…

[Atherosclerosis in inflammatory diseases].

PubMed

Páramo, José A; Rodríguez, José A; Orbe, Josune

2007-05-19

The recognition that inflammation is a hallmark of atherosclerotic disease and its complications has led to a series of studies reporting high prevalence of atherosclerosis in chronic inflammatory diseases. Indeed, chronic immune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, are associated with proinflammation, accelerated atherosclerosis and increased incidence of cardiovascular disease. Since the susceptibility towards cardiovascular events cannot be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors, potentially important for future prevention and treatment of atherosclerosis associated with chronic inflammatory diseases.

"Psychogeritechnology" in Japan: Exemplars from a super-aged society.

PubMed

Leroi, Iracema; Watanabe, Kentaro; Hird, Nick; Sugihara, Taro

2018-05-31

flexible evaluation framework, and consideration of the "wider perspective" including safety-critical issues, ethical issues, and the relation to policy and health economics. Japan, as a rapidly ageing society, is on the forefront of developing technology to support people with dementia. The new field of psychogeritechnology must harness the potential of such developments, while furthering the methodology to implement and evaluate the changes. Copyright © 2018 John Wiley & Sons, Ltd.

Interaction between allergic asthma and atherosclerosis

PubMed Central

Liu, Conglin; Zhang, Jingying; Shi, Guo-Ping

2015-01-01

Prior studies have established an essential role of mast cells in allergic asthma and atherosclerosis. Mast cell deficiency or inactivation protects mice from allergen-induced airway hyper-responsiveness and diet-induced atherosclerosis, suggesting that mast cells share pathologic activities in both diseases. Allergic asthma and atherosclerosis are inflammatory diseases that contain similar sets of elevated numbers of inflammatory cells in addition to mast cells in the airway and arterial wall, such as macrophages, monocytes, T cells, eosinophils, and smooth muscle cells. Emerging evidence from experimental models and human studies points to a potential interaction between the two seemingly unrelated diseases. Patients or mice with allergic asthma have a high risk of developing atherosclerosis or vice versa, despite the fact that asthma is a Th2-oriented disease, whereas Th1 immunity promotes atherosclerosis. In addition to the preferred Th1/Th2 responses that may differentiate the two diseases, mast cells and many other inflammatory cells also contribute to their pathogenesis by much more than just T cell immunity. Here we summarize the different roles of airway and arterial wall inflammatory cells and vascular cells in asthma and atherosclerosis, and propose an interaction between the two diseases, although limited investigations are available to delineate the molecular and cellular mechanisms by which one disease increases the risk of the other. Results from mouse allergic asthma and atherosclerosis models and from human population studies lead to the hypothesis that patients with atherosclerosis may benefit from anti-asthmatic medications, or that the therapeutic regimens targeting atherosclerosis may also alleviate allergic asthma. PMID:26608212

Current trends in stenting for aortic coarctation in Japan: Subanalysis of Japanese Society of Pediatric Interventional Cardiology (JPIC) stent survey.

PubMed

Fujii, Takanari; Tomita, Hideshi; Otsuki, Shinichi; Kobayashi, Toshiki; Ono, Yasuo; Yazaki, Satoshi; Kim, Sung-Hae; Nakanishi, Toshio

2016-02-01

Stenting for aortic coarctation (CoA) has been accepted as an alternative to surgery for adolescents and adults, but only a few case have been reported in Japan. The purpose of this study was to provide a detailed review of Japanese national data on stenting of CoA. In a subanalysis of the data of the Japanese Society of Pediatric Interventional Cardiology (JPIC), we identified 35 patients with CoA who underwent stenting. We analyzed procedural characteristics including factors that may have contributed to hemodynamic effectiveness, and we compared these parameters between the patients under and over 15 years of age. The mean ratio of balloon diameter/minimum lumen diameter (MLD) before stenting was 1.7 (range, 1.2-4.0), and the mean difference between the balloon diameter and the reference vessel diameter was -0.7 mm (range, -5.0 to +3.0 mm). %MLD/balloon diameter, which was defined as [(balloon diameter - MLD after dilation)/balloon diameter] × 100 predicted achievement of <10 mmHg pressure gradient after stenting. The sensitivity and the specificity of its cut-off of 7% were 93% and 47% (AUC, 0.7), respectively. There was no statistical difference between the two age groups under and over 15 years of age, in terms of selection criteria of stent size, balloon type used for deployment and immediate angiographic and hemodynamic result. Stenting for CoA was clinically effective with few complications in Japan, even in patients not fully grown. © 2015 Japan Pediatric Society.

Sleep Characteristics and Carotid Atherosclerosis Among Midlife Women.

PubMed

Thurston, Rebecca C; Chang, Yuefang; von Känel, Roland; Barinas-Mitchell, Emma; Jennings, J Richard; Hall, Martica H; Santoro, Nanette; Buysse, Daniel J; Matthews, Karen A

2017-02-01

Midlife, which encompasses the menopause transition in women, can be a time of disrupted sleep and accelerated atherosclerosis accumulation. Short or poor sleep quality has been associated with cardiovascular disease (CVD) risk; few studies have investigated relations among midlife women. We tested whether shorter actigraphy sleep time or poorer subjective sleep quality was associated with carotid atherosclerosis among midlife women. Two hundred fifty-six peri- and postmenopausal women aged 40-60 years completed 3 days of wrist actigraphy, hot flash monitoring, questionnaires (Pittsburgh Sleep Quality Index [PSQI], Berlin), a blood draw, and carotid ultrasound [intima media thickness (IMT), plaque]. Associations of objective (actigraphy) and subjective (PSQI) sleep with IMT/plaque were tested in regression models (covariates: age, race, education, body mass index, blood pressure, lipids, insulin resistance, medications, snoring, depressive symptoms, sleep hot flashes, and estradiol). Shorter objective sleep time was associated with higher odds of carotid plaque (for each hour shorter sleep, plaque score ≥ 2, odds ratio (OR) [95% confidence interval, CI] = 1.58 [1.11-2.27], p = .01; plaque score = 1, OR [95% CI] = 0.95 [0.68-1.32], p = .75, vs. no plaque, multivariable). Poorer subjective sleep quality was associated with higher mean IMT [β, b (standard error, SE) = 0.004 (0.002), p = .03], maximal IMT [b (SE) = 0.009 (0.003), p = .005], and plaque [plaque score ≥ 2, OR (95% CI) = 1.23 (1.09-1.40), p = .001; score = 1, OR (95% CI) = 1.06 (0.93-1.21), p = .37, vs. no plaque] in multivariable models. Findings persisted additionally adjusting for sleep hot flashes and estradiol. Shorter actigraphy-assessed sleep time and poorer subjective sleep quality were associated with increased carotid atherosclerosis among midlife women. Associations persisted adjusting for CVD risk factors, hot flashes, and estradiol. © Sleep Research Society 2016. Published by Oxford

Ultrasound Imaging for Risk Assessment in Atherosclerosis

PubMed Central

Steinl, David C.; Kaufmann, Beat A.

2015-01-01

Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging. PMID:25938969

Histone deacetylases and atherosclerosis.

PubMed

Zheng, Xia-xia; Zhou, Tian; Wang, Xin-An; Tong, Xiao-hong; Ding, Jia-wang

2015-06-01

Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic. Accumulating evidence suggests that histone deacetylases(HDACs) play crucial roles in arteriosclerosis. This review summarizes the effect of HDACs and HDAC inhibitors(HDACi) on the progress of atherosclerosis. Copyright © 2015. Published by Elsevier Ireland Ltd.

Atherosclerosis affecting vision: therapy.

PubMed

Eggers, H

1966-05-01

The visual consequences and the pathogenesis and therapy of atherosclerosis are discussed. Atherosclerosis apparently is the result of hepatic failure to produce a stable suspension of cholesterol esters in the plasma. In some instances this represents an inherent metabolic defect. Usually it represents improper diet, namely, the excessive intake of saturated fatty acids and the inadequate intake of polyunsaturated fatty acids. Excessive ingestion of carbohydrates, insufficient physical exercise and reduced thyroid function are contributing causes. The final common denominators leading to tissue injury and destruction are vascular insufficiency and hypoxia. Hypertension is a separate disease, often concurrent with atherosclerosis. In diabetes, also a separate disease, atherosclerosis is one of the sequelae. Therapy primarily consists of the reduction or elimination of meat and milk fats from the diet, and the inclusion or increase of marine fats and vegetable oils. Simultaneously, carbohydrate intake is restricted. Adequate thyroid function, a normal hemoglobin level, and sufficient physical exercise are important. A supplementary intake of vitamins B6 and E, and of lipotropic substances is recommended.

Building a Learning Society in Japan, the Republic of Korea and Singapore. UIL Publication Series on Lifelong Learning Policies and Strategies: No. 2

ERIC Educational Resources Information Center

Yang, Jin; Yorozu, Rika

2015-01-01

Japan, the Republic of Korea and Singapore are in the process of adopting approaches that can be characterised by the terms "learning society" and "lifelong learning". This report uses case studies to present a description of the three countries' national socio-economic climates and to assess their political will and…

Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

PubMed

Stroes, Erik S; Thompson, Paul D; Corsini, Alberto; Vladutiu, Georgirene D; Raal, Frederick J; Ray, Kausik K; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M; Laufs, Ulrich; Santos, Raul D; Hegele, Robert A; Hovingh, G Kees; Leiter, Lawrence A; Mach, Francois; März, Winfried; Newman, Connie B; Wiklund, Olov; Jacobson, Terry A; Catapano, Alberico L; Chapman, M John; Ginsberg, Henry N

2015-05-01

Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

The interaction of the international society concerning kidney transplants--a consideration of diseased kidney transplants in Japan and transplant tourism over the world.

PubMed

Kokubo, Asako

2009-04-01

In November 2006 in Japan, it was detected that there were 41 cases that diseased kidneys were harvested from patients and then were transplanted to other renal failure patients. This "Diseased kidney transplant" was prohibited in Japan since 2007 because of a lot of problems. On the other hand, in Japan, although there are about 12,000 patients on a waiting list for a transplant, only 10% of those get a transplant. Recently it appears that some patients have gone overseas for kidney transplants (transplant tourism). Concerning the background of transplant tourism, the issues are three points following. First, globalization caused recipients to go abroad easier and faster. Second, transnational law is difficult to institutionalize. Third, there is economical gap in not only international but also domestic. We should discuss again diseased kidney transplant in not only professionals but also in Japanese civilized society.

Cyanotic congenital heart disease and atherosclerosis.

PubMed

Tarp, Julie Bjerre; Jensen, Annette Schophuus; Engstrøm, Thomas; Holstein-Rathlou, Niels-Henrik; Søndergaard, Lars

2017-06-01

Improved treatment options in paediatric cardiology and congenital heart surgery have resulted in an ageing population of patients with cyanotic congenital heart disease (CCHD). The risk of acquired heart disease such as atherosclerosis increases with age.Previous studies have speculated whether patients with CCHD are protected against atherosclerosis. Results have shown that the coronary arteries of patients with CCHD are free from plaques and stenosis. Decreased carotid intima-media thickness and low total plasma cholesterol may indicate a reduced risk of later development of atherosclerosis. However, the evidence is still sparse and questionable, and a reasonable explanation for the decreased risk of developing atherosclerosis in patients with CCHD is still missing.This review provides an overview of what is known about the prevalence and potential causes of the reduced risk of atherosclerosis in patients with CCHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hypolipidemic and anti-inflammatory effects of aorta and heart tissues of cattle and pigs in the atherosclerosis rat model.

PubMed

Chernukha, Irina M; Fedulova, Liliya V; Kotenkova, Elena A; Takeda, Shiro; Sakata, Ryoichi

2018-05-01

The aim of this study was to investigate the effects of aorta and heart tissues obtained from cattle and pigs on atherosclerosis disorders. Atherosclerosis model rats were provided with the respective diets consisting of aorta and heart tissues. Administration of each tissue suppressed body weight gain as compared to that of the control. In particular, the aorta tissues of pigs and cattle demonstrated significant suppressions in body weight gain in the model rats. The aorta tissues of pigs and cattle showed a significant increase and decrease in the serum high-density lipoproteins and atherogenic index, respectively, which was correlated with the increase in apolipoprotein A1. Hematological analysis revealed that aorta tissues of pigs and cattle clearly reduced the ratio of granulocytes/lymphocytes in the atherosclerosis rats. Serum vascular cellular adhesion molecule-1 levels in the atherosclerosis rats, which were administered these aorta tissues, were also significantly reduced. Additionally, there was an increase in von Willebrand factor in the rat serum. Based on the results obtained, the aorta tissues of pigs and cattle, in particular, demonstrated positive effects in the atherosclerosis rats due to the alteration of lipid metabolism and reduction in inflammation related to atherosclerosis. © 2018 Japanese Society of Animal Science.

Imaging Atherosclerosis

PubMed Central

Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A.P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.

2016-01-01

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

Oral microbiota in patients with atherosclerosis.

PubMed

Fåk, Frida; Tremaroli, Valentina; Bergström, Göran; Bäckhed, Fredrik

2015-12-01

Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) (P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga, Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis.

PubMed

Schumacher, H Christian; Meyers, Philip M; Higashida, Randall T; Derdeyn, Colin P; Lavine, Sean D; Nesbit, Gary M; Sacks, David; Rasmussen, Peter; Wechsler, Lawrence R

2010-12-01

Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis. This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of Neurolnterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebro-vascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should

Literacy in Japan.

ERIC Educational Resources Information Center

Kanaya, Toshio

1979-01-01

Examines three causes for Japan's high literacy rate: (1) emphasis on literacy in Japanese society; (2) pervasive effect of the modern Japanese school system; (3) special structural features of the Japanese language which aid in functional use. (DR)

[Transdisciplinary Approach for Sarcopenia. Sarcopenia and atherosclerosis].

PubMed

Kohara, Katsuhiko

2014-10-01

Risk factors for sarcopenia, including aging, inflammation, oxidative stress, and sedentary life style, are also known as risks for atherosclerosis. Sarcopenia and atherosclerosis relate each other. We found that sarcopenia, especially sarcopenic visceral obesity in male subjects, was associated with higher arterial stiffness and central blood pressure. We also observed that leptin resistance may underlie the link between sarcopenia, sarcopenic obesity and atherosclerosis. In epidemiological studies, it has been demonstrated sarcopenic indices were associated with cardiovascular death. These findings indicate that sarcopenia could be regarded as risk factor for atherosclerosis and cardiovascular events.

Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

PubMed

Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

2014-06-01

Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Animal Models of Atherosclerosis

PubMed Central

Getz, Godfrey S.; Reardon, Catherine A.

2012-01-01

Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits and non-human primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. While not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable. PMID:22383700

Possible roles of platelet-derived microparticles in atherosclerosis.

PubMed

Wang, Zhi-Ting; Wang, Zi; Hu, Yan-Wei

2016-05-01

Platelets and platelet-derived microparticles (PMPs) play important roles in cardiovascular diseases, especially atherosclerosis. Continued research has revealed that PMPs have numerous functions in atherosclerosis, not only in thrombosis formation, but also by induction of inflammation. PMPs also induce formation of foam cells. Recent evidence strongly indicates a significant role of PMPs in atherosclerosis. Here, current research on the function of PMPs in atherosclerosis is reviewed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

View from... JSAP spring meeting 2007: Inside Japan

NASA Astrophysics Data System (ADS)

Won, Rachel; Graydon, Oliver

2007-06-01

Photonics research in Japan is thriving and there is no better place to hear the latest news firsthand than the meetings of the Japan Society of Applied Physics. Nature Photonics decided to pay the 54th Spring Meeting a visit.

Computational modelling of atherosclerosis.

PubMed

Parton, Andrew; McGilligan, Victoria; O'Kane, Maurice; Baldrick, Francina R; Watterson, Steven

2016-07-01

Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organization estimates that approximately 2.5 million deaths occur annually because of the risk from elevated cholesterol, with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This article discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

PubMed

Kijani, Siavash; Vázquez, Ana Maria; Levin, Malin; Borén, Jan; Fogelstrand, Per

2017-07-01

Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on

Assisted reproductive technology in Japan: a summary report of 1992-2014 by the Ethics Committee, Japan Society of Obstetrics and Gynecology.

PubMed

Irahara, Minoru; Kuwahara, Akira; Iwasa, Takeshi; Ishikawa, Tomonori; Ishihara, Osamu; Kugu, Koji; Sawa, Rintaro; Banno, Kouji; Saito, Hidekazu

2017-04-01

The Japan Society of Obstetrics and Gynecology implemented a registry report system for the clinical practice of assisted reproductive technology in 1986. The aggregated results from 1992 to 2014 are reported herein. The total number of registered treatments was 393 745 cycles, of which 66 550 were pregnancy cycles and 46 008 were cycles with a live birth. Compared to the number of registered treatments in 2008, when the cycle-based registry was newly introduced, there was a 2.07-fold increase in the total number of treatments and a 2.25-fold increase in the number of cycles with a live birth. As the average age of patients who receive assisted reproductive technology has become markedly higher year by year, the most common age of those patients who received assisted reproductive technology in 2014 was 40 years. The total numbers of both assisted reproductive technology treatments and assisted reproductive technology live births are likely to be higher in the future. In addition, the trend toward aging patients seems to be continuing into the future.

Precise hypocenter locations of midcrustal low-frequency earthquakes beneath Mt. Fuji, Japan

USGS Publications Warehouse

Nakamichi, H.; Ukawa, M.; Sakai, S.

2004-01-01

Midcrustal low-frequency earthquakes (MLFs) have been observed at seismic stations around Mt. Fuji, Japan. In September - December 2000 and April - May 2001, abnormally high numbers of MLFs occurred. We located hypocenters for the 80 MLFs during 1998-2003 by using the hypoDD earthquake location program (Waldhauser and Ellsworth, 2000). The MLF hypocenters define an ellipsoidal volume some 5 km in diameter ranging from 11 to 16 km in focal depth. This volume is centered 3 km northeast of the summit and its long axis is directed NW-SE. The direction of the axis coincides with the major axis of tectonic compression around Mt. Fuji. The center of the MLF epicenters gradually migrated upward and 2-3 km from southeast to northwest during 1998-2001. We interpret that the hypocentral migration of MLFs reflects magma movement associated with a NW-SE oriented dike beneath Mt. Fuji. Copyright ?? The Society of Geomagnetism and Earth, Planetary and Space Sciences (SGEPSS); The Seismological Society of Japan; The Volcanological Society of Japan; The Geodetic Society of Japan; The Japanese Society for Planetary Sciences.

Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis.

PubMed

Kusumi, Kirsten; Smith, Sally; Barr-Beare, Evan; Saxena, Vijay; Schober, Megan S; Moore-Clingenpeel, Melissa; Schwaderer, Andrew L

2015-11-01

To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Japan: Language Policy and Planning in Transition

ERIC Educational Resources Information Center

Gottlieb, Nanette

2008-01-01

This monograph discusses the language situation in Japan, with an emphasis on language planning and policy. Japan has long considered itself to be a monoethnic and therefore monolingual society, despite the existence of substantial old-comer ethnic minorities, and this--with the instrumental exception of English--has been reflected in its language…

PREFACE: India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation

NASA Astrophysics Data System (ADS)

Onoda, Mitsuyoshi; Malhotra, Bansi D.

2012-04-01

Organic Functional Materials We would like to express our sincere thanks to the organizing committee members of this workshop and the many organizations such as the Japan Society for the Promotion of Science (JSPS), Japan, the Department of Science & Technology (DST), India, the Society of Organic Nanometric Interfacial Controlled Electronic (NICE) Devices, the Japan Society of Applied Physics, Himeji City, Himeji Convention & Visitors Bureau, Delhi Technological University, Delhi, India and the University of Hyogo for their financial support. Thanks are also given to The Japan Society of Applied Physics, Division of Molecular Electronics and Bioelectronics, The Japan Society of Applied Physics (M & BE), the Technical Committee on Dielectric and Electrical Insulation Materials of the Institute of Electrical Engineering in Japan (IEEJ), the Technical Group on Organic Molecular Electronics, Electronics Society of the Institute of Electronics, Information and Communication Engineers (IEICE), and the IEEE Dielectrics and Electrical Insulation Society, Japan Chapter, for their cooperation. Finally, we hope that the many young and active researchers who are participating will enjoy stimulating discussions and exchange ideas with each other at IJWBME 2011, Himeji, Japan. 7 April 2011 IJWBME 2011 Chairs Mitsuyoshi Onoda Graduate School of Engineering, University of Hyogo, Himeji, Japan Bansi D Malhotra Department of Biotechnology, Delhi Technological University, Delhi, India Conference photograph Participants of the India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation 2011, December 7-10 2011, EGRET Himeji, Japan The PDF also contains a list of sponsors.

Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets

PubMed Central

Ramji, Dipak P.; Davies, Thomas S.

2015-01-01

Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions. PMID:26005197

HIV-1-Associated Atherosclerosis: Unraveling the Missing Link.

PubMed

Kearns, Alison; Gordon, Jennifer; Burdo, Tricia H; Qin, Xuebin

2017-06-27

Cardiovascular disease, including atherosclerosis and atherosclerosis-associated complications, is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV) patients in the post-antiretroviral therapy era. HIV alone accelerates atherosclerosis. Antiretroviral therapy; HIV-associated comorbidities, such as dyslipidemia, drug abuse, and opportunistic infections; and lifestyle are risk factors for HIV-associated atherosclerosis. However, our current understanding of HIV-associated atherogenesis is very limited and has largely been obtained from clinical observation. There is a pressing need to experimentally unravel the missing link between HIV and atherosclerosis. Understanding these mechanisms will help to better develop and design novel therapeutic interventions for the treatment of HIV-associated cardiovascular disease. HIV mainly infects T cells and macrophages resulting in the induction of oxidative and endoplasmic reticulum stress, the formation of the inflammasome, and the dysregulation of autophagy. These mechanisms may contribute to HIV-associated atherogenesis. In this review, we will summarize our current understanding and propose potential mechanisms of HIV-associated atherosclerosis. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Plant sterol enriched functional food and atherosclerosis.

PubMed

Köhler, Jürgen; Teupser, Daniel; Elsässer, Albrecht; Weingärtner, Oliver

2017-06-01

Hypercholesterolaemia is a major cardiovascular risk factor. A healthy diet and a healthy lifestyle reduces cardiovascular risk. 'Functional foods' supplemented with phytosterols are recommended for the management of hypercholesterolaemia and have become a widely used non-prescription approach to lower plasma cholesterol levels. Two billion euros are spent world-wide each year on various functional foods, which have regulator-approved health claims for the management of elevated cholesterol levels. While international societies, such as the European Atherosclerosis Society or the National Heart Foundation in Australia, still advise phytosterols as an additional dietary option in the management of hypercholesterolaemia, recently released guidelines such as those from the National Institute of Health and Clinical Excellence in the United Kingdom are more critical of food supplementation with phytosterols and draw attention to significant safety issues. This review challenges whether an intervention with phytosterol supplements is beneficial. We summarize the current evidence from genetic diseases, genetic association studies, clinical trial data and data from animal studies. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2017 The British Pharmacological Society.

Helicobacter pylori infection in Japan

PubMed Central

Shiota, Seiji; Murakawi, Kazunari; Suzuki, Rumiko; Fujioka, Toshio; Yamaoka, Yoshio

2013-01-01

The prevalence of Helicobacter pylori infection is gradually decreasing in Japan. On the main island of Japan, nearly all H. pylori isolates possess cagA and vacA with strong virulence. However, less virulent H. pylori strains are frequently found in Okinawa where cases of gastric cancer are the lowest in Japan. Eradication therapy for peptic ulcer, idiopathic thrombocytopenic purpura, gastric mucosa-associated lymphoid tissue lymphoma and early gastric cancer after endoscopic resection has been approved by the Japanese national health insurance system. However, the Japanese Society for Helicobacter Research recently stated that all ‘H. pylori infection’ was considered as the indication for eradication irrespective of the background diseases. To eliminate H. pylori in Japan, the Japanese health insurance system should approve the eradication of all H. pylori infections. PMID:23265147

Correlation between Mitochondrial Reactive Oxygen and Severity of Atherosclerosis.

PubMed

Dorighello, Gabriel G; Paim, Bruno A; Kiihl, Samara F; Ferreira, Mônica S; Catharino, Rodrigo R; Vercesi, Anibal E; Oliveira, Helena C F

2016-01-01

Atherosclerosis has been associated with mitochondria dysfunction and damage. Our group demonstrated previously that hypercholesterolemic mice present increased mitochondrial reactive oxygen (mtROS) generation in several tissues and low NADPH/NADP+ ratio. Here, we investigated whether spontaneous atherosclerosis in these mice could be modulated by treatments that replenish or spare mitochondrial NADPH, named citrate supplementation, cholesterol synthesis inhibition, or both treatments simultaneously. Robust statistical analyses in pooled group data were performed in order to explain the variation of atherosclerosis lesion areas as related to the classic atherosclerosis risk factors such as plasma lipids, obesity, and oxidative stress, including liver mtROS. Using three distinct statistical tools (univariate correlation, adjusted correlation, and multiple regression) with increasing levels of stringency, we identified a novel significant association and a model that reliably predicts the extent of atherosclerosis due to variations in mtROS. Thus, results show that atherosclerosis lesion area is positively and independently correlated with liver mtROS production rates. Based on these findings, we propose that modulation of mitochondrial redox state influences the atherosclerosis extent.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis.

PubMed

López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A; Huaranga, Marco A Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A

2017-01-06

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

PubMed Central

López-Mejías, Raquel; Corrales, Alfonso; Vicente, Esther; Robustillo-Villarino, Montserrat; González-Juanatey, Carlos; Llorca, Javier; Genre, Fernanda; Remuzgo-Martínez, Sara; Dierssen-Sotos, Trinidad; Miranda-Filloy, José A.; Huaranga, Marco A. Ramírez; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Raya, Enrique; Mijares, Verónica; Ubilla, Begoña; Ferraz-Amaro, Iván; Gómez-Vaquero, Carmen; Balsa, Alejandro; López-Longo, Francisco J.; Carreira, Patricia; González-Álvaro, Isidoro; Ocejo-Vinyals, J. Gonzalo; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, Benjamín; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

2017-01-01

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA. PMID:28059143

Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Sahin, Cagdas; Majidi-Zolbin, Masoumeh; Ge, Guanghao; Mani, Arya; Taylor, Hugh S

2018-02-01

The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE-/- C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol-treated mice compared with those treated with testosterone or vehicle only in the whole aorta (-75%), aortic arch (-80%), and thoracic aorta (-80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression. Copyright © 2018 Endocrine Society.

Anti-cytokine therapy for prevention of atherosclerosis.

PubMed

Kirichenko, Tatiana V; Sobenin, Igor A; Nikolic, Dragana; Rizzo, Manfredi; Orekhov, Alexander N

2016-10-15

Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions. To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations. Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory prevention of atherosclerosis were searched in PubMed Database from their respective inceptions until October 2015. "The role of inflammatory cytokines in the development of atherosclerotic lesions" describes available data on the possible inflammatory mechanisms of the atherogenesis with a special attention to the role of cytokines. "Modern experience of anti-inflammatory therapy for the treatment of atherosclerosis" describes modern anti-inflammatory preparations with anti-atherosclerotic effect including natural preparations. In "the development of anti-inflammatory herbal preparation for atherosclerosis prevention" an algorithm is demonstrated that includes screening of anti-cytokine activity of different natural products, the development of the most effective combination and estimation of its effect in cell culture model, in animal model of the acute aseptic inflammation and in a pilot clinical trial. A natural preparation "Inflaminat" based on black elder berries (Sambucus nigra L.), violet tricolor herb (Viola tricolor L.) and calendula flowers (Calendula officinalis L.) possessing anti-cytokine activity was developed using the designed algorithm. The results of the following 2-year double blind placebo-controlled clinical study show that "Inflaminat" reduces carotid IMT progression, i.e. has anti-atherosclerotic effect. Anti-cytokine therapy may be a promising direction in moderation of atherogenesis, especially when it begins on the early stages

Endothelium Preserving Microwave Treatment for Atherosclerosis

NASA Technical Reports Server (NTRS)

Fink, Patrick; Arndt, G. D.; Ngo, Phong

2003-01-01

This slide presentation reviews the use of microwave technology for treating Atherosclerosis while preserving the endothelium. The system uses catheter antennas as part of the system that is intended to treat atherosclerosis. The concept is to use a microwave catheter for heating the atherosclerotic lesions, and reduce constriction in the artery.

Is atherosclerosis fundamental to human aging? Lessons from ancient mummies.

PubMed

Clarke, Emily M; Thompson, Randall C; Allam, Adel H; Wann, L Samuel; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Cox, Samantha L; Soliman, Muhammad Al-Tohamy; Abd el-Maksoud, Gomaa; Badr, Ibrahem; Miyamoto, Michael I; Frohlich, Bruno; Nur el-din, Abdel-Halim; Stewart, Alexandre F R; Narula, Jagat; Zink, Albert R; Finch, Caleb E; Michalik, David E; Thomas, Gregory S

2014-05-01

Case reports from Johan Czermak, Marc Ruffer, and others a century or more ago demonstrated ancient Egyptians had atherosclerosis three millennia ago. The Horus study team extended their findings, demonstrating that atherosclerosis was prevalent among 76 ancient Egyptian mummies and among 61 mummies from each of the ancient cultures of Peru, the American Southwest, and the Aleutian Islands. These findings challenge the assumption that atherosclerosis is a modern disease caused by present day risk factors. An extensive autopsy of an ancient Egyptian teenage male weaver named Nakht found that he was infected with four parasites: Schistosoma haematobium, Taenia species, Trichinella spiralis, and Plasmodium falciparum. Modern day patients with chronic inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus experience premature atherosclerosis. Could the burden of chronic inflammatory disease have been a risk factor for atherosclerosis in these ancient cultures? The prevalence of atherosclerosis in four diverse ancient cultures is consistent with atherosclerosis being fundamental to aging. The impact of risk factors in modern times, and potentially in ancient times, suggests a strong gene-environmental interplay: human genes provide a vulnerability to atherosclerosis, the environment determines when and if atherosclerosis becomes manifest clinically. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Remote transmission of live endoscopy over the Internet: Report from the 87th Congress of the Japan Gastroenterological Endoscopy Society.

PubMed

Shimizu, Shuji; Ohtsuka, Takao; Takahata, Shunichi; Nagai, Eishi; Nakashima, Naoki; Tanaka, Masao

2016-01-01

Live demonstration of endoscopy is one of the most attractive and useful methods for education and is often organized locally in hospitals. However, problems have been apparent in terms of cost, preparation, and potential risks to patients. Our aim was to evaluate a new approach to live endoscopy whereby remote hospitals are connected by the Internet for live endoscopic demonstrations. Live endoscopy was transmitted to the Congress of the Japan Gastroenterological Endoscopic Society by 13 domestic and international hospitals. Patients with upper and lower gastrointestinal diseases and with pancreatobiliary disorders were the subjects of a live demonstration. Questionnaires were distributed to the audience and were sent to the demonstrators. Questions concerned the quality of transmitted images and sound, cost, preparations, programs, preference of style, and adverse events. Of the audience, 91.2% (249/273) answered favorably regarding the transmitted image quality and 93.8% (259/276) regarding the sound quality. All demonstrators answered favorably regarding image quality and 93% (13/14) regarding sound quality. Preparations were completed without any outsourcing at 11 sites (79%) and were evaluated as 'very easy' or 'easy' at all but one site (92.3%). Preparation cost was judged as 'very cheap' or 'cheap' at 12 sites (86%). Live endoscopy connecting multiple international centers was satisfactory in image and sound quality for both audience and demonstrators, with easy and inexpensive preparation. The remote transmission of live endoscopy from demonstrators' own hospitals was preferred to the conventional style of locally organized live endoscopy. © 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

Teaching Unit: Japan.

ERIC Educational Resources Information Center

Evans, Dina

The cultural diversity of Japan can provide a rewarding learning experience for children of all grade levels. This teaching unit includes resources and ideas for the study of Japanese society, art, folklore, and poetry. Included among the instructional objectives are: (1) children will compare U.S. lifestyles with Japanese lifestyles by reading…

Japan’s Shift to a Proactive Defense Architecture: Challenges Faced by Industry, Government, and Society

DTIC Science & Technology

2017-06-01

DEW Directed-Energy Weapons DOD Department of Defense DPJ Democratic Party of Japan EM Electro-magnetic FMS Foreign Military Sales GSDF Ground...data.oecd.org/japan.htm. 75 Chris Matthews, “Forget Greece, Japan is the World’s Real Economic Time Bomb ,” Fortune, February 26, 2015, http...fortune.com/2015/02/26/japan-economic-time- bomb /. 25 to fund repair facilities, buy parts, or pay contractors? In terms of operating costs, will the JSDF

Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside.

PubMed

Prasad, Kailash; Jadhav, Ashok

2016-01-01

Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease

Vinpocetine attenuates lipid accumulation and atherosclerosis formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Yujun; Li, Jian-Dong; Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu

Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatorymore » agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.« less

Insulin resistance, metabolic stress, and atherosclerosis

PubMed Central

Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

2012-01-01

Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

Photoacoustic tomography: applications for atherosclerosis imaging

NASA Astrophysics Data System (ADS)

Sangha, Gurneet S.; Goergen, Craig J.

2016-08-01

Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

Vinpocetine Attenuates Lipid Accumulation and Atherosclerosis Formation

PubMed Central

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-01-01

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis PMID:23583194

Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

PubMed Central

Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S.; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I.; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T.; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R.; Wright, Samuel D.; Espevik, Terje; Schultze, Joachim L.; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

2016-01-01

Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility, in preventing and reversing atherosclerosis. Here we show that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load, and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques, and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the anti-atherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Since CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

Japan's Global Role: Proceedings from the Symposium (2nd, Honolulu, Hawaii, October 25-26, 1991).

ERIC Educational Resources Information Center

Hawaii Univ., Honolulu. East-West Center.

This document consists of eight presentations with responses given at the second in a series of symposia sponsored by the Japan-America Society of in a series of symposia sponsored by the Japan-America Society of Hawaii. Having emerged as an economic superpower, Japan's role on the global stage is still finding its full range and is a topic of…

Cross-Sectional Comparison of Coronary Artery Calcium Scores Between Caucasian Men in the United States and Japanese Men in Japan

PubMed Central

Fujiyoshi, Akira; Miura, Katsuyuki; Ohkubo, Takayoshi; Kadowaki, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Hisamatsu, Takashi; Sekikawa, Akira; Budoff, Matthew J.; Liu, Kiang; Ueshima, Hirotsugu; Fujiyoshi, Akira; Miura, Katsuyuki; Ohkubo, Takayoshi; Kadowaki, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Hisamatsu, Takashi; Ueshima, Hirotsugu; Miura, Katsuyuki; Hisamatsu, Takashi; Ueshima, Hirotsugu; Ohkubo, Takayoshi; Sekikawa, Akira; Budoff, Matthew J.; Liu, Kiang

2014-01-01

The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45–54, 55–64, or 65–74 years). We used community-based samples of Caucasian men in the United States (2000–2002; n = 1,067) and Japanese men in Japan (2006–2008; n = 832) aged 45–74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45–54, 55–64, and 65–74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. PMID:25125689

G Protein-coupled Estrogen Receptor Protects from Atherosclerosis

PubMed Central

Meyer, Matthias R.; Fredette, Natalie C.; Howard, Tamara A.; Hu, Chelin; Ramesh, Chinnasamy; Daniel, Christoph; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

2014-01-01

Coronary atherosclerosis and myocardial infarction in postmenopausal women have been linked to inflammation and reduced nitric oxide (NO) formation. Natural estrogen exerts protective effects on both processes, yet also displays uterotrophic activity. Here, we used genetic and pharmacologic approaches to investigate the role of the G protein-coupled estrogen receptor (GPER) in atherosclerosis. In ovary-intact mice, deletion of gper increased atherosclerosis progression, total and LDL cholesterol levels and inflammation while reducing vascular NO bioactivity, effects that were in some cases aggravated by surgical menopause. In human endothelial cells, GPER was expressed on intracellular membranes and mediated eNOS activation and NO formation, partially accounting for estrogen-mediated effects. Chronic treatment with G-1, a synthetic, highly selective small molecule agonist of GPER, reduced postmenopausal atherosclerosis and inflammation without uterotrophic effects. In summary, this study reveals an atheroprotective function of GPER and introduces selective GPER activation as a novel therapeutic approach to inhibit postmenopausal atherosclerosis and inflammation in the absence of uterotrophic activity. PMID:25532911

[The receptor theory of atherosclerosis].

PubMed

Likhoded, V G; Bondarenko, V M; Gintsburg, A L

2010-01-01

Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Bell, Elizabeth J; Decker, Paul A; Tsai, Michael Y; Pankow, James S; Hanson, Naomi Q; Wassel, Christina L; Larson, Nicholas B; Cohoon, Kevin P; Budoff, Matthew J; Polak, Joseph F; Stein, James H; Bielinski, Suzette J

2018-05-01

Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

[Atherosclerosis, oxidative stress and physical activity. Review].

PubMed

Calderón, Juan Camilo; Fernández, Ana Zita; María de Jesús, Alina Isabel

2008-09-01

Atherosclerosis and related diseases have emerged as the leading cause of morbidity and mortality in the western world and, therefore, as a problem of public health. Free radicals and reactive oxygen species have been suggested to be part of the pathophysiology of these diseases. It is well known that physical activity plays an important role as a public health measure by reducing the risk of developing atherosclerosis-related cardiovascular events in the general population. It is also known that physical activity increases in some tissues, the reactive oxygen species production. In this review the atherosclerosis-oxidative stress-physical activity relationship is focused on the apparent paradox by which physical activity reduces atherosclerosis and cardiovascular risk in parallel with the activation of an apparently damaging mechanism which is an increased oxidative stress. A hypothesis including the experimental and clinical evidence is presented to explain the aforementioned paradox.

Genetic Basis of Atherosclerosis: Insights from Mice and Humans

PubMed Central

Stylianou, Ioannis M.; Bauer, Robert C.; Reilly, Muredach P.; Rader, Daniel J.

2012-01-01

Atherosclerosis is a complex and heritable disease involving multiple cell types and the interactions of many different molecular pathways. The genetic and molecular mechanisms of atherosclerosis have in part been elucidated by mouse models; at least 100 different genes have been shown to influence atherosclerosis in mice. Importantly, unbiased genome-wide association studies have recently identified a number of novel loci robustly associated with atherosclerotic coronary artery disease (CAD). Here we review the genetic data elucidated from mouse models of atherosclerosis, as well as significant associations for human CAD. Furthermore, we discuss in greater detail some of these novel human CAD loci. The combination of mouse and human genetics has the potential to identify and validate novel genes that influence atherosclerosis, some of which may be candidates for new therapeutic approaches. PMID:22267839

Atherosclerosis profile and incidence of cardiovascular events: a population-based survey.

PubMed

Robinson, Jennifer G; Fox, Kathleen M; Bullano, Michael F; Grandy, Susan

2009-09-15

Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization). Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Of 17,640 respondents, 488 (2.8%) reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p < 0.05]. Incident CVD was twice as high in respondents with subclinical atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p = 0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at greatest risk of experiencing CVD events in the next 2 years. Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

Psychology in Japan.

PubMed

Imada, Hiroshi; Tanaka-Matsumi, Junko

2016-06-01

The purpose of this article is to provide information about Japan and its psychology in advance of the 31st International Congress of Psychology (ICP), to be held in Yokohama, Japan, in 2016. The article begins with the introduction of the Japanese Psychological Association (JPA), the hosting organization of the ICP 2016, and the Japanese Union of Psychological Associations consisting of 51 associations/societies, of which the JPA is a member. This is followed by a brief description of a history of psychology of Japan, with emphasis on the variation in our approach to psychology in three different periods, that is, the pre- and post-Pacific War periods, and the post-1960 period. Next, the international contributions of Japanese psychology/psychologists are discussed from the point of view of their visibility. Education and training in psychology in Japanese universities is discussed with a final positive remark about the long-awaited enactment of the Accredited Psychologist Law in September, 2015. © 2016 International Union of Psychological Science.

Vinpocetine attenuates lipid accumulation and atherosclerosis formation.

PubMed

Cai, Yujun; Li, Jian-Dong; Yan, Chen

2013-05-10

Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Influence of Erythrocyte Membrane Stability in Atherosclerosis.

PubMed

da Silva Garrote-Filho, Mario; Bernardino-Neto, Morun; Penha-Silva, Nilson

2017-04-01

The purpose of this study is to show how an excess of cholesterol in the erythrocyte membrane contributes stochastically to the progression of atherosclerosis, leading to damage in blood rheology and O 2 transport, deposition of cholesterol (from trapped erythrocytes) in an area of intraplaque hemorrhage, and local exacerbation of oxidative stress. Cholesterol contained in the membrane of erythrocytes trapped in an intraplaque hemorrhage contributes to the growth of the necrotic nucleus. There is even a relationship between the amount of cholesterol in the erythrocyte membrane and the severity of atherosclerosis. In addition, the volume variability among erythrocytes, measured by RDW, is predictive of a worsening of this disease. Erythrocytes contribute to the development of atherosclerosis in several ways, especially when trapped in intraplate hemorrhage. These erythrocytes are oxidized and phagocytosed by macrophages. The cholesterol present in the membrane of these erythrocytes subsequently contributes to the growth of the atheroma plaque. In addition, when they rupture, erythrocytes release hemoglobin, which leads to the generation of free radicals. Finally, increased RDW may predict the worsening of atherosclerosis, due to the effects of inflammation and oxidative stress on erythropoiesis and erythrocyte volume. A better understanding of erythrocyte participation in atherosclerosis may contribute to the improvement of the prevention and treatment strategies of this disease.

Development of an interprofessional competency framework in Japan.

PubMed

Haruta, Junji; Sakai, Ikuko; Otsuka, Mariko; Yoshimoto, Hisashi; Yoshida, Kazue; Goto, Michiko; Shimoi, Toshinori

2016-09-01

This article presents a project that aimed to identify a set of competencies (domains and statements) to prepare Japanese students and healthcare practitioners for collaborative practice. The Japan Association for Interprofessional Education (JAIPE) has started a government-funded project to formulate its interprofessional competency framework, in cooperation with professional organisations (e.g. Japan Society for Medical Education) in healthcare and social sciences. This three-year project is underway as part of the Initiative to Build up the Core Healthcare Personnel programme of Mie University. This project consists of five stages: literature review, data collection, prototype development, consensus formation, and finalisation. Our efforts will culminate in Japan's first interprofessional competency framework, with consensus from relevant academic societies and other stakeholders. We hope that the involvement of stakeholder participation will improve the usability of the final interprofessional competency framework.

Roles of Cells from the Arterial Vessel Wall in Atherosclerosis.

PubMed

Wang, Di; Wang, Zhiyan; Zhang, Lili; Wang, Yi

2017-01-01

Atherosclerosis has been identified as a chronic inflammatory disease of the arterial vessel wall. Accumulating evidence indicates that different cells from the tunica intima, media, adventitia, and perivascular adipose tissue not only comprise the intact and normal arterial vessel wall but also participate all in the inflammatory response of atherosclerosis via multiple intricate pathways. For instance, endothelial dysfunction has historically been considered to be the initiator of the development of atherosclerosis. The migration and proliferation of smooth muscle cells also play a pivotal role in the progression of atherosclerosis. Additionally, the fibroblasts from the adventitia and adipocytes from perivascular adipose tissue have received considerable attention given their special functions that contribute to atherosclerosis. In addition, numerous types of cytokines produced by different cells from the arterial vessel wall, including endothelium-derived relaxing factors, endothelium-derived contracting factors, tumor necrosis factors, interleukin, adhesion molecules, interferon, and adventitium-derived relaxing factors, have been implicated in atherosclerosis. Herein, we summarize the possible roles of different cells from the entire arterial vessel wall in the pathogenesis of atherosclerosis.

Atherosclerosis and Stroke

MedlinePlus

... Stroke and atherosclerosis There are two types of ischemic stroke caused by blood clots, narrowing of blood vessels ... 2 What Is an Arteriovenous Malformation (AVM)? 3 Ischemic Strokes (Clots) 4 Hemorrhagic Strokes (Bleeds) 5 What You ...

Diagnostic criteria for Patulous Eustachian Tube: A proposal by the Japan Otological Society.

PubMed

Kobayashi, Toshimitsu; Morita, Masahiro; Yoshioka, Satoshi; Mizuta, Kunihiro; Ohta, Shigeto; Kikuchi, Toshiaki; Hayashi, Tatsuya; Kaneko, Akihiro; Yamaguchi, Nobumasa; Hashimoto, Sho; Kojima, Hiromi; Murakami, Shingo; Takahashi, Haruo

2018-02-01

Patulous Eustachian Tube (PET) is of increasing importance in otology. However, despite the abundance of diseases requiring a differential diagnosis from PET, such as superior semicircular canal dehiscence syndrome, perilymphatic fistula, acute low-tone sensorineural hearing loss, etc., there are currently no established diagnostic criteria for PET. In view of these circumstances, the Japan Otological Society (JOS) Eustachian Tube Committee proposed the diagnostic criteria for Patulous Eustachian Tube in 2012, in order to promote clinical research on PET. A revision was made in 2016, maintaining the original concept that the criteria should be very simple, avoid any contamination of "Definite PET" with uncertain cases. Moreover, it was also intended to minimize the number of cases that could be accidentally excluded even in the presence of some suspected findings ("Possible PET"). The criteria can be used by all otolaryngologists even without using the Eustachian tube function test apparatus. However, the use of such an apparatus may increase the chances of detecting "Definite PET". The algorithm for the diagnosis of PET using the criteria has also been described. The JOS diagnostic criteria for Patulous Eustachian Tube will further promote international scientific communication on PET. Copyright © 2017 Elsevier B.V. All rights reserved.

Current trends in rehabilitation engineering in Japan.

PubMed

Ohnabe, Hisaichi

2006-01-01

In 2005, the elderly generation comprised 20% of the Japanese population. This percentage will grow to approximately 30% in 2030, meaning that nearly one in three people in Japan will be 65 years of age or older. Japan is the first nation in the world to face this situation. This article uses the context of Japanese society to give an overview of the elderly and people with disabilities; the International Classification of Functioning, Disability, and Health model; rehabilitation engineering-related policy; and education. In addition, we examine how governmental programs and Japanese law regarding technical aids may evolve by 2030. Partner robots, intelligent powered wheelchairs, nursing robots, and other technologies are introduced as examples of rehabilitation engineering and assistive technology. We also discuss the volunteer activities of the Rehabilitation Engineering Society of Japan (RESJA) in response to the Asian tsunami disaster and the achievements of a group of students from a Japanese senior high school of industry.

Function of CD147 in atherosclerosis and atherothrombosis

PubMed Central

Wang, Cuiping; Jin, Rong; Zhu, Xiaolei; Yan, Jinchuan; Guohong, Li

2015-01-01

CD147, a member of the immunoglobulin super family, is a well-known potent inducer of extracellular matrix metalloproteinases. Studies show that CD147 is upregulated in inflammatory diseases. Atherosclerosis is a chronic inflammatory disease of the artery wall. Further understanding of the functions of CD147 in atherosclerosis and atherothrombosis may provide a new strategy for preventing and treating cardiovascular disease. In this review, we discuss how CD147 contributes to atherosclerosis and atherothrombosis. PMID:25604960

Association between diabetes mellitus, hypothyroidism or hyperadrenocorticism, and atherosclerosis in dogs.

PubMed

Hess, Rebecka S; Kass, Philip H; Van Winkle, Thomas J

2003-01-01

The objective of this study was to determine whether dogs with atherosclerosis are more likely to have concurrent diabetes mellitus, hypothyroidism, or hyperadrenocorticism than dogs that do not have atherosclerosis. A retrospective mortality prevalence case-control study was performed. The study group included 30 dogs with histopathological evidence of atherosclerosis. The control group included 142 dogs with results of a complete postmortem examination, a final postmortem examination diagnosis of neoplasia, and no histopathological evidence of atherosclerosis. Control dogs were frequency matched for age and year in which the postmortem examination was performed. Proportionate changes in the prevalence of diabetes mellitus, hypothyroidism, and hyperadrenocorticism were calculated by exact prevalence odds ratios (POR), 95% confidence intervals (95% CI), and P values. Multiple logistic regression analysis was used to examine the combined effects of prevalence determinants while controlling for age and year of postmortem examination. Dogs with atherosclerosis were over 53 times more likely to have concurrent diabetes mellitus than dogs without atherosclerosis (POR = 53.6; 95% CI, 4.6-627.5; P = .002) and over 51 times more likely to have concurrent hypothyroidism than dogs without atherosclerosis (POR = 51.1; 95% CI, 14.5-180.1; P < .001). Dogs with atherosclerosis were not found to be more likely to have concurrent hyperadrenocorticism than dogs that did not have atherosclerosis (POR = 1.8; 95% CI, 0.2-17.6; P = .59). Diabetes mellitus and hypothyroidism, but not hyperadrenocorticism, are more prevalent in dogs with atherosclerosis compared to dogs without atherosclerosis on postmortem examination.

RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn; National Institute of Biological Sciences, Beijing 102206; Jin, Wei

Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibitionmore » of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.« less

Political Corruption in Japan.

ERIC Educational Resources Information Center

Reed, Steven R.; And Others

1996-01-01

Provides an overview of political corruption and its place in Japanese culture and society. Discusses recent scandals and efforts at political reform. These efforts are moving Japan from a "boss-patronage" system to a "civic-culture." Includes a table of post-war Japanese prime ministers and corruption scandals. (MJP)

The roles of salusins in atherosclerosis and related cardiovascular diseases.

PubMed

Watanabe, Takuya; Sato, Kengo; Itoh, Fumiko; Iso, Yoshitaka; Nagashima, Masaharu; Hirano, Tsutomu; Shichiri, Masayoshi

2011-01-01

Human salusin-α and -β are related peptides of 28 and 20 amino acids, respectively, produced from the same precursor, prosalusin. Salusin-β exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Human macrophage foam cell formation is significantly stimulated by salusin-β, but suppressed by salusin-α. Chronic salusin-β infusion into apolipoprotein E-knockout mice enhances atherosclerotic lesions, paralleling increases in foam cell formation and upregulation of scavenger receptors and of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in macrophages. In contrast, chronic salusin-α infusion reduces atherosclerotic lesions accompanied by significant suppression of foam cell formation owing to ACAT1 downregulation. Salusin-β is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-α and -β immunoreactivity has been detected in human coronary atherosclerotic plaques, with dominance of salusin-β in macrophage foam cells, VSMCs, and fibroblasts. Serum salusin-α levels are markedly decreased in patients with angiographically proven coronary artery disease compared with patients with mild hypertension and healthy volunteers. Furthermore, among patients with acute coronary syndrome, serum salusin-α levels are decreased in accordance with the severity of coronary atherosclerotic lesions. These findings suggest that salusin-β may contribute to the pathogenesis of atherosclerosis. Decreased levels of salusin-α in circulating blood and vascular tissue are closely linked with human atherosclerosis. Therefore, salusin-α could be a candidate biomarker for atherosclerosis and may be therapeutically useful for prevention of atherosclerotic cardiovascular diseases. Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Increased activity of vascular adenosine deaminase in atherosclerosis and therapeutic potential of its inhibition.

PubMed

Kutryb-Zajac, Barbara; Mateuszuk, Lukasz; Zukowska, Paulina; Jasztal, Agnieszka; Zabielska, Magdalena A; Toczek, Marta; Jablonska, Patrycja; Zakrzewska, Agnieszka; Sitek, Barbara; Rogowski, Jan; Lango, Romuald; Slominska, Ewa M; Chlopicki, Stefan; Smolenski, Ryszard T

2016-11-01

inflammation and improved endothelial function. This study highlights the importance of extracellular nucleotides and adenosine metabolism in the atherosclerotic vessel in both experimental and clinical setting. The increased eADA activity marks an early stage of atherosclerosis, contributes to its progression and could represent a novel target for therapy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Clinical statistics of gynecologic cancers in Japan.

PubMed

Yamagami, Wataru; Nagase, Satoru; Takahashi, Fumiaki; Ino, Kazuhiko; Hachisuga, Toru; Aoki, Daisuke; Katabuchi, Hidetaka

2017-03-01

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Phosphatidylserine in atherosclerosis.

PubMed

Darabi, Maryam; Kontush, Anatol

2016-08-01

It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating cholesterol metabolism, influencing inflammatory response and regulating coagulation system, and discuss promising phosphatidylserine-based therapeutic approaches and detection techniques in atherosclerosis. Phosphatidylserine has been suggested to play important roles in physiological processes, such as apoptosis, inflammation, and coagulation. Recent data demonstrate atheroprotective potential of phosphatidylserine, reflecting its capacity to inhibit inflammation, modulate coagulation, and enhance HDL functionality. Furthermore, modern lipidomic approaches have enabled the investigation of phosphatidylserine properties relevant to the lipid-based drug delivery and development of reconstituted HDL. Studies of phosphatidylserine in relation to atherosclerosis represent an area of opportunity. Additional research elucidating mechanisms underlying experimentally observed atheroprotective effects of phosphatidylserine is required to fully explore therapeutic potential of this naturally occurring phospholipid in cardiovascular disease.

Working Conditions and Lifestyle of Female Surgeons Affiliated to the Japan Neurosurgical Society: Findings of Individual and Institutional Surveys.

PubMed

Fujimaki, Takamitsu; Shibui, Soichiro; Kato, Yoko; Matsumura, Akira; Yamasaki, Mami; Date, Isao; Hongo, Kazuhiro; Kuroda, Satoshi; Matsumae, Mitsunori; Nakao, Naoyuki; Sakurada, Kaori; Shimokawa, Shoko; Kayama, Takamasa

2016-11-15

To investigate the working conditions of female neurosurgeons in Japan, two surveys were conducted by The Japan Neurosurgical Society: one involving female neurosurgeons themselves and the other involving the chiefs of neurosurgical departments. The responses were received from 224 (43.8%) female neurosurgeons and 496 (61.2%) departmental chiefs. About half (50.2%) of the female neurosurgeons were married and 39.2% had children (average number of children, 1.27). Their work was full-time in 80.6% of cases; on average, they worked 51.9 h per week, had night duty 2.8 times per month, and had 5.7 days off per month. Many of them stated that they were satisfied with their job status, but about half of them reported difficulty in maintaining a correct work-life balance. Among the institutions surveyed, 29% had female neurosurgeons. The survey of departmental chiefs revealed that the proxies for maternity leave were not available at most institutions, and that there was only limited availability of night child care (41%) or sick child care (39%); female neurosurgeons did not appear to be well-informed of these support systems. These findings suggest that apart from systematic approaches already in place, female neurosurgeons would prefer to have more understanding from their peers and chiefs.

Working Conditions and Lifestyle of Female Surgeons Affiliated to the Japan Neurosurgical Society: Findings of Individual and Institutional Surveys

PubMed Central

FUJIMAKI, Takamitsu; SHIBUI, Soichiro; KATO, Yoko; MATSUMURA, Akira; YAMASAKI, Mami; DATE, Isao; HONGO, Kazuhiro; KURODA, Satoshi; MATSUMAE, Mitsunori; NAKAO, Naoyuki; SAKURADA, Kaori; SHIMOKAWA, Shoko; KAYAMA, Takamasa

2016-01-01

To investigate the working conditions of female neurosurgeons in Japan, two surveys were conducted by The Japan Neurosurgical Society: one involving female neurosurgeons themselves and the other involving the chiefs of neurosurgical departments. The responses were received from 224 (43.8%) female neurosurgeons and 496 (61.2%) departmental chiefs. About half (50.2%) of the female neurosurgeons were married and 39.2% had children (average number of children, 1.27). Their work was full-time in 80.6% of cases; on average, they worked 51.9 h per week, had night duty 2.8 times per month, and had 5.7 days off per month. Many of them stated that they were satisfied with their job status, but about half of them reported difficulty in maintaining a correct work–life balance. Among the institutions surveyed, 29% had female neurosurgeons. The survey of departmental chiefs revealed that the proxies for maternity leave were not available at most institutions, and that there was only limited availability of night child care (41%) or sick child care (39%); female neurosurgeons did not appear to be well-informed of these support systems. These findings suggest that apart from systematic approaches already in place, female neurosurgeons would prefer to have more understanding from their peers and chiefs. PMID:27302300

Life stress and atherosclerosis: a pathway through unhealthy lifestyle.

PubMed

Mainous, Arch G; Everett, Charles J; Diaz, Vanessa A; Player, Marty S; Gebregziabher, Mulugeta; Smith, Daniel W

2010-01-01

To examine the relationship between a general measure of chronic life stress and atherosclerosis among middle aged adults without clinical cardiovascular disease via pathways through unhealthy lifestyle characteristics. We conducted an analysis of The Multi-Ethnic Study of Atherosclerosis (MESA). The MESA collected in 2000 includes 5,773 participants, aged 45-84. We computed standard regression techniques to examine the relationship between life stress and atherosclerosis as well as path analysis with hypothesized paths from stress to atherosclerosis through unhealthy lifestyle. Our outcome was sub-clinical atherosclerosis measured as presence of coronary artery calcification (CAC). A logistic regression adjusted for potential confounding variables along with the unhealthy lifestyle characteristics of smoking, excessive alcohol use, high caloric intake, sedentary lifestyle, and obesity yielded no significant relationship between chronic life stress (OR 0.93, 95% CI 0.80-1.08) and CAC. However, significant indirect pathways between chronic life stress and CAC through smoking (p = .007), and sedentary lifestyle (p = .03) and caloric intake (.002) through obesity were found. These results suggest that life stress is related to atherosclerosis once paths of unhealthy coping behaviors are considered.

Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

PubMed Central

Stroes, Erik S.; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; Hegele, Robert A.; Hovingh, G. Kees; Leiter, Lawrence A.; Mach, Francois; März, Winfried; Newman, Connie B.; Wiklund, Olov; Jacobson, Terry A.; Catapano, Alberico L.; Chapman, M. John; Ginsberg, Henry N.; Stroes, Erik; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; März, Winfried; Newman, Connie B.; John Chapman, M.; Ginsberg, Henry N.; John Chapman, M.; Ginsberg, Henry N.; de Backer, Guy; Catapano, Alberico L.; Hegele, Robert A.; Kees Hovingh, G.; Jacobson, Terry A.; Leiter, Lawrence; Mach, Francois; Wiklund, Olov

2015-01-01

Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7–29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. PMID:25694464

High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice.

PubMed

Yang, An-Ning; Zhang, Hui-Ping; Sun, Yue; Yang, Xiao-Ling; Wang, Nan; Zhu, Guangrong; Zhang, Hui; Xu, Hua; Ma, Sheng-Chao; Zhang, Yue; Li, Gui-Zhong; Jia, Yue-Xia; Cao, Jun; Jiang, Yi-Deng

2015-12-21

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Amide-adducts in atherosclerosis.

PubMed

Naito, Michitaka

2014-01-01

Too many hypotheses in the etiology of atherosclerosis have been proposed. Classically, lipid insudation hypothesis by Virchow and thrombogenic hypothesis by Rokitansky are famous. However, in the recent progress in the area of atherosclerosis, the response-to-injury hypothesis by Ross (Ross R Glomset JA, N Engl J Med 295:369-377, 420-425, 1976; Ross R, Arteriosclerosis 1:293-311, 1981; Ross R, N Engl J Med 314:488-500, 1986; Ross R, Nature 362:801-809, 1993; Ross R, N Engl J Med 340:115-126, 1999) has been the leading one. In this review, however, the author focuses to the recent debate on the role of oxidative modification of atherogenic lipoproteins.

Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

NASA Astrophysics Data System (ADS)

Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

2016-03-01

Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

Prevalence and Correlates of Subclinical Atherosclerosis in Alaskan Eskimos

PubMed Central

Cutchins, Alexis; Roman, Mary J.; Devereux, Richard B.; Ebbesson, Sven O.E.; Umans, Jason G.; Zhu, Jianhui; Weissman, Neil J.; Howard, Barbara V.

2009-01-01

Background and Purpose The recent increase in clinical cardiovascular disease in Alaska Eskimos suggests that changes in traditional lifestyle may have adverse public health consequences. This study examines the prevalence of subclinical vascular disease and its relation to risk factors in Alaska Eskimos. Methods Participants in the population-based Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study underwent evaluation of cardiovascular disease risk factors and carotid ultrasound. Outcome variables were carotid intimal-medial thickness and presence and extent of atherosclerosis. Results In multivariate analyses, intimal-medial thickness and presence and extent of atherosclerosis were all associated with traditional cardiovascular disease risk factors but not dietary intake of omega-3 fatty acids. Rates of carotid atherosclerosis were higher than those reported in 2 large population-based US studies. Conclusions Alaska Eskimos have similar traditional risk factors for carotid atherosclerosis as other ethnic and racial populations but have higher prevalences of atherosclerosis, possibly attributable to higher rates of smoking. PMID:18617652

Forecasting Trends in Disability in a Super-Aging Society: Adapting the Future Elderly Model to Japan.

PubMed

Chen, Brian K; Jalal, Hawre; Hashimoto, Hideki; Suen, Sze-Chuan; Eggleston, Karen; Hurley, Michael; Schoemaker, Lena; Bhattacharya, Jay

2016-12-01

Japan has experienced pronounced population aging, and now has the highest proportion of elderly adults in the world. Yet few projections of Japan's future demography go beyond estimating population by age and sex to forecast the complex evolution of the health and functioning of the future elderly. This study estimates a new state-transition microsimulation model - the Japanese Future Elderly Model (FEM) - for Japan. We use the model to forecast disability and health for Japan's future elderly. Our simulation suggests that by 2040, over 27 percent of Japan's elderly will exhibit 3 or more limitations in IADLs and social functioning; almost one in 4 will experience difficulties with 3 or more ADLs; and approximately one in 5 will suffer limitations in cognitive or intellectual functioning. Since the majority of the increase in disability arises from the aging of the Japanese population, prevention efforts that reduce age-specific morbidity can help reduce the burden of disability but may have only a limited impact on reducing the overall prevalence of disability among Japanese elderly. While both age and morbidity contribute to a predicted increase in disability burden among elderly Japanese in the future, our simulation results suggest that the impact of population aging exceeds the effect of age-specific morbidity on increasing disability in Japan's future.

Digital Technology at the National Science Museum of Japan

ERIC Educational Resources Information Center

Lydens, Lois; Saito, Yasuji; Inoue, Tohru

2007-01-01

The National Science Museum (NSM) in Japan has recently completed a project using different types of visitor-oriented digital technologies. With sponsorship from the Japan Society for the Promotion of Science (JSPS), the NSM team carried out a four-year study to examine how digital technologies can be used to enhance as well as educationally…

Atherosclerosis in the Erythrocebus patas, an old world monkey.

PubMed Central

Mahley, R. W.; Johnson, D. K.; Pucak, G. J.; Fry, D. L.

1980-01-01

Fifty monkeys of the species Erythrocebus patas were fed a control monkey chow, a semi-synthetic diet containing 25% lard, or a semisynthetic diet containing 25% lard and 0.5% cholesterol for 2 years. The patas monkeys had naturally occurring atherosclerosis that was greatly accelerated by feeding a diet containing cholesterol. The atherosclerosis involved the aorta, predominantly the abdominal portion, the coronary arteries, and various peripheral vessels. Histologically, the atherosclerosis was characterized by intimal proliferative lesions associated with intra- and extracellular lipid deposition. Complicated lesions that developed after 2 years on the cholesterol-containing diet were associated with lipid crystals, necrosis, mineralization, and encroachment upon the media. Adventitial reactions characterized by increased vascularity and the presence of inflammatory cells were seen. All of these observations have been described as components of the human atherosclerotic disease process. The similarity of the patas monkey atherosclerosis to human atherosclerosis, the relatively large size and easy handling of the animals, and the fact that previous studies have shown the lipoproteins of both control and cholesterol-fed monkeys to resemble human lipoproteins all contribute to making the patas monkey a useful model for the study of experimental atherosclerosis. Images Figure 1-5 Figure 6 Figure 7-10 Figure 11 Figure 12 PMID:6766672

Commencement of Geoparks, Geology day and International Earth Science Olympiad, IYPE in Japan

NASA Astrophysics Data System (ADS)

Tsukuda, Eikichi; Kodama, Kisaburo; Miyazaki, Teruki

2010-05-01

The GSJ is the main supporting organization of IYPE Japan, which is an implementation body of IYPE in Japan, serving as its secretariat. During the IYPE triennial activity, the GSJ has been supporting development of Geparks, establishment of "the Geology Day" and the Earth Science Olympiad activities with some academic societies, and has distributed geological maps with IYPE logo. The GSJ also established an outreach network "Geo-networks Tsukuba" as a local legacy of the IYPE, and has managed it with a local government, research organizations, nonprofit corporations and local media to increase geological and environmental literacy of public, especially among young people. The GSJ-AIST has also contributed internationally to IYPE by joining two international projects, OneGeology and the CCOP Book project. Geoparks in Japan are characterized by following features. The Japanese Islands and the surrounding seas are situated in the area of unique geologic features; the place where several tectonic plates meet and collide. This causes earthquakes and volcanic activities, and makes Japan one of most dynamic areas on the earth. The dynamics of the earth bring about not only geological hazards but also a lot of blessings. In August of 2009, three Geoparks, the Toya Caldera and Usu Volcano Geopark, the Itoigawa Geopark and the Unzen Volcanic Area Geopark, were accepted to join the Global Geopark Network from Japan for the first time. Since its launch in 2006, the GSJ has been playing a major role in promoting Geoparks in Japan together with Geological Society of Japan. The GSJ hosts the Japan Geopark Committee (JGC) for quality evaluation, serving as the information center of Geoparks in Japan. The Geology Day of Japan (10th of May) has been set up by the academic societies for geology in Japan and GSJ in 2007. The Geology Day is expected to provide the chances for the public to enjoy field trips and excursions and to understand the importance of geo-diversity. The Day

Indigenous Models of Therapy in Traditional Asian Societies.

ERIC Educational Resources Information Center

Das, Ajit K.

1987-01-01

Presents an overview of some indigenous ways of understanding and dealing with psychological disorders in the traditional societies of Asia. Indigenous approaches to healing and psychotherapy existing in India, China, and Japan are included. Models of healing in these three societies are classified as folk traditions, mystical traditions, and…

Prevention of atherosclerosis with dietary antioxidants: fact or fiction?

PubMed

Duell, P B

1996-04-01

The notion that oxidation of lipids and lipoproteins may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. It is hypothesized that dietary antioxidants may help prevent development and progression of atherosclerosis. The available evidence helps substantiate this hypothesis but is not yet conclusive. The results of several ongoing large randomized intervention trials will provide valuable information about the efficacy and safety of supplemental dietary antioxidants in prevention of atherosclerosis.

Forecasting Japan's Physician Shortage in 2035 as the First Full-Fledged Aged Society

PubMed Central

Yamaguchi, Rui; Matsumura, Tomoko; Murashige, Naoko; Kodama, Yuko; Minayo, Satoru; Imai, Kohzoh; Kami, Masahiro

2012-01-01

Introduction Japan is rapidly becoming a full-fledged aged society, and physician shortage is a significant concern. The Japanese government has increased the number of medical school enrollments since 2008, but some researchers warn that this increase could lead to physician surplus in the future. It is unknown how many physicians will be required to accommodate future healthcare needs. Materials and Methods We simulated changes in age/sex composition of the population, fatalities (the number of fatalities for the consecutive five years), and number of physicians from 2010 to 2035. Two indicators were defined: fatalities per physician and fatalities by physician working hour, based on the data of the working hours of physicians for each tuple of sex and age groups. We estimated the necessary number of physicians in 2035 and the number of new physicians to maintain the indicator levels in 2010. Results The number of physicians per 1,000 population is predicted to rise from 2·00 in 2010 to 3·14 in 2035. The number of physicians aged 60 years or older is expected to increase from 55,375 (20% of physicians) to 141,711 (36%). In 2010 and 2035, fatalities per physician were 23·1 and 24·0 for the total population, and 13·9 and 19·2 for 75 years or older, respectively. Fatalities per physician working hour are predicted to rise from 0·128 to 0·138. If working hours are limited to 48 hours per week in 2035, the number of fatalities per physician working hour is expected to be 0·196, and the number of new physicians must be increased by 53% over the current pace. Discussion The number of physicians per population continues to rise, but the estimated supply will not fulfill the demand for healthcare in the aging society. Strategies to increase the number of physicians and improve working conditions are urgently needed. PMID:23233868

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1

PubMed Central

Sivasubramaniyam, Tharini; Schroer, Stephanie A.; Li, Angela; Luk, Cynthia T.; Shi, Sally Yu; Besla, Rickvinder; Metherel, Adam H.; Kitson, Alex P.; Brunt, Jara J.; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P.; Bendeck, Michelle P.; Robbins, Clinton S.

2017-01-01

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2’s essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection. PMID:28724798

[Neurology in Japan before World War II].

PubMed

Takahashi, Akira

2013-01-01

Modern Western medicine was introduced into Japan by a Dutch doctor Pompe van Meerdervoort in 1855. A German physician EOE von Balz devoted himself to educating medicine at Tokyo Medical School, the predecessor of the present University of Tokyo for 25 years. Hiroshi Kawahara and Kinnosuke Miura, pioneers of Japan Neurology, received their education by him. Kawahara first described X-linked bulvo-spinal muscular atrophy, and published the first Japanese textbook of clinical neurology in 1897. In 1902, Miura and others founded the Japanese Society of Neuro-Psychiatry, the forerunner of the present " Japanese Society of Neurology ". Both Seizo Katsunuma, Professor of Nagoya University, and Junnjiro Kato, Professor of Tohoku University, succeeded Miura's neurology. Miura investigated into the cause of beriberi, but ended in failure. Hasegawa's proposal at the Diet in 1894 that the Japan Government should found an independent department of neurology in the University of Tokyo was unfortunately rejected. There was no foundation of independent institute, department and clinic of neurology before World War II. Consequently Japanese neurology was on the ebb at that time.

Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

PubMed

Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

2014-12-01

The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Viewpoint of Science Council of Japan

NASA Astrophysics Data System (ADS)

Ikeda, Syunsuke

The Science Council of Japan (SCJ) is an academic body that represents Japanese 700,000 scientists. The activity of SCJ is changing rapidly, in which the science associated with society is increasingly important. In this context, the engineering education for ethics is treated at SCJ. The importance of engineering ethics was first recognized at the 5th division of 17th term (1999-2001) of SCJ, in which education for engineering ethics based on the analysis of ethical problems occurred in Japan is recommended and it asked the engineering societies to establish the code of ethics. Following this proposal, SCJ founded a committee to treat the problem at 18th and 19th terms. The committee proposed a procedure to prevent misconduct associated with scientific activities and the importance of education of science and engineering ethics especially for young students at tertiary education.

[CHRONIC FLUORIDE INTOXICATION AS A RISK FACTOR FOR THE DEVELOPMENT OF ATHEROSCLEROSIS].

PubMed

Korotenko, O Yu; Panev, N I; Zakharenkov, V V; Filimonov, S N; Semenova, E A; Panev, R N

2015-01-01

In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology

Suppression of atherosclerosis by synthetic REV-ERB agonist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks comparedmore » to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.« less

Recent Cooperative Research Activities of HDD and Flexible Media Transport Technologies in Japan

NASA Astrophysics Data System (ADS)

Ono, Kyosuke

This paper presents the recent status of industry-university cooperative research activities in Japan on the mechatronics of information storage and input/output equipment. There are three research committees for promoting information exchange on technical problems and research topics of head-disk interface in hard disk drives (HDD), flexible media transport and image printing processes which are supported by the Japan Society of Mechanical Engineering (JSME), the Japanese Society of Tribologists (JAST) and the Japan Society of Precision Engineering (JSPE). For hard disk drive technology, the Storage Research Consortium (SRC) is supporting more than 40 research groups in various different universities to perform basic research for future HDD technology. The past and present statuses of these activities are introduced, particularly focusing on HDD and flexible media transport mechanisms.

Fine particulate matter air pollution and atherosclerosis: Mechanistic insights.

PubMed

Bai, Yuntao; Sun, Qinghua

2016-12-01

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous plaque in the arteries. Its etiology is very complicated and its risk factors primarily include genetic defects, smoking, hyperlipidemia, hypertension, lack of exercise, and infection. Recent studies suggest that fine particulate matter (PM2.5) air pollution may also contribute to the development of atherosclerosis. The present review integrates current experimental evidence with mechanistic pathways whereby PM2.5 exposure can promote the development of atherosclerosis. PM2.5-mediated enhancement of atherosclerosis is likely due to its pro-oxidant and pro-inflammatory effects, involving multiple organs, different cell types, and various molecular mediators. Studies about the effects of PM2.5inhalation on atherosclerosis may yield a better understanding of the link between air pollution and major cardiovascular diseases, and provide useful information for policy makers to determine acceptable levels of PM2.5 air quality. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Copyright © 2016 Elsevier B.V. All rights reserved.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

Plant sterol enriched functional food and atherosclerosis

PubMed Central

Köhler, Jürgen; Teupser, Daniel; Elsässer, Albrecht

2017-01-01

Hypercholesterolaemia is a major cardiovascular risk factor. A healthy diet and a healthy lifestyle reduces cardiovascular risk. ‘Functional foods’ supplemented with phytosterols are recommended for the management of hypercholesterolaemia and have become a widely used non‐prescription approach to lower plasma cholesterol levels. Two billion euros are spent world‐wide each year on various functional foods, which have regulator‐approved health claims for the management of elevated cholesterol levels. While international societies, such as the European Atherosclerosis Society or the National Heart Foundation in Australia, still advise phytosterols as an additional dietary option in the management of hypercholesterolaemia, recently released guidelines such as those from the National Institute of Health and Clinical Excellence in the United Kingdom are more critical of food supplementation with phytosterols and draw attention to significant safety issues. This review challenges whether an intervention with phytosterol supplements is beneficial. We summarize the current evidence from genetic diseases, genetic association studies, clinical trial data and data from animal studies. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:28253422

Myocardin: A novel player in atherosclerosis.

PubMed

Xia, Xiao-Dan; Zhou, Zhen; Yu, Xiao-Hua; Zheng, Xi-Long; Tang, Chao-Ke

2017-02-01

Myocardin (MYOCD) the most important coactivator of serum response factor (SRF), plays a critical role specifically in the development of cardiac myocytes and vascular smooth muscle cells (VSMCs). Binding of Myocardin to the SRF on the CArG box-containing target genes can transcriptionally activate a variety of downstream muscle-specific genes, such as Sm22α, Acta2, Myh11, and several other signaling pathways. Myocardin expression represents a contractile and differentiated SMC phenotype. Loss of Myocardin, however, represents a synthetic and dedifferentiated phenotype, a hallmark in atherosclerosis. Growing evidence shows that Myocardin is involved in lipid metabolism and vascular inflammation, the primary pathogenesis of atherosclerosis. Moreover, Myocardin expression level is altered in atherosclerotic patients and animal models, suggesting more extensive and important roles for Myocardin in atherosclerosis. In the current review, we summarized recent progress on the regulation and signaling of Myocardin, and highlighted its impacts on atherosclerotic disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metabolic profiling of murine plasma reveals eicosapentaenoic acid metabolites protecting against endothelial activation and atherosclerosis.

PubMed

Liu, Yajin; Fang, Xuan; Zhang, Xu; Huang, Jing; He, Jinlong; Peng, Liyuan; Ye, Chenji; Wang, Yingmei; Xue, Fengxia; Ai, Ding; Li, Dan; Zhu, Yi

2018-04-01

Atherosclerosis results from a maladaptive inflammatory response initiated by the intramural retention of LDL in susceptible areas of the arterial vasculature. The ω-3 polyunsaturated fatty acids (ω-3) have protective effects in atherosclerosis; however, their molecular mechanism is still largely unknown. The present study used a metabolomic approach to reveal the atheroprotective metabolites of ω-3 and investigate the underlying mechanisms. We evaluated the development of atherosclerosis in LDL receptor-deficient mice (LDLR -/- ) fed a Western-type diet (WTD) plus ω-3 and also LDLR -/- and fat-1 transgenic (LDLR -/- -fat-1 tg ) mice fed a WTD. The profiles of ω-3 in the plasma were screened by LC-MS/MS using unbiased systematic metabolomics analysis. We also studied the effect of metabolites of eicosapentaenoic acid (EPA) on endothelial activation in vitro. The ω-3 diet and fat-1 transgene decreased monocyte infiltration, inhibited the expression of pro-inflammatory genes and significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in LDLR -/- mice. The content of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17,18-epoxy-eicosatetraenoic acid (17,18-EEQ), from the cytochrome P450 pathway of EPA, was significantly higher in plasma from both ω-3-treated LDLR -/- and LDLR -/- -fat-1 tg mice as compared with WTD-fed LDLR -/- mice. In vitro in endothelial cells, 18-HEPE or 17,18-EEQ decreased inflammatory gene expression induced by TNFα via NF-κB signalling and thereby inhibited monocyte adhesion to endothelial cells. EPA protected against the development of atherosclerosis in atheroprone mice via the metabolites 18-HEPE and/or 17,18-EEQ, which reduced endothelial activation. These compounds may have therapeutic implications in atherosclerosis. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10

Changing roles of academic societies due to globalization.

PubMed

Ehara, Shigeru; Aoki, Shigeki; Honda, Hiroshi

2016-10-01

Because of the globalization of environment around the academic society, the expected roles have changed significantly. In this short communication, we present the current situation in our international activities of the Japan Radiological Society, particularly in the academic activities and clinical practice. Establishing and reinforcing international network is one process of their promotion.

Pregnancy-related acute myocardial infarction in Japan: a review of epidemiology, etiology and treatment from case reports.

PubMed

Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu

2013-01-01

Pregnancy-related acute myocardial infarction (AMI) is uncommon, but can result in maternal and/or fetal death. This study retrospectively reviews pregnancy-related AMI reported from medical institutions in Japan. We electronically or manually searched the literature for reports of pregnancy-related AMI between 1981 and 2011. In total, 62 patients were described and the numbers increased in accordance with the rising average age of the mothers. AMI occurred frequently in women aged 30-34 years (mean age, 33), in the third trimester and postpartum (n=11 and n=28, respectively). The prevalence of conventional risk factors was relatively low (n=21). On the other hand, 29 patients had obstetric and/or non-obstetric complications, and 24 received medication. Only 8 AMI were caused by atherosclerosis, while coronary dissection, thrombus and spasm were the cause in 14, 9 and 12 cases, respectively. All patients with atherosclerosis had conventional risk factors, and some patients with spasm had a history of smoking. Medication with ergot derivatives was associated mostly with spasm, whereas ritodrine was potentially related to dissection. The prevalence of pregnancy-related AMI in Japan seems lower than in Western countries, and the etiology differs considerably. However, as the trend of later childbearing continues, more pregnant women have more risk factors, complications, and require medication. Cardiologists and obstetricians must consider the increased risk of AMI.

Which should be the essential components of stroke centers in Japan? A survey by questionnaires sent to the directors of facilities certified by the Japan stroke society.

PubMed

Uehara, Toshiyuki; Yasui, Nobuyuki; Okada, Yasushi; Hasegawa, Yasuhiro; Nagatsuka, Kazuyuki; Minematsu, Kazuo

2014-01-01

We conducted a survey by questionnaire to identify the essential components of stroke centers in Japan and compared our results with the European Expert Survey. In 2007, a questionnaire was mailed to the directors of 740 facilities certified by the Japan Stroke Society to ask their opinion on the essential components of comprehensive stroke centers (CSC), primary stroke centers (PSC) and any hospital ward (AHW) admitting acute stroke patients. The directors were asked to provide 1 of the following 6 possible answers regarding 112 components: 'irrelevant'; 'useful but not necessary'; 'desirable'; 'important but not absolutely necessary'; 'absolutely necessary', or 'question unclear or ambiguous'. The components considered 'absolutely necessary' by more than 75% of the respondents were compared between our survey and the European Expert Survey. In addition, we compared the rates of neurosurgeons and neurologists who answered 'absolutely necessary' with regard to each component. Responses were obtained from 428 directors (57.8% response rate). Among these respondents, 298 (69.6%) were neurosurgeons. There was no component considered 'absolutely necessary' for AHW by more than 75% of the respondents, and this was similar to the results of the European Expert Survey. The following components were considered 'absolutely necessary' for PSC in our survey: brain CT scanning 24 h a day, 7 days a week (24/7); automated monitoring of the ECG, pulse oximetry, blood pressure and breathing, and respiratory support. In both our survey and the European Expert Survey, the essential components for CSC were as follows: physiotherapist; brain CT scanning 24/7; monitoring of the ECG, pulse oximetry and blood pressure; carotid surgery; angioplasty and stenting, and intravenous recombinant tissue plasminogen activator protocols. The components multidisciplinary stroke team, stroke-trained nurse, ultrasonography, collaboration with an outside rehabilitation center, stroke pathway and

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

PubMed Central

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood

The Issue of Nutrition in an Aging Society.

PubMed

Kido, Yasuhiro

2015-01-01

Viewed from a global perspective, Japan is often considered a country where the progression towards a low birthrate and longevity has been prominent. In 2007, the ratio of the aged population reached 21.5%, propelling Japan into the classification of a super aging society. The long-term care insurance system in Japan was initiated in the year 2000, as a general long-term care service system for the whole society, covering the nutrition, medical care, and welfare fields. The goal of nutrition in an aged society is the extension of healthy life expectancy. The ratio of elderly citizens with malnutrition is high. Due to the loss of teeth, and a decrease in digestive and physical functions, there is often a decrease in appetite, and the inability to obtain enough nutrition for physical homeostasis is related to such conditions as frailty and the partial loss of physical functions due to sarcopenia, as well as a decrease in the quality of life (QOL). The elderly can easily fall into a state of protein and energy malnutrition (PEM), due to a variety of causes. Accordingly, it is important to adopt an appropriate approach that ensures a correct understanding of the causes of malnutrition and the special characteristics of malnutrition in the elderly.

U.S.-Japan Quake Prediction Research

NASA Astrophysics Data System (ADS)

Kisslinger, Carl; Mikumo, Takeshi; Kanamori, Hiroo

For the seventh time since 1964, a seminar on earthquake prediction has been convened under the U.S.-Japan Cooperation in Science Program. The purpose of the seminar was to provide an opportunity for researchers from the two countries to share recent progress and future plans in the continuing effort to develop the scientific basis for predicting earthquakes and practical means for implementing prediction technology as it emerges. Thirty-six contributors, 15 from Japan and 21 from the U.S., met in Morro Bay, Calif.September 12-14. The following day they traveled to nearby sections of the San Andreas fault, including the site of the Parkfield prediction experiment. The conveners of the seminar were Hiroo Kanamori, Seismological Laboratory, California Institute of Technology (Caltech), for the U.S., and Takeshi Mikumo, Disaster Prevention Research Institute, Kyoto University, for Japan . Funding for the participants came from the U.S. National Science Foundation and the Japan Society forthe Promotion of Science, supplemented by other agencies in both countries.

Low-density lipoprotein cholesterol levels and lipid-modifying therapy prescription patterns in the real world: An analysis of more than 33,000 high cardiovascular risk patients in Japan.

PubMed

Teramoto, Tamio; Uno, Kiyoko; Miyoshi, Izuru; Khan, Irfan; Gorcyca, Katherine; Sanchez, Robert J; Yoshida, Shigeto; Mawatari, Kazuhiro; Masaki, Tomoya; Arai, Hidenori; Yamashita, Shizuya

2016-08-01

Low-density lipoprotein cholesterol (LDL-C) is a key modifiable risk factor in the development of cardiovascular (CV) disease. In 2012, the Japan Atherosclerosis Society (JAS) issued guidelines recommending statins as first-line pharmacotherapy for lowering LDL-C in patients at high risk for CV events. This study assessed achievement of recommended LDL-C goals and lipid-modifying therapy (LMT) use in a high CV risk population in Japan. Patients from the Medical Data Vision (MDV) database, an electronic hospital-based claims database in Japan, who met the following inclusion criteria were included in this study: LDL-C measurement in 2013; ≥20 years of age; ≥2 years representation in the database; and a high CV risk condition (recent acute coronary syndrome (ACS), other coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) or diabetes). LDL-C goal attainment was assessed based on LDL-C targets in the JAS guidelines. A total of 33,325 high CV risk patients met the inclusion criteria. Overall, 68% of the cohort achieved guideline recommended LDL-C targets, with only 42% receiving current treatment with statins. Attainment of LDL-C goals was 68% for ACS, 55% for CHD, and 80% each for ischemic stroke, PAD, and diabetes patients. Concomitant use of non-statin LMTs was low. In a high CV risk population in a routine care setting in Japan, guideline recommended LDL-C goal attainment and utilization of statins and other LMT was low. In addition, physicians appeared to be more likely to consider the initiation of statins in patients with higher baseline LDL-C levels. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Cyclooxygenase-2: a new therapeutic target in atherosclerosis?].

PubMed

Páramo, José A; Beloqui, Oscar; Orbe, Josune

2006-05-27

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Systemic inflammatory markers (C reactive protein, cytokines adhesion molecules) also play a role in this process. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. Recent reports by our group have demonstrated increased monocyte COX-2 activity and the production of prostaglandin E2 in relation to cardiovascular risk factors and subclinical atherosclerosis in asymptomatic subjects. Our findings support the notion that the COX-2/prostaglandin E2 axis may have a role, raising the question as to whether its selective inhibition might be an attractive therapeutic target in atherosclerosis. COX-2 inhibitors, collectively called "coxibs" (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise as anti-inflammatory drugs without the some of the side effects of aspirin or non steroidal antiinflammatory agents. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk, and therefore coxibs should be restricted in atherosclerosis-prone patients.

What are the qualifications and selection criteria for women to be appointed to society journal editorial boards?

PubMed

Tomizawa, Yasuko

2014-02-01

Japan ranks extremely low in global ranking of gender equality. It is not easy for female doctors to acquire leadership positions in member societies of the Japanese Association of Medical Science (JAMS). Very few women are included on editorial boards of English medical journals in Japan. Furthermore, until last year, there had been no female editors in English language journals of surgical societies. The qualifications and criteria for selecting editorial board members of medical journals should be clarified. Medical journals in Japan would gain diversity by including women on editorial boards in the same proportion as women membership in the corresponding medical societies.

Current trends in health insurance systems: OECD countries vs. Japan.

PubMed

Sasaki, Toshiyuki; Izawa, Masahiro; Okada, Yoshikazu

2015-01-01

Over the past few decades, the longest extension in life expectancy in the world has been observed in Japan. However, the sophistication of medical care and the expansion of the aging society, leads to continuous increase in health-care costs. Medical expenses as a part of gross domestic product (GDP) in Japan are exceeding the current Organization for Economic Co-operation and Development (OECD) average, challenging the universally, equally provided low cost health care existing in the past. A universal health insurance system is becoming a common system currently in developed countries, currently a similar system is being introduced in the United States. Medical care in Japan is under a social insurance system, but the injection of public funds for medical costs becomes very expensive for the Japanese society. In spite of some urgently decided measures to cover the high cost of advanced medical treatment, declining birthrate and aging population and the tendency to reduce hospital and outpatients' visits numbers and shorten hospital stays, medical expenses of Japan continue to be increasing.

Current Trends in Health Insurance Systems: OECD Countries vs. Japan

PubMed Central

SASAKI, Toshiyuki; IZAWA, Masahiro; OKADA, Yoshikazu

2015-01-01

Over the past few decades, the longest extension in life expectancy in the world has been observed in Japan. However, the sophistication of medical care and the expansion of the aging society, leads to continuous increase in health-care costs. Medical expenses as a part of gross domestic product (GDP) in Japan are exceeding the current Organization for Economic Co-operation and Development (OECD) average, challenging the universally, equally provided low cost health care existing in the past. A universal health insurance system is becoming a common system currently in developed countries, currently a similar system is being introduced in the United States. Medical care in Japan is under a social insurance system, but the injection of public funds for medical costs becomes very expensive for the Japanese society. In spite of some urgently decided measures to cover the high cost of advanced medical treatment, declining birthrate and aging population and the tendency to reduce hospital and outpatients’ visits numbers and shorten hospital stays, medical expenses of Japan continue to be increasing. PMID:25797778

Subclinical atherosclerosis and subsequent cognitive function

PubMed Central

Rossetti, Heidi C.; Weiner, Myron; Hynan, Linda S.; Cullum, C. Munro; Khera, Amit; Lacritz, Laura H.

2016-01-01

Objective To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Method Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8–65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. Results A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥.052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥.455). Conclusion In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. PMID:25957568

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

PubMed Central

Baxter, Samantha; Menon, Arjun; Alaarg, Amr; Sanchez-Gaytan, Brenda L.; Fay, Francois; Zhao, Yiming; Ouimet, Mireille; Braza, Mounia S.; Longo, Valerie A.; Abdel-Atti, Dalya; Duivenvoorden, Raphael; Calcagno, Claudia; Storm, Gert; Tsimikas, Sotirios; Moore, Kathryn J.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Pérez-Medina, Carlos; Fayad, Zahi A.; Reiner, Thomas; Mulder, Willem J. M.

2016-01-01

Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library’s nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe−/−) mouse model of atherosclerosis, we quantitatively evaluated the library’s immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases. PMID:27791119

Testing the iron hypothesis in a mouse model of atherosclerosis

PubMed Central

Kautz, Léon; Gabayan, Victoria; Wang, Xuping; Wu, Judy; Onwuzurike, James; Jung, Grace; Qiao, Bo; Lusis, Aldons J.; Ganz, Tomas; Nemeth, Elizabeta

2013-01-01

SUMMARY Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to contribute to the pathogenesis of atherosclerosis by promoting iron accumulation in plaque macrophages, leading to increased oxidative stress and inflammation in the plaque (the “iron hypothesis”). Hepcidin and iron may thus represent modifiable risk factors in atherosclerosis. We measured hepcidin expression in Apoe−/− mice with varying diets and ages. To assess the role of macrophage iron in atherosclerosis, we generated Apoe−/− mice with macrophage-specific iron accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading was also enhanced by intravenous iron injection. Contrary to the iron hypothesis, we found that hepatic hepcidin expression was not increased at any stage of the atherosclerosis progression in Apoe−/− or Apoe/ffe mice and the atherosclerotic plaque size was not increased in mice with elevated macrophage iron. Our results strongly argue against any significant role of macrophage iron in atherosclerosis progression in mice. PMID:24316081

The walking dead: macrophage inflammation and death in atherosclerosis.

PubMed

Kavurma, Mary M; Rayner, Katey J; Karunakaran, Denuja

2017-04-01

To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis. Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque. Here, we outline the different types of lesional macrophage death: apoptosis, autophagic and the newly defined necroptosis (i.e. a type of programmed necrosis). Recent discoveries demonstrate that macrophage necroptosis directly contributes to necrotic core formation and plaque instability. Further, promoting the resolution of inflammation using preresolving mediators has been shown to enhance efferocytosis and decrease plaque vulnerability. Finally, the canonical 'don't eat me' signal CD47 has recently been described as playing an important role in atherosclerotic lesion progression by impairing efficient efferocytosis. Although we have made significant strides in improving our understanding of cell death and clearance mechanisms in atherosclerosis, there still remains unanswered questions as to how these pathways can be harnessed using therapeutics to promote lesion regression and disease stability. Improving our understanding of the mechanisms that regulate macrophage death in atherosclerosis, in particular apoptosis, necroptosis and efferocytosis, will provide novel therapeutic opportunities to resolve atherosclerosis and promote plaque stability.

Words of Tohkaku Wada: medical heritage in Japan

PubMed Central

Matsumoto, M.; Inoue, K.; Kajii, E.

2001-01-01

The origins of Japan's medical ideas, which are deeply rooted in its religion, culture and history, are not widely understood in medical societies of other countries. We have taken up the task of summarising this tradition here so that some insight can be gained into the unique issues that characterise the practice of medicine in Japan. We borrow from the sayings of Tohkaku Wada, a medical philosopher of late eighteenth-century Japan, for a look at Japanese medical tradition. Wada's medical thought was very much reflective of the Buddhism, Zen, and swordsmanship that informed eighteenth-century philosophy in Japan. His central concepts were "chu" and "sei", that is, complete and selfless dedication to the patient and the practice of medicine. This paper explores Wada's thought, explaining it mainly from the standpoint of Japanese traditional culture. Key Words: Tohkaku Wada • ethics • philosophy • Buddhism • Zen • Japan PMID:11233381

Infectious burden and atherosclerosis: A clinical issue

PubMed Central

Sessa, Rosa; Pietro, Marisa Di; Filardo, Simone; Turriziani, Ombretta

2014-01-01

Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

Japan in the Classroom: Elementary and Secondary Activities, Revised Edition.

ERIC Educational Resources Information Center

Parisi, Lynn; And Others

This activity book is designed to present information and insights on Japanese culture and society. Because few teachers can devote entire units to the study of Japan, the activities focus on teaching about Japan within the context of larger social science units. Some of the lessons can be taught within the context of the humanities and fine arts,…

Suppression of atherosclerosis by synthetic REV-ERB agonist

PubMed Central

Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2015-01-01

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. PMID:25800870

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

PubMed Central

Ng, Chun-Yi; Jaarin, Kamsiah

2015-01-01

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

Intranasal immunization with heat shock protein 60 induces CD4(+) CD25(+) GARP(+) and type 1 regulatory T cells and inhibits early atherosclerosis.

PubMed

Zhong, Y; Tang, H; Wang, X; Zeng, Q; Liu, Y; Zhao, X I; Yu, K; Shi, H; Zhu, R; Mao, X

2016-03-01

Atherosclerosis is an autoimmune inflammatory disease involving both innate and adaptive immune mechanisms. Immune tolerance induction may have therapeutic potential for the suppression of atherosclerosis. Current interest is directed towards mucosal tolerance induction, especially nasal tolerance. Previous studies have shown that heat shock protein 60 (HSP60) is recognized as an important autoantigen in atherosclerosis, and nasal or oral HSP60 can induce tolerance and ameliorate atherosclerosis by inducing several subsets of regulatory T cells (Tregs ) such as latency-associated peptide (LAP)(+) and forkhead box transcription factor 3 (FoxP3)(+) Tregs. However, little is known regarding the detailed mechanisms of nasal tolerance. Here, we again investigated the impact of nasal HSP60 on atherosclerosis and the mechanisms underlying the anti-atherosclerosis responses. We found that nasal HSP60 caused a significant 33·6% reduction in plaque size at the aortic root in the early stages of atherosclerosis (P < 0·001). Notably, a significant increase in activated CD4(+) CD25(+) glycoprotein A repetitions predominant (GARP)(+) Tregs, type 1 Tregs (Tr1 cells), and CD4(+) CD25(+) FoxP3(+) Tregs, as well as a marked decrease in the numbers of type 1 and 17 T helper cells was detected in the spleens and cervical lymph nodes of HSP60-treated mice. Moreover, nasal HSP60 increases the production of transforming growth factor (TGF)-β and interleukin (IL)-10 and decreases the secretion of IFN-γ and IL-17. Interestingly, the atheroprotective role of nasal HSP60 treatment was abrogated partly by the neutralization of IL-10. Our findings show that nasal administration of HSP60 can attenuate atherosclerotic formation by inducing GARP(+) Tregs, Tr1 cells and FoxP3(+) Tregs, and that these Tregs maintain immune homeostasis by secreting IL-10 and TGF-β. © 2015 British Society for Immunology.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

PubMed

Greco, D; Kocyigit, D; Adorni, M P; Marchi, C; Ronda, N; Bernini, F; Gurses, K M; Canpinar, H; Guc, D; Oguz, S H; Gurlek, A; Strazzella, A; Simonelli, S; Tokgozoglu, L; Zimetti, F

2018-05-12

Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-β HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-β HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-β HDL (r 2  = 0.346; p < 0.001) and resistin (r 2  = 0.220; p = 0.009). Our data support vitD supplementation for CV risk prevention. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and

Words of Tohkaku Wada: medical heritage in Japan.

PubMed

Matsumoto, M; Inoue, K; Kajii, E

2001-02-01

The origins of Japan's medical ideas, which are deeply rooted in its religion, culture and history, are not widely understood in medical societies of other countries. We have taken up the task of summarising this tradition here so that some insight can be gained into the unique issues that characterise the practice of medicine in Japan. We borrow from the sayings of Tohkaku Wada, a medical philosopher of late eighteenth-century Japan, for a look at Japanese medical tradition. Wada's medical thought was very much reflective of the Buddhism, Zen, and swordsmanship that informed eighteenth-century philosophy in Japan. His central concepts were "chu" and "sei", that is, complete and selfless dedication to the patient and the practice of medicine. This paper explores Wada's thought, explaining it mainly from the standpoint of Japanese traditional culture.

Therapies targeting innate immunity for fighting inflammation in atherosclerosis.

PubMed

Mendel, Itzhak; Yacov, Niva; Harats, Dror; Breitbart, Eyal

2015-01-01

Atherosclerosis is a smoldering disease of the vasculature that can lead to the occlusion of the arteries, resulting in ischemia of the heart and brain. For many years, the asserted underlying mechanism of atherosclerosis, supported by its epidemiology, was based on the "cholesterol hypothesis" that people with high blood cholesterol are at higher risk of developing cardiovascular disease. This hypothesis instigated a vigorous search for treatment that yielded the generation of statins, which specifically reduce LDL cholesterol. Since then, statins have revolutionized the way people are treated for the prevention of atherosclerosis. Nonetheless, despite this potent class of drugs, cardiovascular disease continues to be the leading cause of death in many parts of the world, suggesting that additional mechanisms are involved in disease pathogenesis. Intensive research has revealed that the atherosclerotic plaque is enriched with leukocytes, and that macrophages constitute the majority of immune cells in the lesion. Monocytes/macrophages are now recognized as the prime immune cells involved in the development of atherosclerosis and are implicated to affect the size, composition and vulnerability of the atherosclerotic plaque. While many of the macrophage-derived pro-inflammatory mechanisms associated with atherogenesis have been characterized, such as cell adhesion, cytokine production and protease secretion, there is a dearth of drugs that specifically target innate immunity for treating patients with atherosclerosis. This review presents pre-clinical studies, and in most cases following clinical trials with antagonists and agonists that have been designed to counteract inflammation in atherosclerosis and associated diseases, highlighting targets expressed predominantly in monocytes.

Macrophage Phenotype and Function in Different Stages of Atherosclerosis

PubMed Central

Tabas, Ira; Bornfeldt, Karin E.

2016-01-01

The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for more than 50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to HDL; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and pro-resolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID:26892964

Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

PubMed

Saito, Isao

2012-01-01

Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

Subclinical atherosclerosis and subsequent cognitive function.

PubMed

Rossetti, Heidi C; Weiner, Myron; Hynan, Linda S; Cullum, C Munro; Khera, Amit; Lacritz, Laura H

2015-07-01

To examine the relationship between measures of subclinical atherosclerosis and subsequent cognitive function. Participants from the Dallas Heart Study (DHS), a population-based multiethnic study of cardiovascular disease pathogenesis, were re-examined 8 years later (DHS-2) with the Montreal Cognitive Assessment (MoCA); N = 1904, mean age = 42.9, range 8-65. Associations of baseline measures of subclinical atherosclerosis (coronary artery calcium, abdominal aortic plaque, and abdominal aortic wall thickness) with MoCA scores measured at follow-up were examined in the group as a whole and in relation to age and ApoE4 status. A significant linear trend of successively lower MoCA scores with increasing numbers of atherosclerotic indicators was observed (F(3, 1150) = 5.918, p = .001). CAC was weakly correlated with MoCA scores (p = .047) and MoCA scores were significantly different between participants with and without CAC (M = 22.35 vs 23.69, p = 0.038). With the exception of a small association between abdominal AWT and MoCA in subjects over age 50, abdominal AWT and abdominal aortic plaque did not correlate with MoCA total score (p ≥ .052). Cognitive scores and atherosclerosis measures were not impacted by ApoE4 status (p ≥ .455). In this ethnically diverse population-based sample, subclinical atherosclerosis was minimally associated with later cognitive function in middle-aged adults. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Complications associated with endobronchial ultrasound-guided transbronchial needle aspiration: a nationwide survey by the Japan Society for Respiratory Endoscopy.

PubMed

Asano, Fumihiro; Aoe, Motoi; Ohsaki, Yoshinobu; Okada, Yoshinori; Sasada, Shinji; Sato, Shigeki; Suzuki, Eiichi; Semba, Hiroshi; Fukuoka, Kazuya; Fujino, Shozo; Ohmori, Kazumitsu

2013-05-10

With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE). A questionnaire about EBUS-TBNA performed between January 2011 and June 2012 was mailed to 520 JSRE-accredited facilities. Responses were obtained from 455 facilities (87.5%). During the study period, EBUS-TBNA was performed in 7,345 cases in 210 facilities (46.2%) using a convex probe ultrasound bronchoscope, for 6,836 mediastinal and hilar lesions and 275 lung parenchymal lesions. Ninety complications occurred in 32 facilities. The complication rate was 1.23% (95% confidence interval, 0.97%-1.48%), with hemorrhage being the most frequent complication (50 cases, 0.68%). Infectious complications developed in 14 cases (0.19%) (Mediastinitis, 7; pneumonia, 4; pericarditis, 1; cyst infection, 1; and sepsis, 1). Pneumothorax developed in 2 cases (0.03%), one of which required tube drainage. Regarding the outcome of the cases with complications, prolonged hospitalization was observed in 14 cases, life-threatening conditions in 4, and death in 1 (severe cerebral infarction) (mortality rate, 0.01%). Breakage of the ultrasound bronchoscope occurred in 98 cases (1.33%) in 67 facilities (31.9%), and that of the puncture needle in 15 cases (0.20%) in 8 facilities (3.8%). Although the complication rate associated with EBUS-TBNA was found to be low, severe complications, including infectious complications, were observed, and the incidence of device breakage was high. Since the use of EBUS-TBNA is

C-reactive protein in relation to early atherosclerosis and periodontitis.

PubMed

Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

2012-02-01

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p < 0.05) and higher serum HDL (p < 0.001) than men. In all patients with periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Increased atherosclerosis in mice with increased vascular biglycan content.

PubMed

Thompson, Joel C; Tang, Tao; Wilson, Patricia G; Yoder, Meghan H; Tannock, Lisa R

2014-07-01

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development. Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4-12 weeks. LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content. Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development. Published by Elsevier Ireland Ltd.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers.

PubMed

Zingg, Sarah; Collet, Tinh-Hai; Locatelli, Isabella; Nanchen, David; Depairon, Michèle; Bovet, Pascal; Cornuz, Jacques; Rodondi, Nicolas

2016-06-01

The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the

Advanced atherosclerosis is associated with increased medial degeneration in sporadic ascending aortic aneurysms.

PubMed

Albini, Paul T; Segura, Ana Maria; Liu, Guanghui; Minard, Charles G; Coselli, Joseph S; Milewicz, Dianna M; Shen, Ying H; LeMaire, Scott A

2014-02-01

The pathogenesis of non-familial, sporadic ascending aortic aneurysms (SAAA) is poorly understood, and the relationship between ascending aortic atherosclerosis and medial degeneration is unclear. We evaluated the prevalence and severity of aortic atherosclerosis and its association with medial degeneration in SAAA. Atherosclerosis was characterized in ascending aortic tissues collected from 68 SAAA patients (mean age, 62.9 ± 12.0 years) and 15 controls (mean age, 56.6 ± 11.4 years [P = 0.07]) by using a modified American Heart Association classification system. Upon histologic examination, 97% of SAAA patients and 73% of controls showed atherosclerotic changes. Most SAAA samples had intermediate (types 2 and 3, 35%) or advanced atherosclerosis (types ≥ 4; 40%), whereas most control samples showed minimal atherosclerosis (none or type 1, 80%; P < 0.001 after adjusting for age). In a separate analysis, we examined the total incidence and grade distribution of medial degenerative changes among SAAA samples according to atherosclerosis grade. Advanced atherosclerosis was associated with higher grades of smooth muscle cell depletion (P < 0.001), elastic fiber depletion (P = 0.02), elastic fiber fragmentation (P < 0.001), and mucopolysaccharide accumulation (P = 0.04). Aortic diameter was larger in SAAA patients with advanced atherosclerosis than in patients with minimal (P = 0.04) or intermediate atherosclerosis (P = 0.04). Immunostaining showed marked CD3+ T-cell and CD68+ macrophage infiltration, MMP-2 and MMP-9 production, and cryopyrin expression in the medial layer adjacent to atherosclerotic plaque. SAAA tissues exhibited advanced atherosclerosis that was associated with severe medial degeneration and increased aortic diameter. Our findings suggest a role for atherosclerosis in the progression of sporadic ascending aortic aneurysms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Endothelial dysfunction in patients with coronary atherosclerosis.

PubMed

Chapidze, L; Kapanadze, S; Dolidze, N; Bakhutashvili, Z; Latsabidze, N

2007-01-01

It is well known that endothelial dysfunction as a nontraditional risk factor is an important early event in the pathogenesis of coronary atherosclerosis, contributing to plaque initiation and progression. In order to assess endothelial function plasma nitric oxide (NO) concentrations were determined. A total of 157 patients (119 men and 38 women, mean age 57+/-5,4 years) with coronary atherosclerosis were enrolled in the research. The study was cross-sectional in design. Most of the patients (n=127) had undergone myocardial revascularization procedures. There was statistically significant difference in mean values of plasma nitric oxide levels between patients with coronary atherosclerosis and healthy subjects (11,1+/-2,52 mkmol/L and 22,3+/-3,27 mkmol/L, respectively. p<0,01). Among all 157 patients only 17% had normal NO concentrations. In 59% cases low and in 24% cases high nitric oxide levels were found. Extent of coronary artery disease was associated with severity of endothelial dysfunction. The patients with three-vessel disease had the lowest mean plasma NO concentration. There was statistically significant negative correlation between mean plasma NO level and extent of coronary artery disease. Measurement of plasma nitric oxide concentration will give useful information for cardiologists, modification of abnormal levels of this parameter may delay progression of aggressive atherosclerotic process and thus, may prevent recurrent coronary events in patients with coronary atherosclerosis.

Review of mental-health-related stigma in Japan.

PubMed

Ando, Shuntaro; Yamaguchi, Sosei; Aoki, Yuta; Thornicroft, Graham

2013-11-01

The aim of this study is to understand the nature and characteristics of mental-health-related stigma among Japanese people. We searched relevant studies in English or Japanese published since 2001 using MEDLINE and PsycINFO, and found 19 studies that examined mental-health-related stigma in Japan. Regarding knowledge about mental illness, reviewed studies showed that in the Japanese general population, few people think that people can recover from mental disorders. Psychosocial factors, including weakness of personality, are often considered the cause of mental illness, rather than biological factors. In addition, the majority of the general public in Japan keep a greater social distance from individuals with mental illness, especially in close personal relationships. Schizophrenia is more stigmatized than depression, and its severity increases the stigmatizing attitude toward mental illness. The literature also showed an association between more direct social contact between health professionals and individuals with mental illness and less stigmatization by these professionals. Less stigmatization by mental health professionals may be associated with accumulation of clinical experience and daily contact with people who have mental illness. Stigmatizing attitudes in Japan are stronger than in Taiwan or Australia, possibly due to institutionalism, lack of national campaigns to tackle stigma, and/or society's valuing of conformity in Japan. Although educational programs appear to be effective in reducing mental-health-related stigma, future programs in Japan need to address problems regarding institutionalism and offer direct social contact with people with mental illness. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

PubMed

Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

The Development of the Counseling Profession in Japan: Past, Present, and Future

ERIC Educational Resources Information Center

Grabosky, Tomoko Kudo; Ishii, Harue; Mase, Shizuno

2012-01-01

The authors provide a sociohistorical overview of the development of the counseling profession in Japan. They describe Japan's major social, cultural, and political changes; growing psychological problems in Japanese society; and an increased need for counseling services. Historical overviews and the current state of counseling are presented with…

[Diagnostic criteria for Menière's disease. Consensus document of the Bárány Society, the Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society].

PubMed

Lopez-Escamez, José A; Carey, John; Chung, Won-Ho; Goebel, Joel A; Magnusson, Måns; Mandalà, Marco; Newman-Toker, David E; Strupp, Michael; Suzuki, Mamoru; Trabalzini, Franco; Bisdorff, Alexandre

2016-01-01

This paper presents diagnostic criteria for Menière's disease jointly formulated by the Classification Committee of the Bárány Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes 2 categories: definite Menière's disease and probable Menière's disease. The diagnosis of definite Menière's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low-to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 min and 12h. Probable Menière's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 min to 24h. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

Resistant Atherosclerosis: The Need for Monitoring of Plaque Burden.

PubMed

Spence, J David; Solo, Karla

2017-06-01

Recent studies indicate that patients with lower levels of low-density lipoprotein cholesterol (LDL-C) have greater regression of coronary plaque. In 2002, we found that carotid plaque progression doubled cardiovascular risk. In 2003, we therefore implemented a new approach, treating arteries instead of risk factors. Since then, we have seen many patients with carotid plaque progression despite very low levels of LDL-C, suggesting other causes of atherosclerosis. We studied the relationship of achieved LDL-C and change in LDL-C to progression/regression of atherosclerosis, before and after 2003. All 4512 patients in our clinic database with at least 2 measurements of LDL-C and carotid total plaque area approximately a year apart and complete data for analyses (n=2025 before and 2487 after December 31, 2003) were included in the study. Baseline total plaque area was significantly higher after 2003 (129.56±134.32 versus 113.33±121.52 mm 2 ; P <0.0001), and plaque progression was significantly less after 2003 (2.94±37.11 versus 12.62±43.24 mm 2 ; P <0.0001). Many patients with LDL-C <1.8 mm had plaque progression (47.5%), and change in LDL-C was not correlated with plaque progression/regression. Increasing age and serum creatinine contributed to resistant atherosclerosis. Many patients have Resistant Atherosclerosis, failing to achieve regression of atherosclerosis despite low levels of LDL-C. Instead of relying on LDL-C, measuring plaque burden may be a more useful way of assessing individual response to therapy, particularly in resistant atherosclerosis. © 2017 American Heart Association, Inc.

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

PubMed

Bertoluci, Marcello Casaccia; Moreira, Rodrigo Oliveira; Faludi, André; Izar, Maria Cristina; Schaan, Beatriz D; Valerio, Cynthia Melissa; Bertolami, Marcelo Chiara; Chacra, Ana Paula; Malachias, Marcus Vinicius Bolivar; Vencio, Sérgio; Saraiva, José Francisco Kerr; Betti, Roberto; Turatti, Luiz; Fonseca, Francisco Antonio Helfenstein; Bianco, Henrique Tria; Sulzbach, Marta; Bertolami, Adriana; Salles, João Eduardo Nunes; Hohl, Alexandre; Trujilho, Fábio; Lima, Eduardo Gomes; Miname, Marcio Hiroshi; Zanella, Maria Teresa; Lamounier, Rodrigo; Sá, João Roberto; Amodeo, Celso; Pires, Antonio Carlos; Santos, Raul D

2017-01-01

Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in

Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-β.

PubMed

Zhang, Cheng; Qin, Juan-Juan; Gong, Fu-Han; Tong, Jing-Jing; Cheng, Wen-Lin; Wang, Haiping; Zhang, Yan; Zhu, Xueyong; She, Zhi-Gang; Xia, Hao; Zhu, Li-Hua

2018-06-15

Mindin, which is a highly conserved extracellular matrix protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes, and immune responses. The aim of the present study was to assess whether mindin contributes to the development of atherosclerosis. A significant up-regulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE -/- mice after high-fat diet treatment. Mindin -/- ApoE -/- mice and macrophage-specific mindin overexpression in ApoE -/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis. The Mindin -/- ApoE -/- mice exhibited significantly ameliorated atherosclerotic burdens in the entire aorta and aortic root and increased atherosclerotic plaque stability. Moreover, bone marrow transplantation further demonstrated that mindin deficiency in macrophages was largely responsible for the alleviated atherogenesis. The Lyz2-mindin-TG mice exhibited the opposite phenotype. Mindin deficiency enhanced foam cell formation by increasing the expression of cholesterol effectors, including ABCA1 and ABCG1. The mechanistic study indicated that mindin ablation promoted LXR-β expression via a direct interaction. Importantly, LXR-β inhibition largely reversed the ameliorating effect of mindin deficiency on foam cell formation and ABCA1 and ABCG1 expression. The present study demonstrated that mindin deficiency serves as a novel mediator that protects against foam cell formation and atherosclerosis by directly interacting with LXR-β. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Frustration in a Chauvinist Society: Japanese Women Today.

ERIC Educational Resources Information Center

Metraux, Daniel A.

1987-01-01

Discusses the status of women in contemporary Japan. Describes their role as mothers and homemakers, the obstacles they face in maintaining developing careers, and the discrimination they face in a patriarchal society. (Author/ABB)

MicroRNAs in the pathobiology of atherosclerosis

PubMed Central

Laffont, Benoit; Rayner, Katey J

2017-01-01

MicroRNAs are short non-coding RNAs, expressed in humans and involved in sequence-specific post-transcriptional regulation of gene expression. They have emerged as key players in a wide array of biological processes, and changes in their expression and/or function have been associated with plethora of human diseases. Atherosclerosis and its related clinical complications, such as myocardial infarction or stroke, represent the leading cause of death in the western world. Accumulating experimental evidence has revealed a key role for microRNAs in regulating cellular and molecular processes related to atherosclerosis development, ranging from risk factors, to plaque initiation and progression, up to atherosclerotic plaque rupture. In this review, we will focus on how microRNAs can influence atherosclerosis biology, as well as the potential clinical applications of microRNAs which are being developed as both targets and therapeutics for a growing industry hoping to harness the power of RNA-guided gene regulation to fight disease and infection. PMID:28232017

Monocytic cell junction proteins serve important roles in atherosclerosis via the endoglin pathway

PubMed Central

Chen, Lina; Chen, Zhongliang; Ge, Menghua; Tang, Oushan; Cheng, Yinhong; Zhou, Haoliang; Shen, Yu; Qin, Fengming

2017-01-01

The formation of atherosclerosis is recognized to be caused by multiple factors including pathogenesis in monocytes during inflammation. The current study provided evidence that monocytic junctions were significantly altered in patients with atherosclerosis, which suggested an association between cell junctions and atherosclerosis. Claudin-1, occludin-1 and ZO-1 were significantly enhanced in atherosclerosis, indicating that the tight junction pathway was activated during the pathogenesis of atherosclerosis. In addition, the gene expression of 5 connexin members involved in the gap junction pathway were quantified, indicating that connexin 43 and 46 were significantly up-regulated in atherosclerosis. Furthermore, inflammatory factors including endoglin and SMAD were observed, suggesting that immune regulative factors were down-regulated in this pathway. Silicon-based analysis additionally identified that connexins and tight junctions were altered in association with monocytic inflammation regulations, endoglin pathway. The results imply that reduced expression of the immune regulation pathway in monocytes is correlated with the generation of gap junctions and tight junctions which serve important roles in atherosclerosis. PMID:28901429

[Cancer treatment situation in Japan with regard to the type of medical facility using medical claim data of Health Insurance Societies].

PubMed

Tanaka, Hirokazu; Nakamura, Fumiaki; Higashi, Takahiro; Kobayashi, Yasuki

2015-01-01

Analyzing the cancer treatment situation in Japan is an important public health issue, especially because of increasing crude cancer morbidity in a rapidly aging society. This study aimed to examine where cancer patients received treatment, with special attention to designated regional cancer hospitals, and the treatment modality they received. Using health insurance claim data (1,064,875 subjects on December 2011) managed by the Japan Medical Data Center, we included patients that received treatments for stomach, colon, liver, lung, or breast cancer, the most common cancers in Japan, between 2005 and 2011. We divided the medical facilities where they were treated into five groups: prefectural designated regional cancer hospitals, local designated regional cancer hospitals, large/medium hospitals (≥100 beds), small hospitals (20-99 beds), and clinics (0-19 beds). We calculated the percentage of patients treated at each type of medical facility with different treatment modalities. The study included 2,901 patients. In total, 43.9% patients were treated at designated regional cancer hospitals (prefectural or local). This percentage was the highest for lung cancer (60.0%) and the lowest for colon cancer (31.3%). Surgeries for liver cancer (67.6%) and lung cancer (61.9%) were performed more at designated regional cancer hospitals (prefectural or local) than surgeries for stomach cancer (45.5%), colon cancer (40.1%), and breast cancer (49.8%). Some procedures were performed at small hospitals or clinics (surgery for stomach cancer [9.4%], surgery for breast cancer [9.3%], endoscopic procedures for stomach cancer [14.1%] and colon cancer [40.6%], and chemotherapy for breast cancer [11.4%]). Colon and breast cancer patients treated at prefectural designated regional cancer hospitals or clinics were younger than those treated at other types of facilities. The distribution of facilities at which cancer patients received treatment differed significantly according to cancer

Macrophage Sortilin Promotes LDL Uptake, Foam Cell Formation, and Atherosclerosis

PubMed Central

Patel, Kevin M.; Strong, Alanna; Tohyama, Junichiro; Jin, Xueting; Morales, Carlos R.; Billheimer, Jeffery; Millar, John; Kruth, Howard; Rader, Daniel J.

2015-01-01

Rationale Non-coding gene variants at the SORT1 locus are strongly associated with LDL-C levels as well as with coronary artery disease (CAD). SORT1 encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apoB-containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown. Objective To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis. Methods and Results We crossed Sort1−/− mice onto a ‘humanized’ Apobec1−/−; hAPOB Tg background and determined that Sort1 deficiency on this background had no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the aorta and aortic root. In order to test whether this effect was a result of macrophage sortilin deficiency, we transplanted Sort1−/−;LDLR−/− or Sort1+/+;LDLR−/− bone marrow into Ldlr−/− mice and observed a similar reduction in atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma LDL-C levels. In an effort to determine the mechanism by which hematopoetic sortilin deficiency reduced atherosclerosis, we found no effect of sortilin deficiency on macrophage recruitment or LPS-induced cytokine release in vivo. In contrast, sortilin deficient macrophages had significantly reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo, whereas sortilin overexpression in macrophages resulted in increased LDL uptake and foam cell formation. Conclusions Macrophage sortilin deficiency protects against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated uptake of native LDL into macrophages may be an important mechanism of foam cell formation and contributor to atherosclerosis development. PMID:25593281

Intracranial atherosclerosis: current concepts.

PubMed

Arenillas, Juan F

2011-01-01

The most relevant ideas discussed in this article are described here. Intracranial atherosclerotic disease (ICAD) represents the most common cause of ischemic stroke worldwide. Its importance in whites may have been underestimated. New technical developments, such as high-resolution MRI, allow direct assessment of the intracranial atherosclerotic plaque, which may have a profound impact on ICAD diagnosis and therapy in the near future. Early detection of ICAD may allow therapeutic intervention while the disease is still asymptomatic. The Barcelonès Nord and Maresme Asymptomatic Intracranial Atherosclerosis Study is presented here. The main prognostic factors that characterize the patients who are at a higher risk for ICAD recurrence are classified and discussed. The best treatment for ICAD remains to be established. The Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Study is currently ongoing to address this crucial issue. These and other topics will be discussed at the Fifth International Intracranial Atherosclerosis Conference (Valladolid, Spain, autumn 2011).

Vascular wall shear stress in zebrafish model of early atherosclerosis

NASA Astrophysics Data System (ADS)

Choi, Woorak; Seo, Eunseok; Yeom, Eunseop; Lee, Sang Joon

2016-11-01

Although atherosclerosis is a multifactorial disease, the role of hemodynamic force has strong influence on the outbreak of the disease. Low and oscillating wall shear stress (WSS) is associated with the incidence of atherosclerosis. Many researchers have investigated relationships between WSS and the occurrence of atherosclerosis using in vitro and in vivo models. However, these models possess technological limitations in mimicking real biophysiological conditions and monitoring the temporal progression of atherosclerosis. In this study, a hypercholesterolaemic zebrafish model was established as a novel model to resolve these technical limitations. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro PIV technique, and the spatial distribution of lipids inside blood vessels was quantitatively visualized using a confocal microscopy. As a result, lipids are mainly deposited in the regions of low WSS. The oscillating WSS is not induced by blood flows in the zebrafish disease model. The present hypercholesterolaemic zebrafish model would be useful for understanding the effect of WSS on the early stage of atherosclerosis. This work was supported by the National Research Foundation of Korea (NRF) under a Grant funded by the Korean government (MSIP) (No. 2008-0061991).

Multi-Ethnic Study of Atherosclerosis (MESA)

ClinicalTrials.gov

2016-07-28

Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José

2005-01-01

Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

Associations of CXCL16/CXCR6 with carotid atherosclerosis in patients with metabolic syndrome.

PubMed

Lv, Yongqing; Hou, Xiaoyang; Ti, Yun; Bu, Peili

2013-10-01

Chemokine CXC ligand 16 (CXCL16) has chemokine, adhesion molecule and scavenger receptor functions involving the immune function. Atherosclerosis is an inflammatory disease. We aimed to study the association of chemokine CXCL16/CXCR6 and carotid atherosclerosis in patients with metabolic syndrome. Carotid ultrasonography was determined in 30 patients with metabolic syndrome and 30 controls. The mRNA levels of CXCL6/CXCR6 were detected by real-time RT-PCR. The activation of T cells and expression of CXCR6 in T lymphocyte cells and natural killer T (NKT) cells was detected by flow cytometry. The serum level of sol-CXCL6 was determined by ELISA. Compared with controls, patients with metabolic syndrome showed significantly increased waist circumference and levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol (all P < 0.001), with increased abnormalities of the structure and function of the carotid artery (P < 0.05). In metabolic syndrome, the levels of sol-CXCL16 and CXCL16mRNA were increased and associated with max IMT and plaque index. Patients with metabolic syndrome showed increased number of CXCR6+ T cells and CXCR6+ NKT cells, which was associated with max IMT and plaque index. CXCL16 and CXCR6 may be associated the formation of carotid atherosclerotic plaque in metabolic syndrome, and T cells may be the important effector cells in the pathogenesis of the atherosclerosis. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Urologic cancer in Japan: role of Japan at the frontier of issues in Asia.

PubMed

Akaza, Hideyuki

2016-01-01

The characteristics of urological cancer in Japan can be summarized in the following points. (i) As the onset of this type of cancer is typically seen in elderly patients, it is becoming a major social issue in Japan that has already become an aging society. (ii) Many diverse treatment methods are available and a response is required that prioritizes quality of life. (iii) Although vigorous research and development efforts into new drugs are being carried out on a global level, resulting in beneficial medical agents becoming more readily available, unless concepts relating to cost vs. effectiveness are further developed and there is a real risk that medical systems and structures in their current form will become unsustainable. (iv) Although at the current point there are no original large-scale clinical trials being conducted in Asia, Japan has a wealth of experience of participating in many international joint clinical trials and it is therefore an urgent and pressing challenge to organize joint clinical trials in Asia and amass a body of knowledge that is unique to Asia. In view of this current situation and given Japan's position at the frontier of issues, it is important for Japan to take the initiative in Asia in cooperating with other Asian nations in efforts to resolve and overcome various challenges. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Yoga Therapy in Japan.

PubMed

Kimura, By Keishin

2017-08-01

This perspective piece gives an overview of the current situation of yoga therapy in Japan today. Traditional yoga in Japan suffered a serious setback in 1995 with a nerve gas terrorist attack on the Tokyo subway, which was carried out by a cult that recruited members through yoga classes. But with the increase in popularity with modern forms of yoga such as Iyengar yoga, Ashtanga yoga and hot yoga in the West, the general public in Japan today is forgetting its aversion to yoga and considers it to be something that can contribute to good health. In 2012, the Japan Yoga Therapy Society (JYTS) conducted a study on adverse events in yoga classes throughout Japan with the University of Kyushu School of Medicine, with support from the Ministry of Health, Labour and Welfare. This study indicated that more than half of people attending yoga classes have some form of chronic illness, with 42.3% receiving outpatient care. This survey was the beginning of growing interest from both the government and universities in yoga therapy. JYTS is beginning to make inroads into bringing yoga therapy into cancer and palliative care, senior citizen homes, alcohol and drug addiction rehabilitation, cardiovascular rehabilitation, and research on trauma and schizophrenia. While there are still limited opportunities for yoga therapists to work in mainstream healthcare services, there is growing interest among medical professionals in both physical and mental health. JYTS is beginning to make inroads into bringing yoga therapy into cancer and palliative care, senior citizen homes, alcohol and drug addiction rehabilitation, cardiovascular rehabilitation, and research on trauma and schizophrenia. While there are still limited opportunities for yoga therapists to work in mainstream healthcare services, there is growing interest among medical professionals in both physical and mental health. This perspective piece introduces some of the developments in yoga therapy research and practice in

Yoga Therapy in Japan.

PubMed

Kimura, Keishin

2017-11-01

This perspective piece gives an overview of the current situation of yoga therapy in Japan today. Traditional yoga in Japan suffered a serious setback in 1995 with a nerve gas terrorist attack on the Tokyo subway, which was carried out by a cult that recruited members through yoga classes. But with the increase in popularity with modern forms of yoga such as Iyengar yoga, Ashtanga yoga and hot yoga in the West, the general public in Japan today is forgetting its aversion to yoga and considers it to be something that can contribute to good health. In 2012, the Japan Yoga Therapy Society (JYTS) conducted a study on adverse events in yoga classes throughout Japan with the University of Kyushu School of Medicine, with support from the Ministry of Health, Labour and Welfare. This study indicated that more than half of people attending yoga classes have some form of chronic illness, with 42.3% receiving outpatient care. This survey was the beginning of growing interest from both the government and universities in yoga therapy. JYTS is beginning to make inroads into bringing yoga therapy into cancer and palliative care, senior citizen homes, alcohol and drug addiction rehabilitation, cardiovascular rehabilitation, and research on trauma and schizophrenia. While there are still limited opportunities for yoga therapists to work in mainstream healthcare services, there is growing interest among medical professionals in both physical and mental health. JYTS is beginning to make inroads into bringing yoga therapy into cancer and palliative care, senior citizen homes, alcohol and drug addiction rehabilitation, cardiovascular rehabilitation, and research on trauma and schizophrenia. While there are still limited opportunities for yoga therapists to work in mainstream healthcare services, there is growing interest among medical professionals in both physical and mental health. This perspective piece introduces some of the developments in yoga therapy research and practice in

Coronary atherosclerosis: Significance of autophagic armour.

PubMed

Arora, Mansi; Kaul, Deepak

2012-09-26

Autophagy is a lysosomal degradation pathway of cellular components such as organelles and long-lived proteins. Though a protective role for autophagy has been established in various patho-physiologic conditions such as cancer, neurodegeneration, aging and heart failure, a growing body of evidence now reveals a protective role for autophagy in atherosclerosis, mainly by removing oxidatively damaged organelles and proteins and also by promoting cholesterol egress from the lipid-laden cells. Recent studies by Razani et al and Liao et al unravel novel pathways that might be involved in autophagic protection and in this commentary we highlight the importance of autophagy in atherosclerosis in the light of these two recent papers.

Corkscrew collaterals in atherosclerosis obliterans.

PubMed

Fujii, Yuichi; Ueda, Tomohiro; Uchimura, Yuko; Teragawa, Hiroki

2017-12-01

Marked calcifications in the femoral artery obscured imaging of the artery in computed tomography (CT) and duplex ultrasonography. The presence of corkscrew collateral arteries in patients with Atherosclerosis obliterans (ASO) indicates total artery occlusion.

Intranasal immunization with chitosan/pCETP nanoparticles inhibits atherosclerosis in a rabbit model of atherosclerosis.

PubMed

Yuan, Xiying; Yang, Xiaorong; Cai, Danning; Mao, Dan; Wu, Jie; Zong, Li; Liu, Jingjing

2008-07-04

In search of a convenient and pain-free route of administration of DNA vaccine against atherosclerosis, the plasmid pCR-X8-HBc-CETP (pCETP) encoding B-cell epitope of cholesteryl ester transfer protein C-terminal fragment displayed by Hepatitis B virus core particle was condensed with chitosan to form chitosan/pCETP nanoparticles. Cholesterol-fed rabbits were then intranasally immunized with the chitosan/pCETP nanoparticles to evaluate antiatherogenic effects. The results showed that significant serum antibodies against CETP were detected by enzyme-linked immunosorbent analysis and verified by Western blot analysis. The significant anti-CETP IgG lasted for 21 weeks in the rabbits immunized intranasally. Moreover, the atherogenic index was significantly lower compared with the saline control (5.95 versus 2.39, p<0.05). In addition, the average percentage of aortic lesions in the entire aorta area in the rabbits intranasally vaccinated with nanoparticles was 59.2% less than those treated with saline (29.0+/-10.9% versus 71.0+/-14.4%, p<0.01) and was similar to those intramuscularly injected with pCETP solution (29.0+/-10.9% versus 21.2+/-14.2%, p>0.05). Thus, chitosan/pCETP nanoparticles could significantly attenuate the progression of atherosclerosis by intranasal immunization. The results suggested that intranasal administration could be potentially developed as a vaccination route against atherosclerosis.

Current affairs in earthquake prediction in Japan

NASA Astrophysics Data System (ADS)

Uyeda, Seiya

2015-12-01

As of mid-2014, the main organizations of the earthquake (EQ hereafter) prediction program, including the Seismological Society of Japan (SSJ), the MEXT Headquarters for EQ Research Promotion, hold the official position that they neither can nor want to make any short-term prediction. It is an extraordinary stance of responsible authorities when the nation, after the devastating 2011 M9 Tohoku EQ, most urgently needs whatever information that may exist on forthcoming EQs. Japan's national project for EQ prediction started in 1965, but it has made no success. The main reason for no success is the failure to capture precursors. After the 1995 Kobe disaster, the project decided to give up short-term prediction and this stance has been further fortified by the 2011 M9 Tohoku Mega-quake. This paper tries to explain how this situation came about and suggest that it may in fact be a legitimate one which should have come a long time ago. Actually, substantial positive changes are taking place now. Some promising signs are arising even from cooperation of researchers with private sectors and there is a move to establish an "EQ Prediction Society of Japan". From now on, maintaining the high scientific standards in EQ prediction will be of crucial importance.

Insights into Atherosclerosis Using Nanotechnology

PubMed Central

Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

2010-01-01

A developing forefront in vascular disease research is the application of nanotechnology, the engineering of devices at the molecular scale, for diagnostic and therapeutic applications in atherosclerosis. Promising research in this field over the past decade has resulted in the preclinical validation of nanoscale devices that target cellular and molecular components of the atherosclerotic plaque, including one of its prominent cell types, the macrophage. Nanoscale contrast agents targeting constituents of plaque biology have been adapted for application in multiple imaging modalities, leading toward more detailed diagnostic readouts, whereas nanoscale drug delivery devices can be tailored for site-specific therapeutic activity. This review highlights recent progress in utilizing nanotechnology for the clinical management of atherosclerosis, drawing upon recent preclinical studies relevant to diagnosis and treatment of the plaque and promising future applications. PMID:20425261

Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Tain-Junn; Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Tainan 710, Taiwan; Department of Occupational Medicine, Chi Mei Medical Center, 901 Chung-Hwa Road, Yongkang, Tainan 710, Taiwan

2011-10-15

Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoproteinmore » cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor {beta} (LXR{beta}) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXR{beta} activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXR{beta} and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: > Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. > Arsenic may promote atherosclerosis with transient

Induction of atherosclerosis in mice and hamsters without germline genetic engineering.

PubMed

Bjørklund, Martin Maeng; Hollensen, Anne Kruse; Hagensen, Mette Kallestrup; Dagnaes-Hansen, Frederik; Christoffersen, Christina; Mikkelsen, Jacob Giehm; Bentzon, Jacob Fog

2014-05-23

Atherosclerosis can be achieved in animals by germline genetic engineering, leading to hypercholesterolemia, but such models are constrained to few species and strains, and they are difficult to combine with other powerful techniques involving genetic manipulation or variation. To develop a method for induction of atherosclerosis without germline genetic engineering. Recombinant adeno-associated viral vectors were engineered to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants, and mice were given a single intravenous vector injection followed by high-fat diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total cholesterol increased rapidly and were maintained at high levels, and after 12 weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic root showed progression of lesions to the fibroatheromatous stage. To demonstrate the applicability of this method for rapid analysis of the atherosclerosis susceptibility of a mouse strain and for providing temporal control over disease induction, we demonstrated the accelerated atherosclerosis of mature diabetic Akita mice. Furthermore, the versatility of this approach for creating atherosclerosis models also in nonmurine species was demonstrated by inducing hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters. Single injections of proprotein convertase subtilisin/kexin type 9-encoding recombinant adeno-associated viral vectors are a rapid and versatile method to induce atherosclerosis in animals. This method should prove useful for experiments that are high-throughput or involve genetic techniques, strains, or species that do not combine well with current genetically engineered models. © 2014 American Heart Association, Inc.

Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation*

PubMed Central

Gregory, Jill C.; Buffa, Jennifer A.; Org, Elin; Wang, Zeneng; Levison, Bruce S.; Zhu, Weifei; Wagner, Matthew A.; Bennett, Brian J.; Li, Lin; DiDonato, Joseph A.; Lusis, Aldons J.; Hazen, Stanley L.

2015-01-01

Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility. PMID:25550161

A review of plant-based compounds and medicinal plants effective on atherosclerosis

PubMed Central

Sedighi, Mehrnoosh; Bahmani, Mahmoud; Asgary, Sedigheh; Beyranvand, Fatemeh; Rafieian-Kopaei, Mahmoud

2017-01-01

Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications. PMID:28461816

A review of plant-based compounds and medicinal plants effective on atherosclerosis.

PubMed

Sedighi, Mehrnoosh; Bahmani, Mahmoud; Asgary, Sedigheh; Beyranvand, Fatemeh; Rafieian-Kopaei, Mahmoud

2017-01-01

Atherosclerosis is one of the most important cardiovascular diseases that involve vessels through the development of fatty streaks and plaques. Plant-based compounds can help treat or prevent atherosclerosis through affecting the involved factors. The main purpose of this review article is to investigate and introduce medicinal plants and their potential activities regarding antioxidant properties, effective on lipids level and development of plaque, atherosclerosis, and progression of atherosclerosis as well as the development of cardiovascular disease and ischemia. To search for the relevant articles indexed in Information Sciences Institute, PubMed, Scientific Information Database, IranMedex, and Scopus between 1980 and 2013, with further emphasis on those indexed from 2004 to 2015, we used these search terms: atherosclerosis, antioxidant, cholesterol, inflammation, and the medicinal plants below. Then, the articles with inclusion criteria were used in the final analysis of the findings. Plant-based active compounds, including phenols, flavonoids, and antioxidants, can be effective on atherosclerosis predisposing factors and hence in preventing this disease and associated harmful complications, especially through reducing cholesterol, preventing increase in free radicals, and ultimately decreasing vascular plaque and vascular resistance. Hence, medicinal plants can contribute to treating atherosclerosis and preventing its progression through reducing cholesterolemia, free radicals, inflammation, vascular resistance, and certain enzymes. They, alone or in combination with hypocholesterolemic drugs, can therefore be useful for patients with hyperlipidemia and its complications.

Maximizing the potential of scientists in Japan: promoting equal participation for women scientists through leadership development.

PubMed

Homma, Miwako Kato; Motohashi, Reiko; Ohtsubo, Hisako

2013-07-01

In order to examine the current status of gender equality in academic societies in Japan, we inquired about the number of women involved in leadership activities at society conferences and annual meetings, as these activities are critical in shaping scientific careers. Our findings show a clear bias against female scientists, and a need to raise consciousness and awareness in order to move closer to equality for future generations. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

EXPERIMENTAL ATHEROSCLEROSIS AND BLOOD PRESSURE IN THE RABBIT

PubMed Central

Dominguez, R.

1927-01-01

1. Van Leersum's range for the normal blood pressure in the rabbit, as recorded by his method, is confirmed. 2. Van Leersum's conclusion concerning the influence of a liver diet on the blood pressure of the rabbit is not substantiated by his data, since the fluctuations of blood pressure he obtained do not surpass his own recorded figures for normal animals. 3. Fluctuations of systolic blood pressure beyond the "normal" range are not necessary for the production of experimental atherosclerosis of the aorta in rabbits. Inversely, egg yolk feeding experiments in rabbits in which atherosclerosis of varying degree, even extreme, is obtained, are not accompanied by an elevation of blood pressure outside the "normal" range. 4. The fluctuations of blood pressure observed during experimental atherosclerosis do not simulate the condition of essential hypertension in man. PMID:19869349

[Mechanism of Tongsaimai tablet for atherosclerosis based on network pharmacology].

PubMed

Li, Na; Zhang, Xin-Zhuang; Wang, Yan-Ru; Cao, Liang; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei; Xu, Xiao-Jie

2016-05-01

Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis, 97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein (docking score ≥ 7), and 37 molecules of them could act on more than 2 targets (≥ 2) with higher betweenness, suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore, the predicted active compounds contained more flavonoids and saponins, reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that, the active compounds of Tongsaimai tablets could regulate inflammation, stabilize plaque, protect vascular endothelial cell, regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins, such as Toll-like receptors (TLR1, TLR2), matrix metalloproteinase (MMP1, MMP2, MMP3, MMP9), angiotensin converting enzyme (ACE), leukotriene A4 hydrolase (LTA4-H), 5-lipoxidase (5-LOX), peroxisome proliferators-activated receptors (PPARα, PPARγ). These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile, verified the characteristics of multi-components, multi-targets and integral regulation for Tongsaimai tablets, providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet. Copyright© by the Chinese Pharmaceutical Association.

The Constituent Elements of Comparative Education in Japan: A Comparison with North America

ERIC Educational Resources Information Center

Yamada, Shoko

2015-01-01

This article, with the aim of identifying elements that constitute the characteristics of an academic space within comparative education, analyzes how comparative education has been discussed and practiced in Japan, based on a questionnaire completed by 264 members of the Japan Comparative Education Society and classification of articles published…

Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.

PubMed

Thompson, Randall C; Allam, Adel H; Lombardi, Guido P; Wann, L Samuel; Sutherland, M Linda; Sutherland, James D; Soliman, Muhammad Al-Tohamy; Frohlich, Bruno; Mininberg, David T; Monge, Janet M; Vallodolid, Clide M; Cox, Samantha L; Abd el-Maksoud, Gomaa; Badr, Ibrahim; Miyamoto, Michael I; el-Halim Nur el-Din, Abd; Narula, Jagat; Finch, Caleb E; Thomas, Gregory S

2013-04-06

Atherosclerosis is thought to be a disease of modern human beings and related to contemporary lifestyles. However, its prevalence before the modern era is unknown. We aimed to evaluate preindustrial populations for atherosclerosis. We obtained whole body CT scans of 137 mummies from four different geographical regions or populations spanning more than 4000 years. Individuals from ancient Egypt, ancient Peru, the Ancestral Puebloans of southwest America, and the Unangan of the Aleutian Islands were imaged. Atherosclerosis was regarded as definite if a calcified plaque was seen in the wall of an artery and probable if calcifications were seen along the expected course of an artery. Probable or definite atherosclerosis was noted in 47 (34%) of 137 mummies and in all four geographical populations: 29 (38%) of 76 ancient Egyptians, 13 (25%) of 51 ancient Peruvians, two (40%) of five Ancestral Puebloans, and three (60%) of five Unangan hunter gatherers (p=NS). Atherosclerosis was present in the aorta in 28 (20%) mummies, iliac or femoral arteries in 25 (18%), popliteal or tibial arteries in 25 (18%), carotid arteries in 17 (12%), and coronary arteries in six (4%). Of the five vascular beds examined, atherosclerosis was present in one to two beds in 34 (25%) mummies, in three to four beds in 11 (8%), and in all five vascular beds in two (1%). Age at time of death was positively correlated with atherosclerosis (mean age at death was 43 [SD 10] years for mummies with atherosclerosis vs 32 [15] years for those without; p<0·0001) and with the number of arterial beds involved (mean age was 32 [SD 15] years for mummies with no atherosclerosis, 42 [10] years for those with atherosclerosis in one or two beds, and 44 [8] years for those with atherosclerosis in three to five beds; p<0·0001). Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in

The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients.

PubMed

Lo, Janet; Plutzky, Jorge

2012-06-01

Complications of atherosclerosis, including myocardial infarction and stroke, are the leading cause of death and disability worldwide. Recent data strongly implicate cardiovascular death as a contributor to mortality among patients with human immunodeficiency virus (HIV) infection, with evidence suggesting increased incidence of atherosclerosis among these patients. Therefore, greater understanding of atherosclerotic mechanisms and how these responses may be similar or distinct in HIV-infected patients is needed. Key concepts in atherosclerosis are reviewed, including the evidence that inflammation and abnormal metabolism are major drivers of atherosclerosis, and connected to the current literature regarding atherosclerosis in the context of HIV.

English Textbooks in Japan and Korea

ERIC Educational Resources Information Center

Yuasa, Katsura

2010-01-01

English education in Japan and Korea are similar in some respects. Although both countries are not completely but mostly monolingual societies, where citizens do not need English in their daily life, they have begun to realize the importance of English as a tool for international communication, and as a result their English education is becoming…

Protein kinase C isoforms in atherosclerosis: pro- or anti-inflammatory?

PubMed

Fan, Hueng-Chuen; Fernández-Hernando, Carlos; Lai, Jenn-Haung

2014-03-15

Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future. Copyright © 2014 Elsevier Inc. All rights reserved.

The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis

PubMed Central

Yu, Megan; Tsai, Sheng-Feng; Kuo, Yu-Min

2017-01-01

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed “exerkines”) are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed. PMID:28608819

Possibility of Low Carbon Society Formation by Using Aqua Science & Technologies (Establishment of an Ecologically Sustainable Society)

NASA Astrophysics Data System (ADS)

Yamasaki, Nakamichi

2010-11-01

Basic resolution of environmental problems needs a change of paradigm. In order to form a closed system and sustainable society, Japanese culture and civilization of EDO period (esthetics of self-control) must be considered. Quality technology of Japan is leading the world in environmental resolution. Many Japanese forget the traditional spirit (the original fail is in education). The combination of esthetics and technology is a characteristics of Japanese Goods. The origin of Japanese religion (ethos) is Japanese language and situation of Japan. The global aspects of closed earth system was showed. Practical examples of closed system, Biomass Applications, PVC recycling, poly-diamond synthesis are shown.

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

PubMed Central

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

2016-01-01

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

[Rabies contingency plan in Japan].

PubMed

Inoue, Satoshi

2005-12-01

In Japan, rabies has been culled out since 1957 thanks to the strong implementation of measures against rabies, such as vaccination of dogs, quarantine and control of wild dogs under the 'Rabies Prevention Law' enacted in 1950. Nevertheless one cannot deny the possibility of introduction of rabies into Japan in view of the recent increase in the international movements of people and animals. Should an outbreak of rabies be suspected now in Japan, the society would probably overreact due to a decreased awareness of risks and a lack of correct knowledge about this disease. Officials of the government and the municipalities, veterinarians and doctors should exchange correct information on rabies and on prevention control and raise their awareness, while providing also information to the public on a timely basis. Besides it is needless to say that it is important to set up a crisis management system allowing a quick and adequate response in case of an outbreak of rabies and to continue to implement appropriate prevention measures in normal times.

Taeniasis and cysticercosis due to Taenia solium in Japan.

PubMed

Yanagida, Tetsuya; Sako, Yasuhito; Nakao, Minoru; Nakaya, Kazuhiro; Ito, Akira

2012-01-17

Taenia solium is a zoonotic cestode that causes taeniasis and cysticercosis in humans. The parasite is traditionally found in developing countries where undercooked pork is consumed under poor sanitary conditions and/or as part of traditional food cultures. However, the recent increase in international tourism and immigration is spreading the disease into non-endemic developed countries such as the United States. Although there has been concern that the number of cysticercosis cases is increasing in Japan, the current situation is not clear. This is largely because taeniasis and cysticercosis are not notifiable conditions in Japan and because there have been no comprehensive reviews of T. solium infections in Japan conducted in the last 15 years. Herein, we provide an overview of the status of T. solium infection in Japan over the past 35 years and point out the potential risks to Japanese society.

Why did ancient people have atherosclerosis?: from autopsies to computed tomography to potential causes.

PubMed

Thomas, Gregory S; Wann, L Samuel; Allam, Adel H; Thompson, Randall C; Michalik, David E; Sutherland, M Linda; Sutherland, James D; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Valladolid, Clide M; Abd El-Maksoud, Gomaa; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; el-Halim Nur el-Din, Abd; Clarke, Emily M; Thomas, Ian G; Miyamoto, Michael I; Kaplan, Hillard S; Frohlich, Bruno; Narula, Jagat; Stewart, Alexandre F R; Zink, Albert; Finch, Caleb E

2014-06-01

Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors. Copyright © 2014 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Lineage tracing of cells involved in atherosclerosis.

PubMed

Albarrán-Juárez, Julián; Kaur, Harmandeep; Grimm, Myriam; Offermanns, Stefan; Wettschureck, Nina

2016-08-01

Despite the clinical importance of atherosclerosis, the origin of cells within atherosclerotic plaques is not fully understood. Due to the lack of a definitive lineage-tracing strategy, previous studies have provided controversial results about the origin of cells expressing smooth muscle and macrophage markers in atherosclerosis. We here aim to identify the origin of vascular smooth muscle (SM) cells and macrophages within atherosclerosis lesions. We combined a genetic fate mapping approach with single cell expression analysis in a murine model of atherosclerosis. We found that 16% of CD68-positive plaque macrophage-like cells were derived from mature SM cells and not from myeloid sources, whereas 31% of αSMA-positive smooth muscle-like cells in plaques were not SM-derived. Further analysis at the single cell level showed that SM-derived CD68(+) cells expressed higher levels of inflammatory markers such as cyclooxygenase 2 (Ptgs2, p = 0.02), and vascular cell adhesion molecule (Vcam1, p = 0.05), as well as increased mRNA levels of genes related to matrix synthesis such as Col1a2 (p = 0.01) and Fn1 (p = 0.04), than non SM-derived CD68(+) cells. These results demonstrate that smooth muscle cells within atherosclerotic lesions can switch to a macrophage-like phenotype characterized by higher expression of inflammatory and synthetic markers genes that may further contribute to plaque progression. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Multicultural and Multiethnic Education in Japan

ERIC Educational Resources Information Center

Nomoto, Hiroyuki

2009-01-01

In Japan, the Ainu people have been living mainly in Hokkaido and many Koreans continue to live since the end of the World War Two. Since 1990's, the number of migrant workers has increased rapidly. In this sense, Japanese society has been multicultural and multiethnic. However, those minority groups have been strictly discriminated against in…

[Analysis and design structure of an aging society].

PubMed

Fujimasa, Iwao

2012-01-01

On observing present Japanese society, we can find deep gaps between the present system and its probable future. One of the gaps may be due to the misconception that future societal make up is not definite. The aim of the current study was to investigate a future societal structure and to develop methods of adding a timed dimension policy to the societal structure. This is named "A theory of structuralism economics". We developed 3 societal structure projection engines and applied a system of dynamics language to estimate the future total population of Japan. The Japan total population reached a maximum in 2005, and thereafter depopulation begun. The populations in the younger working age group (from 25 to 54 years old) and those in the elderly working age group (from 55 to 84 years old) became almost equal in 2010. As economic growth rate depends upon an increase in the working population, the increase in national income rate of Japan approached over 10% per year between 1950 to 1970. The increased working age population of the same period exceeded 2.5% annually. However, after 2005 depopulation began in Japan. In future, national income will decrease proportional to the working age population, but personal national income will hold almost unchanged. We propose a new strategy for future society structure. The working age should be extended by 10 years. Labor power will come to exceed 60% of the population and will thereafter become stable.

[Establishment of anatomical terminology in Japan].

PubMed

Shimada, Kazuyuki

2008-12-01

The history of anatomical terminology in Japan began with the publication of Waran Naikei Ihan-teimŏ in 1805 and Chŏtei Kaitai Shinsho in 1826. Although the establishment of Japanese anatomical terminology became necessary during the Meiji era when many western anatomy books imported into Janan were translated, such terminology was not unified during this period and varied among translators. In 1871, Tsukumo Ono's Kaibŏgaku Gosen was published by the Ministry of Education. Although this book is considered to be the first anatomical glossary terms in Japan, its contents were incomplete. Overseas, the German Anatomical Society established a unified anatomical terminology in 1895 called the Basle Nomina Anatomica (B.N.A.). Based on this development, Kaibŏgaku Meishŭ which follows the BNA, by Buntarŏ Suzuki was published in 1905. With the subsequent establishment in 1935 of Jena Nomina Anatomica (J.N.A.), the unification of anatomical terminology was also accelerated in Japan, leading to the further development of terminology.

MAOA Genotype, Childhood Trauma and Subclinical Atherosclerosis: A Twin Study

PubMed Central

Zhao, Jinying; Bremner, James D.; Goldberg, Jack; Quyyumi, Arshed A.; Vaccarino, Viola

2013-01-01

Objective A functional promoter polymorphism in the MAOA gene has been implicated in neuropsychiatric disorders and also moderates the association between early life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis. Methods A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors. Results General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%) and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma (β ≥ 0.36). There was no significant evidence for a main effect for the MAOA genotype (β = 0.02, p = 0.82) or childhood trauma (0.005 < β < 0.10, p > 0.54) on early atherosclerosis. However, a significant interaction was observed between MAOA genotype and physical (βinteraction = 0.37, p = 0.026) or emotional abuse (βinteraction = 0.43, p = 0.025) on subclinical atherosclerosis. Conclusion This study provides initial evidence that childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors. PMID:23723362

Characteristics of erythrocyte-derived microvesicles and its relation with atherosclerosis.

PubMed

Li, Kai-Yin; Zheng, Lei; Wang, Qian; Hu, Yan-Wei

2016-12-01

Microvesicles are formed under many circumstances, especially in atheromatous plaques. Erythrocyte-derived microvesicles (ErMVs) have been proved to promote atherosclerosis by promoting hypercoagulation, mediating inflammation and inducing cell adhesion. Several clinical studies have reported potential roles of ErMVs in cardiovascular disease diagnosis, but the current understanding of ErMVs remains insufficient. In this paper, we will review current research on the formation and degradation of ErMVs and the possible effects of ErMVs in atherosclerosis, discuss potential clinical applications in cardiovascular disease, and hope to raise awareness of the relation with atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis

PubMed Central

Linton, MacRae F.; Babaev, Vladimir R.; Huang, Jiansheng; Linton, Edward F.; Tao, Huan; Yancey, Patricia G.

2017-01-01

Macrophage apoptosis and the ability of macrophages to clean up dead cells, a process called efferocytosis, are crucial determinants of atherosclerosis lesion progression and plaque stability. Environmental stressors initiate endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR). Unresolved ER stress with activation of the UPR initiates apoptosis. Macrophages are resistant to apoptotic stimuli, because of activity of the PI3K/Akt pathway. Macrophages express 3 Akt isoforms, Akt1, Akt2 and Akt3, which are products of distinct but homologous genes. Akt displays isoform-specific effects on atherogenesis, which vary with different vascular cell types. Loss of macrophage Akt2 promotes the anti-inflammatory M2 phenotype and reduces atherosclerosis. However, Akt isoforms are redundant with regard to apoptosis. c-Jun NH2-terminal kinase (JNK) is a pro-apoptotic effector of the UPR, and the JNK1 isoform opposes anti-apoptotic Akt signaling. Loss of JNK1 in hematopoietic cells protects macrophages from apoptosis and accelerates early atherosclerosis. IκB kinase α (IKKα, a member of the serine/threonine protein kinase family) plays an important role in mTORC2-mediated Akt signaling in macrophages, and IKKα deficiency reduces macrophage survival and suppresses early atherosclerosis. Efferocytosis involves the interaction of receptors, bridging molecules, and apoptotic cell ligands. Scavenger receptor class B type I is a critical mediator of macrophage efferocytosis via the Src/PI3K/Rac1 pathway in atherosclerosis. Agonists that resolve inflammation offer promising therapeutic potential to promote efferocytosis and prevent atherosclerotic clinical events. PMID:27725526

Incremental prognostic value of coronary and systemic atherosclerosis after myocardial infarction.

PubMed

Calais, Fredrik; Eriksson Östman, Maja; Hedberg, Pär; Rosenblad, Andreas; Leppert, Jerzy; Fröbert, Ole

2018-06-15

The role of systemic atherosclerosis in myocardial infarction (MI) patients is not fully understood. We investigated the incremental prognostic value of coronary and systemic atherosclerosis after acute MI by estimating extra-cardiac artery disease (ECAD) and extent of coronary atherosclerosis. The study included 544 prospective MI patients undergoing coronary angiography. For all patients, the longitudinal coronary atherosclerotic extent, expressed as Sullivan extent score (SES) was calculated. In addition, the patients underwent non-invasive screening for ECAD in the carotid, aortic, renal and lower limb. SES was found to be associated with ECAD independent of baseline clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI) 1.02-1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the combination of extensive coronary disease (SES ≥ 17) and ECAD, was associated with higher risk for all-cause mortality compared to limited systemic atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9-4.5, P < 0.001, adjusted for Global Registry of Acute Coronary Events risk score parameters 1.8, 95% CI 1.1-3.0, P = 0.019). The risk for the composite endpoint of cardiovascular death or hospitalization was significantly higher in patients with extensive systemic atherosclerosis compared to patients with limited systemic atherosclerosis (HR 3.1, 95% CI 2.1-4.7, P < 0.001, adjusted HR 1.9, 95% CI 1.2-3.1, P < 0.004). Visual estimation of the longitudinal coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of extensive coronary disease and ECAD defines a group with particularly poor prognosis after MI. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Protective Effects of Hydroxychloroquine against Accelerated Atherosclerosis in Systemic Lupus Erythematosus

PubMed Central

Cauli, Alberto

2018-01-01

Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect. PMID:29670462

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice.

PubMed

Hoving, Lisa R; de Vries, Margreet R; de Jong, Rob C M; Katiraei, Saeed; Pronk, Amanda; Quax, Paul H A; van Harmelen, Vanessa; Willems van Dijk, Ko

2018-02-03

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden ( E3L ) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol.

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

PubMed Central

de Jong, Rob C. M.; Katiraei, Saeed; Pronk, Amanda; van Harmelen, Vanessa

2018-01-01

The prebiotic inulin has proven effective at lowering inflammation and plasma lipid levels. As atherosclerosis is provoked by both inflammation and hyperlipidemia, we aimed to determine the effect of inulin supplementation on atherosclerosis development in hypercholesterolemic APOE*3-Leiden (E3L) mice. Male E3L mice were fed a high-cholesterol (1%) diet, supplemented with or without 10% inulin for 5 weeks. At week 3, a non-constrictive cuff was placed around the right femoral artery to induce accelerated atherosclerosis. At week 5, vascular pathology was determined by lesion thickness, vascular remodeling, and lesion composition. Throughout the study, plasma lipids were measured and in week 5, blood monocyte subtypes were determined using flow cytometry analysis. In contrast to our hypothesis, inulin exacerbated atherosclerosis development, characterized by increased lesion formation and outward vascular remodeling. The lesions showed increased number of macrophages, smooth muscle cells, and collagen content. No effects on blood monocyte composition were found. Inulin significantly increased plasma total cholesterol levels and total cholesterol exposure. In conclusion, inulin aggravated accelerated atherosclerosis development in hypercholesterolemic E3L mice, accompanied by adverse lesion composition and outward remodeling. This process was not accompanied by differences in blood monocyte composition, suggesting that the aggravated atherosclerosis development was driven by increased plasma cholesterol. PMID:29401645

Cultural Pluralism in Japan: A Sociolinguistic Outline.

ERIC Educational Resources Information Center

Honna, Nobuyuki

1980-01-01

Addressing the common misconception that Japan is a mono-ethnic, mono-cultural, and monolingual society, this article focuses on several areas of sociolinguistic concern. It discusses: (1) the bimodalism of the Japanese deaf population between Japanese Sign Language as native language and Japanese Spoken Language as acquired second language; (2)…

Proliferating macrophages prevail in atherosclerosis.

PubMed

Randolph, Gwendalyn J

2013-09-01

Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

Mice deficient in PKCbeta and apolipoprotein E display decreased atherosclerosis.

PubMed

Harja, Evis; Chang, Jong Sun; Lu, Yan; Leitges, Michael; Zou, Yu Shan; Schmidt, Ann Marie; Yan, Shi-Fang

2009-04-01

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) betaII is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKCbeta in regulating key events linked to atherosclerosis and show that the aortas of apoE(-/-) mice display an age-dependent increase in PKCbetaII antigen in membranous fractions vs. C57BL/6 animals with a approximately 2-fold increase at age 6 wk and a approximately 4.5-fold increase at age 24 wk. Consistent with important roles for PKCbeta in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKCbeta(-/-)/apoE(-/-) vs. apoE(-/-) mice by approximately 5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE(-/-) mice. Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKCbeta-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKCbeta may be beneficial in mitigating endothelial perturbation and atherosclerosis.

Innate lymphoid cells in atherosclerosis.

PubMed

Engelbertsen, Daniel; Lichtman, Andrew H

2017-12-05

The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

Taeniasis and cysticercosis due to Taenia solium in Japan

PubMed Central

2012-01-01

Taenia solium is a zoonotic cestode that causes taeniasis and cysticercosis in humans. The parasite is traditionally found in developing countries where undercooked pork is consumed under poor sanitary conditions and/or as part of traditional food cultures. However, the recent increase in international tourism and immigration is spreading the disease into non-endemic developed countries such as the United States. Although there has been concern that the number of cysticercosis cases is increasing in Japan, the current situation is not clear. This is largely because taeniasis and cysticercosis are not notifiable conditions in Japan and because there have been no comprehensive reviews of T. solium infections in Japan conducted in the last 15 years. Herein, we provide an overview of the status of T. solium infection in Japan over the past 35 years and point out the potential risks to Japanese society. PMID:22248435

Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

NASA Technical Reports Server (NTRS)

Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

2000-01-01

The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice

PubMed Central

Chung, Rosanna W. S.; Wang, Zeneng; Bursill, Christina A.; Wu, Ben J.; Barter, Philip J.

2017-01-01

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice. PMID:29240800

Plasma Cholesterol–Induced Lesion Networks Activated before Regression of Early, Mature, and Advanced Atherosclerosis

PubMed Central

Björkegren, Johan L. M.; Hägg, Sara; Jain, Rajeev K.; Cedergren, Cecilia; Shang, Ming-Mei; Rossignoli, Aránzazu; Takolander, Rabbe; Melander, Olle; Hamsten, Anders; Michoel, Tom; Skogsberg, Josefin

2014-01-01

Plasma cholesterol lowering (PCL) slows and sometimes prevents progression of atherosclerosis and may even lead to regression. Little is known about how molecular processes in the atherosclerotic arterial wall respond to PCL and modify responses to atherosclerosis regression. We studied atherosclerosis regression and global gene expression responses to PCL (≥80%) and to atherosclerosis regression itself in early, mature, and advanced lesions. In atherosclerotic aortic wall from Ldlr−/−Apob 100/100 Mttp flox/floxMx1-Cre mice, atherosclerosis regressed after PCL regardless of lesion stage. However, near-complete regression was observed only in mice with early lesions; mice with mature and advanced lesions were left with regression-resistant, relatively unstable plaque remnants. Atherosclerosis genes responding to PCL before regression, unlike those responding to the regression itself, were enriched in inherited risk for coronary artery disease and myocardial infarction, indicating causality. Inference of transcription factor (TF) regulatory networks of these PCL-responsive gene sets revealed largely different networks in early, mature, and advanced lesions. In early lesions, PPARG was identified as a specific master regulator of the PCL-responsive atherosclerosis TF-regulatory network, whereas in mature and advanced lesions, the specific master regulators were MLL5 and SRSF10/XRN2, respectively. In a THP-1 foam cell model of atherosclerosis regression, siRNA targeting of these master regulators activated the time-point-specific TF-regulatory networks and altered the accumulation of cholesterol esters. We conclude that PCL leads to complete atherosclerosis regression only in mice with early lesions. Identified master regulators and related PCL-responsive TF-regulatory networks will be interesting targets to enhance PCL-mediated regression of mature and advanced atherosclerotic lesions. PMID:24586211

Expansion of CD25+ Innate Lymphoid Cells Reduces Atherosclerosis

PubMed Central

Engelbertsen, Daniel; Foks, Amanda C.; Alberts-Grill, Noah; Kuperwaser, Felicia; Chen, Tao; Lederer, James A.; Jarolim, Petr; Grabie, Nir; Lichtman, Andrew H.

2015-01-01

Objective Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that promote tissue homeostasis and protect against pathogens. ILCs produce cytokines also produced by T lymphocytes that have been shown to affect atherosclerosis, but the influence of ILCs on atherosclerosis has not been explored. Approach and Results We demonstrate that CD25+ ILCs that produce type 2 cytokines (ILC2s) are present in the aorta of atherosclerotic immunodeficient ldlr−/−rag1−/− mice. To investigate the role of ILCs in atherosclerosis, ldlr−/−rag1−/− mice were concurrently fed an atherogenic diet and treated with either ILC-depleting anti-CD90.2 antibodies or with IL-2/anti-IL-2 complexes that expand CD25+ ILCs. Lesion development was not affected by anti-CD90.2 treatment, but was reduced in IL-2/anti-IL-2 -treated mice. These IL-2 treated mice had reduced VLDL cholesterol and increased triglycerides compared to controls and reduced apolipoprotein B100 gene expression in the liver. IL-2/anti-IL-2 treatment caused expansion of ILC2s in aorta and other tissues, elevated levels of IL-5, systemic eosinophila and hepatic eosinophilic inflammation. Blockade of IL-5 reversed the IL-2-complex-induced eosinophilia but did not change lesion size. Conclusions This study demonstrates that expansion of CD25-expressing ILCs by IL-2/anti-IL-2 complexes leads to a reduction in VLDL cholesterol and atherosclerosis. Global depletion of ILCs by anti-CD90.2 did not significantly affect lesion size indicating that different ILC subsets may have divergent effects on atherosclerosis. PMID:26494229

CXCR4 blockade induces atherosclerosis by affecting neutrophil function

PubMed Central

Bot, Ilze; Daissormont, Isabelle T.M.N.; Zernecke, Alma; van Puijvelde, Gijs H.M.; Kramp, Birgit; de Jager, Saskia C.A.; Sluimer, Judith C.; Manca, Marco; Hérias, Veronica; Westra, Marijke M.; Bot, Martine; van Santbrink, Peter J.; van Berkel, Theo J.C.; Su, Lishan; Skjelland, Mona; Gullestad, Lars; Kuiper, Johan; Halvorsen, Bente; Aukrust, Paul; Koenen, Rory R.; Weber, Christian; Biessen, Erik A.L.

2015-01-01

Aims The SDF-1α/CXCR4 dyad was previously shown by us and others to be instrumental in intimal hyperplasia as well as early stage atherosclerosis. We here sought to investigate its impact on clinically relevant stages of atherosclerosis in mouse and man. Methods and results Immunohistochemical analysis of CXCR4 expression in human atherosclerotic lesions revealed a progressive accumulation of CXCR4+ cells during plaque progression. To address causal involvement of CXCR4 in advanced stages of atherosclerosis we reconstituted LDLr−/− mice with autologous bone marrow infected with lentivirus encoding SDF-1α antagonist or CXCR4 degrakine, which effects proteasomal degradation of CXCR4. Functional CXCR4 blockade led to progressive plaque expansion with disease progression, while also promoting intraplaque haemorrhage. Moreover, CXCR4 knockdown was seen to augment endothelial adhesion of neutrophils. Concordant with this finding, inhibition of CXCR4 function increased adhesive capacity and reduced apoptosis of neutrophils and resulted in hyperactivation of circulating neutrophils. Compatible with a role of the neutrophil CXCR4 in end-stage atherosclerosis, CXCR4 expression by circulating neutrophils was lowered in patients with acute cardiovascular syndromes. Conclusion In conclusion, CXCR4 contributes to later stages of plaque progression by perturbing neutrophil function. PMID:24816217

Genomic Analysis of Circulating Cells: A Window into Atherosclerosis

PubMed Central

Kang, Ju-Gyeong; Patino, Willmar D.; Matoba, Satoaki; Hwang, Paul M.

2006-01-01

Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments using diseased tissue or surrogate specimens. This review details the rationale and findings of a study using freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched normal subjects. Using this cardiovascular tissue surrogate, the mRNA levels of the Finkel-Biskis-Jinkins osteosarcoma (FOS) gene in circulating monocytes were found to correlate with atherosclerosis severity in patients, and with HMG CoA reductase inhibitor (statin) therapy in normal subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate their reports. They also provide us with insights into pathogenesis that may impact future translational applications. PMID:16781950

The detection of autoantibodies to ATP-binding cassette transporter A1 and its role in the pathogenesis of atherosclerosis in patients with systemic lupus erythematosus.

PubMed

Zeng, Ting; Li, Shu-Jie; Ao, Wen; Zheng, Hui; Wu, Feng-Xia; Chen, Yi; Yang, Cheng-De

2012-11-01

To investigate the prevalence of autoantibodies against ATP-binding cassette transporter A1 (ABCA1) in SLE patients, and evaluate the association between anti-ABCA1 autoantibodies and atherosclerosis in SLE. The sera of 75 SLE patients and 75 healthy controls were tested by immunoblotting. Then, we examined the effect of anti-ABCA1 autoantibodies on cholesterol efflux in vitro. The prevalence of anti-ABCA1 antibodies in SLE patients was significantly higher than the controls (p<0.05). The prevalence in the SLE-plaque group was higher than that in the SLE-non-plaque group (p<0.05). The IgG purified from anti-ABCA1-antibody positive sera can inhibit cellular cholesterol efflux from THP-1 cells in vitro with a significantly higher inhibition ratio than that of the healthy controls. Our observations suggest that anti-ABCA1 autoantibodies are involved in the pathogenesis of lupus atherosclerosis and that autoantibodies against ABCA1 may act as biomarkers for atherosclerosis in SLE. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The impact of atherosclerosis and vascular collagen on energy-based vessel sealing.

PubMed

Martin, Kimberly; Krugman, Kimberly; Latimer, Cassandra; Moore, Camille

2013-12-01

Bipolar energy ligation of vessels in surgery is common. Although rare, serious failures occur. Atherosclerosis may contribute to seal failures by altering vascular compressibility and collagen content; however, no data exist. Femoral and iliac arteries of six Yucatan swine with an identified genetic locus predisposing them to atherosclerosis were denuded with a Fogarty catheter. Animals were fed a high-fat diet for 28 wk. A Yorkshire pig was used as a normal control and fed a standard diet. At 28 wk, arteries were measured for their diameters, sealed, and divided in vivo with LigaSure. The sealed artery sections were excised and subjected to burst pressure testing. Half of the seal distal to the aorta was kept intact for histology and collagen and elastin quantification. A multiple linear regression model was used to assess variables contributing to burst pressure. Covariates included were vessel diameter, degree of atherosclerosis, and collagen content. Experimental animals were hypercholesterolemic. Atherosclerosis occurred in 90% of seals in induced animals, with severe atherosclerosis in 62% of seals. There was site-selective deposition of atherosclerotic plaques in larger diameter iliac vessels. A model including collagen and size best predicted burst pressure. Every 10-U increase in collagen resulted in 15% increase in burst pressure (95% confidence interval = 0.2%-32%, P = 0.047, R(2) = 0.36). Atherosclerosis was unrelated to burst pressure controlling for collagen and size. Collagen and size provide the best model fit for predicting burst pressure. Quantitative research in human vasculature is warranted to better understand the influence of atherosclerosis and collagen content on seal failures. Copyright © 2013 Elsevier Inc. All rights reserved.

Predictive value of apolipoprotein for coronary atherosclerosis in asymptomatic non-diabetic population.

PubMed

Song, Xiang; Tian, Shu-ping; Ju, Hai-yue; Zhang, Fan; Li, Ying-na; Wu, Fang; Yang, Li

2015-02-01

To explore the potential correlation between apolipoprotein (Apo) levels and coronary atherosclerosis and investigate its predictive value for coronary artery lesions in asymptomatic population without diabetes. We performed a retrospective analysis of data collected from 401 asymptomatic patients who took health check-ups. They were divided into atherosclerosis group (n=224)and control group (n=177) based on the outcome of CT angiography and blood biochemical findings. The risk factors, lipid profiles, and Apo levels were compared between these two groups. The best biochemical indicators for predicting the coronary atherosclerosis were explored. The levels of ApoB, ApoC2,ApoC3,and ApoE and ApoB/ApoA1 ratio were significantly higher in the atherosclerosis group than in the control group (all P<0.01), whereas the ApoA1,ApoA2, and lipoprotein a levels showed no such significant difference (all P>0.05). Logistic regression analysis revealed that age, male, hypertension,ApoC3(OR=1.572,95%CI 1.200-2.061) and ApoB/ApoA1 ratio (OR=1.767,95% CI 1.335-2.338) were independently correlated with coronary atherosclerosis (all P<0.01). In the prediction of the presence of plaque, ApoB had the largest area under curves, and the optimal cutoff point was 1.005 g/L. ApoC3 is closely associated with subclinical coronary atherosclerosis,while the decrease of ApoA1 level is not obvious during this period. Compared with other lipid indicators, ApoB is the strongest predictor for coronary atherosclerosis in asymptomatic non-diabetic population.

Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans.

PubMed

Diodati, J G; Dakak, N; Gilligan, D M; Quyyumi, A A

1998-07-07

We investigated whether luminal release of nitric oxide (NO) contributes to inhibition of platelet activation and whether these effects are reduced in patients with atherosclerosis. Femoral blood flow velocity and ex vivo whole blood platelet aggregation by impedance aggregometry were measured in femoral venous blood during femoral arterial infusion of acetylcholine (ACh; 30 microg/min) in 30 patients, 19 of whom had angiographic atherosclerosis. Measurements were repeated with sodium nitroprusside (40 microg/min), L-arginine (160 micromol/min), and N(G)-monomethyl-L-arginine (L-NMMA; 16 micromol/min). There was significant inhibition of collagen-induced platelet aggregation with ACh (45+/-9.5% lower, P<0.001), and this inhibition was greater in patients without atherosclerosis (68.7+/-10.4% reduction) than in those with atherosclerosis (32.5+/-8.1%, P=0.04). The magnitude of inhibition correlated with vasodilation with ACh, indicating an association between the smooth muscle and antiplatelet effects of endothelium-dependent stimulation. Neither L-NMMA nor sodium nitroprusside altered platelet aggregation. L-Arginine inhibited platelet aggregation equally in vitro (34+/-8% reduction, P<0.01) and in vivo (37+/-13% reduction, P<0.01). Stimulation of NO release into the vascular lumen with ACh inhibits platelet aggregation, an effect that is attenuated in patients with atherosclerosis and endothelial dysfunction. Basal NO release does not appear to contribute to platelet passivation in vivo. L-Arginine inhibited platelet aggregation by its direct action on platelets. These findings provide a pathophysiological basis for the observed increase in thrombotic events in atherosclerosis. Use of L-arginine and other strategies to improve endothelial NO activity may impact favorably on thrombotic events in atherosclerosis.

The lightest market in the world: light and mild cigarettes in Japan.

PubMed

Assunta, Mary; Chapman, Simon

2008-05-01

This article reviews the history of the introduction and use of light and mild labeled cigarettes in Japan, the "lightest" market in the world. Systematic keyword and opportunistic Web site searches were conducted on tobacco industry internal documents relevant to Japan, supplemented with relevant material from the tobacco trade and sociological literatures. Certain "market quirks" of the Japanese society benefited the tobacco industry in promoting its light and mild cigarettes. Japan's is a trend-conscious society with a penchant for new fashion and products. The Japanese are innovative, with the propensity to transform concepts into something characteristically their own marked by a distinct cultural style, such as the concept of keihaku tansho ("light-thin-short-small"). With big-budget sophisticated advertising, tobacco companies developed a lucrative market for mild, light, and ultra-low-tar cigarettes. Smokers had a preference for charcoal filters, which they believed protected them. Tar numbers meant little to smokers. The transnational tobacco companies capitalized on consumer concerns about the health hazards of smoking to promote low-tar cigarettes as a safer alternative. This may be one factor that explains why smoking prevalence in Japan remains high. Light and mild cigarettes are popular in Japan because Japanese smokers believe low tar/nicotine cigarette with charcoal filters protect them and help mollify their health concerns about smoking.

Atherosclerosis associated with pericardial effusion in a central bearded dragon (Pogona vitticeps).

PubMed

Schilliger, Lionel; Lemberger, Karin; Chai, Norin; Bourgeois, Aude; Charpentier, Maud

2010-09-01

Atherosclerosis is a common disease in pet birds, particularly in psittacines, and is frequently found when performing postmortem examinations on adult and old dogs, in which it is mainly associated with endocrine diseases, such as hypothyroidism and diabetes mellitus. However, atherosclerosis is poorly documented in reptiles and consequently poorly understood. In the current case report, atherosclerosis and pericardial effusion were diagnosed in a 2-year-old male central bearded dragon (Pogona vitticeps) based on ultrasound visualization, necropsy, and histologic examination.

Hematocrit is associated with carotid atherosclerosis in men but not in women.

PubMed

Irace, Concetta; Ciamei, Monica; Crivaro, Andrea; Fiaschi, Elio; Madia, Angela; Cortese, Claudio; Gnasso, Agostino

2003-06-01

It is known that blood and plasma viscosities are associated with clinical manifestations of atherosclerosis, though evidence is not conclusive particularly in women. To verify whether hematocrit and blood and plasma viscosities are independently associated with carotid atherosclerosis and whether their measurement can improve the definition of the global coronary heart disease (CHD) risk. Eight hundred and ninety-two participants in a cardiovascular disease prevention campaign were examined with regard to conventional CHD risk factors (age, blood pressure, lipids, glucose, body mass index, waist/hip ratio, cigarette smoking and diabetes), hematocrit and blood and plasma viscosities. According to the degree of carotid atherosclerosis, investigated by echo-Doppler, participants were divided in three groups: those without atherosclerosis, those with a low degree of atherosclerosis and those with a high degree of atherosclerosis. In men, age, blood pressure, intima-media thickness (IMT), hematocrit (47.4+/-3.7%, 47.8+/-3.7%, 48.4+/-3.7%, P<0.05) and blood viscosity (4.69+/-0.51 cP, 4.77+/-0.55 cP, 4.82+/-0.51 cP, P=0.05) increased with increasing degree of carotid atherosclerosis. In women, age, blood pressure, total cholesterol and low-density lipoprotein-cholesterol, IMT and plasma viscosity (1.42+/-0.12 cP, 1.44+/-0.11 cP, 1.46+/-0.13 cP, P<0.05) increased with increasing carotid score. Analysis of covariance (ANCOVA) showed that after adjusting for hematocrit, blood viscosity was no longer different in the three groups. In discriminant analysis, hematocrit, among the hemorheological variables investigated, was independently associated with carotid score in men (F=3.66, P<0.05). Neither hematocrit nor blood and plasma viscosities were significantly associated with carotid score in women. These findings suggest that in men, both hematocrit and blood viscosity are related to carotid atherosclerosis but hematocrit would appear to have an independent effect over and

Contribution of fibroblast growth factor 23 to Framingham risk score for identifying subclinical atherosclerosis in Chinese men.

PubMed

Hu, X; Ma, X; Luo, Y; Xu, Y; Xiong, Q; Pan, X; Bao, Y; Jia, W

2017-02-01

Fibroblast growth factor 23 (FGF23) was demonstrated to be involved in the occurrence and development of cardiovascular disease (CVD). The goal of the present study was to investigate the relationship between serum FGF23 levels and carotid intima-media thickness (C-IMT) in men with a low-to-moderate CVD risk. Subjects with normal kidney function were selected from the Shanghai Obesity Study. Serum FGF23 levels were determined by sandwich enzyme-linked immunosorbent assay. C-IMT was measured by ultrasonography. The Framingham risk score (FRS) was used to assess CVD risk. A total of 392 men with low CVD risk and 372 men with moderate CVD risk were enrolled. The recognition rate of an elevated C-IMT was 85.66% with the combination of a moderate CVD risk and high serum FGF23 levels, which was greater than that with either parameter alone (65.44% and 61.03%, respectively). Subjects with high serum FGF23 levels, and either low or moderate CVD risk, were more likely to have elevated C-IMT than those with low serum FGF23 levels and low CVD risk (P = 0.014 and 0.001, respectively). The serum FGF23 levels were independently and positively associated with C-IMT in subjects with low or moderate CVD risk (both P = 0.007). In men with low-to-moderate CVD risk, serum FGF23 levels were associated independently and positively with C-IMT. As a complementary index, serum FGF23 levels strengthen the capacity of the FRS to identify subclinical atherosclerosis. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

View from... JSAP Spring Meeting 2012: Photonics news from Japan

NASA Astrophysics Data System (ADS)

Horiuchi, Noriaki

2012-05-01

Scientists gathered at the spring meeting of the Japan Society of Applied Physics to discuss quantum devices based on silicon and diamond, imaging using the X-ray Berry-phase effect and terahertz near-field microscopy.

Women in surgery: little change in gender equality in Japanese medical societies over the past 3 years.

PubMed

Tomizawa, Yasuko

2013-10-01

Japan lags behind other industrialized nations in terms of gender equality. To improve the work environment for surgeons, the opinions of female surgeons must be respected. The Committee on Women Surgeons of the Japan Surgical Society (JSS) conducted two surveys 3 years apart of the numbers of female councilors and directors in the member societies of the Japanese Association of Medical Sciences. In the nonsurgical medical societies, although there was an increase in the number of female councilors, only one female director was named over the past 3 years. On the other hand, there were no female directors in any of the 12 surgical societies in 2011. The JSS was founded in 1899. No female surgeon has ever been elected as director and there are currently no female councilors due to the new election system. The Gender Equality Bureau of the Cabinet Office should therefore provide greater support to improve gender equality in Japan.

Habitual fish intake and clinically silent carotid atherosclerosis

PubMed Central

2014-01-01

Background Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (≥ 0.90 mm), in non-diabetic participants. Methods Nine hundred-sixty-one (range of age: 18–89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. Results Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of ≥ 2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness ≥ 0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P = 0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR = 1.12; 95% CI = 1.09-1.14), hypertension on pharmacologic treatment (OR = 1.81; 95% CI = 1.16-2.82), and pulse pressure (OR = 1.03; 95% CI = 1.01-1.04), while consuming ≥2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR = 0.46; 95% CI = 0.26-0.80). Conclusions High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish

Habitual fish intake and clinically silent carotid atherosclerosis.

PubMed

Buscemi, Silvio; Nicolucci, Antonio; Lucisano, Giuseppe; Galvano, Fabio; Grosso, Giuseppe; Belmonte, Serena; Sprini, Delia; Migliaccio, Silvia; Cianferotti, Luisella; Brandi, Maria Luisa; Rini, Giovam Battista

2014-01-09

Fish consumption is recommended as part of a healthy diet. However, there is a paucity of data concerning the relation between fish consumption and carotid atherosclerosis. We investigated the association between habitual fish consumption and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness (≥ 0.90 mm), in non-diabetic participants. Nine hundred-sixty-one (range of age: 18-89 yrs; 37.1% males) adult participants without clinically known atherosclerotic disease were randomly recruited among the customers of a shopping mall in Palermo, Italy, and cross-sectionally investigated. Each participant answered a food frequency questionnaire and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Routine laboratory blood measurements were obtained in a subsample of 507 participants. Based on habitual fish consumption, participants were divided into three groups: non-consumers or consumers of less than 1 serving a week (24.0%), consumers of 1 serving a week (38.8%), and consumers of ≥ 2 servings a week (37.2%). Age-adjusted prevalence of carotid atherosclerosis (presence of plaques or intima media thickness ≥ 0.9 mm) was higher in the low fish consumption group (13.3%, 12.1% and 6.6%, respectively; P = 0.003). Multivariate analysis evidenced that carotid atherosclerosis was significantly associated with age (OR = 1.12; 95% CI = 1.09-1.14), hypertension on pharmacologic treatment (OR = 1.81; 95% CI = 1.16-2.82), and pulse pressure (OR = 1.03; 95% CI = 1.01-1.04), while consuming ≥2 servings of fish weekly was protective compared with the condition of consumption of <1 serving of fish weekly (OR = 0.46; 95% CI = 0.26-0.80). High habitual fish consumption seems to be associated with less carotid atherosclerosis, though adequate interventional trials are necessary to confirm the role of fish consumption in prevention of cardiovascular

[WHO Healthy City Initiative in Japan].

PubMed

Yoshizawa, Kazuko

2013-01-01

City environmental conditions are associated with health outcomes in people living there. World Health Organization (WHO) initiated Healthy City in 1986. To promote the networking, Alliance for Healthy Cities (AFHC) was launched in 2003 with local offices including AFHC Japan. As of 2010, 26 cities are members of AFHC Japan. A questionnaire was sent to those member cities. It includes questions on why they became an AFHC member, which section is in charge of the initiatives, what factors are important for promotion, and others. Out of the 26 cities, 13 cities returned the completed questionnaire. As for factors important for promoting the initiatives, 10 (77%) out of the 13 cities answered "consciousness of residents", while five (38%) chose "budget". This result suggests that community participation is a more important factor than budget for promoting and succeeding in the initiatives. Aging is a problem in any of the member cities, and six cities out the 13 falls under the category of superaged society, which is defined as a society with the proportion of aged people < 65 years being greater than 21% of the whole population. Eleven cities (85%) agreed that bicycles are an alternative means of transportation to cars; however, infrastructure for ensuring safety needs further improvement. In the promotion of Healthy City, networking among the member cities in Japan and worldwide should be promoted. Community participation with empowerment from the planning stage should lead to sustainable initiatives. The function of AFHC in collaboration among the members should be strengthened to cope with the rapidly changing city environment.

Japan.

PubMed

1987-02-01

Japan is composed of 4 main islands and more than 3900 smaller islands and has 317.7 persons/square kilometer. This makes it one of the most densely populated nations in the world. Religion is an important force in the life of the Japanese and most consider themselves Buddhists. Schooling is free through junior high but 90% of Japanese students complete high school. In fact, Japan enjoys one of the highest literacy rates in the world. There are over 178 newspapers and 3500 magazines published in Japan and the number of new book titles issued each year is greater than that in the US. Since WW1, Japan expanded its influence in Asia and its holdings in the Pacific. However, as a direct result of WW2, Japan lost all of its overseas possessions and was able to retain only its own islands. Since 1952, Japan has been ruled by conservative governments which cooperate closely with the West. Great economic growth has come since the post-treaty period. Japan as a constitutional monarchy operates within the framework of a constitution which became effective in May 1947. Executive power is vested in a cabinet which includes the prime minister and the ministers of state. Japan is one of the most politically stable of the postwar democracies and the Liberal Democratic Party is representative of Japanese moderate conservatism. The economy of Japan is strong and growing. With few resources, there is only 19% of Japanese land suitable for cultivation. Its exports earn only about 19% of the country's gross national product. More than 59 million workers comprise Japan's labor force, 40% of whom are women. Japan and the US are strongly linked trading partners and after Canada, Japan is the largest trading partner of the US. Foreign policy since 1952 has fostered close cooperation with the West and Japan is vitally interested in good relations with its neighbors. Relations with the Soviet Union are not close although Japan is attempting to improve the situation. US policy is based on

The Misunderstood Problem of Consumer Protection in Japan: The Roles of Lawyers and the Government.

ERIC Educational Resources Information Center

Waxman, Michael Peter

1995-01-01

Introduces the role of law and government in consumer protection in Japan. Suggests that recognition of cultural differences between U.S. and Japanese societies can provide insights that will stimulate the U.S. consumer movement to confront the anticonsumer structures in Japan while respecting their internal values. (Author/JOW)

Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsieh, Yi-Chen; Lien, Li-Ming; School of Medicine, Taipei Medical University, Taipei, Taiwan

2011-08-15

Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study.more » Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis

Prevention of Coronary Atherosclerosis: The Role of a College Health Service.

ERIC Educational Resources Information Center

Manchester, Ralph A.; Greenland, Philip

1987-01-01

This paper reviews the concept of behavioral risk factors for atherosclerosis which become entrenched in adolescence or young adulthood. Evidence favoring intervention in the adolescent years and a screening program at the University of Rochester Health Service are described. A preliminary strategy for prevention of atherosclerosis on campus is…

Validation of an Interview-Based Rating Scale Developed in Japan for Pervasive Developmental Disorders

ERIC Educational Resources Information Center

Ito, Hiroyuki; Tani, Iori; Yukihiro, Ryoji; Adachi, Jun; Hara, Koichi; Ogasawara, Megumi; Inoue, Masahiko; Kamio, Yoko; Nakamura, Kazuhiko; Uchiyama, Tokio; Ichikawa, Hironobu; Sugiyama, Toshiro; Hagiwara, Taku; Tsujii, Masatsugu

2012-01-01

The pervasive developmental disorders (PDDs) Autism Society Japan Rating Scale (PARS), an interview-based instrument for evaluating PDDs, has been developed in Japan with the aim of providing a method that (1) can be used to evaluate PDD symptoms and related support needs and (2) is simpler and easier than the currently used "gold…

Japan.

PubMed

1989-02-01

Japan consists of 3900 islands and lies off the east coast of Asia. Even though Japan is one of the most densely populated nations in the world, its growth rate has stabilized at .5%. 94% of all children go to senior high school and almost 90% finish. Responsibility for the sick, aged, and infirmed is changing from the family and private sector to government. Japan was founded in 600 BC and its 1st capital was in Nara (710-1867). The Portuguese, the 1st Westerners to make contact with Japan in 1542, opened trade which lasted until the mid 17th century. US Navy Commodore Matthew Perry forced Japan to reopen in 1854. Following wars with China and Russia in the late 1800s and early 1900s respectively, Japan took part in World Wars I and II. In between these wars Japan invaded Manchuria and China. The US dropped an atomic bomb on Hiroshima and Nagasaki and the Japanese surrendered in September, 1945 ending World War II (WWII). Following, WWII, the Allied Powers guided Japan's establishment as a nonthreatening nation and a democratic parliamentary government (a constitutional monarchy) with a limited defense force. Japan remains one of the most politically stable of all postwar democracies. The Liberal Democratic Party's Noboru Takeshita became prime minister in 1987. Japan has limited natural resources and only 19% of the land is arable. Japanese ingenuity and skill combine to produce one of the highest per hectare crop yields in the world. Japan is a major economic power, and its and the US economies are becoming more interdependent. Its exports, making up only 13% of the gross national product, mainly go to Canada and the US. Many in the US are concerned, however, with the trade deficit with Japan and are seeking ways to make trade more equitable. Japan wishes to maintain good relations with its Asian neighbors and other nations. The US and Japan enjoy a strong, productive relationship.

Frequency of Subclinical Atherosclerosis in Brazilian HIV-Infected Patients.

PubMed

Salmazo, Péricles Sidnei; Bazan, Silméia Garcia Zanati; Shiraishi, Flávio Gobbis; Bazan, Rodrigo; Okoshi, Katashi; Hueb, João Carlos

2018-04-09

AIDS as well as atherosclerosis are important public health problems. The longer survival among HIV-infected is associated with increased number of cardiovascular events in this population, and this association is not fully understood. To identify the frequency of subclinical atherosclerosis in HIV-infected patients compared to control subjects; to analyze associations between atherosclerosis and clinical and laboratory variables, cardiovascular risk factors, and the Framingham coronary heart disease risk score (FCRS). Prospective cross-sectional case-control study assessing the presence of subclinical atherosclerosis in 264 HIV-infected patients and 279 controls. Clinical evaluation included ultrasound examination of the carotid arteries, arterial stiffness by pulse wave velocity (PWV) and augmentation index (AIx), laboratory analysis of peripheral blood, and cardiovascular risk according to FCRS criteria. The significance level adopted in the statistical analysis was p < 0.05. Plaques were found in 37% of the HIV group and 4% of controls (p < 0.001). Furthermore, carotid intima-media thickness was higher in the HIV group than in controls (p < 0.001). Patients with carotid plaque had higher fasting glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than those without plaques. The presence of HIV, adjusted for age, overweight/obesity, and smoking increased by almost fivefold the risk of atherosclerotic carotid plaque (OR: 4.9; 95%CI: 2.5-9.9; p < 0.001). Exposure to protease inhibitors did not influence carotid intima-media thickness, was not associated with carotid plaque frequency, and did not alter the mechanical characteristics of the arterial system (PWV and AIx). HIV-infected patients are at increased risk of atherosclerosis in association with classical cardiovascular risk factors. Treatment with protease inhibitors does not promote functional changes in the arteries, and shows no association with increased frequency of

Improved animal models for testing gene therapy for atherosclerosis.

PubMed

Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

2014-04-01

Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications

PubMed Central

Kratz, Jeremy D.; Chaddha, Ashish; Bhattacharjee, Somnath

2016-01-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

PubMed

Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

2016-02-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design

PubMed Central

2011-01-01

Background Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Methods/Design Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. Discussion The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

PubMed

López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

2011-02-17

Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from

[The history and perspective of gender-specific medicine in Japan].

PubMed

Shimokawa, Hiroaki

2015-04-01

The history of gender-specific medicine started when Barbara Seaman, a female American journalist, started the women's health movement in 1957. Since then, the National Institutes of Health(NIH) and the Food and Drug Administration(FDA) have promoted gender-specific medicine in USA, including the Women's Health Initiative(WHI) by NIH in 1991 and the Office on Women's Health(OWH) by FDA in 1995. In Japan, being stimulated by the movements in USA, Dr. Chuwa Tei founded Japan' s first women' s clinic in Kagoshima University in 2001, and Dr. Keiko Amano founded the Association for Gender-Specific Medicine in 2004. These activities developed into the establishment of the Japanese Association for Gender-Specific Medicine in 2008, for which Dr.Tei served as the first president for 4 years, followed by Hiroaki Shimokawa since 2012. Furthermore, the importance of gender-specific medicine has been emerging worldwide, resulting in the establishment of International Society of Gender Medicine in 2012. Indeed, the history of gender-specific medicine is 60 years worldwide and is only 15 years in Japan. However, gender-specific medicine will become more and more important not only in medicine but also in the whole society.

Overview of Atherosclerosis and Chemical Stressors

EPA Science Inventory

Dr. Cascio’s presentation at the workshop titled, “titled “Understanding the Combined Effects of Environmental Chemical and Non-Chemical Stressors: Atherosclerosis as a Model” will highlight atherosclerosis’s rapidly growing role as a cause of increa...

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of adiposity on cellular adhesion: The Multi-Ethnic Study of atherosclerosis (MESA).

PubMed

Christoph, Mary J; Allison, Matthew A; Pankow, James S; Decker, Paul A; Kirsch, Phillip S; Tsai, Michael Y; Sale, Michele M; de Andrade, Mariza; Sicotte, Hugues; Tang, Weihong; Hanson, Naomi Q; Berardi, Cecilia; Wassel, Christina L; Larson, Nicholas B; Bielinski, Suzette J

2016-01-01

At the cellular level, how excess adiposity promotes atherogenesis is not fully understood. One pathway involves secretion of adipokines that stimulate endothelial dysfunction through increased expression of adhesion molecules. However, the relationship of adiposity to adhesion molecules that promote atherosclerosis is largely unknown. Linear regression models were used to assess the sex-specific associations of soluble cellular adhesion molecules (sP- and sL-selectin, sICAM-1, sVCAM-1, and sHGF) and adiposity in 5,974 adults examined as part of the Multi-Ethnic Study of Atherosclerosis (MESA). Adiposity measures included body mass index (BMI), waist-to-hip-ratio (WHR), and computed tomography measures of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The mean age was 64 years and 52% were female. In multivariable models adjusting for traditional cardiovascular risk factors, sHGF was positively associated with BMI, WHR, and VAT in both males and females, and sP-selectin with WHR and VAT in males. sVCAM-1 was inversely associated with VAT in females only. Our results showed the relation of adiposity to soluble cellular adhesion proteins was similar across adiposity measures and for both sexes. However, the relationship between adiposity and sVCAM-1 and P-selectin may be modified by sex and the measure used to assess adiposity. © 2015 The Obesity Society.

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

PubMed

Dotsenko, O; Chaturvedi, N; Thom, S A McG; Wright, A R; Mayet, J; Shore, A; Schalkwijk, C; Hughes, A D

2007-10-01

Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?

PubMed

Nieto, F J; Iribarren, C; Gross, M D; Comstock, G W; Cutler, R G

2000-01-01

the evidence of a potential beneficial role of antioxidants in preventing atherosclerotic disease is not entirely consistent. to assess the longitudinal association of serum total antioxidant capacity and serum antioxidants with the presence of subclinical carotid atherosclerosis. Prospective case-control study nested within an historical cohort. Cases were 150 individuals with elevated carotid intimal-medial thickness measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities Study (1987-92). Controls were 150 age-gender-matched individuals with low carotid intimal-medial thickness. Serum antioxidant vitamins, uric acid, and serum total antioxidant capacity were measured in frozen serum samples collected from the same individuals in 1974 (13-15 years prior to the determination of case-control status). Compared to controls, atherosclerosis cases had significantly higher levels of serum total antioxidant capacity in 1974 than controls. This difference was almost entirely explained by increased serum concentration of uric acid in cases. In contrast with cross-sectional results, uric acid serum concentration in 1974, was significantly higher in cases than in controls, even after adjusting for the main cardiovascular risk factors. Cases had significantly lower levels of alpha-carotene in the 1974 sera than controls, but no other differences in serum antioxidant vitamin concentrations were observed. The higher serum uric acid concentration seemed associated with elevated total serum antioxidant capacity among individuals with atherosclerosis. This finding is consistent with experimental evidence suggesting that hyperuricemia may be a compensatory mechanism to counteract oxidative damage related to atherosclerosis and aging in humans.

Myeloid Kdm6b deficiency results in advanced atherosclerosis.

PubMed

Neele, Annette E; Gijbels, Marion J J; van der Velden, Saskia; Hoeksema, Marten A; Boshuizen, Marieke C S; Prange, Koen H M; Chen, Hung-Jen; Van den Bossche, Jan; van Roomen, Cindy P P A; Shami, Annelie; Levels, Johannes H M; Kroon, Jeffrey; Lucas, Tina; Dimmeler, Stefanie; Lutgens, Esther; de Winther, Menno P J

2018-06-01

Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression. Bone marrow of myeloid Kdm6b deficient (Kdm6b del ) mice or wild type littermates (Kdm6b wt ) was transplanted to lethally irradiated Ldlr -/- mice fed a high fat diet for 9 weeks to induce atherosclerosis. Lesion size was similar in Kdm6b wt and Kdm6b del transplanted mice. However, lesions of Kdm6b del mice contained more collagen and were more necrotic. Pathway analysis on peritoneal foam cells showed that the pathway involved in leukocyte chemotaxis was most significantly upregulated. Although macrophage and neutrophil content was similar after 9 weeks of high fat diet feeding, the relative increase in collagen content and necrosis revealed that atherosclerotic lesions in Kdm6b del mice progress faster. Myeloid Kdm6b deficiency results in more advanced atherosclerosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

The Multifaceted Uses and Therapeutic Advantages of Nanoparticles for Atherosclerosis Research.

PubMed

DiStasio, Nicholas; Lehoux, Stephanie; Khademhosseini, Ali; Tabrizian, Maryam

2018-05-08

Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies.

Barriers to mental health care in Japan: Results from the World Mental Health Japan Survey.

PubMed

Kanehara, Akiko; Umeda, Maki; Kawakami, Norito

2015-09-01

The reasons for accessing and maintaining access to mental health services in Japan may be different to those in other countries. Using the World Health Organization World Mental Health Japan survey data, this study investigated the prevalence of sociodemographic correlates of barriers for the use of, reasons for delayed access to, and reasons for dropping out from mental health care in a Japanese community-based sample. An interview survey was conducted with a random sample of residents living in 11 communities across Japan during the years 2002-2006. Data from 4130 participants were analyzed. The most frequently reported reason for not seeking mental health care was a low perceived need (63.9%). The most common reason for delaying access to help was the wish to handle the problem on one's own (68.8%), while the most common reason for dropping out of care was also a low perceived need (54.2%). Being a woman and of younger age were key sociodemographic barriers to the use of mental health services. Low perceived need was a major reason for not seeking, delay in using, and dropout from mental health services in Japan. In addition, low perceived need and structural barriers were more frequently reported than attitudinal barriers, with the exception of a desire to handle the problem on one's own. These findings suggest that improving therapist-patient communication and quality of mental health care, as well as mental health literacy education in the community, might improve access to care in Japan. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

What can ancient mummies teach us about atherosclerosis?

PubMed

Wann, Samuel; Thomas, Gregory S

2014-10-01

Ancient mummies have captivated a wide variety of audiences for centuries. In order to better understand the evolution and causative features of atherosclerosis, the Horus group is applying modern scientific methods to study ancient mummies. We have used CT scanning to detect calcification in arteries as an indication of the presence of atherosclerosis, and are correlating these results with cultural and lifestyle features of various populations of ancient people as represented by their ancient mummified remains. We are also pursuing related studies of ancient DNA to define genotypes associated with atherosclerotic phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Current status of cardiovascular surgery in Japan, 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database (JCVSD). 1: Mission and history of JCVSD.

PubMed

Takamoto, Shinichi; Motomura, Noboru; Miyata, Hiroaki; Tsukihara, Hiroyuki

2018-01-01

The Japan Cardiovascular Surgery Database (JCVSD) was created in 2000 with the support of the Society of Thoracic Surgeons (STS). The STS database content was translated to Japanese using the same disease criteria and in 2001, data entry for adult cardiac surgeries was initiated online using the University Hospital Medical Information Network (UMIN). In 2008, data entry for congenital heart surgeries was initiated in the congenital section of JCVSD and preoperative expected mortality (JapanSCORE) in adult cardiovascular surgeries was first calculated using the risk model of JCVSD. The Japan Surgical Board system merged with JCVSD in 2011, and all cardiovascular surgical data were registered in the JCVSD from 2012 onward. The reports resulting from the data analyses of the JCVSD will encourage further improvements in the quality of cardiovascular surgeries, patient safety, and medical care in Japan.

[Introduction of the psychoprophylactic method and its influence on the prenatal care program for institutional parturition in Japan: the practice in the Central Hospital of Maternity of the Japanese Red Cross Society and Oomori Red Cross Hospital, 1953-1964].

PubMed

Fujihara, Satoko; Tsukisawa, Miyoko

2014-03-01

The psychoprophylactic method is one of the methods for providing 'painless childbirth without drugs' and was invented by applying I. Pavlov's theory of higher nervous activity. In 1951, it was adopted as a national policy in the Union of Soviet Socialist Republics. This method was then introduced in the People's Republic of China in 1952. In 1953, it was brought to Japan by Masatomo SUGAI, an obstetrician, and was introduced into the Central Hospital of Maternity of the Japanese Red Cross Society with the support of the director, Naotarou KUJI. The practice of this method by the research team, which consisted of the obstetricians and midwives of the Central Hospital of Maternity of the Japanese Red Cross Society and Oomori Red Cross Hospital, resulted in the initiation and characterization of the prenatal care program to encourage the autonomy of the pregnant women for normal parturition in the institutions of Japan.

[Gender equality activity in the Bioimaging Society].

PubMed

Suzaki, Etsuko

2013-09-01

Gender equality activity in the Bioimaging Society was initiated in 2005 when it joined the Japan Inter-Society Liaison Association Committee for Promoting Equal Participation of Men and Women in Science and Engineering (EPMEWSE). The Gender Equality Committee of the Bioimaging Society is acting on this issue by following the policy of the EPMEWSE, and has also been planning and conducting lectures at annual meetings of the society to gain the understanding, consents, and cooperation of the members of the society to become conscious of gender equality. Women's participation in the society has been promoted through the activities of the Gender Equality Committee, and the number of women officers in the society has since increased from two women out of 40 members in 2005 to five out of 44 in 2013. The activities of the Gender Equality Committee of the Japanese Association of Anatomists (JAA) have just started. There are more than 400 women belonging to the JAA. When these women members join together and collaborate, women's participation in the JAA will increase.

Evaluation of Chlamydophila psittaci infection and other risk factors for atherosclerosis in pet psittacine birds.

PubMed

Pilny, Anthony A; Quesenberry, Katherine E; Bartick-Sedrish, Tracey E; Latimer, Kenneth S; Berghaus, Roy D

2012-06-15

To determine whether the presence of Chlamydophila psittaci antigen, plasma cholesterol concentration, diet, sex, species, and age are risk factors for the development of atherosclerosis in pet psittacine birds. Retrospective case-control study. 31 psittacine birds with atherosclerosis (study birds) and 31 psittacine birds without atherosclerosis (control birds). Necropsy reports were reviewed, birds with a histopathologic diagnosis of atherosclerosis were identified, and available medical records were reviewed. Signalment, history, clinicopathologic findings, and other relevant data were recorded and evaluated. Control birds did not have atherosclerosis and were chosen by both convenience sampling and population demographics. Histologic sections of great vessels from all birds (study and control birds) were reviewed and then submitted for immunohistochemical staining for the presence of C psittaci antigen. Result of immunohistochemical staining for C psittaci antigen in blood vessels was significantly associated with atherosclerosis. After adjusting for age, species origin, and type of illness, the odds of atherosclerosis was 7 times as high for birds with positive immunohistochemical staining for C psittaci antigen, compared with that of birds with negative immunohistochemical staining. Study birds and control birds differed significantly only with respect to plasma cholesterol concentrations. The median plasma cholesterol concentration of study birds (421 mg/dL) was significantly higher than that of control birds (223 mg/dL). Infection with C psittaci and a high plasma cholesterol concentration may be risk factors for developing atherosclerosis in pet psittacine birds.

[Screening for atherosclerosis to prevent cardiovascular risk : a pro-contra debate].

PubMed

Nanchen, David; Genest, Jacques

2018-02-28

Detecting atherosclerosis using imaging techniques is the subject of intense debate in the scientific community. Among the arguments in favor of screening, a better identification or better stratification of cardiovascular risk is mentioned, compared to cardiovascular risk scores based solely on traditional risk factors, such as blood pressure or cholesterol levels. Imaging techniques are also used to monitor the progression of atherosclerosis among patients using lipid-lowering or antihypertensive drugs in primary prevention. However, several experts in recent years have challenged the clinical utility of these imaging techniques in asymptomatic adults. This article proposes a debate « for or against » to describe the main arguments for or against the use of imaging for screening for atherosclerosis.

Reversal of coronary atherosclerosis: Role of life style and medical management.

PubMed

Parsons, Christine; Agasthi, Pradyumna; Mookadam, Farouk; Arsanjani, Reza

2018-05-17

Atherosclerotic coronary artery disease continues to be a major global health burden in developing and developed nations. Newer imaging techniques afford an accurate assessment of plaque burden and characteristics as well as the effects of treatment. Lifestyle interventions and pharmacotherapy remain the mainstay of non-interventional treatment of coronary atherosclerosis, with reversal seen in many studies. In addition, control of modifiable risk factors can be beneficial. As a better understanding of atherosclerosis pathophysiology is achieved, new therapeutic targets and combination therapies may join the armamentarium that promotes regression of atherosclerotic plaque. We present a review of the literature regarding lifestyle and medical therapies that can promote the reversal of coronary atherosclerosis. Copyright © 2018. Published by Elsevier Inc.

Periodontal disease and carotid atherosclerosis: A meta-analysis of 17,330 participants.

PubMed

Zeng, Xian-Tao; Leng, Wei-Dong; Lam, Yat-Yin; Yan, Bryan P; Wei, Xue-Mei; Weng, Hong; Kwong, Joey S W

2016-01-15

The association between periodontal disease and carotid atherosclerosis has been evaluated primarily in single-center studies, and whether periodontal disease is an independent risk factor of carotid atherosclerosis remains uncertain. This meta-analysis aimed to evaluate the association between periodontal disease and carotid atherosclerosis. We searched PubMed and Embase for relevant observational studies up to February 20, 2015. Two authors independently extracted data from included studies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was assessed by the chi-squared test (P<0.1 for statistical significance) and quantified by the I(2) statistic. Data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. Fifteen observational studies involving 17,330 participants were included in the meta-analysis. The overall pooled result showed that periodontal disease was associated with carotid atherosclerosis (OR: 1.27, 95% CI: 1.14-1.41; P<0.001) but statistical heterogeneity was substantial (I(2)=78.90%). Subgroup analysis of adjusted smoking and diabetes mellitus showed borderline significance (OR: 1.08; 95% CI: 1.00-1.18; P=0.05). Sensitivity and cumulative analyses both indicated that our results were robust. Findings of our meta-analysis indicated that the presence of periodontal disease was associated with carotid atherosclerosis; however, further large-scale, well-conducted clinical studies are needed to explore the precise risk of developing carotid atherosclerosis in patients with periodontal disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Molecular intravascular imaging approaches for atherosclerosis.

PubMed

Press, Marcella Calfon; Jaffer, Farouc A

2014-10-01

Coronary artery disease (CAD) is an inflammatory process that results in buildup of atherosclerosis, typically lipid-rich plaque in the arterial wall. Progressive narrowing of the vessel wall and subsequent plaque rupture can lead to myocardial infarction and death. Recent advances in intravascular fluorescence imaging techniques have provided exciting coronary artery-targeted platforms to further characterize the molecular changes that occur within the vascular wall as a result of atherosclerosis and following coronary stent-induced vascular injury. This review will summarize exciting recent developments in catheter-based imaging of coronary arterial-sized vessels; focusing on two-dimensional near-infrared fluorescence imaging (NIRF) molecular imaging technology as an approach to specifically identify inflammation and fibrin directly within coronary artery-sized vessels. Intravascular NIRF is anticipated to provide new insights into the in vivo biology underlying high-risk plaques, as well as high-risks stents prone to stent restenosis or stent thrombosis.

Bone mineral density and atherosclerosis: The Multi-Ethnic Study of Atherosclerosis, Abdominal Aortic Calcium Study

PubMed Central

Hyder, Joseph A; Allison, Matthew A; Barrett-Connor, Elizabeth; Detrano, Robert; Wong, Nathan D; Sirlin, Claude; Gapstur, Susan M; Ouyang, Pamela; Carr, J Jeffrey; Criqui, Michael H

2009-01-01

Context Molecular and cell biology studies have demonstrated an association between bone and arterial wall disease, but the significance of a population-level association is less clear and potentially confounded by inability to account for shared risk factors. Objective To test population-level associations between atherosclerosis types and bone integrity. Main Outcome Measures Volumetric trabecular lumbar bone mineral density (vBMD), ankle-brachial index (ABI), intima-media thickness of the common carotid (CCA-IMT) and internal carotid (ICA-IMT) arteries, and carotid plaque echogenicity. Design, Setting and Participants A random subset of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) assessed between 2002 and 2005. Results 904 post-menopausal female (62.4 years; 62% non-white; 12% ABI<1; 17% CCA-IMT>1mm; 33% ICA-IMT>1mm) and 929 male (61.4 years; 58% non-white; 6% ABI<1; 25% CCA-IMT>1mm; 40% ICA-IMT>1mm) were included. In serial, sex-specific regression models adjusting for age, ethnicity, body mass index, dyslipidemia, hypertension, smoking, alcohol consumption, diabetes, homocysteine, interleukin-6, sex hormones, and renal function, lower vBMD was associated with lower ABI in men (p for trend <0.01) and greater ICA-IMT in men (p for trend <0.02). CCA-IMT was not associated with vBMD in men or women. Carotid plaque echogenicity was independently associated with lower vBMD in both men (trend p=0.01) and women (trend p<0.04). In all models, adjustment did not materially affect results. Conclusions Lower vBMD is independently associated with structural and functional measures of atherosclerosis in men and with more advanced and calcified carotid atherosclerotic plaques in both sexes. PMID:19819456

Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling

PubMed Central

Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun; Wang, Xiaoke; Kherada, Nisharahmed; Desikan, Rajagopal; Mihai, Georgeta; Burns, Patrick; Sun, Qinghua; Rajagopalan, Sanjay

2016-01-01

Objective Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. Methods and Results Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. Conclusion Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID:26859892

Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers.

PubMed

Bednarska-Makaruk, Małgorzata; Rodo, Maria; Markuszewski, Cezary; Rozenfeld, Anna; Swiderska, Malgorzata; Habrat, Bogusław; Wehr, Hanna

2005-01-01

To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events.

Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation

PubMed Central

Jeong, Jeong-Hee; Na, Hyun Sik; Kim, Eun-Kyung; Lee, Seung Hoon; Jung, KyungAh; Min, Jun-Ki; Cho, Mi-La

2017-01-01

Atherosclerosis is a chronic inflammatory disease caused by the accumulation of excess lipid in the aorta and the severity is regulated by T lymphocytes subsets. Rebamipide has therapeutic activity in collagen induced arthritis (CIA) by controlling the balance between T helper (Th) 17 and regulatory T (Treg) cells. In this study, we aimed to determine whether rebamipide reduces the development of atherosclerosis. To investigate the therapeutic effect of rebamipide, ApoE-KO mice fed a western diet were administered rebamipide orally for 8 weeks. Mice were sacrificed followed by the evaluation of plaque formation in the aorta or immunohistochemistry for IL-17 and Foxp3. Serum was also prepared to determine the pro-inflammatory cytokine levels. The ability of rebamipide to regulate lipid metabolism or inflammation was confirmed ex vivo. Results The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases. PMID:28241014

Evaluation of the biomechanics of atherosclerosis by acoustic microscopy

NASA Astrophysics Data System (ADS)

Saijo, Yoshifumi; Nitta, Shin-ichi; Schiott Jorgensen, Claus; Falk, Erling

2001-07-01

Acoustic microscopy provides not only the morphology, but also the biomechanical properties of the biological soft tissues. The biomechanics of atherosclerosis is important because the pathophysiology of atherosclerosis is closely related with mechanical properties and mechanical stress. Rupture of the fibrous cap of atheromatous plaque is the initial event in acute coronary syndrome such as acute myocardial infarction or unstable angina. In addition to extrinsic physical stresses to the plaque, the intrinsic biomechanical property of the plaque is important for assessing the mechanism of the rupture. Two sets of SAMs operating in 100 to 200 MHz and in 800 MHz to 1.3 GHz were equipped to measure the acoustic properties of atherosclerosis of human or mouse arteries. The values of attenuation and sound speed in the tissue components of atherosclerosis were measured by analyzing the frequency dependent characteristics of the amplitude and phase signals. Both values were highest in calcification and lowest in lipid pool. Although attenuation and sound speed were relatively high in intimal fibrosis, the inhomogeneity of acoustic parameters was found within the fibrous cap. Polarized microscopy for the collagen stained with Picrosirius red showed that the attenuation of ultrasound was significantly higher in type I collagen with orange polarized color compared to type III collagen with green color. SAM has shown the possibility to detect the plaque vulnerability and it might improve our understanding of the sudden rupture from micro-mechanical point of view.

Potential therapeutic effects of mTOR inhibition in atherosclerosis

PubMed Central

Kurdi, Ammar; De Meyer, Guido R. Y.

2015-01-01

Despite significant improvement in the management of atherosclerosis, this slowly progressing disease continues to affect countless patients around the world. Recently, the mechanistic target of rapamycin (mTOR) has been identified as a pre‐eminent factor in the development of atherosclerosis. mTOR is a constitutively active kinase found in two different multiprotein complexes, mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the value of mTORC1 inhibition to prevent the development of atherosclerotic plaques in several animal models. Rapalog‐eluting stents have also shown extraordinary results in humans, even though the exact mechanism for this anti‐atherosclerotic effect remains elusive. Unfortunately, rapalogs are known to trigger diverse undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These adverse effects include dyslipidaemia and insulin resistance, both known triggers of atherosclerosis. Several strategies, such as combination therapy with statins and metformin, have been suggested to oppose rapalog‐mediated adverse effects. Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine monophosphate‐activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis. Intermittent regimens and dose reduction have also been proposed to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2‐related side effects. PMID:26551391

Effects of catechins and caffeine on the development of atherosclerosis in mice.

PubMed

Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

PDGFRβ signaling regulates local inflammation and synergizes with hypercholesterolemia to promote atherosclerosis

PubMed Central

He, Chaoyong; Medley, Shayna C.; Hu, Taishan; Hinsdale, Myron E.; Lupu, Florea; Virmani, Renu; Olson, Lorin E.

2015-01-01

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (VSMCs). However, the direct effects of PDGF receptor β (PDGFRβ) activation on VSMCs have not been studied in the context of atherosclerosis. Here, we present a new mouse model of atherosclerosis with an activating mutation in PDGFRβ. Increased PDGFRβ signaling induces chemokine secretion and leads to leukocyte accumulation in the adventitia and media of the aorta. Furthermore, PDGFRβD849V amplifies and accelerates atherosclerosis in hypercholesterolemic ApoE−/− or Ldlr−/− mice. Intriguingly, increased PDGFRβ signaling promotes advanced plaque formation at novel sites in the thoracic aorta and coronary arteries. However, deletion of the PDGFRβ-activated transcription factor STAT1 in VSMCs alleviates inflammation of the arterial wall and reduces plaque burden. These results demonstrate that PDGFRβ pathway activation has a profound effect on vascular disease and support the conclusion that inflammation in the outer arterial layers is a driving process for atherosclerosis. PMID:26183159

Implementation process and challenges for the community-based integrated care system in Japan

PubMed Central

Tsutsui, Takako

2014-01-01

Background Since 10 years ago, Japan has been creating a long-term vision to face its peak in the number of older people that will be reached in 2025 when baby boomers will turn 75 years of age. In 2003, the government set up a study group called “Caring for older people in 2015” which led to a first reform of the Long-Term Care Insurance System in 2006. This study group was the first to suggest the creation of a community-based integrated care system. Reforms Three measures were taken in 2006: ‘Building an active ageing society: implementation of preventive care services’, ‘Improve sustainability: revision of the remuneration of facilities providing care’ and ‘Integration: establishment of a new service system’. These reforms are at the core of the community-based integrated care system. Discussion The socialization of long-term care that came along with the ageing of the population, and the second shift in Japan towards an increased reliance on the community can provide useful information for other ageing societies. As a super ageing society, the attempts from Japan to develop a rather unique system based on the widely spread concept of integrated care should also become an increasing focus of attention. PMID:24478614

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

PubMed

López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular

Child abuse and neglect in Japan: coin-operated-locker babies.

PubMed

Kouno, A; Johnson, C F

1995-01-01

The coin-operated-locker baby is a type of child abuse that may be unique to Japan. The term refers to newborns who are placed, while alive or dead, in coin-operated lockers. This practice has been decreased by specific measures. It is likely that social and economic variables in Japan account for differences in the frequency and types of child abuse cases when compared to American or European societies as social conditions in Japan change the reported incidence of child abuse may increase in the future. Recently, the government of Osaka organized a group specifically designed to deal with the detection and protection of abused and neglected children. In 1993, they published a manual on how to deal with child abuse, but the Japanese judicial administration still uses old laws for abuse cases. The development of new laws is occurring in parts of the country now. This paper introduces the present status of coping with child abuse and neglect in Japan.

[25 year experience with using surgical correction of dislipidemia in treatment of patients with atherosclerosis].

PubMed

Sedov, V M; Mirchuk, K K; Sedletskiĭ, Iu I

2011-01-01

An analysis of results of using partial ileoshunting for the treatment of dislipidemia in 159 patients with atherosclerosis has shown that operation of partial ileoshunting has an obligatory, pronounced and lifelong lipidcorrecting effect. An antiatherogenic effect of the operation of partial ileoshunting is manifested as the improvement of the clinical course of the disease caused by atherosclerosis, by less number of thrombotic complications of atherosclerosis and less lethality from cardio-vascular diseases. At a longer follow-up period, the efficiency of partial ileoshunting as a means of secondary prophylactics of atherosclerosis is confirmed but in case of liquidation after operation of dislipoproteidemia.

Effects of transplanted circulating endothelial progenitor cells and platelet microparticles in atherosclerosis development.

PubMed

Georgescu, Adriana; Alexandru, Nicoleta; Andrei, Eugen; Dragan, Emanuel; Cochior, Daniel; Dias, Sérgio

2016-08-01

Atherosclerosis is an inflammatory disease, in which risk factors such as hyperlipidemia and hypertension affect the arterial endothelium, resulting in dysfunction, cell damage or both. The number of circulating endothelial progenitor cells and microparticles provides invaluable outcome prediction for atherosclerosis disease. However, evidence for the therapeutic potential of endothelial progenitor cells and microparticles in atherosclerosis development is limited. Our study was designed to investigate the possible protective role of a cell therapy-based approach, using endothelial progenitor cells and the dual behaviour of circulating platelet microparticles, on atherosclerosis development in hypertensive-hypercholesterolemic hamster model. Consequently, control hamsters received four intravenous inoculations of: (1) 1×10(5) endothelial progenitor cells of healthy origins in one dose per month, during four months of diet-induced atherosclerosis, and after hypertensive-hypercholesterolemic diet for further four months; (2) in a second set of experiments, 1×10(5) endothelial progenitor cells of healthy origins or/and 1×10(5) platelet microparticles of atherosclerotic origins were inoculated every other month during hypertensive-hypercholesterolemic diet. Endothelial progenitor cell treatment had the following effects: (1) re-established plasmatic parameters: cholesterol and triglyceride concentrations, blood pressure, heart rate, cytokine and chemokine profiles, platelet microparticle pro-thrombotic activity and endothelial progenitor cell paracrine activity reflected by cytokine/chemokine detection; (2) reduced lipid, macrophage and microparticle accumulation in liver; (3) reduced atherosclerosis development, revealed by decreased lipid, macrophage and microparticle content of arterial wall; (4) induced the recruitment and incorporation of endothelial progenitor cells into liver and arterial wall; (5) improved arterial dysfunction by increasing contraction and

Screening Tool for Older Persons' Appropriate Prescriptions for Japanese: Report of the Japan Geriatrics Society Working Group on "Guidelines for medical treatment and its safety in the elderly".

PubMed

Kojima, Taro; Mizukami, Katsuyoshi; Tomita, Naoki; Arai, Hiroyuki; Ohrui, Takashi; Eto, Masato; Takeya, Yasushi; Isaka, Yoshitaka; Rakugi, Hiromi; Sudo, Noriko; Arai, Hidenori; Aoki, Hiroaki; Horie, Shigeo; Ishii, Shinya; Iwasaki, Koh; Takayama, Shin; Suzuki, Yusuke; Matsui, Toshifumi; Mizokami, Fumihiro; Furuta, Katsunori; Toba, Kenji; Akishita, Masahiro

2016-09-01

In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the "Guidelines for medical treatment and its safety in the elderly 2005." The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required. A total of 15 diseases, conditions and special areas related to their clinical care were selected. We originated clinical questions and keywords for these 15 areas, carried out a systematic review using these search criteria, and formulated guidelines applying the Grading of Recommendations Assessment, Development and Evaluation system advocated by Minds2014. If we did not find good evidence despite the drug being clinically important, we looked for evidence of efficacy and for disease-specific guidelines, and incorporated them into our guidelines. We selected 2098 articles (140 articles per area), and extracted another 186 articles through a manual search. We further added guidelines based on disease entity and made two lists, one of "drugs to be prescribed with special caution" and the other of "drugs to consider starting," primarily considering individuals aged 75 years or older or those who are frail or in need of special care. New lists of potentially inappropriate medications and potential prescribing omissions called "Screening Tool for Older Person's Appropriate Prescriptions for Japanese" were constructed. We anticipate that future studies will highlight more evidence regarding the safety of high-quality drugs, further improving the provision of appropriate medical care for the elderly. Geriatr Gerontol Int 2016: 16: 983-1001. © 2016 Japan Geriatrics Society.

New diagnostic criteria of adrenal subclinical Cushing's syndrome: opinion from the Japan Endocrine Society.

PubMed

Yanase, Toshihiko; Oki, Yutaka; Katabami, Takuyuki; Otsuki, Michio; Kageyama, Kazunori; Tanaka, Tomoaki; Kawate, Hisaya; Tanabe, Makito; Doi, Masaru; Akehi, Yuko; Ichijo, Takamasa

2018-04-26

New diagnostic criteria and the treatment policy for adrenal subclinical Cushing's syndrome (SCS) are proposed on behalf of the Japan Endocrine Society. The Japanese version has been published, and the essential contents are presented in this English-language version. The current diagnostic criteria for SCS have elicited two main problems: (i) the relatively low reliability of a low range of serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone suppression test (DST); (ii) different cutoff values for serum cortisol after a 1-mg DST compared with those of other countries. Thus, new criteria are needed. In the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8 μg/dL, after a 1-mg DST are presented. Serum cortisol ≥5 μg/dL after a 1-mg DST alone is considered sufficient to judge autonomous cortisol secretion for the diagnosis of SCS, and the current criterion based on serum cortisol ≥3 μg/dL after a 1-mg DST can continue to be used. Clinical evidence suggests that serum cortisol ≥1.8-2.9 μg/dL after a 1-mg DST is not always normal, so cases who meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and nocturnal serum cortisol ≥5 μg/dL are proposed to have SCS. We suggest surgery if cases show serum cortisol ≥5 μg/dL after a 1-mg DST (or are disheartened by treatment-resistant problems) or suspicious cases of adrenal cancer according to tumor imaging.

TRIGLYCERIDES, ATHEROSCLEROSIS, AND CARDIOVASCULAR OUTCOME STUDIES: FOCUS ON OMEGA-3 FATTY ACIDS.

PubMed

Handelsman, Yehuda; Shapiro, Michael D

2017-01-01

To provide an overview of the roles of triglycerides and triglyceride-lowering agents in atherosclerosis in the context of cardiovascular outcomes studies. We reviewed the published literature as well as ClinicalTrials.gov entries for ongoing studies. Despite improved atherosclerotic cardiovascular disease (ASCVD) outcomes with statin therapy, residual risk remains. Epidemiologic data and recent genetic insights provide compelling evidence that triglycerides are in the causal pathway for the development of atherosclerosis, thereby renewing interest in targeting triglycerides to improve ASCVD outcomes. Fibrates, niacin, and omega-3 fatty acids (OM3FAs) are three classes of triglyceride-lowering drugs. Outcome studies with triglyceride-lowering agents have been inconsistent. With regard to OM3FAs, the JELIS study showed that eicosapentaenoic acid (EPA) significantly reduced major coronary events in statin-treated hypercholesterolemic patients. Regarding other agents, extended-release niacin and fenofibrate are no longer recommended as statin add-on therapy (by some guidelines, though not all) because of the lack of convincing evidence from outcome studies. Notably, subgroup analyses from the outcome studies have generated the hypothesis that triglyceride lowering may provide benefit in statin-treated patients with persistent hypertriglyceridemia. Two ongoing OM3FA outcome studies (REDUCE-IT and STRENGTH) are testing this hypothesis in high-risk, statin-treated patients with triglyceride levels of 200 to 500 mg/dL. There is consistent evidence that triglycerides are in the causal pathway of atherosclerosis but inconsistent evidence from cardiovascular outcomes studies as to whether triglyceride-lowering agents reduce cardiovascular risk. Ongoing outcomes studies will determine the role of triglyceride lowering in statin-treated patients with high-dose prescription OM3FAs in terms of improved ASCVD outcomes. AACE = American Association of Clinical Endocrinologists

FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells

PubMed Central

Zhu, Min; Zhang, Qing-Jun; Wang, Lin; Li, Hao; Liu, Zhi-Ping

2011-01-01

Objectives FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis. Methods and Results Apolipoprotein E-deficient (apoE−/−) mice were crossbred with animals lacking Foxo4 (Foxo4−/−). After 10 weeks on a high fat diet (HFD), Foxo4−/−apoE−/− mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE−/− mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4−/− bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4−/−apoE−/− mice compared to those of apoE−/− mice. Conclusions FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention. PMID:22005198

A Correlational Study on Cerebral Microbleeds and Carotid Atherosclerosis in Patients with Ischemic Stroke.

PubMed

Zhao, Fang-Fang; Gao, Hao-Yuan; Gao, Yuan; Zhao, Zhuan; Li, Juan; Ning, Fang-Bo; Zhang, Xin-Na; Wang, Zhi-Gao; Yu, Ai-Ling; Guo, Yan-Yong; Sun, Bao-Liang

2018-05-11

This study aimed to investigate the correlation between cerebral microbleeds and carotid atherosclerosis in patients with ischemic stroke. Patients with ischemic stroke treated in a hospital in China from 2016 to 2017 were enrolled in the study. Based on the results from susceptibility-weighted imaging, the patients were divided into cerebral microbleed and noncerebral microbleed groups. The degree of carotid atherosclerosis was assessed with carotid intima-media thickness (CIMB) and Crouse score of carotid plaque. The details of patients' demographic information, cerebrovascular disease-related risk factors, carotid atherosclerosis indices, cerebral microbleed distribution, and grading were recorded, compared, and analyzed. Logistic regression analysis of the 198 patients showed that CIMB and Crouse score were significantly correlated with the occurrence of cerebral microbleeds. The CIMB thickening group (P = .03) and the plaque group (P = .01) were more susceptible to cerebral microbleeds. In the distribution of cerebral microbleed sites, Crouse scores were the highest in the mixed group and showed a statistically significant difference (P < .01). As the degree of carotid atherosclerosis increased, the average number of cerebral microbleeds also increased (P < .01). The receiver operating characteristic curve analysis of the carotid atherosclerosis indices showed a statistically significant difference. The CIMB value combined with the Crouse score was the best indicator (P < .01). In patients with ischemic stroke, cerebral microbleeds are closely related to carotid atherosclerosis. Active control of carotid atherosclerosis is important to prevent cerebral microbleeds in patients with ischemic stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A Laboratory-based Analysis of Nontuberculous Mycobacterial Lung Disease in Japan from 2012 to 2013.

PubMed

Morimoto, Kozo; Hasegawa, Naoki; Izumi, Kiyohiko; Namkoong, Ho; Uchimura, Kazuhiro; Yoshiyama, Takashi; Hoshino, Yoshihiko; Kurashima, Atsuyuki; Sokunaga, Jun; Shibuya, Shunsuke; Shimojima, Masahiro; Ato, Manabu; Mitarai, Satoshi

2017-01-01

Since 2010, mycobacterial examination results have been used widely to survey nontuberculous mycobacteria (NTM) lung disease. To reveal the clinical and epidemiological status of NTM lung disease in Japan. All data on the isolation and identification of mycobacteria in 2012 and 2013 were obtained from three dominant commercial laboratories in Japan. Pulmonary NTM disease was defined on the basis of bacteriological diagnostic criteria issued by the American Thoracic Society/Infectious Diseases Society of America. The coverage population was estimated using the ratio between national tuberculosis registration data and laboratory results for each of the eight regions of Japan. A total of 113,313 mycobacterial specimens from 4,710 institutes were collected, and specimens from 26,059 patients tested positive for NTM cultures at least once. Among patients with positive cultures, 7,167 (27.5%) satisfied the American Thoracic Society/Infectious Diseases Society of America criteria for NTM lung disease, resulting in a 2-year prevalence rate of 24.0 per 100,000. Mycobacterium avium complex (MAC) was the most commonly isolated species (93.3%), and 29.0% of the patients from whom MAC was isolated satisfied the criteria for NTM lung disease. Individuals older than 70 years of age accounted for the majority of cases, and 65.5% of cases involved females. After MAC, Mycobacterium kansasii and Mycobacterium abscessus exhibited the highest (43.6%) and second-highest (37.1%) incidence per isolation, respectively. The prevalence of M. kansasii was highest in the Kinki region (P < 0.05), and M. abscessus had the greatest prevalence in the Kyushu-Okinawa region (P < 0.005). The proportion of Mycobacterium intracellulare in MAC cases was higher in the southwestern part of Japan than in other regions. The period prevalence was highest in the southwestern part of Japan, and the standardized prevalence ratio was highest in central regions. Evaluations of clarithromycin

Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40-49 in Japan than in the US, despite a less favorable profile of major risk factors

PubMed Central

Sekikawa, Akira; Ueshima, Hirotsugu; Riad Zaky, Wahid; Kadowaki, Takashi; Edmundowicz, Daniel; Okamura, Tomonori; Sutton-Tyrrell, Kim; Nakamura, Yasuyuki; Egawa, Katsuya; Kanda, Hideyuki; Kashiwagi, Atsunori; Kita, Yoshiyuki; Maegawa, Hiroshi; Mitsunami, Kenichi; Murata, Kiyoshi; Nishio, Yoshihiko; Tamaki, Shinji; Ueno, Yoshiki; Kuller, Lewis H.

2013-01-01

SUMMARY Background Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the United States (US) and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 between the US and Japan. Methods We conducted a cross sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography. Results Systolic blood pressure, total cholesterol, LDL-cholesterol and smoking rates were higher among the Japanese (122.6 ± 14.1 versus 113.7 ± 9.6 mmHg, p<0.01; 5.72 ± 0.90 versus 4.99 ± 0.81 mmol/l (220.9 ± 34.6 versus 192.8 ± 31.3 mg/dl), p<0.01; 3.52 ± 1.01 versus 3.10 ± 0.78 mmol/l (136.0 ± 39.0 versus 119.7 ± 30.0 mg/dl), p<0.01; and 48 versus 15%, p<0.01, respectively). Triglycerides and fibrinogen were similar. HDL-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score > 0 was strikingly lower among the Japanese than the Americans (13 % versus 47 %, p <0.01). Conclusions Much lower prevalence of coronary calcium despite a less favorable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance. PMID:15563587

Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

PubMed Central

Chistiakov, Dimitry A.; Nikiforov, Nikita G.

2016-01-01

Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances. PMID:27493969

Xanthine Oxidase Inhibition by Febuxostat Attenuates Experimental Atherosclerosis in Mice

PubMed Central

Nomura, Johji; Busso, Nathalie; Ives, Annette; Matsui, Chieko; Tsujimoto, Syunsuke; Shirakura, Takashi; Tamura, Mizuho; Kobayashi, Tsunefumi; So, Alexander; Yamanaka, Yoshihiro

2014-01-01

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE−/− mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE−/− mice without affecting plasma cholesterol levels. In vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis. PMID:24686534

Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential.

PubMed

Spitz, Charlotte; Winkels, Holger; Bürger, Christina; Weber, Christian; Lutgens, Esther; Hansson, Göran K; Gerdes, Norbert

2016-03-01

Atherosclerosis is a chronic inflammatory disease that is mediated by innate and adaptive immune responses. The disease is characterized by sub-endothelial accumulation and modification of lipids in the artery wall triggering an inflammatory reaction which promotes lesion progression and eventual plaque rupture, thrombus formation, and the respective clinical sequelae such as myocardial infarction or stroke. During the past decade, T-cell-mediated immune responses, especially control of pro-inflammatory signals by regulatory T cells (Tregs), have increasingly attracted the interest of experimental and clinical researchers. By suppression of T cell proliferation and secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-β, Tregs exert their atheroprotective properties. Atherosclerosis-prone, hyperlipidemic mice harbor systemically less Tregs compared to wild-type mice, suggesting an imbalance of immune cells which affects local and systemic inflammatory and potentially metabolic processes leading to atherogenesis. Restoring or increasing Treg frequency and enhancing their suppressive capacity by various modulations may pose a promising approach for treating inflammatory conditions such as cardiovascular diseases. In this review, we briefly summarize the immunological basics of atherosclerosis and introduce the role and contribution of different subsets of T cells. We then discuss experimental data and current knowledge pertaining to Tregs in atherosclerosis and perspectives on manipulating the adaptive immune system to alleviate atherosclerosis and cardiovascular disease.

Diffusion reflection technique for diagnosis of atherosclerosis in mice using gold nanorods

NASA Astrophysics Data System (ADS)

Chakraborty, Ruchira; Ankri, Rinat; Leshem-Lev, Dorit; Lev, Eli I.; Hochhauser, Edith; Motiei, Menachem; Fixler, Dror

2018-02-01

Atherosclerosis, the leading cause of morbidity and mortality of cardiovascular disease, occur due to hardening and narrowing of arteries for development of vulnerable plaques made of cholesterols, tissue macrophages, foam cells and smooth muscle cells. Early detection of atherosclerosis is essential for proper treatment. Our group has already reported about the potential application of the non-invasive diffusion reflection (DR) technique in the detection of atherosclerosis using gold nanorods (GNRs) as contrast agent in carotid artery injured mice model. The basics of the study lie on the uptake GNRs by macrophages that located at the vulnerable plaques, which act as a good absorption contrast for DR measurement. Accumulations of GNRs cause changes in the optical property of the tissues and in turn cause changes in DR profile. In this study, we report the potential application of DR measurement in the detection of atherosclerosis in high-fat diet mice. Here, we have used PEG-coated GNRs with absorption maxima around 660nm. The time kinetics showed that after 24h of GNR injection the DR can find the atherosclerotic plaques and with time (up to 72h) the GNR accumulation in plaques were faded out, but still can be detectable by DR. Our result strongly suggests that in future DR can be used for early detection of atherosclerosis.

LOX-1 in atherosclerosis: biological functions and pharmacological modifiers

PubMed Central

Xu, Suowen; Ogura, Sayoko; Chen, Jiawei; Little, Peter J.; Moss, Joel; Liu, Peiqing

2013-01-01

Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis. PMID:23124189

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PubMed

Jones, Shannon M; Mann, Adrien; Conrad, Kelsey; Saum, Keith; Hall, David E; McKinney, Lisa M; Robbins, Nathan; Thompson, Joel; Peairs, Abigail D; Camerer, Eric; Rayner, Katey J; Tranter, Michael; Mackman, Nigel; Owens, A Phillip

2018-06-01

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. © 2018 American Heart Association, Inc.

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

PubMed Central

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

PubMed

Liu, Ting Ting; Zeng, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

2017-07-01

Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata, exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr -/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation

Ambient Air Pollution and Atherosclerosis in Los Angeles

PubMed Central

Künzli, Nino; Jerrett, Michael; Mack, Wendy J.; Beckerman, Bernardo; LaBree, Laurie; Gilliland, Frank; Thomas, Duncan; Peters, John; Hodis, Howard N.

2005-01-01

Associations have been found between long-term exposure to ambient air pollution and cardiovascular morbidity and mortality. The contribution of air pollution to atherosclerosis that underlies many cardiovascular diseases has not been investigated. Animal data suggest that ambient particulate matter (PM) may contribute to atherogenesis. We used data on 798 participants from two clinical trials to investigate the association between atherosclerosis and long-term exposure to ambient PM up to 2.5 μm in aerodynamic diameter (PM2.5). Baseline data included assessment of the carotid intima-media thickness (CIMT), a measure of subclinical atherosclerosis. We geocoded subjects’ residential areas to assign annual mean concentrations of ambient PM2.5. Exposure values were assigned from a PM2.5 surface derived from a geostatistical model. Individually assigned annual mean PM2.5 concentrations ranged from 5.2 to 26.9 μg/m3 (mean, 20.3). For a cross-sectional exposure contrast of 10 μg/m3 PM2.5, CIMT increased by 5.9% (95% confidence interval, 1–11%). Adjustment for age reduced the coefficients, but further adjustment for covariates indicated robust estimates in the range of 3.9–4.3% (p-values, 0.05–0.1). Among older subjects (≥60 years of age), women, never smokers, and those reporting lipid-lowering treatment at baseline, the associations of PM2.5 and CIMT were larger with the strongest associations in women ≥60 years of age (15.7%, 5.7–26.6%). These results represent the first epidemiologic evidence of an association between atherosclerosis and ambient air pollution. Given the leading role of cardiovascular disease as a cause of death and the large populations exposed to ambient PM2.5, these findings may be important and need further confirmation. PMID:15687058

P2Y receptors and atherosclerosis in apolipoprotein E-deficient mice

PubMed Central

Guns, Pieter-Jan DF; Hendrickx, Jan; Van Assche, Tim; Fransen, Paul; Bult, Hidde

2010-01-01

Background and purpose: P2Y nucleotide receptors are involved in the regulation of vascular tone, smooth muscle cell (SMC) proliferation and inflammatory responses. The present study investigated whether they are involved in atherosclerosis. Experimental approach: mRNA of P2Y receptors was quantified (RT-PCR) in atherosclerotic and plaque-free aorta segments of apolipoprotein E-deficient (apoE–/–) mice. Macrophage activation was assessed in J774 macrophages, and effects of non-selective purinoceptor antagonists on atherosclerosis were evaluated in cholesterol-fed apoE–/– mice. Key results: P2Y6 receptor mRNA was consistently elevated in segments with atherosclerosis, whereas P2Y2 receptor expression remained unchanged. Expression of P2Y1 or P2Y4 receptor mRNA was low or undetectable, and not influenced by atherosclerosis. P2Y6 mRNA expression was higher in cultured J774 macrophages than in cultured aortic SMCs. Furthermore, immunohistochemical staining of plaques demonstrated P2Y6-positive macrophages, but few SMCs, suggesting that macrophage recruitment accounted for the increase in P2Y6 receptor mRNA during atherosclerosis. In contrast to ATP, the P2Y6-selective agonist UDP increased mRNA expression and activity of inducible nitric oxide synthase and interleukin-6 in J774 macrophages; this effect was blocked by suramin (100–300 µM) or pyridoxal-phosphate-6-azophenyl-2′-4′-disulphonic acid (PPADS, 10–30 µM). Finally, 4-week treatment of cholesterol-fed apoE–/– mice with suramin or PPADS (50 and 25 mg·kg−1·day−1 respectively) reduced plaque size, without changing plaque composition (relative SMC and macrophage content) or cell replication. Conclusions and implications: These results suggest involvement of nucleotide receptors, particularly P2Y6 receptors, during atherosclerosis, and warrant further research with selective purinoceptor antagonists or P2Y6 receptor-deficient mice. PMID:20050854

Association of subclinical atherosclerosis using carotid intima-media thickness, carotid plaque, and coronary calcium score with left ventricular dyssynchrony: the multi-ethnic Study of Atherosclerosis.

PubMed

Sharma, Ravi K; Donekal, Sirisha; Rosen, Boaz D; Tattersall, Matthew C; Volpe, Gustavo J; Ambale-Venkatesh, Bharath; Nasir, Khurram; Wu, Colin O; Polak, Joseph F; Korcarz, Claudia E; Stein, James H; Carr, James; Watson, Karol E; Bluemke, David A; Lima, João A C

2015-04-01

The role of atherosclerosis in the progression of global left ventricular dysfunction and cardiovascular events has been well recognized. Left ventricular (LV) dyssynchrony is a measure of regional myocardial dysfunction. Our objective was to investigate the relationship of subclinical atherosclerosis with mechanical LV dyssynchrony in a population-based asymptomatic multi-ethnic cohort. Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at exam 5 were evaluated using 1.5T cardiac magnetic resonance (CMR) imaging, carotid ultrasound (n = 2062) for common carotid artery (CCA) and internal carotid artery (ICA) intima-media thickness (IMT), and cardiac computed tomography (n = 2039) for coronary artery calcium (CAC) assessment (Agatston method). Dyssynchrony indices were defined as the standard deviation of time to peak systolic circumferential strain (SD-TPS) and the difference between maximum and minimum (max-min) time to peak strain using harmonic phase imaging in 12 segments (3-slices × 4 segments). Multivariable regression analyses were performed to assess associations after adjusting for participant demographics, cardiovascular risk factors, LV mass, and ejection fraction. In multivariable analyses, SD-TPS was significantly related to measures of atherosclerosis, including CCA-IMT (8.7 ms/mm change in IMT, p = 0.020), ICA-IMT (19.2 ms/mm change in IMT, p < 0.001), carotid plaque score (1.2 ms/unit change in score, p < 0.001), and log transformed CAC+1 (0.66 ms/unit log-CAC+1, p = 0.018). These findings were consistent with other parameter of LV dyssynchrony i.e. max-min. In the MESA cohort, measures of atherosclerosis are associated with parameters of subclinical LV dyssynchrony in the absence of clinical coronary event and left-bundle-branch block. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Premenopausal Antimullerian Hormone Concentration is Associated with Subsequent Atherosclerosis

PubMed Central

Appt, Susan E.; Chen, Haiying; Clarkson, Thomas B.; Kaplan, Jay R.

2012-01-01

Objective To determine if premenopausal ovarian reserve is associated with susceptibility for atherosclerosis. Methods Female cynomologus macaques (n = 66, women’s equivalent age = 45 yrs) consumed an atherogenic diet for ~5 months prior to the measurement of a marker of ovarian reserve (antimüllerian hormone, AMH), plasma lipids, follicular phase estradiol (E2) and body weight (BW). Monkeys were then ovariectomized (OVX, n =17) remained premenopausal (PRE, n=20) or induced to have reduce ovarian reserve (ROR, n=29). After 26 additional months on the diet, atherosclerosis measurements and risk variables were reassessed. Results No differences in baseline AMH, plasma lipids, BW, E2 or post-diet lipids and BW, were observed among the groups subsequently assigned to OVX, PRE or ROR conditions. Post-diet measurements of atherosclerosis extent did not differ among the groups. However, analysis of plaque size by tertile of baseline AMH revealed that plaques were largest in monkeys that began the experiment with the lowest baseline AMH, followed by those in the middle and high tertiles (plaque extent mm2: Low AMH = 0.76 ± 0.12, Mid AMH = 0.46 ± 0.1, High AMH = 0.34 ± 0.08, p=0.02). Baseline AMH and plaque size were also correlated negatively (r = −0.31, p = 0.01). Plasma lipids were also correlated significantly with plaque extent (all p’s <0.01), but not with AMH. Conclusions We report for the first time an inverse relationship between a marker of ovarian reserve (AMH) and subsequent atherosclerosis risk. PMID:22929037

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.

PubMed

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-10-15

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD + -dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.

The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis

PubMed Central

Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke

2016-01-01

Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis. PMID:27744418

Questionnaire survey on recruitment for Japanese Neurology Society.

PubMed

Nishiyama, Kazutoshi; Amano, Takahiro; Aoki, Masashi; Inuzuka, Takashi; Taniwaki, Takayuki; Toyoshima, Itaru; Hashimoto, Yoichiro; Fukutake, Toshio; Yoshii, Fumihito; Ando, Yukio

2016-12-28

Many claim that they do not have enough neurologists in Japan, but supply and demand of neurologists remains to be analyzed. To investigate the recruitment for the Japanese Society of Neurology (JSN), the subcommittee of JSN for education performed a questionnaire-based survey in 80 medical universities and 271 board-certified education facilities throughout Japan. The response rate to the questionnaire was 77.5% in medical universities and 42.4% in education facilities. It was shown that each department of neurology in university recruits average 2.2 doctors, while they supposed that more than 4 doctors to be recruited every year. The questionnaire survey included what measures JSN should take in order to promote recruitment for JSN.

Airflow obstruction, atherosclerosis and cardiovascular risk factors in the AGES Reykjavik study.

PubMed

Gudmundsson, Gunnar; Margretardottir, Olof Birna; Sigurdsson, Martin Ingi; Harris, Tamara B; Launer, Lenore J; Sigurdsson, Sigurdur; Olafsson, Orn; Aspelund, Thor; Gudnason, Vilmundur

2016-09-01

Airflow limitation, i.e. reduced forced expiratory volume in 1-s (FEV1), is associated with increased prevalence of atherosclerosis, however, causal mechanisms remain elusive. The objective of the study was to determine if the association between airflow obstruction and markers of atherosclerosis is mediated by systemic inflammation. 1154 subjects from the longitudinal AGES Reykjavik study were included. Population characteristics, systemic inflammation markers from blood (white blood cell counts (WBC) and level of C-reactive protein (CRP)) were compared between patients with and without airflow limitation defined by reduced FEV1 on spirometry. Atherosclerosis burden was quantified by measurements of coronary artery calcium, aortic arch and distal aortic calcification in addition to carotid intimal media thickness (CIMT). Subjects were split into four groups according to smoking status and whether airflow limitation was present. There was a higher overall burden of atherosclerosis in ever-smokers compared to never-smokers, and in individuals with airflow obstruction compared to individuals without airflow obstruction. After adjusting for population characteristics, Framingham cardiovascular risk factors and markers of systemic inflammation (WBC and CRP), there was a significantly increased aortic arch and distal aorta calcification and higher CIMT measurement in individuals with airflow obstruction compared to individuals without airflow obstruction. After adjusting for population characteristics, Framingham cardiovascular risk factors and markers of systemic inflammation (WBC and CRP), there was a significantly increased aortic arch and distal aorta calcification and higher CIMT measurement in individuals with airflow obstruction compared to individuals without airflow obstruction. Systemic inflammation (WBC and CRP) does not appear to mediate the association between airflow limitation and atherosclerosis. Only airflow limitation and not systemic inflammation (WBC

Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation.

PubMed

Jhun, JooYeon; Kwon, Jeong-Eun; Kim, Se-Young; Jeong, Jeong-Hee; Na, Hyun Sik; Kim, Eun-Kyung; Lee, Seung Hoon; Jung, KyungAh; Min, Jun-Ki; Cho, Mi-La

2017-01-01

The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.

Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

PubMed Central

Abdelhalim, Mohamed Anwar K.; Moussa, Sherif A. Abdelmottaleb; AL-Mohy, Yanallah Hussain

2013-01-01

Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100 g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470 ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbit's blood serum and blood hematology were measured in Rabbit's blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192 nm. In addition, they showed that supplementation of zinc (350 ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280 nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis. PMID:24350281

The blood of my veins - mercury, Minamata and the soul of Japan.

PubMed

O'Malley, Gerald F

2017-09-01

The methylmercury contamination of Minamata Bay during the WWII postwar period resulted in thousands of Japanese citizens suffering horrific neurological injury. Fear and miscommunication destroyed and changed family and social structure. In addition, the Minamata poisoning caused momentous changes in the civic discourse in Japan and was an instrumental event in the democratization of the country. This manuscript describes the effects that the environmental contamination and human poising had in the transition of Japan from a feudal society to a democratic one.

S100A12 and the S100/Calgranulins - Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets

PubMed Central

Oesterle, Adam; Hofmann Bowman, Marion A

2016-01-01

Atherosclerosis is mediated by local and systematic inflammation. The multi-ligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans, and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell targeted expression of S100A12 demonstrate increased coronary and aortic calcification as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis susceptible Apolipoprotein E (ApoE) null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the Quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 ApoE null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis. PMID:26515415

Fluorescence spectroscopic detection of virus-induced atherosclerosis

NASA Astrophysics Data System (ADS)

Yan, Wei-dong; Perk, Masis; Nation, Patric N.; Power, Robert F.; Liu, Liying; Jiang, Xiuyan; Lucas, Alexandra

1994-07-01

Laser-induced fluorescence (LF) has been developed as a diagnostic tool for the detection of atherosclerosis. We have examined the use of LF for the identification of accelerated atherosclerotic plaque growth induced by Marek's Disease Virus (MDV) infection in White Leghorn rooster chicks (R) as well as plaque regression after treatment. Twenty-eight newborn R were infected with 12,000 cfu of MDV. Twelve parallel control R had saline injection. LF spectra were recorded from the arteries in vitro with a CeramOptec laser angioplasty catheter during 308 nm XeCl excimer laser excitation. Significant differences were detected at 440 to 475, 525, 550, 600, and 650 nm in MDV-R (p<0.05). In a subsequent study, 60 R were infected with 5,000 cfu of MDV, and were then treated with either Pravastatin (PRV) or placebo at 3 months post infection. These PRV-R were followed for 6 months to detect changes in atherosclerotic plaque development. PRV reduced intimal proliferation produced by MDV infection on histological examination (PRV-R 128.0+/- 44.0 micrometers , placebo-R 412.2+/- 91.5 micrometers , pequals0.007). MDV infected, PRV treated R were examined for LF changes that correlated with decreased atherosclerosis. There was an associated significant increase in LF intensity in PRV-R at 405 to 425 nm (p<0.001). In conclusion, LF can detect intimal proliferation in virus- induced atherosclerosis and atherosclerotic plaque regression after PRV therapy.

The Effect of Low-Dose Proteasome Inhibition on Pre-Existing Atherosclerosis in LDL Receptor-Deficient Mice

PubMed Central

Wilck, Nicola; Fechner, Mandy; Dan, Cristian; Stangl, Verena; Stangl, Karl; Ludwig, Antje

2017-01-01

Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in atherosclerosis development. However, the nature of UPS dysfunction has been proposed to be specific to certain stages of atherosclerosis development, which has implications for proteasome inhibition as a potential treatment option. Recently, low-dose proteasome inhibition with bortezomib has been shown to attenuate early atherosclerosis in low-density lipoprotein receptor-deficient (LDLR−/−) mice. The present study investigates the effect of low-dose proteasome inhibition with bortezomib on pre-existing advanced atherosclerosis in LDLR−/− mice. We found that bortezomib treatment of LDLR−/− mice with pre-existing atherosclerosis does not alter lesion burden. Additionally, macrophage infiltration of aortic root plaques, total plasma cholesterol levels, and pro-inflammatory serum markers were not influenced by bortezomib. However, plaques of bortezomib-treated mice exhibited larger necrotic core areas and a significant thinning of the fibrous cap, indicating a more unstable plaque phenotype. Taking recent studies on favorable effects of proteasome inhibition in early atherogenesis into consideration, our data support the hypothesis of stage-dependent effects of proteasome inhibition in atherosclerosis. PMID:28387708

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

PubMed Central

Corbi, Graziamaria; Bianco, Andrea; Turchiarelli, Viviana; Cellurale, Michele; Fatica, Federica; Daniele, Aurora; Mazzarella, Gennaro; Ferrara, Nicola

2013-01-01

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD+-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems. PMID:23774840

Building A Culture Of Peace For A Civil Society

ERIC Educational Resources Information Center

Foo, Sue Fan, Ed.; Starlin, Clay M., Ed.

2008-01-01

"Building a Culture of Peace for a Civil Society" consists of papers from scholars from around the world including: Canada, India, Japan, Nigeria, Philippines, Thailand, Turkey and the United States. This volume includes selected papers and lectures delivered at the 12th World Conference on Education of the World Council of Curriculum…

Q fever in Japan: an update review.

PubMed

Porter, Sarah Rebecca; Czaplicki, Guy; Mainil, Jacques; Horii, Yoichiro; Misawa, Naoaki; Saegerman, Claude

2011-05-05

As neglected zoonosis for many years, Q fever is now ubiquitous in Japan. Similarly to elsewhere in the world, domestic animals are considered to be important reservoirs of the causal agent, Coxiella burnetii, a resistant intracellular bacterium. Infected animals shed bacteria in milk, feces, urine, vaginal mucous and birth products. Inhalation of bacteria present in the environment is the main route of animal and human infection. Shedding of C. burnetii in milk by domestic ruminants has a very limited impact as raw milk is seldom ingested by the Japanese population. The clinical expression of Q fever in Japan is similar to its clinical expression elsewhere. However clinical cases in children are more frequently reported in this country. Moreover, C. burnetii is specified as one of the causative organisms of atypical pneumonia in the Japanese Respiratory Society Guideline for the management of community-acquired pneumonia. In Japan, C. burnetii isolates are associated with acute illness and are mainly of moderate to low virulence. Cats are considered a significant source of C. burnetii responsible for human outbreaks in association with the presence of infected parturient cats. Since its recognition as a reportable disease in 1999, 7-46 clinical cases of Q fever have been reported by year. The epidemiology of Q fever in Japan remains to be elucidated and the exact modes of transmission are still unproven. Important further research is necessary to improve knowledge of the disease itself, the endogenous hosts and reservoirs, and the epidemiological cycle of coxiellosis in Japan. Copyright © 2010 Elsevier B.V. All rights reserved.

The Way of Japan: A Series of Workshop Papers.

ERIC Educational Resources Information Center

Arizona Univ., Tucson. East Asia Center.

The seven essays in this booklet are summaries of presentations made at the Way of Japan Workshop Series. Topics range from traditional Japanese history and culture to modern Japanese society and U.S.-Japanese relations. A welcome from Yoshi Okawara, Japanese ambassador to the United States, delineates how American and Japanese may think in…

Lifelong Learning: An Instrument for Improving School Education in Japan?

ERIC Educational Resources Information Center

Sawano, Yukiko

Although Japanese society has long valued and practiced lifelong learning, it has not yet been successful in building an ethic that prizes learning, teaches creativity, and includes everyone. Bureaucratic and legal mechanisms undertaken in Japan to promote lifelong learning have included the establishment of Lifelong Learning Councils, a system…

Olive oil and postprandial hyperlipidemia: implications for atherosclerosis and metabolic syndrome.

PubMed

Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Cardelo, Magdalena P; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2016-12-07

Olive oil is the primary source of fat in the Mediterranean diet, which is associated with a significant improvement in health status, as measured by reduced mortality from several chronic diseases. The current pandemic of obesity, metabolic syndrome, and type 2 diabetes is intimately associated with an atherogenic dyslipidemic phenotype. The core components of the dyslipidemia of the metabolic syndrome, which most likely initiate atherosclerosis, are the "lipid triad" consisting of high plasma triglycerides, low levels of high-density lipoproteins, and a preponderance of small, dense low-density lipoproteins at fasting. However, postprandial (non-fasting) TGs (postprandial hyperlipidemia) are also recognized as an important component for atherosclerosis. Herein, the purpose of this review was to provide an update on the effects and mechanisms related to olive oil on postprandial hyperlipidemia and its implications for the onset and progression of atherosclerosis and metabolic syndrome.

Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

PubMed Central

Otani, Hajime

2013-01-01

Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD) in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR) and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span. PMID:23738041

B-cell-specific depletion of tumour necrosis factor alpha inhibits atherosclerosis development and plaque vulnerability to rupture by reducing cell death and inflammation.

PubMed

Tay, Christopher; Liu, Yu-Han; Hosseini, Hamid; Kanellakis, Peter; Cao, Anh; Peter, Karlheinz; Tipping, Peter; Bobik, Alex; Toh, Ban-Hock; Kyaw, Tin

2016-09-01

B2 lymphocytes promote atherosclerosis development but their mechanisms of action are unknown. Here, we investigated the role of tumour necrosis factor alpha (TNF-α) produced by B2 cells in atherogenesis. We found that 50% of TNF-α-producing spleen lymphocytes were B2 cells and ∼20% of spleen and aortic B cells produced TNF-α in hyperlipidemic ApoE(-/-) mice. We generated mixed bone marrow (80% μMT/20% TNF-α(-/-)) chimeric LDLR(-/-) mice where only B cells did not express TNF-α. Atherosclerosis was reduced in chimeric LDLR(-/-) mice with TNF-α-deficient B cells. TNF-α expression in atherosclerotic lesions and in macrophages were also reduced accompanied by fewer apoptotic cells, reduced necrotic cores, and reduced lesion Fas, interleukin-1β and MCP-1 in mice with TNF-α-deficient B cells compared to mice with TNF-α-sufficient B cells. To confirm that the reduced atherosclerosis is attributable to B2 cells, we transferred wild-type and TNF-α-deficient B2 cells into ApoE(-/-) mice deficient in B cells or in lymphocytes. After 8 weeks of high fat diet, we found that atherosclerosis was increased by wild-type but not TNF-α-deficient B2 cells. Lesions of mice with wild-type B2 cells but not TNF-α-deficient B2 cells also had increased apoptotic cells and necrotic cores. Transferred B2 cells were found in lesions of recipient mice, suggesting that TNF-α-producing B2 cells promote atherosclerosis within lesions. We conclude that TNF-α produced by B2 cells is a key mechanism by which B2 cells promote atherogenesis through augmenting macrophage TNF-α production to induce cell death and inflammation that promote plaque vulnerability. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

PubMed

Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

2018-01-01

The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

The Adaptation of the Treatise on Cold Damage in Eighteenth-century Japan: Text, Society, and Readers.

PubMed

Daidoji, Keiko

This paper examines how the Shanghanlun , translated as the Treatise on Cold Damage (i.e., the Treatise ), one of the most revered Chinese medical texts of the Han dynasty, was used in Japanese traditional medicine (Kanpō ), and particularly how it was reconfigured to fit with the societal shifts of the Edo period in Japan. The versatility of the Treatise in the formation of Kanpō is exemplified by the medicine of Yoshimasu Tōdō, an innovative eighteenth-century Japanese doctor. In this analysis of Tōdō's unique interpretation of the Treatise , some of his transitional ideas about medicine, the human body, and illness, as well as the transcultural influence from China, will be elucidated. To this end, first Tōdō's application of the Treatise will be re-defined within the historical context of changing medical needs in the consumer society of the Edo period. Secondly, by focusing on the idea of poison that forms the core of Tōdō's theory and practice, I show how his pathology resonated with the period's popular notions of the human body and illness, although it was said at the time to be drawn from Chinese classics. Associating Tōdō's use of the Treatise with such phenomena as the commercialisation and popularisation of medical treatment and the popular imagination of illness, I show the applicability of the Treatise to the evolution of Kanpō in the context of the surrounding social structure and cross-cultural intellectual ebb and flow across East Asia.

[Mental support for the victim of Japan earthquake].

PubMed

Asada, Takashi

2012-01-01

First the Japan earthquake, then tsunami, now a country with more than 20,000 known dead and missing must cope with the threat of nuclear contamination. Disaster may place survivors at risk for a range of negative outcomes. Disaster-related mental health problems may include acute stress disorder, post-traumatic stress disorder, and depression. The individuals with psychologically wounded by this disaster will leave their imprint for years, even decades, to come. We are now planning to open a new department named Psychiatric services for the survivors of natural disasters. Through the activities of this department, we aim to continue daily psychiatric services and to promote wellness of the survivors. Thus, we are making a system to recruit and dispatch psychiatrists for the psychiatric services at the damaged areas. On the other hand, in modern Japan society, namely aging society with low birth rate, the latent ability of university students is indispensable for the recovery after big disasters. We will take their academic ability into the activities of the new department. We also plan to promote their wellness through this kind of volunteer acidity.

A mechanism by which dietary trans fats cause atherosclerosis.

PubMed

Chen, Chun-Lin; Tetri, Laura H; Neuschwander-Tetri, Brent A; Huang, Shuan Shian; Huang, Jung San

2011-07-01

Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia. Copyright © 2011 Elsevier Inc. All rights reserved.

Estimating the burden of foodborne diseases in Japan

PubMed Central

Kumagai, Yuko; Gilmour, Stuart; Ota, Erika; Momose, Yoshika; Onishi, Toshiro; Bilano, Ver Luanni Feliciano; Kasuga, Fumiko; Sekizaki, Tsutomu

2015-01-01

Abstract Objective To assess the burden posed by foodborne diseases in Japan using methods developed by the World Health Organization’s Foodborne Disease Burden Epidemiology Reference Group (FERG). Methods Expert consultation and statistics on food poisoning during 2011 were used to identify three common causes of foodborne disease in Japan: Campylobacter and Salmonella species and enterohaemorrhagic Escherichia coli (EHEC). We conducted systematic reviews of English and Japanese literature on the complications caused by these pathogens, by searching Embase, the Japan medical society abstract database and Medline. We estimated the annual incidence of acute gastroenteritis from reported surveillance data, based on estimated probabilities that an affected person would visit a physician and have gastroenteritis confirmed. We then calculated disability-adjusted life-years (DALYs) lost in 2011, using the incidence estimates along with disability weights derived from published studies. Findings In 2011, foodborne disease caused by Campylobacter species, Salmonella species and EHEC led to an estimated loss of 6099, 3145 and 463 DALYs in Japan, respectively. These estimated burdens are based on the pyramid reconstruction method; are largely due to morbidity rather than mortality; and are much higher than those indicated by routine surveillance data. Conclusion Routine surveillance data may indicate foodborne disease burdens that are much lower than the true values. Most of the burden posed by foodborne disease in Japan comes from secondary complications. The tools developed by FERG appear useful in estimating disease burdens and setting priorities in the field of food safety. PMID:26478611

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets.

PubMed

Ren, Kun; Jiang, Ting; Zheng, Xi-Long; Zhao, Guo-Jun

2017-07-01

Furin, a member of the mammalian proprotein convertases family, can promote the proteolytic maturation of proproteins. It is known that furin is predominantly present in certain cell types of human atherosclerotic lesions and neointima in animal models, including vascular smooth muscle cells, endothelial cells and mononuclear inflammatory cells. Evidence suggests that furin participates in the initiation and progression of atherosclerosis through regulation of lipid and cholesterol metabolism, inflammatory response, blood pressure and the formation of atherosclerotic lesions. This review provides a panorama of the roles of furin in atherosclerosis and the insights into the prevention and treatment of atherosclerosis and cardiovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

A Protocol for Diagnosis and Management of Aortic Atherosclerosis in Cardiac Surgery Patients

PubMed Central

Brandon Bravo Bruinsma, George J.; Van 't Hof, Arnoud W. J.; Grandjean, Jan G.; Nierich, Arno P.

2017-01-01

In patients undergoing cardiac surgery, use of perioperative screening for aortic atherosclerosis with modified TEE (A-View method) was associated with lower postoperative mortality, but not stroke, as compared to patients operated on without such screening. At the time of clinical implementation and validation, we did not yet standardize the indications for modified TEE and the changes in patient management in the presence of aortic atherosclerosis. Therefore, we designed a protocol, which combined the diagnosis of atherosclerosis of thoracic aorta and the subsequent considerations with respect to the intraoperative management and provides a systematic approach to reduce the risk of cerebral complications. PMID:28852575

What is nuclear power in Japan?

NASA Astrophysics Data System (ADS)

Suzuki, Toshikazu

2011-03-01

The aggressive use of such non-fossil energy as the atomic energy with high power density and energy production efficiency is an indispensable choice aiming at the low-carbon society. There is a trial calculation that the carbon dioxide emission of 40000 ton can be suppressed by nuclear power generation by one ton of uranium. The basis of nuclear research after the Second World War in Japan was established by the researchers learnt in Argonne National Laboratory. In 2010, NPPs under operation are 54 units and the total electric generating power is 48.85GW. The amount of nuclear power generation per person of the people is 0.38kW in Japan, and it is near 0.34kW of the United States. However, the TMI accident and the Chernobyl disaster should have greatly stagnated the nuclear industry of Japan although it is not more serious than the United States. A lot of Japanese unconsciously associate a nuclear accident with the atomic bomb. According to the investigation which Science and Technology Agency carried out to the specialist in 1999, ``What will be the field where talent should be emphatically sent in the future?'' the rank of nuclear technology was the lowest in 32 fields. The influence of the nuclear industry stagnation was remarkable in the education. The subject related to the atomic energy of a university existed 19 in 1985 that was the previous year of the Chernobyl disaster decreased to 7 in 2003. In such a situation, we have to rely on the atomic energy because Japan depends for 96% of energy resources on import. The development of the fuel reprocessing and the fast breeder reactor has been continued in spite of a heavy failure. That is the only means left behind for Japan to be released from both fossil fuel and carbon dioxide.

Cardiorespiratory Fitness and Atherosclerosis: Recent Data and Future Directions.

PubMed

Mehanna, Emile; Hamik, Anne; Josephson, Richard A

2016-05-01

Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard. This article reviews and explores the bidirectional nature, delineating the effects, generally positive, on the cardiovascular system and atherosclerosis. Exercise augments eNOS, affects redox potential, and favorably affects mediators of atherosclerosis including lipids, glucose homeostasis, and inflammation. There are direct effects on the vasculature as well as indirect benefits related to exercise-induced changes in body composition and skeletal muscle. Application of aerobic exercise to specific populations is described, with the hope that this knowledge will move the science forward and improve individual patient outcome.

Cardiorespiratory Fitness and Atherosclerosis: Recent Data and Future Directions

PubMed Central

Mehanna, Emile; Hamik, Anne; Josephson, Richard A

2017-01-01

Historically the relationship between exercise and the cardiovascular system was viewed as unidirectional, with disease resulting in exercise limitation and hazard. This article reviews and explores the bidirectional nature, delineating the effects, generally positive, on the cardiovascular system and atherosclerosis. Exercise augments eNOS, affects redox potential, and favorably affects mediators of atherosclerosis including lipids, glucose homeostasis, and inflammation. There are direct effects on the vasculature as well as indirect benefits related to exercises induced changes in body composition and skeletal muscle. Application of aerobic exercise to specific populations is described, with the hope that this knowledge will move the science forward and improve individual patient outcome. PMID:27005804

[The Continuity Between World War II and the Postwar Period: Grant Distribution by the Japan Society for the Promotion of Science and the Subsidiary Fund for Scientific Research].

PubMed

Mizusawa, Hikari

2015-01-01

This paper analyzes the distribution of the Subsidiary Fund for Scientific Research, a predecessor to the Grant-in-Aid for Scientific Research (KAKENHI), which operated in Japan from the 1930s to 1950s. It reveals that the Japanese government maintained this wide-ranging promotion system since its establishment during the war until well into the postwar period. Previous studies insist that, at the end of the war, the Japanese government generally only funded the research that it considered immediately and practically useful. In contrast to this general perception, my analysis illustrates that both before and after the war, funding was allotted to four research areas: natural science, engineering, agriculture, and medicine. In order to illuminate this continuity, I compare the Subsidiary Fund with another research fund existing from 1933 to 1947: the Grant of the Japan Society for the Promotion of Science (JSPS). The comparison demonstrates that the JSPS received externally raised capital from the military and munitions companies. However, while this group focused upon engineering and military-related research as the war dragged on, the Subsidiary Fund has consistently entrusted scientists with the authority to decide the allocation of financial support.

Connecting the Lines between Hypogonadism and Atherosclerosis

PubMed Central

Fahed, Akl C.; Gholmieh, Joanna M.; Azar, Sami T.

2012-01-01

Epidemiological studies show that atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and point to gender differences with ageing males being at highest risk. Atherosclerosis is a complex process that has several risk factors and mediators. Hypogonadism is a commonly undiagnosed disease that has been associated with many of the events, and risk factors leading to atherosclerosis. The mechanistic relations between testosterone levels, atherosclerotic events, and risk factors are poorly understood in many instances, but the links are clear. In this paper, we summarize the research journey that explains the link between hypogonadism, each of the atherosclerotic events, and risk factors. We look into the different areas from which lessons could be learned, including epidemiological studies, animal and laboratory experiments, studies on androgen deprivation therapy patients, and studies on testosterone-treated patients. We finish by providing recommendations for the clinician and needs for future research. PMID:22518131

Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men

PubMed Central

Suzuki, Sentaro; Arima, Hisatomi; Miyazaki, Soichiro; Fujiyoshi, Akira; Kadota, Aya; Takashima, Naoyuki; Hisamatsu, Takashi; Kadowaki, Sayaka; Zaid, Maryam; Torii, Sayuki; Horie, Minoru; Murata, Kiyoshi; Miura, Katsuyuki; Ueshima, Hirotsugu

2018-01-01

Aim: There are few data regarding associations between sleep duration and subclinical atherosclerosis in Japan. The aim of this study was to evaluate associations of self-reported sleep duration with calcification in the coronary arteries (CAC) and carotid intima media thickness (IMT) in Japanese men. Methods: This was a cross-sectional survey of 1093 randomly selected men from Kusatsu City, Japan. Average sleep duration on weekdays was estimated through questionnaire; CAC by computed tomography; and carotid IMT by ultrasonography. Results: The prevalence of CAC was 50.0% for participants with sleep duration < 5.5 h, 43.9% with 5.5–6.4 h, 50.0% with 6.5–7.4 h, 49.3% with 7.5–8.4 h, and 62.5% with ≥ 8.5 h. In univariate analysis, participants with sleep duration ≥ 8.5 h had significantly higher prevalence of CAC than those with 6.5–7.4 h (p = 0.043). After adjustment for age and other risk factors, however, the association was not significant (p = 0.776). The average IMT was 0.85 mm for participants with sleep duration < 5.5 h, 0.83 mm with 5.5–6.4 h, 0.85 mm with 6.5–7.4 h, 0.88 mm with 7.5–8.4 h, and 0.90 mm with ≥ 8.5 h. None of the differences in IMT observed in crude or multivariable-adjusted analyses was significant (all p > 0.1). Conclusion: Self-reported sleep duration was not associated with increased CAC or carotid IMT in a general population of Japanese men. PMID:28747590

Impact of Prediabetic Status on Coronary Atherosclerosis

PubMed Central

Kurihara, Osamu; Takano, Masamichi; Yamamoto, Masanori; Shirakabe, Akihiro; Kimata, Nakahisa; Inami, Toru; Kobayashi, Nobuaki; Munakata, Ryo; Murakami, Daisuke; Inami, Shigenobu; Okamatsu, Kentaro; Ohba, Takayoshi; Ibuki, Chikao; Hata, Noritake; Seino, Yoshihiko; Mizuno, Kyoichi

2013-01-01

OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself. PMID:23223344

Association between diabetic retinopathy and subclinical atherosclerosis in China: Results from a community-based study.

PubMed

Liu, Yu; Teng, Xiangyu; Zhang, Wei; Zhang, Ruifeng; Liu, Wei

2015-09-01

To evaluate the association of diabetic retinopathy with subclinical atherosclerosis in middle-aged and elderly Chinese with type 2 diabetes. A cross-sectional community-based study was performed among 1607 patients aged 40 years or older in Shanghai. Non-mydriatic digital fundus photography examination was used in diabetic retinopathy detection. Presence of elevated carotid intima-media thickness or carotid plaque was defined as subclinical atherosclerosis. The prevalence of diabetic retinopathy was 15.1% in total patients. Patients with diabetic retinopathy were more likely to have elevated carotid intima-media thickness, carotid plaque and subclinical atherosclerosis than those without diabetic retinopathy (37.9% vs 30.7%, 57.6% vs 49.6% and 64.6% vs 57.1%, respectively). The presence of diabetic retinopathy was significantly associated with increased odds of subclinical atherosclerosis (odds ratio = 1.93, 95% confidence interval = 1.03-3.60) after full adjustments. The presence of diabetic retinopathy was significantly associated with subclinical atherosclerosis in middle-aged and elderly patients with type 2 diabetics in China. © The Author(s) 2015.

Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.

PubMed

Zhang, Linjie; Yang, Li

2014-12-26

Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines-this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke.

Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

NASA Astrophysics Data System (ADS)

Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

2012-07-01

Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates Atherosclerosis.

PubMed

McCurdy, Sara; Baumer, Yvonne; Toulmin, Emma; Lee, Bog-Hieu; Boisvert, William A

2017-11-15

Atherosclerosis, the progressive buildup of plaque within arterial blood vessels, can lead to fatal downstream events, such as heart attack or stroke. A key event contributing to the development of atherosclerosis is the infiltration of monocytes and its associated inflammation, as well as the formation of lipid-laden macrophage foam cells within the vessel wall. IL-37 is recognized as an important anti-inflammatory cytokine expressed especially by immune cells. This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis. Expression of human IL-37 was achieved with a macrophage-specific overexpression system, using the CD68 promoter in mouse primary bone marrow-derived macrophages via retroviral transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M-CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also inhibited macrophage proliferation, apoptosis, and transmigration, as well as reduced lipid uptake, compared with controls in vitro. The in vivo effects of macrophage-expressed IL-37 were investigated through bone marrow transplantation of transduced hematopoietic stem cells into irradiated atherosclerosis-prone Ldlr -/- mice. After 10 wk on a high-fat/high-cholesterol diet, mice with IL-37-expressing macrophages showed reduced disease pathogenesis, which was demonstrated by significantly less arterial plaque development and systemic inflammation compared with control mice. The athero-protective effect of macrophage-expressed IL-37 has implications for development of future therapies to treat atherosclerosis, as well as other chronic inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

Monoamine oxidase A genotype, childhood trauma, and subclinical atherosclerosis: a twin study.

PubMed

Zhao, Jinying; Bremner, James D; Goldberg, Jack; Quyyumi, Arshed A; Vaccarino, Viola

2013-06-01

A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated in neuropsychiatric disorders and also moderates the association between early-life stress and mental disorders, which often co-occur with cardiovascular disease. No study has examined the relationship between MAOA genotype, childhood trauma, and subclinical atherosclerosis. The objective of this investigation was to examine whether childhood trauma moderates the association between MAOA genotype and subclinical atherosclerosis. A sample including 289 middle-aged male twin pairs was studied. Subclinical atherosclerosis was assessed by brachial flow-mediated dilation (FMD) using ultrasound. Childhood trauma, before age 18 years, was measured with the Early Trauma Inventory and included physical, emotional, and sexual abuse as well as general trauma. Generalized estimating equation models were used to test the main and interactive effects of the MAOA genotype and each domain of childhood trauma on FMD, adjusting for known risk factors. General trauma was the most prevalent childhood trauma (28.4%), followed by physical abuse (25.0%), emotional abuse (19.4%), and sexual abuse (11.6%). MAOA genotype was not associated with any domain of childhood trauma. There was no significant evidence for a main effect for the MAOA genotype (β = .02, p = .82) or childhood trauma (.005 < β < .10, p > .54) FMD. However, a significant interaction was observed between MAOA genotype and physical (β interaction = .37, p = .026) or emotional abuse (β interaction = .43, p = .025) on subclinical atherosclerosis. Childhood trauma modulates the impact of MAOA variant on subclinical atherosclerosis, independent of traditional cardiovascular risk factors.

Risk model of valve surgery in Japan using the Japan Adult Cardiovascular Surgery Database.

PubMed

Motomura, Noboru; Miyata, Hiroaki; Tsukihara, Hiroyuki; Takamoto, Shinichi

2010-11-01

Risk models of cardiac valve surgery using a large database are useful for improving surgical quality. In order to obtain accurate, high-quality assessments of surgical outcome, each geographic area should maintain its own database. The study aim was to collect Japanese data and to prepare a risk stratification of cardiac valve procedures, using the Japan Adult Cardiovascular Surgery Database (JACVSD). A total of 6562 valve procedure records from 97 participating sites throughout Japan was analyzed, using a data entry form with 255 variables that was sent to the JACVSD office from a web-based data collection system. The statistical model was constructed using multiple logistic regression. Model discrimination was tested using the area under the receiver operating characteristic curve (C-index). The model calibration was tested using the Hosmer-Lemeshow (H-L) test. Among 6562 operated cases, 15% had diabetes mellitus, 5% were urgent, and 12% involved preoperative renal failure. The observed 30-day and operative mortality rates were 2.9% and 4.0%, respectively. Significant variables with high odds ratios included emergent or salvage status (3.83), reoperation (3.43), and left ventricular dysfunction (3.01). The H-L test and C-index values for 30-day mortality were satisfactory (0.44 and 0.80, respectively). The results obtained in Japan were at least as good as those reported elsewhere. The performance of this risk model also matched that of the STS National Adult Cardiac Database and the European Society Database.

Combined Vitamin C and Vitamin E Deficiency Worsens Early Atherosclerosis in ApoE-Deficient Mice

PubMed Central

Babaev, Vladimir R.; Li, Liying; Shah, Sanket; Fazio, Sergio; Linton, MacRae F.; May, James M.

2010-01-01

Objective Atherosclerosis is an inflammatory condition associated with oxidative stress, but controversy persists regarding whether antioxidants such as vitamins C and E are preventative. To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis, four combinations of vitamin supplementation (Low C/Low E, Low C/High E, High C/Low E, High C/High E) were studied in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice also unable to synthesize their own vitamin C (gulo−/−). The effect of a more severe depletion of vitamin C alone was evaluated in a second experiment using gulo−/− mice carrying the hemizygous deletion of SVCT2, the vitamin C transporter. Methods and Results After 8 weeks on a high-fat diet (16% lard, 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2-3-fold in males, although only plaque macrophage content was increased in females. A more severe deficiency of vitamin C in gulo−/− mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apoE−/− mice compared to littermates on a diet replete in vitamin C, again most clearly in males. Conclusion Combined vitamin E and C deficiencies are required to worsen early atherosclerosis in an apoE-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete. PMID:20558818

The "Mevalonate hypothesis": a cholesterol-independent alternative for the etiology of atherosclerosis.

PubMed

Keizer, Hiskias G

2012-11-05

The "cholesterol hypothesis" is the leading theory to explain the cause of atherosclerosis. The "cholesterol hypothesis" assumes that plasma (LDL) cholesterol is an important causal factor for atherosclerosis.However, data of at least seven placebo controlled randomized prospective trials with various cholesterol lowering drugs show that plasma cholesterol lowering does not necessarily lead to protection against cardiovascular disease. Therefore an alternative hypothesis for the etiology of cardiovascular disease is formulated. This alternative hypothesis, the "mevalonate hypothesis", assumes that after stimulation of the mevalonate pathway in endothelial cells by inflammatory factors, these cells start producing cholesterol and free radicals. In this hypothesis, only the latter play a role in the etiology of atherosclerosis by contributing to the formation of oxidized cholesterol which is a widely accepted causal factor for atherosclerosis.Regardless of how the mevalonate pathway is activated (by withdrawal of statin drugs, by inflammatory factors or indirectly by reduced intracellular cholesterol levels) in all these cases free radical production is observed as well as cardiovascular disease. Since in the "mevalonate hypothesis" cholesterol is produced at the same time as the free radicals causing atherosclerosis, this hypothesis provides an explanation for the correlation which exists between cardiovascular disease and plasma cholesterol levels. From an evolutionary perspective, concomitant cholesterol production and free radical production in response to inflammatory factors makes sense if one realizes that both activities potentially protect cells and organisms from infection by gram-negative bacteria.In conclusion, data have been collected which suggest that activation of the mevalonate pathway in endothelial cells is likely to be a causal factor for atherosclerosis. This "mevalonate hypothesis" provides a better explanation for results obtained from recent

Polymer-Based Therapeutics: Nanoassemblies and Nanoparticles for Management of Atherosclerosis

PubMed Central

Lewis, Daniel R.; Kamisoglu, Kubra; York, Adam; Moghe, Prabhas V.

2012-01-01

Coronary arterial disease, one of the leading causes of adult mortality, is triggered by atherosclerosis. A disease with complex etiology, atherosclerosis results from the progressive long-term combination of atherogenesis, the accumulation of modified lipoproteins within blood vessel walls, along with vascular and systemic inflammatory processes. The management of atherosclerosis is challenged by the localized flare-up of several multipronged signaling interactions between activated monocytes, atherogenic macrophages and inflamed or dysfunctional endothelial cells. A new generation of approaches is now emerging founded on multifocal, targeted therapies that seek to reverse or ameliorate the athero-inflammatory cascade within the vascular intima. This article reviews the various classes and primary examples of bioactive configurations of nanoscale assemblies. Of specific interest are polymer-based or polymer-lipid micellar assemblies designed as multimodal receptor-targeted blockers or drug carriers whose activity can be tuned by variations in polymer hydrophobicity, charge, and architecture. Also reviewed are emerging reports on multifunctional nanoassemblies and nanoparticles for improved circulation and enhanced targeting to athero-inflammatory lesions and atherosclerotic plaques. PMID:21523920

Targeting sortilin in immune cells reduces proinflammatory cytokines and atherosclerosis

PubMed Central

Mortensen, Martin B.; Kjolby, Mads; Gunnersen, Stine; Larsen, Jakob V.; Palmfeldt, Johan; Falk, Erling; Nykjaer, Anders; Bentzon, Jacob F.

2014-01-01

Genome-wide association studies have identified a link between genetic variation at the human chromosomal locus 1p13.3 and coronary artery disease. The gene encoding sortilin (SORT1) has been implicated as the causative gene within the locus, as sortilin regulates hepatic lipoprotein metabolism. Here we demonstrated that sortilin also directly affects atherogenesis, independent of its regulatory role in lipoprotein metabolism. In a mouse model of atherosclerosis, deletion of Sort1 did not alter plasma cholesterol levels, but reduced the development of both early and late atherosclerotic lesions. We determined that sortilin is a high-affinity receptor for the proinflammatory cytokines IL-6 and IFN-γ. Moreover, macrophages and Th1 cells (both of which mediate atherosclerotic plaque formation) lacking sortilin had reduced secretion of IL-6 and IFN-γ, but not of other measured cytokines. Transfer of sortilin-deficient BM into irradiated atherosclerotic mice reduced atherosclerosis and systemic markers of inflammation. Together, these data demonstrate that sortilin influences cytokine secretion and that targeting sortilin in immune cells attenuates inflammation and reduces atherosclerosis. PMID:25401472

THE INFLUENCE OF INTRAVENOUSLY ADMINISTERED SURFACE-ACTIVE AGENTS ON THE DEVELOPMENT OF EXPERIMENTAL ATHEROSCLEROSIS IN RABBITS

PubMed Central

Kellner, Aaron; Correll, James W.; Ladd, Anthony T.

1951-01-01

A study was made of the relationship of blood lipids to the development of experimental atherosclerosis. Rabbits fed a diet containing cholesterol were found to develop hyperlipemia characterized by a great increase in blood cholesterol and a much lesser increase in blood phospholipids; after several weeks they manifested conspicuous atherosclerosis of the aorta, as has often been observed by others. Comparable rabbits fed the same diets containing added cholesterol were given in addition repeated intravenous injections of the surface-active agents Tween 80 and Triton A20; these animals developed hyperlipemia which was characterized by a great increase in blood cholesterol and an equivalent or even greater increase in phospholipids, and they had much less atherosclerosis than did the control rabbits fed cholesterol alone. In further experiments it was observed that repeated intravenous injections of Tween 80 did not result in resorption of previously induced atherosclerosis in rabbits. The findings are discussed in relation to the pathogenesis of natural and experimental atherosclerosis. PMID:14824410

Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

2013-10-09

Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?

PubMed

Gerdes, N; Zirlik, A

2011-11-01

A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals. In addition, many of these proteins enfold T cell-independent pro-atherogenic functions on a variety of cell types. Accordingly they represent potential targets for immune-modulatory and/or anti-inflammatory therapy of atherosclerosis. This review focuses on the diverse role of co-stimulatory molecules of the B7 and tumour necrosis factor (TNF)-superfamily and their downstream signalling effectors in atherosclerosis. In particular, the contribution of CD28/CD80/CD86/CTLA4, ICOS/ICOSL, PD-1/PDL-1/2, TRAF, CD40/CD154, OX40/OX40L, CD137/CD137L, CD70/CD27, GITR/GITRL, and LIGHT to arterial disease is reviewed. Finally, the potential for a therapeutic exploitation of these molecules in the treatment of atherosclerosis is discussed.

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

PubMed

Cañas, Laura; Bayés, Beatriz; Granada, Maria L; Ibernon, Meritxell; Porrini, Esteban; Benítez, Rosa; Díaz, Juan M; Lauzurica, Ricardo; Moreso, Francesc; Torres, Armando; Lampreabe, Ildefonso; Serra, Assumpta; Romero, Ramon

2012-01-01

The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) μg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis. © 2011 John Wiley & Sons A/S.

[Psychosocial factors as predictors of atherosclerosis and cardiovascular events: contribution from animal models].

PubMed

Alboni, Paolo; Alboni, Marco

2006-11-01

Conventional risk factors (abnormal lipids, hypertension, etc.) are independent predictors of atherosclerosis and cardiovascular events; however, these factors are not specific since about half patients with acute myocardial infarction paradoxically result at low cardiovascular risk. Recent prospective studies provide convincing evidence that some psychosocial factors are independent predictors of atherosclerosis and cardiovascular events, as well. Psychosocial factors that promote atherosclerosis can be divided into two general categories: chronic stressors, including social isolation/low social support and work stress (subordination without job control) and emotional factors, including affective disorders such as depression, severe anxiety and hostility/anger. The emotional factors, such as the chronic stressors, activate the biological mechanisms of chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis, sympathetic system and inflammation processes, which have atherogenic effects, and an increase in blood coagulation. In spite of the amount of published data, psychosocial factors receive little attention in the medical setting. About 30 years ago, Kuller defined the criteria for a causal relation between a risk factor and atherosclerosis and cardiac events. The first of these criteria states that experimental research should demonstrate that any new factor would increase the extent of atherosclerosis or its complications in suitable animal models. We carried out a bibliographic research in order to investigate whether the results of the studies dealing with animal examination and experimentation support the psychosocial factors as predictors of atherosclerosis. Contributions related to some of the psychosocial factors such as social isolation, subordination and hostility/anger have been found. In these studies atherosclerotic extension has been evaluated at necroscopy; however, the incidence of cardiovascular events has not been

Progress and future opportunities in the development of vaccines against atherosclerosis.

PubMed

Govea-Alonso, Dania O; Beltrán-López, Josué; Salazar-González, Jorge A; Vargas-Morales, Juan; Rosales-Mendoza, Sergio

2017-04-01

Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis. Several targets have been identified including sequences of apolipoprotein B100 (ApoB100), cholesteryl ester transfer protein (CETP), heat shock proteins (HSP), extracellular matrix proteins, T cell receptor β chain variable region 31 (TRBV31), the major outer membrane protein (MOMP), and the outer membrane protein 5 (Pomp5) from Chlamydia pneumoniae. Humoral and cellular immunities to these targets have been associated with therapeutic effects in murine models and humans. The evaluation of some candidates in clinical trials is ongoing. Expert commentary: New research paths based on the use of next generation vaccine production platforms are envisioned.

Iron and Atherosclerosis: Nailing Down a Novel Target with Magnetic Resonance

PubMed Central

Sharkey-Toppen, Travis P.; Tewari, Arun K.; Raman, Subha V.

2014-01-01

Iron is an essential mineral in many proteins and enzymes in human physiology, with limited means of iron elimination to maintain iron balance. Iron accrual incurs various pathological mechanisms linked to cardiovascular disease. In atherosclerosis, iron catalyzes the creation of reactive oxygen free radicals that contribute to lipid modification, which is essential to atheroma formation. Inflammation further fuels iron-related pathologic processes associated with plaque progression. Given iron’s role in atherosclerosis development, in vivo detection techniques sensitive iron are needed for translational studies targeting iron for earlier diagnosis and treatment. Magnetic resonance imaging (MRI) is uniquely able to quantify iron in human tissues noninvasively and without ionizing radiation, offering appealing for longitudinal and interventional studies. Particularly intriguing is iron’s complementary biology vs. calcium, which is readily detectable by computed tomography (CT). This review summarizes the role of iron in atherosclerosis with considerable implications for novel diagnostic and therapeutic approaches. PMID:24590608

Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

PubMed Central

Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

2015-01-01

Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

MitoNEET in Perivascular Adipose Tissue Blunts Atherosclerosis under Mild Cold Condition in Mice

PubMed Central

Xiong, Wenhao; Zhao, Xiangjie; Garcia-Barrio, Minerva T.; Zhang, Jifeng; Lin, Jiandie; Chen, Y. Eugene; Jiang, Zhisheng; Chang, Lin

2017-01-01

Background: Perivascular adipose tissue (PVAT), which surrounds most vessels, is de facto a distinct functional vascular layer actively contributing to vascular function and dysfunction. PVAT contributes to aortic remodeling by producing and releasing a large number of undetermined or less characterized factors that could target endothelial cells and vascular smooth muscle cells, and herein contribute to the maintenance of vessel homeostasis. Loss of PVAT in mice enhances atherosclerosis, but a causal relationship between PVAT and atherosclerosis and the possible underlying mechanisms remain to be addressed. The CDGSH iron sulfur domain 1 protein (referred to as mitoNEET), a mitochondrial outer membrane protein, regulates oxidative capacity and adipose tissue browning. The roles of mitoNEET in PVAT, especially in the development of atherosclerosis, are unknown. Methods: The brown adipocyte-specific mitoNEET transgenic mice were subjected to cold environmental stimulus. The metabolic rates and PVAT-dependent thermogenesis were investigated. Additionally, the brown adipocyte-specific mitoNEET transgenic mice were cross-bred with ApoE knockout mice. The ensuing mice were subsequently subjected to cold environmental stimulus and high cholesterol diet challenge for 3 months. The development of atherosclerosis was investigated. Results: Our data show that mitoNEET mRNA was downregulated in PVAT of both peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)- and beta (Pgc1β)-knockout mice which are sensitive to cold. MitoNEET expression was higher in PVAT of wild type mice and increased upon cold stimulus. Transgenic mice with overexpression of mitoNEET in PVAT were cold resistant, and showed increased expression of thermogenic genes. ApoE knockout mice with mitoNEET overexpression in PVAT showed significant downregulation of inflammatory genes and showed reduced atherosclerosis development upon high fat diet feeding when kept in a 16�

[The impact of electronic cigarettes usage on the endothelial function and the progression of atherosclerosis].

PubMed

Knura, Miłosz; Dragon, Jonasz; Łabuzek, Krzysztof; Okopień, Bogusław

2018-01-23

The exponetial growth in popularity of electronic cigarettes in the world markets intensifies the debate about their health effects. The smoking of traditional tabacoo products is a factor associated with the endothelium damage and progression of atherosclerosis. The elimination of the combustion process in electronic cigarettes allows to conclude that they are less harmful to a vascular endothelium than traditional tobacco products. E-cigarette aerosol contains many compounds that have an influence on initiation and progression of atherosclerosis. Nicotine protherogenic action is not fully explained. On one hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas epidemiological studies do not show an increased risk of cardiovascular disease in the population using nicotine replacement therapy or snuff. Acrolein, formaldehyde and the ultrafine particles generated during e-liquid heating have an impact on initiation and progression of atherosclerosis, but their level is lower than that of tobacco smoke. In order to assess accurately the longterm effects of e-cigarettes, it is necessary to conduct epidemiological studies measuring the effects of using e-cigarettes. It is claimed that the use of electronic cigarettes has a potential impact on the development of atherosclerosis, but is significantly lower than that of traditional cigarettes.

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

PubMed

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

Atherosclerosis, cholesterol, nutrition, and statins – a critical review

PubMed Central

Gebbers, Jan-Olaf

2007-01-01

Atherosclerosis, which causes approximately half of all deaths of adults over age 60 in industrialized nations, is a pandemic among inappropriately nourished and/or physically hypoactive children, adolescents, and adults world wide. Although nowadays statins are widely prescribed to middle age and elderly adults with high blood lipid levels as pharmacological prevention for the late complications of atherosclerosis, from a critical point of view statins seem not to solve the problem, especially when compared with certain natural ingredients of our nutrition like micronutrients as alternative strategy. Statin ingestion is associated with lowering of serum cholesterol and low-density lipoprotein concentrations; some prospective studies have shown statistical associations with subsequent modest reduction of mortality from cardiovascular disease. However, specific biochemical pathways and pharmacological roles of statins in prevention of atherosclerosis, if any, are unknown. Moreover, there have been no systematic cost-benefit analyses of life-style prophylaxis versus statin prophylaxis versus combined life-style plus statin prophylaxis versus neither life-style nor statin prophylaxis for clinically significant complications of cardiovascular diseases in the elderly. Further, in the trials of effectiveness statins were not compared with management of nutrition, which is the most appropriate alternative intervention. Such studies seem to be important, as the ever increasing world population, especially in developing countries, now demand expensive statins, which may be unaffordable for mitigating the pandemic. Studies of this kind are necessary to identify more precisely those patients for whom cardiovascular benefits will outweigh the risks and costs of the statin treatment in comparison with nutritional interventions. Against the background of the current pathogenetic concept of atherogenesis some of its possible risk factors, particularly the roles of cholesterol and

Pediatric allergy and immunology in Japan.

PubMed

Ebisawa, Motohiro; Nishima, Sankei; Ohnishi, Hidenori; Kondo, Naomi

2013-11-01

The Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) was started in 1966 and currently has 3613 members as of August 1, 2012. The number of pediatricians specializing in allergies who have been certified by the Japanese Society of Allergology is 817. Among these, there are 125 training directors and training facilities for allergy and clinical immunology. The JSPACI first published an asthma guideline specific for children in 2000, and this has been revised every 3 yrs, contributing to better control of pediatric asthma. Food allergy management guidelines were first developed in 2005, which have helped to improve the care of food allergy patients. Among 514 pediatric training programs by the Japanese Society of Pediatrics, there are 312 facilities routinely performing oral food challenges. Among these, there were already 53 facilities performing oral immunotherapy at the end of 2011, treating 1400 cases of food allergy. The prevalence of pediatric allergic diseases has increased in Japan over the past 50 yrs. A number of International Study of Asthma and Allergies in Childhood surveys have been conducted in the past at specific times. The prevalence of wheezing among children aged 13-14 yrs in 2002 was 13.0%. Multi-year surveys found a 1.5- to 2-fold increase every 10 yrs until 2002. However, according to the latest data in 2012, asthma prevalence seems to have slightly decreased in Japan. Food allergy mainly associated with infantile atopic eczema among infants younger than 1 yr of age is the most common form as with other developed countries. The estimated food allergy prevalence based on data from several surveys is 5-10% among infants (0-6 yrs) and 1-2% among schoolchildren (6-15 yrs). A variety of patients suffering from primary deficiency syndrome have been actively analyzed. Previously, antibody defects and well-defined syndromes with immunodeficiency were analyzed, but recent research is focusing on not only acquired immune

Inter-prefecture disparity in under-5 mortality: 115 year trend in Japan.

PubMed

Nagata, Chie; Moriichi, Akinori; Morisaki, Naho; Gai-Tobe, Ruoyan; Ishiguro, Akira; Mori, Rintaro

2017-07-01

Child poverty is a growing, serious issue in Japan, where various social disparities are increasing. Numerous reports have focused on the relationship between social inequity and health, but few studies have assessed how the overall magnitude of disparities in child health has changed in the course of drastic social and economic transitions from 1899 to more recent times. In this study, we assessed the trend of the under-5 mortality rate (U5MR) and its inter-prefecture disparity in Japan. This is a secondary analysis of Japan's vital statistics data from 1899 to 2014 (115 years), which covers a core period of modern Japan. We calculated the U5MR of each prefecture and its Theil index by year to assess the trend of inter-prefecture disparity in child health from 1899 to 2014. The U5MR monotonically decreased from 238 per 1,000 births in 1899 to 3 in 2014. The Theil index of the U5MR increased in the post-war period, peaked in 1962 (0.027) and gradually reduced to <0.01 in the 1970s. In the 2000s, however, even though U5MR continued to decrease, the Theil index started to increase, and in 2014 (0.013) it exceeded that in 1970 and was more similar to that before World War II. The disparities in child health appear to be widening, and may serve as a warning to today's society that increasing socioeconomic gradients may lead to rising health inequity among children. Further investigations into the causes, mechanisms, and possible interventions are needed. © 2017 Japan Pediatric Society.

Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study

ClinicalTrials.gov

2016-02-05

Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, Non-insulin Dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus

The Adaptation of the Treatise on Cold Damage in Eighteenth-century Japan: Text, Society, and Readers

PubMed Central

Daidoji, Keiko

2015-01-01

This paper examines how the Shanghanlun, translated as the Treatise on Cold Damage (i.e., the Treatise), one of the most revered Chinese medical texts of the Han dynasty, was used in Japanese traditional medicine (Kanpō 漢方), and particularly how it was reconfigured to fit with the societal shifts of the Edo period in Japan. The versatility of the Treatise in the formation of Kanpō is exemplified by the medicine of Yoshimasu Tōdō, an innovative eighteenth-century Japanese doctor. In this analysis of Tōdō’s unique interpretation of the Treatise, some of his transitional ideas about medicine, the human body, and illness, as well as the transcultural influence from China, will be elucidated. To this end, first Tōdō’s application of the Treatise will be re-defined within the historical context of changing medical needs in the consumer society of the Edo period. Secondly, by focusing on the idea of poison that forms the core of Tōdō’s theory and practice, I show how his pathology resonated with the period’s popular notions of the human body and illness, although it was said at the time to be drawn from Chinese classics. Associating Tōdō’s use of the Treatise with such phenomena as the commercialisation and popularisation of medical treatment and the popular imagination of illness, I show the applicability of the Treatise to the evolution of Kanpō in the context of the surrounding social structure and cross-cultural intellectual ebb and flow across East Asia. PMID:26778941

Psychological trauma after the Great East Japan Earthquake.

PubMed

Matsumoto, Kazunori; Sakuma, Atsushi; Ueda, Ikki; Nagao, Ayami; Takahashi, Yoko

2016-08-01

The Great East Japan Earthquake (GEJE) struck the northeastern part of Japan on 11 March 2011 and triggered a devastating tsunami, causing widespread destruction along the coast of northeastern Japan. The tsunami also led to an accident at the Fukushima Daiichi nuclear power plant. Incidents occurring in such major disasters are known to lead to psychological trauma. This paper has summarized English-language documentation regarding GEJE-related psychological trauma or post-traumatic stress disorder (PTSD). Research thus far has reported the possibility of higher probable PTSD prevalence among residents of the GEJE areas than in the average Japanese population during normal times. At the very least, many people have experienced trauma symptoms at self-recognition levels 1 year or longer after the disaster. It appears that the percentage of persons with high PTSD risk was higher in regions with radiation-related impacts than in regions where the main damage was caused by the earthquake and tsunami. Results have not been limited to showing relations between severe exposure to a traumatic event and PTSD symptoms but also show that a variety of factors, including social factors, has been shown to interact with PTSD symptoms. The fact that Japanese society as a whole united against the trauma of the GEJE may have worked to minimize the effects of trauma. To grasp a full picture of the effects of psychological trauma due to the GEJE, further surveys and research are necessary. It will be necessary to continue engagements related to these problems and issues into the future. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

The truth lies somewhere in the middle: Swinging between globalization and regionalization of medical education in Japan.

PubMed

Saiki, Takuya; Imafuku, Rintaro; Suzuki, Yasuyuki; Ban, Nobutaro

2017-10-01

Japan is well known as a super-aging society, with a low birth rate, and has been ranked as one of the countries having the highest quality of healthcare system. Japan's society is currently approaching a major turning point with regard to societal and healthcare reforms, which are influenced by international trends and regional needs. Development of Japanese healthcare human resources, including medical students, is now expected to ride the wave of globalization, while resolving regional problems in the training and delivery of healthcare. Terms and global trends in medical education, such as outcome-based education, community-based education, reflective learning, international accreditation of medical education, and professionalization of educators are well translated into the Japanese language and embraced positively among the Japanese medical educators. However, these trends occasionally sit uncomfortably with cultural variations that are often a common approach in Japan; notably, "hansei" (introspection) and "kaizen" (change for the better). In the world facing a new era where people are unsettled between globalism and regionalism, Japan's future mission is to steer a balanced route that recognizes both global and regional influences and produce global health professionals educators.

International models of investigator-initiated trials: implications for Japan

PubMed Central

Trimble, E. L.; Ledermann, J.; Law, K.; Miyata, T.; Imamura, C. K.; Nam, B.-H.; Kim, Y.H.; Bang, Y.-J.; Michaels, M.; Ardron, D.; Amano, S.; Ando, Y.; Tominaga, T.; Kurokawa, K.; Takebe, N.

2012-01-01

Background Academic/institutional investigator-initiated clinical trials benefit individuals and society by supplementing gaps in industry-sponsored clinical trials. Materials In May 2010, experts from Japan, the Republic of Korea, the UK, and the United States, met at a symposium in Tokyo, Japan, to discuss how policies related to the conduct of clinical trials, which have been shown to be effective, may be applied to other regions of the world. Results In order to increase the availability of anticancer drugs world-wide, nations including Japan should examine the benefits of increasing the number of investigator-initiated clinical trials. These trials represent one of the most effective ways to translate basic scientific knowledge into clinical practice. These trials should be conducted under GCP guidelines and include Investigational New Drug application submissions with the ultimate goal of future drug approval. Conclusions To maximize the effectiveness of these trials, a policy to educate health care professionals, cancer patients and their families, and the public in general on the benefits of clinical trials should be strengthened. Finally, policies that expedite the clinical development of novel cancer drugs which have already been shown to be effective in other countries are needed in many nations including Japan to accelerate drug approval. PMID:22843420

Minorities and Education in Multicultural Japan: An Interactive Perspective. Asia's Transformations

ERIC Educational Resources Information Center

Tsuneyoshi, Ryoko, Ed.; Okano, Kaori H., Ed.; Boocock, Sarane, Ed.

2011-01-01

This volume examines how Japan's increasingly multicultural population has impacted on the lives of minority children and their peers at school, and how schools are responding to this trend in terms of providing minority children with opportunities and preparing them for the adult society. The contributors focus on interactions between individuals…

[The role of subclinical inflammation in progression of multifocal atherosclerosis during one year after myocardial infarction].

PubMed

Barbarash, O L; Usol'tseva, E N; Kashtalap, V V; Kolomytseva, I S; Sizova, I N; Volykova, M A; Shibanova, I A

2014-01-01

To elucidate role of subclinical inflammation in progression of atherosclerotic process in magistral noncoronary arteries in patients during one year after ST-elevation myocardial infarction (MI). We examined 168 men with MI (mean age 59.5 years). All patients during hospitalization underwent coronary angiography and color duplex scanning of brachiocephalic arteries. In a year ultrasound study of noncoronary vessels was repeated and progression of atherosclerosis assessed. Parameters of inflammation in blood serum were measured on days 10-14 of MI and after one year. At repeat study most patients demonstrated progression of noncoronary atherosclerosis. Some biomarkers measured during inhospital phase of MI (low concentration of anti-inflammatory interleukin 10 - IL-10, elevated N-terminal pro brain natriuretic peptide) allowed to distinguish group of patients with subsequent progression of noncoronary atherosclerosis. Elevated concentrations of C-reactive protein and 11-10 registered in a year after MI were also associated with more severe progression of atherosclerosis. Serum levels of neopterin and IL-12 remained stable in patients with and decreased in patients without pronounced progression of atherosclerosis.

Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

PubMed

Tay, Christopher; Liu, Yu-Han; Kanellakis, Peter; Kallies, Axel; Li, Yi; Cao, Anh; Hosseini, Hamid; Tipping, Peter; Toh, Ban-Hock; Bobik, Alex; Kyaw, Tin

2018-05-01

B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Using mixed chimeric Ldlr -/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr -/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications. © 2018 American Heart Association, Inc.

Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: the Suita study.

PubMed

Kosaka, Takayuki; Kokubo, Yoshihiro; Ono, Takahiro; Sekine, Shinichi; Kida, Momoyo; Kikui, Miki; Yamamoto, Masaaki; Watanabe, Makoto; Amano, Atsuo; Maeda, Yoshinobu; Miyamoto, Yoshihiro

2014-11-01

Salivary biomarkers have been recently useful of periodontal disease, which is also risk factor of atherosclerosis. However, there are few studies of the association between salivary inflammatory cytokines and carotid atherosclerosis. We aimed to clarify the association between salivary inflammatory cytokines and periodontal disease and carotid atherosclerosis in a general urban population. We studied 608 Japanese men and women (mean age: 65.4 years) in the Suita study. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intima-media thickness (IMT). Periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary levels of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay. The risks of carotid atherosclerosis (≥75th percentiles of mean- [0.88 mm] and Max-IMT [1.50 mm]) according to the quartiles of salivary inflammatory cytokines were compared using of adjusted-logistic regression models. All salivary inflammatory cytokines were positively associated with CPI. The adjusted odds ratios for carotid atherosclerosis of mean-IMT in the highest quartile of interleukin-6 and TNF-α were higher than those in the lowest quartiles (OR = 2.32 and 2.88; 95% confidence intervals = 1.19-4.51 and 1.51-5.49, respectively). The adjusted odds ratio for carotid atherosclerosis of mean-IMT in the highest quartile of PGE2 was greater than those in the lowest quartile in women (OR = 2.78; 95% confidence intervals = 1.11-6.95). In conclusion, higher levels of salivary inflammatory cytokines were associated with both periodontal disease and carotid atherosclerosis. Selected salivary inflammatory cytokines may be useful screening markers for periodontal disease and carotid atherosclerosis. Copyright © 2014. Published by Elsevier Ireland Ltd.

The imminent healthcare and emergency care crisis in Japan.

PubMed

Suzuki, Tetsuji; Nishida, Masamichi; Suzuki, Yuriko; Kobayashi, Kunio

2008-05-01

Japan has a universal healthcare system, and this paper describes the reality of the healthcare services provided, as well as current issues with the system. Academic, government, and press reports on Japanese healthcare systems and healthcare guidelines were reviewed. The universal healthcare system of Japan is considered internationally to be both low-cost and effective because the Japanese population enjoys good health status with a long life expectancy, while healthcare spending in Japan is below the average given by the Organization for Economic Corporation and Development (OECD). However, in many regions of Japan the existing healthcare resources are seriously inadequate, especially with regard to the number of physicians and other health professionals. Because healthcare is traditionally viewed as "sacred" work in Japan, healthcare professionals are expected to make large personal sacrifices. Also, public attitudes toward medical malpractice have changed in recent decades, and medical professionals are facing legal issues without experienced support of the government or legal professionals. Administrative response to the lack of resources and collaboration among communities are beginning, and more efficient control and management of the healthcare system is under consideration. The Japanese healthcare system needs to adopt an efficient medical control organization to ease the strain on existing healthcare professionals and to increase the number of physicians and other healthcare resources. Rather than continuing to depend on healthcare professionals being able and willing to make personal sacrifices, the government, the public and medical societies must cooperate and support changes in the healthcare system.

Agent Based Modeling of Atherosclerosis: A Concrete Help in Personalized Treatments

NASA Astrophysics Data System (ADS)

Pappalardo, Francesco; Cincotti, Alessandro; Motta, Alfredo; Pennisi, Marzio

Atherosclerosis, a pathology affecting arterial blood vessels, is one of most common diseases of the developed countries. We present studies on the increased atherosclerosis risk using an agent based model of atherogenesis that has been previously validated using clinical data. It is well known that the major risk in atherosclerosis is the persistent high level of low density lipoprotein (LDL) concentration. However, it is not known if short period of high LDL concentration can cause irreversible damage and if reduction of the LDL concentration (either by life style or drug) can drastically or partially reduce the already acquired risk. We simulated four different clinical situations in a large set of virtual patients (200 per clinical scenario). In the first one the patients lifestyle maintains the concentration of LDL in a no risk range. This is the control case simulation. The second case is represented by patients having high level of LDL with a delay to apply appropriate treatments; The third scenario is characterized by patients with high LDL levels treated with specific drugs like statins. Finally we simulated patients that are characterized by several oxidative events (smoke, sedentary life style, assumption of alcoholic drinks and so on so forth) that effective increase the risk of LDL oxidation. Those preliminary results obviously need to be clinically investigated. It is clear, however, that SimAthero has the power to concretely help medical doctors and clinicians in choosing personalized treatments for the prevention of the atherosclerosis damages.

Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study.

PubMed

Reiner, Alexander P; Kahn, Arnold; Eisner, Brian H; Pletcher, Mark J; Sadetsky, Natalia; Williams, O Dale; Polak, Joseph F; Jacobs, David R; Stoller, Marshall L

2011-03-01

Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo

NASA Astrophysics Data System (ADS)

Wu, Chenxin; Zhang, Yejun; Li, Zhen; Li, Chunyan; Wang, Qiangbin

2016-06-01

Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe-/- mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications.Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self-assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively

Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

PubMed Central

Busso, Dolores; Mascareño, Lilian; Salas, Francisca; Berkowitz, Loni; Santander, Nicolás; Quiroz, Alonso; Amigo, Ludwig; Valdés, Gloria; Rigotti, Attilio

2014-01-01

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition. PMID:25295255

Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis.

PubMed

Potekhina, Alexandra V; Pylaeva, Ekaterina; Provatorov, Sergey; Ruleva, Natalya; Masenko, Valery; Noeva, Elena; Krasnikova, Tatiana; Arefieva, Tatiana

2015-01-01

Objective. Immune processes play a significant role in atherosclerosis plaque progression. Regulatory T cells and T helpers 17 were shown to possess anti- and pro-atherogenic activity, respectively. We aimed to investigate the balance of circulating Treg and Th17 in stable angina patients with different stages of coronary atherosclerosis. Methods. Treg, Th17 and Th1 cell frequencies were studied in 117 patients via direct immunofluorescence staining and flow cytometry. Group 1 had intact coronary arteries. Group 2 and Group 3 had undergone previous coronary stenting; in Group 2 no coronary atherosclerosis progression was found, in Group 3 patients had disease progression in non-invaded coronary arteries. Group 4 had severe coronary atherosclerosis. Results. The frequencies of CD4+CD25highCD127low, CD4+foxp3+, and CD4+IL10 + T cells were decreased, and CD4+IL17 + T cells frequencies were increased in group 4 vs. 1. Treg/Th17 ratios were declined in groups 3 and 4 vs. groups 1 and 2. IL-10 level was lower while hsCRP and sCD25 levels were higher in group 4 vs. 1. Conclusion. We assume that the imbalance in pro- and anti-inflammatory/atherogenic lymphocyte subpopulations is associated with atherosclerosis progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Non-proinflammatory and responsive nanoplatforms for targeted treatment of atherosclerosis.

PubMed

Dou, Yin; Chen, Yue; Zhang, Xiangjun; Xu, Xiaoqiu; Chen, Yidan; Guo, Jiawei; Zhang, Dinglin; Wang, Ruibing; Li, Xiaohui; Zhang, Jianxiang

2017-10-01

Atherosclerosis is the leading cause of many fatal cardiovascular and cerebrovascular diseases. Whereas nanomedicines are promising for targeted therapy of atherosclerosis, great challenges remain in development of effective, safe, and translational nanotherapies for its treatment. Herein we hypothesize that non-proinflammatory nanomaterials sensitive to low pH or high reactive oxygen species (ROS) may serve as effective platforms for triggerable delivery of anti-atherosclerotic therapeutics in cellular and tissue microenvironments of inflammation. To demonstrate this hypothesis, an acid-labile material of acetalated β-cyclodextrin (β-CD) (Ac-bCD) and a ROS-sensitive β-CD material (Ox-bCD) were separately synthesized by chemical modification of β-CD, which were formed into responsive nanoparticles (NPs). Ac-bCD NP was rapidly hydrolyzed in mildly acidic buffers, while hydrolysis of Ox-bCD NP was selectively accelerated by H 2 O 2 . Using an anti-atherosclerotic drug rapamycin (RAP), we found stimuli-responsive release of therapeutic molecules from Ac-bCD and Ox-bCD nanotherapies. Compared with non-responsive poly(lactide-co-glycolide) (PLGA)-based NP, Ac-bCD and Ox-bCD NPs showed negligible inflammatory responses in vitro and in vivo. By endocytosis in cells and intracellularly releasing cargo molecules in macrophages, responsive nanotherapies effectively inhibited macrophage proliferation and suppressed foam cell formation. After intraperitoneal (i.p.) delivery in apolipoprotein E-deficient (ApoE -/- ) mice, fluorescence imaging showed accumulation of NPs in atherosclerotic plaques. Flow cytometry analysis indicated that the lymphatic translocation mediated by neutrophils and monocytes/macrophages may contribute to atherosclerosis targeting of i.p. administered NPs, in addition to targeting via the leaky blood vessels. Correspondingly, i.p. treatment with different nanotherapies afforded desirable efficacies. Particularly, both pH and ROS

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

PubMed

Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

2006-04-01

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Prevention of oxLDL uptake leads to decreased atherosclerosis in hematopoietic NPC1-deficient Ldlr-/- mice.

PubMed

Jeurissen, Mike L J; Walenbergh, Sofie M A; Houben, Tom; Gijbels, Marion J J; Li, Jieyi; Hendrikx, Tim; Oligschlaeger, Yvonne; van Gorp, Patrick J; Binder, Christoph J; Donners, Marjo M P C; Shiri-Sverdlov, Ronit

2016-12-01

Atherosclerosis is a chronic inflammatory disease of medium and large vessels and is typically characterized by the predominant accumulation of low-density lipoprotein (LDL)-cholesterol inside macrophages that reside in the vessel walls. Previous studies clearly demonstrated an association specifically between the oxidized type of LDL (oxLDL) and atherosclerotic lesion formation. Further observations revealed that these atherosclerotic lesions displayed enlarged, lipid-loaded lysosomes. By increasing natural antibodies against oxLDL, pneumococcal vaccination has been shown to reduce atherosclerosis in LDL receptor knockout (Ldlr -/- ) mice. Relevantly, loss of the lysosomal membrane protein Niemann-Pick Type C1 (NPC1) led to lysosomal accumulation of various lipids and promoted atherosclerosis. Yet, the importance of lysosomal oxLDL accumulation inside macrophages, compared to non-modified LDL, in atherosclerosis has never been established. By transplanting NPC1 bone marrow into lethally irradiated Ldlr -/- mice, a hematopoietic mouse model for lysosomal cholesterol accumulation was created. Through injections with heat-inactivated pneumococci, we aimed to demonstrate the specific contribution of lysosomal oxLDL accumulation inside macrophages in atherosclerosis development. While there were no differences in plaque morphology, a reduction in plaque size and plaque inflammation was found in immunized NPC1 mut -transplanted mice, compared to non-immunized NPC1 mut -transplanted mice. Lysosomal oxLDL accumulation within macrophages contributes to murine atherosclerosis. Future intervention strategies should focus specifically on preventing oxLDL, unlike non-modified LDL, from being internalized into lysosomes. Such an intervention can have an additive effect to current existing treatments against atherosclerosis. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

CD8{sup +}CD25{sup +} T cells reduce atherosclerosis in apoE(−/−) mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Jianchang; Dimayuga, Paul C.; Zhao, Xiaoning

2014-01-17

Highlights: •The role of a sub-population of CD8{sup +} T cells with suppressor functions was investigated in atherosclerosis. •CD8{sup +}CD25{sup +} T cells from adult apoE(−/−) mice had phenotype characteristics of T suppressor cells. •These CD8{sup +}CD25{sup +} T cells reduced CD4{sup +} T cell proliferation and CD8{sup +} cytotoxic activity in vitro. •Adoptive transfer of CD8{sup +}CD25{sup +} T cells significantly reduced atherosclerosis. •CD8{sup +}CD25{sup +} T cells have a suppressive function in atherosclerosis. -- Abstract: Background: It is increasingly evident that CD8{sup +} T cells are involved in atherosclerosis but the specific subtypes have yet to be defined.more » CD8{sup +}CD25{sup +} T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis were investigated in this study. Methods and results: CD8{sup +}CD25{sup +} T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8{sup +}CD25{sup +} T cells from apoE(−/−) mice. Depletion of CD8{sup +}CD25{sup +} from total CD8{sup +} T cells rendered higher cytolytic activity of the remaining CD8{sup +}CD25{sup −} T cells. Adoptive transfer of CD8{sup +}CD25{sup +} T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4{sup +} T cells and significantly reduced atherosclerosis in recipient mice. Conclusions: Our study has identified an athero-protective role for CD8{sup +}CD25{sup +} T cells in experimental atherosclerosis.« less

Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, M.-M.; Graduate Institute of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Chiou, H.-Y.

2006-10-01

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated bymore » dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.« less

[Uncertainty of cross calibration-applied beam quality conversion factor for the Japan Society of Medical Physics 12].

PubMed

Kinoshita, Naoki; Kita, Akinobu; Takemura, Akihiro; Nishimoto, Yasuhiro; Adachi, Toshiki

2014-09-01

The uncertainty of the beam quality conversion factor (k(Q,Q0)) of standard dosimetry of absorbed dose to water in external beam radiotherapy 12 (JSMP12) is determined by combining the uncertainty of each beam quality conversion factor calculated for each type of ionization chamber. However, there is no guarantee that ionization chambers of the same type have the same structure and thickness, so there may be individual variations. We evaluated the uncertainty of k(Q,Q0) for JSMP12 using an ionization chamber dosimeter and linear accelerator without a specific device or technique in consideration of the individual variation of ionization chambers and in clinical radiation field. The cross calibration formula was modified and the beam quality conversion factor for the experimental values [(k(Q,Q0))field] determined using the modified formula. It's uncertainty was calculated to be 1.9%. The differences between (k(Q,Q0))field of experimental values and k(Q,Q0) for Japan Society of Medical Physics 12 (JSMP12) were 0.73% and 0.88% for 6- and 10-MV photon beams, respectively, remaining within ± 1.9%. This showed k(Q,Q0) for JSMP12 to be consistent with (k(Q,Q0))field of experimental values within the estimated uncertainty range. Although inter-individual differences may be generated, even when the same type of ionized chamber is used, k(Q,Q0) for JSMP12 appears to be consistent within the estimated uncertainty range of (k(Q,Q0)field.

Combined vitamin C and vitamin E deficiency worsens early atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Babaev, Vladimir R; Li, Liying; Shah, Sanket; Fazio, Sergio; Linton, MacRae F; May, James M

2010-09-01

To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C/low E, low C/high E, high C/low E, and high C/high E) were studied in atherosclerosis-prone apolipoprotein E-deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase(-/-)); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase(-/-) mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter). After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase(-/-) mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E(-/-) mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males. Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete.

Diagnosis and treatment of urea cycle disorder in Japan.

PubMed

Nakamura, Kimitoshi; Kido, Jun; Mitsubuchi, Hiroshi; Endo, Fumio

2014-08-01

Urea cycle disorder (UCD) is an inborn error of the metabolic pathway producing urea from ammonia, which occurs primarily in the liver. Decreased excretion of nitrogen in the urea cycle due to deficiency of carbamoyl phosphate synthase I (CPSI), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and N-acetyl glutamate synthase (NAGS) causes hyperammonemia. We examined the clinical manifestations, treatment, and prognosis of 177 patients with UCD from January 1999 to March 2009 in Japan. Compared with a previous study conducted in Japan, a larger number of patients survived without mental retardation, even when the peak blood ammonia was >360 μmol/L. In those with peak blood ammonia >360 μmol/L, an indicator of poor prognosis, the frequency of convulsions, mental retardation, brain abnormality on magnetic resonance imaging, hemodialysis, liver transplantation, and intake of non-protein formulas was significantly higher than in those with peak blood ammonia <360 μmol/L. In this article, we have reported the current state of UCD to evaluate prognosis and its relationship with peak blood ammonia and hemodialysis. © 2014 Japan Pediatric Society.

The new standard of fluids for hemodialysis in Japan.

PubMed

Kawanishi, Hideki; Masakane, Ikuto; Tomo, Tadashi

2009-01-01

The standard of fluids for hemodialysis is being evaluated by the International Organization for Standardization (ISO), and will be decided within a few years. In 2008, the Japanese Society for Dialysis Therapy (JSDT) proposed the standard of fluids for hemodialysis by taking the draft ISO standard into consideration and the circumstances in Japan. It was characteristically a standard for Japan, where the central dialysis fluid delivery system (CDDS) is routinely used. In addition, the therapeutic application of each dialysis fluid is clarified. Since high-performance dialyzers are frequently employed in Japan, the standard recommends that ultrapure dialysis fluid be used for all dialysis modalities at all dialysis facilities. It also recommends that the dialysis equipment safety management committee at each facility validate the microbiological qualities of online-prepared substitution fluid, making the responsibility of the dialysis facility clear. This standard is more rigid than those of other countries, and is expected to contribute to improvements in the survival outcome of dialysis patients. (c) 2009 S. Karger AG, Basel.

Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

PubMed Central

Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

2012-01-01

Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

Intracranial atherosclerosis is associated with progression of neurological deficit in subcortical stroke.

PubMed

Hallevi, Hen; Chernyshev, Oleg Y; El Khoury, Ramy; Soileau, Michael J; Walker, Kyle C; Grotta, James C; Savitz, Sean I

2012-01-01

Progression of neurological deficit (PND) is a frequent complication of acute subcortical ischemic stroke (SCS). The role of intracranial atherosclerosis (IAS) in PND is controversial. Our goal was to evaluate IAS on admission, as predictor of PND in SCS patients. SCS patients were identified from our prospective database from 2004 to 2008. Clinical and laboratory data were collected from charts, and radiographic data from original radiographs. The proximal intracranial arteries were graded as patent, irregular, stenotic, or occlusion. IAS was defined as irregularity or stenosis. PND was defined as a change in the National Institutes of Health Stroke Scale >1 point. Two hundred and two SCS patients were identified. In 14%, PND occurred at a median of 2 days from onset. Univariate analysis by infarct location showed the following to be associated with PND: for anterior circulation infarcts (centrum semiovale/basal ganglia), M1 atherosclerosis (p = 0.042); for posterior circulation infarcts, vertebral artery atherosclerosis (p = 0.018). For both groups, we found a non-significant association with age (p = 0.2) and HbA1c levels (p = 0.095). No association was found with admission glucose levels. Multivariate analysis showed the following association with PND: for anterior circulation infarcts, M1 atherosclerosis (OR 4.7; 95% CI 1.2-18.8; p = 0.03); for pontine infarcts, vertebral artery atherosclerosis (OR 5.8; 95% CI 1.1-29.4; p = 0.033). There was an increase in PND likelihood with an increasing number of atherosclerotic vessels. In our cohort of SCS patients, PND was associated with IAS of the responsible vessels. These results suggest a role for IAS in the pathogenesis of PNF in SCS patients. Copyright © 2011 S. Karger AG, Basel.

The University and the Technical Revolution in Japan: A Model for Developing Countries?

ERIC Educational Resources Information Center

Kobayashi, Tetsuya

1980-01-01

The role of the university in Japan's technological and industrial development is discussed. Problems including the westernization of a non-Western society, coordination between education and industry, the government and freedom of the university, and nationalism and internationalism are described. (Author/MLW)

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

PubMed

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice

PubMed Central

Subramanian, Savitha; Han, Chang Yeop; Chiba, Tsuyoshi; McMillen, Timothy S.; Wang, Shari A.; Haw, Antonio; Kirk, Elizabeth A.; O’Brien, Kevin D.; Chait, Alan

2009-01-01

Objective Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results LDLR-/- mice were fed chow, high fat, high carbohydrate (diabetogenic) diet without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation and local inflammation were observed in intra-abdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation and increased atherosclerosis in this mouse model. PMID:18239153

Thymic stromal lymphopoietin-induced HOTAIR activation promotes endothelial cell proliferation and migration in atherosclerosis

PubMed Central

Peng, Yudong; Meng, Kai; Jiang, Lili; Zhong, Yucheng; Yang, Yong; Lan, Yin

2017-01-01

Endothelial cells’ (EC) injury is a major step for the pathological progression of atherosclerosis. Recent study demonstrated that thymic stromal lymphopoietin (TSLP) exerts a protective role in atherosclerosis. However, the effect of TSLP and the exact molecular mechanism involved in EC remains unknown. In the present study, we found that long noncoding RNA (lncRNA) HOTAIR was much lower in EC from atherosclerotic plaque. Functional assays showed that HOTAIR facilitated cell proliferation and migration, and suppressed apoptosis in EC. Moreover, we demonstrated that TSLP functions upstream of HOTAIR. We found that serum level of TSLP was decreased in atherosclerosis patients and serum TSLP level positively correlated with HOTAIR expression in EC. Further investigation demonstrated that TSLP activated HOTAIR transcription through PI3K/AKT-IRF1 pathway and then regulates the EC proliferation and migration. TSLP-HOTAIR axis also plays a protective role in low-density lipoprotein (ox-LDL)-induced EC injury. Taken together, TSLP-HOTAIR may be a potential therapy for EC dysfunction in atherosclerosis. PMID:28615347

Increased Th9 cells and IL-9 levels accelerate disease progression in experimental atherosclerosis.

PubMed

Li, Qing; Ming, Tingting; Wang, Yuanmin; Ding, Shaowei; Hu, Chaojie; Zhang, Cuiping; Cao, Qi; Wang, Yiping

2017-01-01

Atherosclerosis (AS) is the number one killer in developed countries, and currently considered a chronic inflammatory disease. The central role of T cells in the pathogenesis of atherosclerosis is well documented. However, little is known about the newly described T cell subset-Th9 cells and their role in AS pathogenesis. Here, the amounts of Th9 cells as well as their key transcription factors and relevant cytokines during atherosclerosis were assessed in ApoE -/- mice and age-matched C57BL/6J mice. Significantly increased Th9 cell number, Th9 related cytokine (IL-9), and key transcription factor (PU.1) were found in ApoE -/- mice compared with age-matched C57BL/6J mice. Additionally, treatment with rIL-9 accelerated atherosclerotic development, which was attenuated by anti-IL-9 antibodies. These data suggested that both Th9 cells and related IL-9 play key roles in the pathogenesis of atherosclerosis, and antibodies against these antigens offer a novel therapeutic approach in AS treatment.

Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation.

PubMed

Saetta, A; Fanourakis, G; Agapitos, E; Davaris, P S

2000-01-01

Several studies suggest that certain viral and bacterial pathogens may contribute to the process of atherogenesis. However, this relation between infectious agents and atherosclerosis has not yet been established with certainty. The aim of this study was to investigate the presence of CMV in carotid endarterectomies from 40 patients suffering from atherosclerosis using immunohistochemistry and the polymerase chain reaction (PCR). None of the specimens examined gave a positive result, indicating absence of CMV particles or CMV DNA sequences in the walls of carotid arteries. This finding suggests it is possible that CMV infection may not play a major role in the formation of atheroma. Therefore, further investigation is required in order to clarify the etiology of atherosclerosis.

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study.

PubMed

Nozue, Tsuyoshi; Fukui, Kazuki; Koyama, Yutaka; Fujii, Hiroyuki; Kunishima, Tomoyuki; Hikita, Hiroyuki; Hibi, Kiyoshi; Miyazawa, Akiyoshi; Michishita, Ichiro

2016-05-01

Patients with diabetes mellitus are at high risk for developing coronary artery disease (CAD), even if they are treated with statins. Several studies have shown the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the cardiovascular system in an animal model. However, recent clinical trials using DPP-4 inhibitors have shown that these inhibitors fail to reduce the occurrence of cardiovascular events. Therefore, this study will be performed to evaluate the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis in patients with type 2 diabetes. This study will be a prospective, open-label, randomized multicenter trial performed in 6 centers in Japan. Stable CAD patients with type 2 diabetes who have undergone successful percutaneous coronary intervention under integrated backscatter (IB)-intravascular ultrasound (IVUS) guidance will be studied. They will be randomly assigned to either the sitagliptin group or a control group. After 48 weeks' treatment, the IVUS examination will be repeated in the same coronary artery as at baseline. The primary end point will be the percentage change in plaque volume measured using grayscale IVUS from baseline to the 48-week follow-up. This study will be the first multicenter trial to evaluate the effects of a DPP-4 inhibitor on coronary atherosclerosis evaluated using IB-IVUS, and the findings will clarify the anti-atherogenic effects of sitagliptin.

Atherosclerosis in chronic kidney disease: the role of macrophages

PubMed Central

Kon, Valentina; Linton, MacRae F.; Fazio, Sergio

2013-01-01

Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe−/− mice are enriched in cholesterol owing to downregulation of cholesterol transporter ATP-binding cassette subfamily A member 1 levels and activation of nuclear factor κB, which leads to impaired cholesterol efflux. Interestingly, treatment with an angiotensin-II-receptor blocker (ARB) improves these effects. Moreover, atherosclerotic aortas from Apoe−/− mice transplanted into renal-ablated normocholesterolemic recipients show plaque progression and increased macrophage content instead of the substantial regression seen in recipient mice with intact kidneys. ARBs reduce atherosclerosis development in mice with partial renal ablation. These results, combined with the clinical benefits of angiotensin-converting-enzyme (ACE) inhibitors and ARBs in patients with CKD, suggest an important role for the angiotensin system in the enhanced susceptibility to atherosclerosis seen across the spectrum of CKD. The role of macrophages could explain why these therapies may be effective in end-stage renal disease, one of the few conditions in which statins show no clinical benefit. PMID:21102540

Human cells involved in atherosclerosis have a sex.

PubMed

Franconi, Flavia; Rosano, Giuseppe; Basili, Stefania; Montella, Andrea; Campesi, Ilaria

2017-02-01

The influence of sex has been largely described in cardiovascular diseases. Atherosclerosis is a complex process that involves many cell types such as vessel cells, immune cells and endothelial progenitor cells; however, many, if not all, studies do not report the sex of the cells. This review focuses on sex differences in human cells involved in the atherosclerotic process, emphasizing the role of sex hormones. Furthermore, we report sex differences and issues related to the processes that determine the fate of the cells such as apoptotic and autophagic mechanisms. The analysis of the data reveals that there are still many gaps in our knowledge regarding sex influences in atherosclerosis, largely for the cell types that have not been well studied, stressing the urgent need for a clear definition of experimental conditions and the inclusion of both sexes in preclinical studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Myeloid interferon-γ receptor deficiency does not affect atherosclerosis in LDLR(-/-) mice.

PubMed

Boshuizen, Marieke C S; Neele, Annette E; Gijbels, Marion J J; van der Velden, Saskia; Hoeksema, Marten A; Forman, Ruth A; Muller, Werner; Van den Bossche, Jan; de Winther, Menno P J

2016-03-01

Atherosclerosis is a chronic lipid-driven inflammatory disease of the arterial wall. Interferon gamma (IFNγ) is an important immunomodulatory cytokine and a known pro-atherosclerotic mediator. However, cell-specific targeting of IFNγ or its signaling in atherosclerosis development has not been studied yet. As macrophages are important IFNγ targets, we here addressed the involvement of myeloid IFNγ signaling in murine atherosclerosis. Bone marrow was isolated from interferon gamma receptor 2 chain (IFNγR2) wildtype and myeloid IFNγR2 deficient mice and injected into lethally irradiated LDLR(-/-) mice. After recovery mice were put on a high fat diet for 10 weeks after which atherosclerotic lesion analysis was performed. In addition, the accompanying liver inflammation was assessed. Even though absence of myeloid IFNγ signaling attenuated the myeloid IFNγ response, no significant differences in atherosclerotic lesion size or phenotype were found. Also, when examining the liver inflammatory state no effects of IFNγR2 deficiency could be observed. Overall, our data argue against a role for myeloid IFNγR2 in atherosclerosis development. Since myeloid IFNγ signaling seems to be nonessential throughout atherogenesis, it is important to understand the mechanisms by which IFNγ acts in atherogenesis. In the future new studies should be performed considering other cell-specific targets. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

History of Japan-U.S./High Pressure Mineral Physics Seminars: 1976 to 2012

NASA Astrophysics Data System (ADS)

Liebermann, Robert Cooper

2014-03-01

Under the auspices of the U.S.-Japan Cooperative Science Program between the U.S. National Science Foundation and the Japan Society for the Promotion of Science, the first U.S.-Japan joint seminar on High Pressure Research Applications in Geophysics was held in Honolulu, Hawaii, 5-8 July 1976 and was attended by 47 scientists. Originated as bilateral U.S.-Japan seminars on high-pressure research applications in geophysics by Murli Manghnani and Syun-iti Akimoto, this series continued at 5-year intervals under those auspices from 1976 to 1996 [1981 in Hakone, Japan 1986 in Turtle Bay, Hawaii, 1991 in Ise, Japan, and 1996 in Maui, Hawaii], with venues alternating between Hawaii and Japan. In the 21st century, as a result of growing international interest in high-pressure mineral physics, the seminar series was re-envisioned with a broader focus “more international” focus than the original U.S.-Japan bilateral series. The first of the new meetings entitled “High Pressure Mineral Physics Seminars” [HPMP-6] took place in Verbania, Italy on August 26-31, 2002. More than 84 scientists from Asia, Australia, the Americas and Europe attended. HPMPS-7 took place in Matsushima, Japan on May 8-12, 2007 and was attended by 134 scientists from throughout the world. In this paper, we review this history culminating with the HPMPS-8 at Lake Tahoe, California in July 2012, which was held jointly with the Annual Meeting of COMPRES: Consortium for Materials Properties Research in Earth Sciences.

Amelioration of Atherosclerosis by the New Medicinal Mushroom Grifola gargal Singer

PubMed Central

Harada, Etsuko; D'Alessandro-Gabazza, Corina N.; Toda, Masaaki; Morizono, Toshihiro; Chelakkot-Govindalayathil, Ayshwarya-Lakshmi; Roeen, Ziaurahman; Urawa, Masahito; Yasuma, Taro; Yano, Yutaka; Sumiya, Toshimitsu

2015-01-01

ABSTRACT The beneficial effects of edible mushrooms for improving chronic intractable diseases have been documented. However, the antiatherogenic activity of the new medicinal mushroom Grifola gargal is unknown. Therefore, we evaluated whether Grifola gargal can prevent or delay the progression of atherosclerosis. Atherosclerosis was induced in ApoE lipoprotein-deficient mice by subcutaneous infusion of angiotensin II. Grifola gargal extract (GGE) was prepared and intraperitoneally injected. The weight of heart and vessels, dilatation/atheroma formation of thoracic and abdominal aorta, the percentage of peripheral granulocytes, and the blood concentration of MCP-1/CCL2 were significantly reduced in mice treated with GGE compared to untreated mice. By contrast, the percentage of regulatory T cells and the plasma concentration of SDF-1/CXCL12 were significantly increased in mice treated with the mushroom extract compared to untreated mice. In vitro, GGE significantly increased the secretion of SDF-1/CXCL12, VEGF, and TGF-β1 from fibroblasts compared to control. This study demonstrated for the first time that Grifola gargal therapy can enhance regulatory T cells and ameliorate atherosclerosis in mice. PMID:25799023

Loss of TIMP3 exacerbates atherosclerosis in ApoE null mice.

PubMed

Stöhr, Robert; Cavalera, Michele; Menini, Stefano; Mavilio, Maria; Casagrande, Viviana; Rossi, Claudia; Urbani, Andrea; Cardellini, Marina; Pugliese, Giuseppe; Menghini, Rossella; Federici, Massimo

2014-08-01

Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of various proteases and receptors. We have previously shown TIMP3 to be downregulated in metabolic and inflammatory disorders, such as type 2 diabetes mellitus. We have now generated an ApoE(-/-)Timp3(-/-) mouse model in which, through the use of genetics, metabolomics and in-vivo phenotypical analysis we investigated the role of TIMP3 in the development of atherosclerosis. En face aorta analysis and aortic root examination showed that ApoE(-/-)Timp3(-/-) mice show increased atherosclerosis with increased infiltration of macrophages into the plaque. Serum concentration of MCP-1 were elevated in the serum of ApoE(-/-)Timp3(-/-) mice coupled with an expansion of the inflammatory (M1) Gr1+ macrophages, both in the circulation and within the aortic tissue. Targeted analysis of metabolites revealed a trend to reduced short chain acylcarnitines. Our study shows that lack of TIMP3 increases inflammation and polarizes macrophages towards a more inflammatory phenotype resulting in increased atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Japan.

ERIC Educational Resources Information Center

Geiger, Rita; And Others

The document offers practical and motivating techniques for studying Japan. Dedicated to promoting global awareness, separate sections discuss Japan's geography, history, culture, education, government, economics, energy, transportation, and communication. Each section presents a topical overview; suggested classroom activities; and easily…

Selection and concentration of obstetric facilities in Japan: Longitudinal study based on national census data.

PubMed

Matsumoto, Masatoshi; Koike, Soichi; Matsubara, Shigeki; Kashima, Saori; Ide, Hiroo; Yasunaga, Hideo

2015-06-01

A shortage of obstetricians with increased workload is a social problem in Japan. In response, the government and professional bodies have accelerated the 'selection and concentration' of obstetric facilities. The aim of this study was to evaluate the recent trend of selection and concentration. We used data on the number of deliveries and of obstetricians in each hospital and clinic in Japan, according to the Static Survey of Medical Institutions in 2005, 2008 and 2011. To evaluate the inter-facility equality of distribution of the number of deliveries, number of obstetricians and number of deliveries per obstetrician, Gini coefficients were calculated. The number of obstetric hospitals decreased by 20% and the number of deliveries per hospital increased by 26% between 2005 and 2011. Hospital obstetricians increased by 16% and the average number of obstetricians per hospital increased by 19% between 2008 and 2011. Gini coefficient of deliveries has significantly decreased. In contrast, Gini coefficient of deliveries per obstetrician has significantly increased. The degree of increase in obstetricians and of decrease in deliveries per obstetrician was largest at the hospitals with the highest proportion of cesarean sections. The proportion of obstetric hospitals with the optimal volume of deliveries and obstetricians, as defined by Japan Society of Obstetrics and Gynecology, was 4% in 2008, and it had doubled to 8.1% 3 years later. The selection and concentration of obstetric facilities is progressing rapidly and effectively in Japan. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Human Resource Development for Knowledge-based Society and Challenges of Nagoya University

NASA Astrophysics Data System (ADS)

Miyata, Takashi

Innovation in the previous century resulted in development of useful products ranging from automobiles and aircraft to cellular phones. However, the innovation and development of science and technology have changed the society and brought about negative issues. The issues emerged in the previous century remain in the excessive forms in the 21st century. The 21st century is seeing the rise of knowledge-based society, and paradigm shift is now going on. Human resources of university for creation of innovation are being called on to contribute to solving issues. Young people who pass through a doctor program must play a role as an innovator who can promote the paradigm shift. However, the higher education system of the universities in Japan is now required to be changed to dissolve the mismatch on the doctor program with industries, government and students. The discussion in the Business-University Forum of Japan for innovation of education system and a few challenges of the Nagoya University are introduced in this paper.

Endothelial dysfunction: the early predictor of atherosclerosis.

PubMed

Mudau, Mashudu; Genis, Amanda; Lochner, Amanda; Strijdom, Hans

2012-05-01

Since the discovery in the 1980s that nitric oxide (NO) is in fact the elusive endothelium-derived relaxing factor, it has become evident that NO is not only a major cardiovascular signalling molecule, but that changes in its bioavailability are crucial in determining whether atherosclerosis will develop or not. Sustained high levels of harmful circulating stimuli associated with cardiovascular risk factors such as diabetes mellitus elicit responses in endothelial cells that appear sequentially, namely endothelial cell activation and endothelial dysfunction (ED). ED, characterised by reduced NO bioavailability, is now recognised by many as an early, reversible precursor of atherosclerosis. The pathogenesis of ED is multifactorial; however, oxidative stress appears to be the common underlying cellular mechanism in the ensuing loss of vaso-active, inflammatory, haemostatic and redox homeostasis in the body's vascular system. The role of ED as a pathophysiological link between early endothelial cell changes associated with cardiovascular risk factors and the development of ischaemic heart disease is of importance to basic scientists and clinicians alike.

Duplicative medications in patients who visit multiple medical institutions among the insured of a corporate health insurance society in Japan.

PubMed

Kinoshita, Hiroki; Kobayashi, Yasuki; Fukuda, Takashi

2008-01-01

The objective of this paper is to describe the frequency of duplicative medication use and to estimate the drug cost associated with duplicative medications in patients who visit multiple medical institutions in Japan. The subjects of this study were insurants of a corporate health insurance society. We examined claims of insurants who received prescriptions from multiple medical institutions in April 2002. We examined characteristics of insurants who received duplicative medications and calculated the cost of duplicated drugs. 8.8% received drugs with the same mechanism of action for overlapping administration periods. In terms of comparison among three age groups, 0-19 years old, 20-69 years old, and 70 years old or older, the percentage was higher in 0-19-year-old patients than in the other age groups. The cost of duplicated drugs was found to be 0.7% or 0.5% of the total drug cost, when calculated with higher-priced drugs and lower-priced drugs, respectively. This study suggests that pediatric and teenage patients as well as elderly patients require prudent management of medication to avoid duplicative medications and that at least an estimated 5.2-7.2 billion yen may be saved if duplicative medications can be completely eliminated nationwide.

[Long non-coding RNAs in the pathophysiology of atherosclerosis].

PubMed

Novak, Jan; Vašků, Julie Bienertová; Souček, Miroslav

2018-01-01

The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution. Today we already know that non-coding RNAs fulfil a variety of regulatory functions in our body - they intervene into epigenetic processes from chromatin remodelling to histone methylation, or into the transcription process itself, or even post-transcription processes. Long non-coding RNAs (lncRNA) are one of the classes of non-coding RNAs that have more than 200 nucleotides in length (non-coding RNAs with less than 200 nucleotides in length are called small non-coding RNAs). lncRNAs represent a widely varied and large group of molecules with diverse regulatory functions. We can identify them in all thinkable cell types or tissues, or even in an extracellular space, which includes blood, specifically plasma. Their levels change during the course of organogenesis, they are specific to different tissues and their changes also occur along with the development of different illnesses, including atherosclerosis. This review article aims to present lncRNAs problematics in general and then focuses on some of their specific representatives in relation to the process of atherosclerosis (i.e. we describe lncRNA involvement in the biology of endothelial cells, vascular smooth muscle cells or immune cells), and we further describe possible clinical potential of lncRNA, whether in diagnostics or therapy of atherosclerosis and its clinical manifestations.Key words

Educational Practices in an Age of Information Innovation: Audiovisual Education Prize Winning Papers in 1998. AVE in Japan No. 38.

ERIC Educational Resources Information Center

Japan Audiovisual Information Center for International Service, Tokyo.

This booklet contains two papers that won the 1998 Audiovisual Education Prize of the Japan Audio-Visual Education Association. "Nurturing the Ability To Live in an Advanced Information Network Society: Making the Most Effective Use of Networking" reports on a study of 7th grade students in Okazaki City (Japan). The focus was on an…

Subclinical carotid atherosclerosis and hyperuricemia in relation to renal impairment in a rural Japanese population: the Nagasaki Islands study.

PubMed

Shimizu, Yuji; Sato, Shimpei; Koyamatsu, Jun; Yamanashi, Hirotomo; Tamai, Mami; Kadota, Koichiro; Arima, Kazuhiko; Yamasaki, Hironori; Takamura, Noboru; Aoyagi, Kiyoshi; Maeda, Takahiro

2014-04-01

The influence of hyperuricemia on atherosclerosis is controversial. Subclinical carotid atherosclerosis can be defined in two ways in terms of mean and maximum carotid intima-media thickness (CIMT): one with mean CIMT≥1.1 mm and the other with maximum CIMT≥1.1 mm. However, no studies have been reported of the association between hyperuricemia and subclinical carotid atherosclerosis while taking the two different ways of classification into account. We conducted a cross-sectional study of 4133 subjects (1492 men and 2641 women) aged 30-89 years undergoing general health check-ups. For analysis of various associations, we calculated the multivariable odds ratios (ORs) for the two ways classifications of subclinical carotid atherosclerosis in relation to hyperuricemia. Hyperuricemia-related renal impairment constitutes a significant marker for subclinical carotid atherosclerosis with mean CIMT≥1.1 mm for both men and women, while hyperuricemia per se was found to be beneficially associated with risk of subclinical carotid atherosclerosis with maximum CIMT≥1.1 mm for men. The classical cardiovascular risk factors without adjustment for glomerular filtration rate (GFR) of ORs for subclinical carotid atherosclerosis (mean CIMT≥1.1 mm) and subclinical carotid atherosclerosis (maximum CIMT≥1.1 mm) were 2.20(1.10-4.22) and 0.84(0.63-1.13) for men and 2.12(1.02-4.38) and 0.92(0.66-1.27) for women. After further adjustment for GFR, the corresponding values were 1.54(0.74-3.20) and 0.67(0.49-0.92) for men and 1.32(0.61-2.88) and 0.80(0.57-1.12) for women. Hyperuricemia-related renal impairment is a significant marker for subclinical carotid atherosclerosis for both men and women, while hyperuricemia per se may be inversely associated with subclinical carotid atherosclerosis for men as seen in a rural community-dwelling Japanese population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Selective serotonin reuptake inhibitors and risk of major congenital anomalies for pregnancies in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

PubMed

Nishigori, Hidekazu; Obara, Taku; Nishigori, Toshie; Mizuno, Satoshi; Metoki, Hirohito; Hoshiai, Tetsuro; Watanabe, Zen; Sakurai, Kasumi; Ishikuro, Mami; Tatsuta, Nozomi; Nishijima, Ichiko; Fujiwara, Ikuma; Kuriyama, Shinichi; Arima, Takahiro; Nakai, Kunihiko; Yaegashi, Nobuo

2017-05-01

We analyzed data from the Japan Environment and Children's Study (JECS), on the association between selective serotonin reuptake inhibitors (SSRI) use during pregnancy and the risk of developing of major congenital anomalies in Japan. JECS is an ongoing nationwide birth cohort study. The study includes 95 994 single pregnant women and their offspring. Among them, 172 used any SSRI up to the 12 th gestational week. Crude analyses show a significantly increased incidence of upper limb, abdominal, and urogenital abnormalities. In particular, the incidence of microcephaly, hydrencephalus, esophageal atresia, small intestinal atresia, and achondroplasia was significantly higher with than without exposure to these substances. On multivariate analyses, urogenital abnormality was significant (odds ratio 3.227; 95% confidence interval: 1.460-7.134). This Japanese nationwide birth cohort survey clarified that the use of any SSRI until the 12 th gestational week was associated with urogenital abnormality in children. The survey for association with minor classification abnormality needs further examination in Japan. © 2016 Japanese Teratology Society.

Prediabetes is not a risk factor for subclinical coronary atherosclerosis.

PubMed

Park, Gyung-Min; Cho, Young-Rak; Lee, Seung-Whan; Yun, Sung-Cheol; Won, Ki-Bum; Ann, Soe Hee; Kim, Yong-Giun; Kim, Shin-Jae; Roh, Jae-Hyung; Kim, Young-Hak; Yang, Dong Hyun; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Koh, Eun Hee; Lee, Woo Je; Kim, Min-Seon; Lee, Ki-Up; Park, Joong-Yeol; Kim, Hong-Kyu; Choe, Jaewon; Lee, Sang-Gon

2017-09-15

There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals. We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively. Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80-1.22, p=0.888), any plaque (0.96, 95% CI 0.86-1.07, p=0.483), calcified plaque (0.90, 95% CI 0.79-1.01, p=0.080), non-calcified plaque (1.02, 95% CI 0.88-1.17, p=0.803), and mixed plaque (1.00, 95% CI 0.82-1.22, p=0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34-2.19, p<0.001), any plaque (1.45, 95% CI 1.26-1.68, p<0.001), calcified plaque (1.35, 95% CI 1.15-1.57, p<0.001), non-calcified plaque (1.33, 95% CI 1.11-1.59, p=0.002), and mixed plaque (1.64, 95% CI 1.30-2.07, p<0.001) of diabetic individuals were significantly higher than those of the normal individuals. In asymptomatic individuals, diabetic individuals had a higher risk for subclinical coronary atherosclerosis, but prediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

PubMed

Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

2018-02-01

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study.

PubMed

Blasco-Colmenares, Elena; Moreno-Franco, Belén; Latre, Montserrat León; Mur-Vispe, Eusebio; Pocovi, Miguel; Jarauta, Estíbaliz; Civeira, Fernando; Laclaustra, Martín; Casasnovas, José A; Guallar, Eliseo

2018-05-03

Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities. We performed a cross-sectional analysis of 1968 men, 40-60 years of age, participating in the Aragon Workers' Health Study (AWHS). Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound. In fully adjusted models, the odds ratios (95% CI) for CACS >0 comparing sleep durations of ≤5, 6, and ≥8 h with 7 h were 1.34 (0.98-1.85), 1.35 (1.08-1.69) and 1.21 (0.90-1.62), respectively (p = 0.04). A similar U-shaped association was observed for CACS ≥100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were ≤5, 6, and ≥8 h with 7 h were 1.23 (0.88-1.72), 1.09 (0.86-1.38), and 0.86 (0.63-1.17), respectively (p = 0.31), and for the presence of at least one femoral plaque were 1.25 (0.87-1.80), 1.19 (0.93-1.51) and 1.17 (0.86-1.61), respectively (p = 0.39). Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Sleep characteristics of young children in Japan: internet study and comparison with other Asian countries.

PubMed

Kohyama, Jun; Mindell, Jodi A; Sadeh, Avi

2011-10-01

A recent international Internet-based study of young children (birth to 36 months) found that total sleep duration in Japan was the shortest among 17 countries/regions. The present study compared features of children's sleep in Japan relative to those in other Asian countries/regions. Parents of 872 infants and toddlers in Japan (48.6% boys), and parents of 20 455 infants and toddlers in 11 other Asian countries/regions (48.1% boys; China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam) completed an Internet-based expanded version of the Brief Infant Sleep Questionnaire. Young children in Japan exhibited significantly fewer nocturnal wakings and shorter daytime sleep in comparison with other Asian countries/regions. Although the former finding was apparent in all age groups, the reduced duration of daytime sleep in Japan was not present until after 3 months of age. Interestingly, sleep problems were reported by significantly fewer parents in Japan compared with those in other Asian countries/regions, although parents in Japan reported significantly more difficulty at bedtime. The short sleep duration of young children in Japan is largely due to a relatively short duration of daytime sleep. Significant differences in sleep characteristics in Japan relative to other Asian regions were found primarily after 3 months of age. Future studies should further explore the underlying causes and the potential impacts of these sleep differences. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP.

PubMed

Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei; Zeng, Qiutang

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE-/- mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells.

Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP

PubMed Central

Zhao, Xiaoqi; Liu, Yuzhou; Zhong, Yucheng; Liu, Bo; Yu, Kunwu; Shi, Huairui; Zhu, Ruirui; Meng, Kai; Zhang, Wei; Wu, Bangwei

2015-01-01

Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. PMID:26063978

The Japan Lung Cancer Society–Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer

PubMed Central

Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao

2017-01-01

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1–11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS–JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. PMID:27609192

Gender-Specific Association of Desacylated Ghrelin with Subclinical Atherosclerosis in the Metabolic Syndrome.

PubMed

Zanetti, Michela; Gortan Cappellari, Gianluca; Semolic, Annamaria; Burekovic, Ismet; Fonda, Maurizio; Cattin, Luigi; Barazzoni, Rocco

2017-07-01

Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. To investigate potential associations of total, AG and DAG with carotid atherosclerosis and with gender in the MS. Plasma total ghrelin, AG, DAG and carotid artery IMT (cIMT) were measured in 46 MS patients (NCEP-ATP III criteria, 22M/24F). Compared with males, females had higher (p <0.05) total and DAG. In the association analysis, age and plasma glucose were positively (p <0.05) correlated with cIMT in all MS patients. The positive (p <0.05) association between cIMT and age was also confirmed in males, while that between cIMT and glucose was significant in women. In contrast, neither total ghrelin nor AG and DAG were associated with cIMT in all MS patients nor in the male subgroup. In females, a negative (p <0.05) association between carotid artery IMT, DAG and glucose was detected, but not between cIMT, total ghrelin and AG. In multivariate modeling, DAG remained negatively (p <0.05) associated with cIMT after adjusting for plasma glucose and cardiovascular risk factors. These data indicate a negative independent association between DAG and cIMT in middle-aged women with the MS and suggest a gender-specific modulatory function of DAG in the development of atherosclerosis. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development.

PubMed

Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

2012-07-01

As olive oil is the main source of calories in the Mediterranean diet, a great deal of research has been devoted to characterizing its role in atherosclerosis. Virgin olive oil is an oily matrix that contains hydrocarbons, mainly squalene; triterpenes such as uvaol, erythrodiol, oleanolic, and maslinic acid; phytosterols; and a wide range of phenolic compounds comprising simple phenols, flavonoids, secoiridoids, and lignans. In this review, we analyze the studies dealing with atherosclerosis and olive oil in several species. A protective role of virgin olive oil against atherosclerosis has been shown in ApoE-deficient mice and hamsters. In the former animal, sex, dose, and dietary cholesterol are modulators of the outcome. Contradictory findings have been reported for rabbits, a circumstance that could be due to the profusion of experimental designs, differing in terms of doses and animal strains, as well as sources of olive oils. This role has yet to be fully validated in humans. Minor components of olive oil have been shown to be involved in atherosclerosis protection. Nevertheless, evidence of the potential of isolated compounds or the right combination of them to achieve the antiatherosclerotic effect of virgin olive oil is inconclusive and will undoubtedly require further experimental support. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the extent of westernization of lifestyle on the progression of preclinical atherosclerosis in Japanese subjects.

PubMed

Egusa, Genshi; Watanabe, Hiroshi; Ohshita, Kayo; Fujikawa, Rumi; Yamane, Kiminori; Okubo, Masamichi; Kohno, Nobuoki

2002-01-01

To clarify the influence of a westernized lifestyle on the risk factors for atherosclerosis and preclinical atherosclerosis in Japanese subjects, we surveyed a Japanese population and Japanese immigrants in the United States. Based on the extent of westernization of their lifestyle, the subjects were classified as Japanese (J), first generation Japanese-Americans (JA-I), and second or later generation Japanese-Americans (JA-II). The consumption of animal fat and simple carbohydrates increased in the order of J, JA-I, and JA-II, while the subjects with strenuous physical activity decreased in the same order. The waist-hip ratio, fasting insulin level, serum cholesterol and triglyceride levels, and prevalence of hypertension increased in the same order as the dietary changes. The carotid intima-media wall thickness and the plaque size, which are indices of preclinical atherosclerosis, also increased in the order of J, JA-I, and JA-II. These data indicate that a westernized lifestyle aggravates the risk factors for atherosclerosis and influences the progression of preclinical atherosclerosis, in correspondence with the extent of westernization.

Transformation of Discourse: Multilingual Resources and Practices among Filipino Mothers in Japan

ERIC Educational Resources Information Center

Takeuchi, Miwa

2016-01-01

Family language practice can be significantly influenced by social, historical, and political contexts, especially in immigrant households where a society's minority languages are used. Set in a large city in Japan, this study examines how institutional power can affect Filipino mothers' language use at home. Drawing from the cultural historical…

Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

PubMed Central

Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

2012-01-01

Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

Characteristics of an external employee assistance programme in Japan.

PubMed

Muto, Takashi; Fujimori, Yuiko; Suzuki, Keiko

2004-12-01

Mental health care is now a major occupational health issue in Japan. Although realizing effective use of external employee assistance programmes (EAPs) has been identified as crucial for mental health care, few scientific papers describe or analyse the characteristics of EAPs in Japan. This study sought to clarify the characteristics of an external EAP in Japan. The characteristics of an external EAP were clarified in terms of programme description and utilization. A total of 10,260 counselling sessions from 1996 to 2000 were used for utilization analysis. The EAP studied had contracts with 133 organizations, half of which were health insurance societies. The EAP provided employees and family members with free, confidential counselling. Annual mean utilization rate per 1000 individuals increased from 1.3 in 1996 to 2.7 in 2000. Less than one-third of counselling sessions were for work-related mental health issues, and male users (30%) consulted significantly more often than female users (14%) for such problems. Among men, career development issues were most common, while job dissatisfaction was highest among women. Absenteeism, depression and fatigue were the most frequently observed problems in both sexes. EAP use in Japan is rising. The majority of its use is for non-work-related health issues. Male users were more likely to consult for work-related mental health problems.

ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

PubMed

Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

2015-06-01

Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

MicroRNAs and lipoproteins: a connection beyond atherosclerosis?

PubMed Central

Norata, Giuseppe Danilo; Sala, Federica; Catapano, Alberico Luigi; Fernández-Hernando, Carlos

2014-01-01

MicroRNAs (miRNAs) are involved in the pathogenesis of a number of cardiovascular diseases. In this review article, we have summarized the role of miRNAs in regulating lipid metabolism and how their therapeutical inhibition may lead to new approaches to treat cardiometabolic diseases, including atherosclerosis and metabolic syndrome. Specific miRNAs, such as miR-33a and -33b, represent one of the most interesting and attractive targets for metabolic-related disorders and anti-miR33 approaches are under intensive investigation. In addition to miR-33, other miRNAs, including miR-122, are also emerging as key players in lipid metabolism. More recently miRNAs were shown to exert their activities in a paracrine manner and also systemically. The latter is possible due to lipid-carriers, including lipoproteins, that transport and protect miRNAs from degradation. The emerging strong connection between miRNAs, lipoproteins and lipid metabolism indicates the existence of a reciprocal modulation that might go beyond atherosclerosis. PMID:23260873

Chronic heart failure in Japan: implications of the CHART studies.

PubMed

Shiba, Nobuyuki; Shimokawa, Hiroaki

2008-01-01

The prognosis of patients with chronic heart failure (CHF) still remains poor, despite the recent advances in medical and surgical treatment. Furthermore, CHF is a major public health problem in most industrialized countries where the elderly population is rapidly increasing. Although the prevalence and mortality of CHF used to be relatively low in Japan, the disorder has been markedly increasing due to the rapid aging of the society and the Westernization of lifestyle that facilitates the development of coronary artery disease. The Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-1 study was one of the largest cohorts in Japan. The study has clarified the characteristics and prognosis of Japanese patients with CHF, demonstrating that their prognosis was similarly poor compared with those in Western countries. However, we still need evidence for the prevention and treatment of CHF based on the large cohort studies or randomized treatment trials in the Japanese population. Since the strategy for CHF management is now changing from treatment to prevention, a larger-size prospective cohort, called the CHART-2 study, has been initiated to evaluate the risk factors of CHF in Japan. This review summarizes the current status of CHF studies in Japan and discusses their future perspectives.

Current research on chronic active Epstein-Barr virus infection in Japan.

PubMed

Fujiwara, Shigeyoshi; Kimura, Hiroshi; Imadome, Ken-ichi; Arai, Ayako; Kodama, Eiichi; Morio, Tomohiro; Shimizu, Norio; Wakiguchi, Hiroshi

2014-04-01

Epstein-Barr virus (EBV) infection is usually asymptomatic and persists lifelong. Although EBV-infected B cells have the potential for unlimited proliferation, they are effectively removed by the virus-specific cytotoxic T cells, and EBV-associated lymphoproliferative disease develops only in immunocompromised hosts. Rarely, however, individuals without apparent immunodeficiency develop chronic EBV infection with persistent infectious mononucleosis-like symptoms. These patients have high EBV-DNA load in the peripheral blood and systemic clonal expansion of EBV-infected T cells or natural killer (NK) cells. Their prognosis is poor with life-threatening complications including hemophagocytic lymphohistiocytosis, organ failure, and malignant lymphomas. The term "chronic active EBV infection" (CAEBV) is now generally used for this disease. The geographical distribution of CAEBV is markedly uneven and most cases have been reported from Japan and other East Asian countries. Here we summarize the current understanding of CAEBV and describe the recent progress of CAEBV research in Japan. © 2014 Japan Pediatric Society.

Regressing Atherosclerosis by Resolving Plaque Inflammation

DTIC Science & Technology

2017-07-01

Atherosclerosis is a chronic inflammatory disease that develops in the setting of hyperlipidemia, with progression a consequence of the failure to...measured in distilled water because of the increased ionic strength on the surface of NPs in PBS solution [29]. In contrast, NPs(550) with a lipid-PEG...J.A. is a recipient of a Scientist Development Grant from the American Heart Association (16SDG27550012). A.M. was supported by an NYU training

The Role of Education in Reinforcing the Group Model in Japanese Society.

ERIC Educational Resources Information Center

Collins, Kevin

Many attempts have been made to explain how modern Japan has, with speed and minimal stress, become competitive with Western nations in terms of military strength and industrial productivity. One factor commonly mentioned is the "groupishness," the collective orientation,that is basic to Japanese society. Some research has suggested that…

Citrullus lanatus `Sentinel' (Watermelon) Extract Reduces Atherosclerosis in LDL Receptor Deficient Mice

PubMed Central

Poduri, Aruna; Rateri, Debra L.; Saha, Shubin K.; Saha, Sibu; Daugherty, Alan

2012-01-01

Watermelon (Citrullus lanatus or C. lanatus) has many potentially bioactive compounds including citrulline, which may influence atherosclerosis. In this study, we determined the effects of C. lanatus, provided as an extract of the cultivar `sentinel', on hypercholesterolemia-induced atherosclerosis in mice. Male LDL receptor deficient mice at 8 weeks old were given either C. lanatus `sentinel' extract (2% vol/vol; n=10) or a mixture of matching carbohydrates (2% vol/vol; n=8) as the control in drinking water, while fed a saturated fat-enriched diet for 12 weeks ad libitum. Mice consuming C. lanatus `sentinel' extract had significantly increased plasma citrulline concentrations. Systolic blood pressure was comparable between the two groups. Consumption of C. lanatus `sentinel' extract led to lower body weight and fat mass without influencing lean mass. There were no differences in food and water intake, and urine output between the two groups. C. lanatus `sentinel' extract administration decreased plasma cholesterol concentrations that were attributed to reductions of intermediate/low density lipoprotein cholesterol. Plasma concentrations of MCP-1 and IFN-γ were decreased and IL-10 increased in mice consuming C. lanatus `sentinel' extract. Intake of C. lanatus `sentinel' extract resulted in reductions of atherosclerosis in both aortic arch and thoracic regions. In conclusion, consumption of C. lanatus `sentinel' extract led to reduced body weight gain, decreased plasma cholesterol concentrations, improved homeostasis of pro- and anti-inflammatory cytokines, and attenuated development of atherosclerosis without affecting systolic blood pressure in hypercholesterolemic mice. PMID:22902326

17-β Estradiol reduces atherosclerosis without exacerbating lupus in ovariectomized systemic lupus erythematosus-susceptible LDLr(-/-) mice.

PubMed

Shelton, K A; Cline, J M; Cann, J A

2013-04-01

To test the hypothesis that estrogen treatment in a radiation chimera mouse model of systemic lupus erythematosus (SLE) and atherosclerosis will increase SLE-associated atherosclerosis by increasing autoantibody production and inflammation. We used a radiation chimera mouse model in which bone marrow from the polygenic B6.Sle1.2.3 model of SLE was transferred to the low density lipoprotein receptor knock out (LDLr(-/-)) model of atherosclerosis on a C57BL/6 background (Sle/LDLr(-/-)). Ovariectomized chimeric mice were treated for 10 weeks with either 5.6 μg/day of 17β-estradiol or placebo; outcomes included atherosclerosis plaque size, anti-dsDNA autoantibody production and renal pathology. Mean atherosclerosis plaque size was 67.4 ± 7.6% smaller in the estrogen treated group (p < 0.0001). Estrogen treated Sle/LDLr(-/-) mice had no significant difference in serum cholesterol concentration, lipoprotein distribution, anti-dsDNA autoantibody concentration, antibody isotype concentration and renal histopathology score compared to placebo. However, they had significantly lower mean urine protein to urine creatinine ratio (UP:UC). There was no correlation between atherosclerosis lesion size and either the renal histology score or UP:UC ratio in Sle/LDLr(-/-) mice. These results indicate that 17β-estradiol is atheroprotective within the context of murine SLE independent of changes in serum cholesterol concentration, autoantibody concentration, or renal pathology. The SLE phenotype in Sle/LDLr(-/-) mice is not exacerbated by exogenous 17β-estradiol administration, and the reduced UP:UC ratio suggests a protective effect against lupus nephritis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Observations on the State of Indigenous Human Rights in Light of the UN Declaration on the Rights of Indigenous Peoples: Japan

ERIC Educational Resources Information Center

Cultural Survival, 2008

2008-01-01

Over the past 20 years, Japan has taken legislative and symbolic steps to recognize the Ainu as an indigenous people and to eliminate state-sanctioned racial discrimination. But the Ainu still experience discrimination from other sectors of society as a result of Japan's mono-cultural national identity, and the lack of judicial remedies to respond…

The role of fibroblast growth factor 21 in atherosclerosis.

PubMed

Kokkinos, John; Tang, Shudi; Rye, Kerry-Anne; Ong, Kwok Leung

2017-02-01

The metabolic properties of the endocrine fibroblast growth factor 21 (FGF21) have been extensively studied in the past decade. Previous studies have demonstrated the lipid-lowering, anti-inflammatory and anti-oxidant properties of FGF21. FGF21 is mainly secreted in the liver and adipose tissue in response to a range of physiological and pathological stimuli. In animal and in vitro studies, FGF21 has been shown to improve lipid profiles and inhibit key processes in the pathogenesis of atherosclerosis. It exerts its effects on the cardiovascular system via adiponectin dependent and independent mechanisms. However, the signalling pathways by which FGF21 exerts its effects on endothelial cells remains unknown and needs to be further investigated. The elevation of circulating FGF21 levels in cardiovascular disease has also raised questions as to whether FGF21 can be used as a biomarker to predict subclinical atherosclerosis and cardiovascular events. Recent findings from population studies must be validated in independent cohorts before FGF21 can be used as a biomarker in the clinical setting. The anti-atherosclerotic effects of FGF21 have been investigated in two recent clinical trials, where treatment with an FGF21 analog significantly improved the cardiometabolic profile in obese patients with type 2 diabetes. This review will evaluate recent advances that suggest there may be a role for FGF21 in atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Interleukins and atherosclerosis: a dysfunctional family grows.

PubMed

Spears, Larry D; Razani, Babak; Semenkovich, Clay F

2013-11-05

Atherosclerosis is driven by the release of cytokines from macrophages, and the β isoform of interleukin-1 (IL-1β) is a prime suspect in disease progression. Freigang et al. (2013) now suggest that IL-1α, a close relative, is selectively induced by fatty acids independent of the inflammasome to promote vascular inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

Neurosurgery certification in member societies of the World Federation of Neurosurgical Societies: Asia.

PubMed

Gasco, Jaime; Braun, Jonathan D; McCutcheon, Ian E; Black, Peter M

2011-01-01

To objectively compare the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies. This study centers in continental Asia. We provide here an analysis based on the responses provided to a 13-item survey. The data received were analyzed, and three Regional Complexity Scores (RCS) were designed. To compare national board experience, eligibility requirements for access to the certification process, and the obligatory nature of the examinations, an RCS-Organizational score was created (20 points maximum). To analyze the complexity of the examination, an RCS-Components score was designed (20 points maximum). The sum of both is presented in a Global RCS score. Only those countries that responded to the survey and presented nationwide homogeneity in the conduction of neurosurgery examinations could be included within the scoring system. In addition, a descriptive summary of the certification process per responding society is also provided. On the basis of the data provided by our RCS system, the highest global RCS was achieved by South Korea and Malaysia (21/40 points) followed by the joint examination of Singapore and Hong-Kong (FRCS-Ed) (20/40 points), Japan (17/40 points), the Philippines (15/40 points), and Taiwan (13 points). The experience from these leading countries should be of value to all countries within Asia. Copyright © 2011 Elsevier Inc. All rights reserved.

Heparin Cofactor II in Atherosclerotic Lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study

PubMed Central

Rau, Jill C.; Deans, Carolyn; Hoffman, Maureane R.; Thomas, David B.; Malcom, Gray T.; Zieske, Arthur W.; Strong, Jack P.; Koch, Gary G.; Church, Frank C.

2009-01-01

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma. PMID:19747479

β-arrestins Regulate Atherosclerosis and Neointimal Hyperplasia by Controlling Smooth Muscle Cell Proliferation and Migration

PubMed Central

Kim, Jihee; Zhang, Lisheng; Peppel, Karsten; Wu, Jiao-Hui; Zidar, David A.; Brian, Leigh; DeWire, Scott M.; Exum, Sabrina T.; Lefkowitz, Robert J.; Freedman, Neil J.

2009-01-01

Atherosclerosis and arterial injury-provoked neointimal hyperplasia involve medial smooth muscle cell (SMC) proliferation and migration into the arterial intima. Because many 7-transmembrane and growth factor receptors promote atherosclerosis, we hypothesized that the multifunctional adaptor proteins β-arrestin1 and -2 might regulate this pathologic process. Deficiency of β-arrestin2 in ldlr-/- mice reduced aortic atherosclerosis by 40%, and decreased the prevalence of atheroma SMCs by 35%—suggesting that β-arrestin2 promotes atherosclerosis through effects on SMCs. To test this potential atherogenic mechanism more specifically, we performed carotid endothelial denudation in congenic WT, β-arrestin1-/-, and β-arrestin2-/- mice. Neointimal hyperplasia was enhanced in β-arrestin1-/- mice, and diminished in β-arrestin2-/- mice. Neointimal cells expressed SMC markers and did not derive from bone marrow progenitors, as demonstrated by bone marrow transplantation with GFP-transgenic cells. Moreover, the reduction in neointimal hyperplasia seen in β-arrestin2-/- mice was not altered by transplantation with either WT or β-arrestin2-/- bone marrow cells. After carotid injury, medial SMC ERK activation and proliferation were increased in β-arrestin1-/- and decreased in β-arrestin2-/- mice. Concordantly, thymidine incorporation, ERK activation and migration evoked by 7-transmembrane receptors were greater than WT in β-arrestin1-/- SMCs, and less in β-arrestin2-/- SMCs. Proliferation was less than WT in β-arrestin2-/- SMCs, but not in β-arrestin2-/- endothelial cells. We conclude that β-arrestin2 aggravates atherosclerosis through mechanisms involving SMC proliferation and migration, and that these SMC activities are regulated reciprocally by β-arrestin2 and β-arrestin1. These findings identify inhibition of β-arrestin2 as a novel therapeutic strategy for combating atherosclerosis and arterial restenosis after angioplasty. PMID:18519945

An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA).

PubMed

Liang, C Jason; Budoff, Matthew J; Kaufman, Joel D; Kronmal, Richard A; Brown, Elizabeth R

2012-07-02

Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

Preclinical carotid atherosclerosis in patients with rheumatoid arthritis.

PubMed

Roman, Mary J; Moeller, Elfi; Davis, Adrienne; Paget, Stephen A; Crow, Mary K; Lockshin, Michael D; Sammaritano, Lisa; Devereux, Richard B; Schwartz, Joseph E; Levine, Daniel M; Salmon, Jane E

2006-02-21

Rheumatoid arthritis is associated with increased morbidity and mortality because of cardiovascular disease, independent of traditional risk factors. To determine the prevalence of preclinical atherosclerosis in patients with rheumatoid arthritis and to identify clinical and biological markers for atherosclerotic disease in this patient population. Matched, cross-sectional study. Hospital for Special Surgery in New York City. 98 consecutive outpatients with rheumatoid arthritis who were followed by rheumatologists and 98 controls matched on age, sex, and ethnicity. Cardiovascular risk factor ascertainment and carotid ultrasonography in all participants; disease severity, disease treatment, and inflammatory markers in patients with rheumatoid arthritis. Despite a more favorable risk factor profile, patients with rheumatoid arthritis had a 3-fold increase in carotid atherosclerotic plaque (44% vs. 15%; P < 0.001). The relationship between rheumatoid arthritis and carotid atherosclerotic plaque remained after accounting for age, serum cholesterol levels, smoking history, and hypertensive status; adjusted predicted prevalence was 7.4% (95% CI, 3.4% to 15.2%) for the control group and 38.5% (CI, 25.4% to 53.5%) for patients with rheumatoid arthritis. Age (P < 0.001) and current cigarette use (P < 0.014) were also significantly associated with carotid atherosclerotic plaque. Among patients with rheumatoid arthritis, atherosclerosis was related to age, hypertension status, and use of tumor necrosis factor-alpha inhibitors (a possible marker of disease severity). The study had a cross-sectional design, and inflammatory markers were determined only once. Patients with rheumatoid arthritis have a high prevalence of preclinical atherosclerosis independent of traditional risk factors, suggesting that chronic inflammation and, possibly, disease severity are atherogenic in this population.

Science as a Matter of Honour: How Accused Scientists Deal with Scientific Fraud in Japan.

PubMed

Pellegrini, Pablo A

2017-06-26

Practices related to research misconduct seem to have been multiplied in recent years. Many cases of scientific fraud have been exposed publicly, and journals and academic institutions have deployed different measures worldwide in this regard. However, the influence of specific social and cultural environments on scientific fraud may vary from society to society. This article analyzes how scientists in Japan deal with accusations of scientific fraud. For such a purpose, a series of scientific fraud cases that took place in Japan has been reconstructed through diverse sources. Thus, by analyzing those cases, the social basis of scientific fraud and the most relevant aspects of Japanese cultural values and traditions, as well as the concept of honour which is deeply involved in the way Japanese scientists react when they are accused of and publicly exposed in scientific fraud situations is examined.

Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp; Seko, Ayumi; Sonoda, Akinaga

2008-03-15

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atheroscleroticmore » light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.« less

Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans.

PubMed

Castillo-Richmond, A; Schneider, R H; Alexander, C N; Cook, R; Myers, H; Nidich, S; Haney, C; Rainforth, M; Salerno, J

2000-03-01

African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary heart disease risk factors and cardiovascular mortality in African Americans. B-mode ultrasound is useful for the noninvasive evaluation of carotid atherosclerosis. This randomized controlled clinical trial evaluated the effects of the TM program on carotid IMT in hypertensive African American men and women, aged >20 years, over a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects completed pretest and posttest carotid IMT data. The assigned interventions were either the TM program or a health education group. By use of B-mode ultrasound, mean maximum IMT from 6 carotid segments was used to determine pretest and posttest IMT values. Regression analysis and ANCOVA were performed. Age and pretest IMT were found to be predictors of posttest IMT values and were used as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038, 2-tailed). Stress reduction with the TM program is associated with reduced carotid atherosclerosis compared with health education in hypertensive African Americans. Further research with this stress-reduction technique is warranted to confirm these preliminary findings.

Genetic evidence supporting a critical role of endothelial caveolin-1 during the progression of atherosclerosis

PubMed Central

Fernández-Hernando, Carlos; Yu, Jun; Suárez, Yajaira; Rahner, Christoph; Dávalos, Alberto; Lasunción, Miguel A.; Sessa, William C.

2009-01-01

SUMMARY The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis. PMID:19583953