• Title/Summary/Keyword: cause of disease and pathogenesis

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Inhibition of ER Stress by 2-Aminopurine Treatment Modulates Cardiomyopathy in a Murine Chronic Chagas Disease Model

  • Ayyappan, Janeesh Plakkal;lizardo, Kezia;Wang, Sean;Yurkow, Edward;Nagajyothi, Jyothi F
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.386-394
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    • 2019
  • Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

The Literature Study Medical History of Medieval Obstetrics and Gynecology (중세(中世) 부산과(婦産科)의 의사학적(醫史學的) 연구(硏究))

  • Cho, Myun-Hwi;Park, Hyun-Kuk
    • The Journal of Dong Guk Oriental Medicine
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    • v.5
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    • pp.231-271
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    • 1996
  • Obstetrics and Gynecology include gynecology which is concerned with the treatment for the disease based on physiology and pathology of women, and obstetrics which is concerned with pregnancy delivery. These obstetics and gynecology can be said to date from the birth of human beings. This paper has carried on the studies about the generating and developing process of obstetics and gynecology. The results of this study are as follows : Distinction in Northern and Southern Dynasties were much more Obstetrics and Gynecology studying the Obstetrics and Gynecology books in that time, the study about "oncosis" (腫瘤) and forms of drug, pill, powder, pIaster were carried on. The highest distinction in Sui age were research and development on pathogenesis and cause of disease about Obstetrics and Gynecology disease and it was appeared representatively in "Zhubingyuanhoulun""諸病源候論" which was special book on cause of disease and pathogenesis and syndrome, And it was explained about abnormal vaginal discharge in this book. Obstetrics and Bynecology were developed on theory and clincis in Tang age when "Taiyshu"(太醫暑) was established. "Taiyshu"(太醫暑) taked complete charge of medical operation and education, published much excellent Obstetrics and Gynecology books than the past. Among them specially "Qianjinyaofang""千金要方" explained Obstetrics and Gynecology matter first in three volumes and "Qianjinyifang""千金翼方" explained this matter first in four volumes. This point indicate that Obstetrics and Gynecology's importance was established in Tang age, so Obstetrics and Gynecology's developmental history, Song age was the acme period. "Taiyju"(太醫局) was established in "xining""熙?" 9 year and Obstetrics belonged to one of nine departments under "Taiyun"(太醫局), so Obstetrics and Gynecology was separated from the other medical parts and it was prepared of it's progressing bases independently and appeared of changes in quality and increase in quantity about theory and prescription of Obstetrics and Gynecology, specially determination of treatment based on the differentiation of symptoms and sighs was taked a serious view. Besides four great physicians in Jing and Yuan dynasies diversified Obstetrics and Gynecology contents through their only medical theory and clinical treatment.

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Non-Fibrillar $\beta$-Amyloid Exerts Toxic Effect on Neuronal Cells

  • Kim, Hyeon-Jin;Hong, Seong-Tshool
    • Animal cells and systems
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    • v.5 no.2
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    • pp.139-143
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    • 2001
  • Alzheimer's disease is the most common form of dementia and no cure is known so far. Extensive genetic works and in vitro experiments combined with clinical observations link amyloid $\beta$--protein (A$\beta$-) to the pathogenesis of Alzheimer's disease (AD). It was hypothesized that $A\beta$- becomes toxic when it adopts a fibrillar conformation. Recently, non-fibrillar form of $A\beta$- was observed and the potential role in the pathogenesis of AD became an interesting subject. In this study, the cytotoxicity of non-fibrillar $A\beta$- and fibrillar $A\beta$- was compared on oxidative stress, membrane damage, or nucleosome break down. Non-fibrillar $A\beta$- was not toxic in peripheral nervous system-derived cells but significantly toxic in central nervous system-derived cells while fibrillar $A\beta$- was non-selectively toxic in both cell culture. The neurotoxicity of non-fibrillar $A\beta$- was reproduced in semi-in vivo culture of mouse brain slice. In conclusion, non-fibrillar $A\beta$- could be more relevant to the selective neurodegeneration in Alzheimer's brains than fibrillar $A\beta$- and further research needs to be done for identification of the cause of AD.

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Developing Questionnaire for Pathogenesis Analysis of Pyungweesan Symptom (평위산증(平胃散證)의 병인논적(病因論的) 분석(分析)을 위한 설문문항(說問問項) 개발(開發))

  • Lim, Jun-Sung;Park, Young-Bae;Lee, Sang-Chul;Oh, Hwan-Sup
    • The Journal of the Society of Korean Medicine Diagnostics
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    • v.11 no.1
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    • pp.72-81
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    • 2007
  • Background & Objective: Pathogenesis treats cause of disease. pyungweesan is pathogenesis prescription of indigestion. prescription has been determined subjectively because there is no standardized prescription. so this study developed questionnaire for a objective and standardized prescription. Method: To determine objective pyungweesan prescription, 24 items of questionnaire are researched two times by delphi method. The questionnaire is selected through 5 reference book and opinions of korean medical doctor. Result: By delphi method and average value, 20 items of questionnaire are chosen. Conclusions: This study becomes basic data for a profound research henceforth. The questionnaire will be developed through being verified by korean medical doctor clinically.

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The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease

  • Nurwidya, Fariz;Damayanti, Triya;Yunus, Faisal
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.1
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    • pp.5-13
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    • 2016
  • Chronic obstructive pulmonary disease (COPD) is a chronic and progressive inflammatory disease of the airways and lungs that results in limitations of continuous airflow and is caused by exposure to noxious gasses and particles. A major cause of morbidity and mortality in adults, COPD is a complex disease pathologically mediated by many inflammatory pathways. Macrophages, neutrophils, dendritic cells, and CD8+ T-lymphocytes are the key inflammatory cells involved in COPD. Recently, the non-coding small RNA, micro-RNA, have also been intensively investigated and evidence suggest that it plays a role in the pathogenesis of COPD. Here, we discuss the accumulated evidence that has since revealed the role of each inflammatory cell and their involvement in the immunopathogenesis of COPD. Mechanisms of steroid resistance in COPD will also be briefly discussed.

Update on Non-alcoholic Fatty Liver Disease in Children (소아 비알코올성 지방간의 최신 지견)

  • Lee, Kyung-Hun
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.12 no.sup1
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    • pp.62-71
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    • 2009
  • Non-alcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease. Similar to NAFLD in adults, NAFLD in children is associated with obesity and insulin resistance and requires liver histology for diagnosis and staging. However, significant histological differences exist between adult and pediatric NAFLD. The rise in childhood obesity has been accompanied by an increase in pediatric NAFLD. Age, gender and race/ethnicity are significant determinants of risk, and sex hormones, insulin sensitivity and adipocytokines are implicated in the pathogenesis of pediatric NAFLD. There is no consensus for treatment of NAFLD, however, data suggest that diet, exercise and some pharmacological therapies may be of benefit. To evaluate and effectively treat pediatric NAFLD, the pathophysiology and natural history of the disease should be clarified and non-invasive methods for screening, diagnosis, and longitudinal assessment developed.

Stem Cells and Cell-Cell Communication in the Understanding of the Role of Diet and Nutrients in Human Diseases

  • Trosko James E.
    • Journal of Food Hygiene and Safety
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    • v.22 no.1
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    • pp.1-14
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    • 2007
  • The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

Study on Comparison and Mutual Complementary Development between Sasang Constitutional Medicine and Syndrome Identification and Treatment Medicine (사상체질의학(四象體質醫學)과 증치의학(證治醫學)의 비교(比較) 및 상호(相互) 보완(補完) 방안(方案) 연구(硏究))

  • Kim, Myoung;Choi, Na-Rae;Oh, Seoung-Yun;Joo, Jong-Cheon
    • Journal of the Korean Institute of Oriental Medical Informatics
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    • v.21 no.2
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    • pp.11-23
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    • 2015
  • Objectives : Through a comparative study between Sasang constitutional medicine and Syndrome identification and treatment medicine about the theory of diagnosis, the theory of herbal medicine, the theory of prescription, the theory of acupuncture and constitutional medicine to put forward a complementary perfect solution which has good clinical utility. Methods : We compared and sorted out the textbook of Korean Sasang constitutional medicine which named Sasang medicine, and also the textbook of Chinese TCM which was including Basic theory of TCM, Diagnostics of TCM, Science of Chinese materia medica, Pharmacology of traditional Chinese medical formulae, Science of acupuncture and moxibustion, Constitution of TCM, and also related papers. Results : (1) Through a comparative study between Sasang constitutional medicine and Syndrome identification and treatment medicine about diagnosis, herbal medicine, prescription and acupuncture, Sasang constitutional medicine is a medical system which gives priority to balance of organs, when Syndrome identification and treatment medicine is a medical system that gives priority to improve symptom. (2) The prescriptions of Sasang constitutional medicine are used for the treatment of basic pathogenesis in the chronic stage of the disease, which can recover vital qi, when Syndrome identification and treatment medicine are used for the treatment of stage pathogenesis in the acute stage of the disease, which can get rid of pathogenic factors. (3) There are two kind of complementary perfect solution between Sasang constitutional medicine and Syndrome identification and treatment medicine. One perfect complementary medicine is that Sasang constitutional medicine plays a major role when Syndrome identification and treatment medicine plays a supporting role. The other one is that Syndrome identification and treatment medicine plays a major role when Sasang constitutional medicine plays a supporting role. It determined by the usual symptoms and the symptoms now, vital qi and pathogenic factors, symptom and the root cause, acute stage and chronic stage, and the state of pathogenesis. Conclusion : A new perfect complementary medicine can be created which is based on the setting that Sasang constitutional medicine primarily treat the usual symptoms, vital qi, the root cause, chronic stage and basic pathogenesis when Syndrome identification and treatment medicine primarily treat the symptoms now, pathogenic factors, symptom, acute stage and stage pathogenesis.

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The Evolving Epidemiology of Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Strains Isolated from Adults in Crete, Greece, 2009-2016

  • Maraki, Sofia;Mavromanolaki, Viktoria Eirini;Stafylaki, Dimitra;Hamilos, George;Samonis, George
    • Infection and chemotherapy
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    • v.50 no.4
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    • pp.328-339
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    • 2018
  • Background: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009-2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). Materials and Methods: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ${\geq}2$ non-${\beta}$-lactam antimicrobials. Results: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. Conclusion: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

Review of a novel disease entity, immunoglobulin G4-related disease

  • Maehara, Takashi;Moriyama, Masafumi;Nakamura, Seiji
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.46 no.1
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    • pp.3-11
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    • 2020
  • Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.