WorldWideScience

Sample records for disease pathogenesis prevention

  1. Renal stone disease: Pathogenesis, prevention, and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Pak, C.Y.C.

    1987-01-01

    This book contains 10 chapters. Some of the chapter titles are: Radiologic considerations; Physiochemistry of urinary stone formations; Nutritional aspects of stone disease; Prevention of recurrent nephrolithiasis; Struvite stones; and Contemporary approaches to removal of renal and ureteral calculi.

  2. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters.

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    Hammerbeck, Christopher D; Brocato, Rebecca L; Bell, Todd M; Schellhase, Christopher W; Mraz, Steven R; Queen, Laurie A; Hooper, Jay W

    2016-07-15

    Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are

  3. Nutritional rickets: pathogenesis and prevention.

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    Pettifor, John M

    2013-06-01

    Nutritional rickets remains a public health concern in many areas of the world despite cheap and effective means of preventing the disease. The roles of vitamin D deficiency, low dietary calcium intakes and the interrelationships between the two in the pathogenesis of the disease are discussed. It is now recognized that vitamin D deficiency in the pregnant and lactating mother predisposes to the development of rickets in the breastfed infant, and that cultural and social factors are important in the pathogenesis of the disease during the adolescent growth spurt. Prevention of rickets is dependent on the awareness of the medical profession and the general public of the need to ensure adequate intakes of vitamin D in at-risk populations, and of the importance of increasing dietary intakes of calcium using locally available and inexpensive foods in communities in which dietary calcium deficiency rickets is prevalent.

  4. [Pseudomembranous colitis: pathogenesis, prevention, treatment].

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    Zakharova, N V; Fil', T S

    2013-01-01

    The article reviews a pathogenesis of Pseudomembranous colitis. Questions of prevention and treatment of Clostridium difficile--associated diarrhea are shown by the Evidence-based medicine. There is an accent on the rational prescription of antibiotics.

  5. Type 1 diabetes pathogenesis - Prevention???

    Directory of Open Access Journals (Sweden)

    C S Muralidhara Krishna

    2015-01-01

    Full Text Available Pathogenesis of type 1 diabetes is multi-faceted, including, autoimmunity, genetics and environment. Autoimmunity directed against pancreatic islet cells results in slowly progressive selective beta-cell destruction ("Primary autoimmune insulitis", culminating over years in clinically manifested insulin-dependent diabetes mellitus (IDDM. Circulating serum autoantibodies directed against the endocrine cells of the islets of Langerhans (Islet cell autoantibodies - ICAb are an important hallmark of this disease. Assays for islet cell autoantibodies have facilitated the investigation and understanding of several facets in the pathogenesis of autoimmune diabetes. Their applications have extended into clinical practice and have opened new avenues for early preclinical prediction and preventive prophylaxis in IDDM/type 1 DM. Recently, surprisingly, differences in insulin content between T1DM islets, as well as, ′patchy′ or ′lobular′ destruction of islets have been described. These unique pathobiological phenomena, suggest that beta cell destruction may not always be inexorable and inevitably complete/total, and thus raise hopes for possible therapeutic interruption of beta cell autoimmunity - destruction and cure of type 1 diabetes. "Recurrent or secondary autoimmune insulitis" refers to the rapid reappearance of islet cell autoantibodies post pancreas transplant, and selective islet beta cell destruction in the grafted pancreas [never forgetting or "anamnestic" beta cell destructive memory], in the absence of any graft pancreas rejection [monozygotic twin to twin transplantation]. The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The putative predisposing factors are viruses, gluten and cow′s milk. The putative protective factors include gut flora, helminths, viral infections, and Vitamin D. Prevention of T1DM can include: Primary prevention strategies

  6. Pathogenesis and preventive treatment for animal disease due to locoweed poisoning.

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    Chenchen, Wu; Wenlong, Wang; Xiaoxue, Liu; Feng, Ma; Dandan, Cao; Xiaowen, Yang; Shanshan, Wang; Pengshuai, Geng; Hao, Lu; Baoyu, Zhao

    2014-01-01

    Locoweeds are perennial herbaceous plants included in Astragalus spp. and Oxytropis spp. that contain the toxic indolizidine alkaloid swainsonine. The livestock that consume locoweed feeding can suffer from a type of toxicity called "locoism." There are aliphatic nitro compounds, selenium, selenium compounds and alkaloids in locoweed. The toxic component in locoweeds has been identified as swainsonine, an indolizidine alkaloid. Swainsonine inhibits lysosomal α-mannosidase and mannosidase II, resulting in altered oligosaccharide degradation and incomplete glycoprotein processing. As a result, livestock that consume locoweeds exhibit several symptoms, including dispirited behavior, staggering gait, chromatopsia, trembling, ataxia, and cellular vacuolar degeneration of most tissues by pathological observation. Locoism results in significant annual economic losses. Recently, locoweed populations have increased domestically in China and abroad, resulting in an increase in the incidence of poisoning. Therefore, in this paper, we review the current research on locoweed, including on species variation, pathogenesis, damage and poisoning prevention measures. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Inflammatory bowel disease: pathogenesis.

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    Zhang, Yi-Zhen; Li, Yong-Yu

    2014-01-07

    Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas.

  8. [Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment].

    Science.gov (United States)

    Di Munno, Ombretta; Delle Sedie, Andrea

    2006-01-01

    Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO) is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD) is greatest in the first few months of GC use; fracture (Fx) risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34). Bisphosphonates (alendronate, risedronate) are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged > or =65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment.

  9. Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment

    Directory of Open Access Journals (Sweden)

    Andrea Delle Sedie

    2011-09-01

    Full Text Available Glucocorticoids (GC are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD is greatest in the first few months of GC use; fracture (Fx risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34. Bisphosphonates (alendronate, risedronate are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged ³65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment

  10. Early life respiratory infections and asthma development: role in disease pathogenesis and potential targets for disease prevention

    Science.gov (United States)

    Beigelman, Avraham; Bacharier, Leonard B.

    2016-01-01

    Purpose of review To present recent findings and perspectives on the relationship between early life respiratory infections and asthma inception and to discuss emerging concepts on strategies that target these infectious agents for asthma prevention. Recent findings Cumulative evidence supports the role of early life viral infections, especially respiratory syncytial virus and human rhinovirus, as major antecedents of childhood asthma. These viruses may have different mechanistic roles in the pathogenesis of asthma. The airway microbiome and virus-bacteria interactions in early life have emerged as additional determinants of childhood asthma. Innovative strategies for the prevention of these early life infections, or for attenuation of acute infection severity, are being investigated and may identify effective strategies for the primary and secondary prevention of childhood asthma. Summary Early life infections are major determinants of asthma development. The pathway from early life infections to asthma is the result of complex interactions between the specific type of the virus, genetic and environmental factors. Novel intervention strategies that target these infectious agents have been investigated in proof-of-concepts trials, and further study is necessary to determine their capacity for asthma prevention. PMID:26854761

  11. Meningococcal disease: History, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention

    Directory of Open Access Journals (Sweden)

    Manchanda V

    2006-01-01

    Full Text Available Meningoccocal disease has repeatedly caused outbreaks worldwide. There has been sudden surge of cases of meningococcemia and meningococcal meningitis in early 2005 in Delhi, India and neighboring states of Uttar Pradesh and Haryana. As of June 17, 2005, 429 probable cases of meningococcal disease have been reported in Delhi out of which 128 cases have revealed microbiological evidence of Neisseria meningitidis . It is possible that the number of cases was in excess of the numbers notified. During this episode drug susceptibility testing by MIC method (E-test using break points recently recommended by NCCLS/CLSI, revealed that all isolates were sensitive to penicillin, ampicillin, rifampicin and ceftriaxone. As regards to ciprofloxacin, about two third of the isolates tested were found to be ′non-susceptible′ (MIC =0.03µg/mL- 0.190µg/mL. All the isolates were found resistant to cotrimoxazole (MIC> 16µg/mL. Repeated outbreaks, decreased susceptibility to ciprofloxacin, which is commonly used for chemoprophylaxis of meningococcal disease, highlights the need for a constant surveillance system. Present review deals with various aspects of Neisseria meningitidis and meningococcal disease in view of recent episode.

  12. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  13. Huntington disease: pathogenesis and treatment.

    Science.gov (United States)

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment.

  14. Diabetic nephropathy. Pathogenesis and prevention.

    Science.gov (United States)

    Westberg, N G

    1980-01-01

    Already at the time of diagnosis of juvenile onset diabetes mellitus, there are morphological and functional changes in the kidney. The kidneys and the individual glomeruli are considerably enlarged, and the glomerular filtration increased. In experimental diabetes mellitus the metabolism of the glomerular basement membrane is increased. These abnormalities are reversible by meticulous metabolic control. Their relationship to the diabetic glomerulosclerosis that causes uremia twenty to thirty years later is not clear. Carefully analyzed extensive clinical experience confirms that good metabolic control delays the onset of symptomatic diabetic renal disease, as expected from experimental studies. Normalization of even a slightly elevated blood pressure may be important to slow the progression of the renal insufficiency. Better methods for the management of the diabetic state and better education of the patients may be important to postpone the heroic endeavours of renal or pancreatic transplantation or dialysis.

  15. Molecular pathogenesis of Parkinson disease.

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    Eriksen, Jason L; Wszolek, Zbigniew; Petrucelli, Leonard

    2005-03-01

    Parkinson disease (PD), the most common neurodegenerative movement disorder, is characterized by an extensive and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. One of the pathological hallmarks of PD is the presence of Lewy bodies, intracellular inclusions of aggregated alpha-synuclein. Although the cause and pathogenesis of selective loss of dopamine neurons and the accumulation of alpha-synuclein in PD remain elusive, growing lines of evidence from environmental risk factors and early-onset genetics point to a convergence between energy metabolism and the disposal of damaged proteins in the development of PD. These findings suggest that impairments in mitochondrial and ubiquitin-proteasome system function can significantly contribute to the pathogenesis of PD. This review will summarize recent insights gained from genetic and environmental studies of PD that underscore this association.

  16. The early pathogenesis of foot-and-mouth disease

    Science.gov (United States)

    Understanding the early pathogenesis of foot-and-mouth disease (FMD) is of critical importance to ongoing and future efforts to decrease the impact of FMD in endemic regions and prevent incursions to disease-free territories. The importance of the early phase of virus-host interaction lies in two ke...

  17. Autophagy in lung disease pathogenesis and therapeutics

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2015-04-01

    Full Text Available Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  18. GLUCOCORTICOID-INDUCED OSTEOPOROSIS: PATHOGENESIS, PREVENTION, TREATMENT

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    Irina Aleksandrovna Baranova

    2010-06-01

    Full Text Available Osteoporosis (OP is a serious problem to patients who have long taken glucocorticoids. In the past two decade, much knowledge has been accumulated about the epidemiology of the disease and drugs with proven efficacy for its prevention and treatment have emerged. However, a large number of studies suggest that there is a serious shortage in care to patients with glucocorticoid-induced OP, which calls for effective measures to bring the real level of its prevention and treatment in compliance with the current clinical guidelines

  19. GLUCOCORTICOID-INDUCED OSTEOPOROSIS: PATHOGENESIS, PREVENTION, TREATMENT

    Directory of Open Access Journals (Sweden)

    Irina Aleksandrovna Baranova

    2010-01-01

    Full Text Available Osteoporosis (OP is a serious problem to patients who have long taken glucocorticoids. In the past two decade, much knowledge has been accumulated about the epidemiology of the disease and drugs with proven efficacy for its prevention and treatment have emerged. However, a large number of studies suggest that there is a serious shortage in care to patients with glucocorticoid-induced OP, which calls for effective measures to bring the real level of its prevention and treatment in compliance with the current clinical guidelines

  20. The Pathogenesis of Ebola Virus Disease.

    Science.gov (United States)

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  1. Pathogenesis and management of Wilson disease.

    Science.gov (United States)

    Harada, Masaru

    2014-04-01

    Hepatolenticular degeneration, commonly known as Wilson disease, is an autosomal recessive inherited disease of abnormal copper metabolism, characterized by the accumulation of copper in the body due to decreased biliary excretion of copper from hepatocytes. Wilson disease protein, ATP7B, functions in copper excretion into bile and in copper secretion to the bloodstream coupled with ceruloplasmin synthesis. Various kinds of mutations of ATP7B cause Wilson disease. Wilson disease is a rare genetic disease that can be treated pharmacologically. Recognition and prompt diagnosis are very important, because Wilson disease is fatal if left untreated. In this review, I summarize the pathogenesis and management of Wilson disease.

  2. Pathogenesis of Alzheimer′s disease

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    Russell H Swerdlow

    2007-10-01

    Full Text Available Russell H SwerdlowDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, VA, USAAbstract: Alzheimer’s disease (AD is incredibly common. Increasing longevity ensures its prevalence will rise even further. Ongoing efforts to understand AD pathogenesis reveal numerous tantalizing leads. Formulating a comprehensive AD pathogenesis theory capable of incorporating these disparate leads, though, has proven difficult. This review discusses current attempts to formulate a comprehensive AD pathogenesis theory. In doing so, it focuses on clinical and molecular relationships between AD and aging. A better understanding of these relationships could inform and impact future development of AD-directed treatment strategies.Keywords: Alzheimer’s disease, aging, amyloid, cascade, mitochondria

  3. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

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    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

  4. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

    Institute of Scientific and Technical Information of China (English)

    Naiyana Gujral; Hugh J Freeman; Alan BR Thomson

    2012-01-01

    Celiac disease (CD) is one of the most common diseases,resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both bans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical'; In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.

  5. H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

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    Wall, Susan M.; Klein, Janet D.

    2008-09-01

    The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

  6. Inflammatory bowel disease pathogenesis: where are we?

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    Fiocchi, Claudio

    2015-03-01

    Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  7. Alzheimer's Disease: Genes, pathogenesis and risk prediction

    NARCIS (Netherlands)

    K. Sleegers (Kristel); C.M. van Duijn (Cock)

    2001-01-01

    textabstractWith the aging of western society the contribution to morbidity of diseases of the elderly, such as dementia, will increase exponentially. Thorough preventative and curative strategies are needed to constrain the increasing prevalence of these disabling diseases. Better understanding of

  8. Huntingtin processing in pathogenesis of Huntington disease

    Institute of Scientific and Technical Information of China (English)

    Zhenghong QIN; Zhenlun GU

    2004-01-01

    Huntington's disease (HD) is caused by an expansion of the polyglutamine tract in the protein named huntingtin.The expansion of polyglutamine tract induces selective degeneration of striatal projection neurons and cortical pyramidal neurons. The bio-hallmark of HD is the formation of intranuclear inclusions and cytoplasmic aggregates in association with other cellular proteins in vulnerable neurons. Accumulation of N-terminal mutant huntingtin in HD brains is prominent. These pathological features are related to protein misfolding and impairments in protein processing and degradation in neurons. This review focused on the role of proteases in huntingtin cleavage and degradation and the contribution of altered processing of mutant huntingtin to HD pathogenesis.

  9. Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

    Science.gov (United States)

    Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

    2014-01-01

    Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

  10. The pathogenesis of bornaviral diseases in mammals.

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    Tizard, Ian; Ball, Judith; Stoica, George; Payne, Susan

    2016-12-01

    Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.

  11. Modern views on etiology and pathogenesis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    А.V. Kutsak

    2016-12-01

    Full Text Available Aim. To analyze the specialized scientific literature for data generalization concerning current views on etiology and pathogenesis of Parkinson's disease (PD. PD is a chronic progressive CNS disease, mainly associated with degeneration of brain’s dopamine-producing neurons, motor and non-motor violations and resulting in persistent disability. Although the PD is the most studied disease among all parkinsonism disorders, there is no consensus on its nature until now. The basis of PD pathomorphology and neurological degeneration is a violation of a-synuclein protein with Lewy’s bodies accumulation in the cells. The formation of pathological a-synuclein is connected with features of genotype, environmental agents and internal processes in the body. The review presents the current data about etiological and pathogenic mechanisms of PD development. Special attention is paid to the role of genetics, the influence of exogenous agents and the basic factors in the pathogenesis of the disease. Conclusions. A number of questions of PD etiology and pathogenesis are not quite certain for today. Pathogenetic mechanism of degeneration in PD is heterogeneous: mitochondrial dysfunction, oxidative stress, of proteolytic functions violations (ubiquitin-proteasome system. The reasons which start the degenerative process are varied, and can be both external and internal, as well as their interaction also is possible, which determines the probability of PD development. Sporadic forms of PD pathogenesis are noticeably different from disease with hereditary predisposition. Verification of risk factors if genes predisposing to the disease development are present has a key role for the complex preventive measures formation in patients with a predisposition to the disease. Despite the fact that genetics has the primary importance in the process initiation for persons with a family history, varied clinical scenario of PD with the presence of identical genetic

  12. CD40 signaling and Alzheimer's disease pathogenesis.

    Science.gov (United States)

    Town, T; Tan, J; Mullan, M

    2001-01-01

    The interaction between CD40 and its cognate ligand, CD40 ligand, is a primary regulator of the peripheral immune response, including modulation of T lymphocyte activation, B lymphocyte differentiation and antibody secretion, and innate immune cell activation, maturation, and survival. Recently, we and others have identified CD40 expression on a variety of CNS cells, including endothelial cells, smooth muscle cells, astroglia and microglia, and have found that, on many of these cells, CD40 expression is enhanced by pro-inflammatory stimuli. Importantly, the CD40-CD40 ligand interaction on microglia triggers a series of intracellular signaling events that are discussed, beginning with Src-family kinase activation and culminating in microglial activation as evidenced by tumor necrosis factor-alpha secretion. Based on the involvement of microglial activation and brain inflammation in Alzheimer's disease pathogenesis, we have investigated co-stimulation of microglia, smooth muscle, and endothelial cells with CD40 ligand in the presence of low doses of freshly solubilized amyloid-beta peptides. Data reviewed herein show that CD40 ligand and amyloid-beta act synergistically to promote pro-inflammatory responses by these cells, including secretion of interleukin-1 beta by endothelial cells and tumor necrosis factor-alpha by microglia. As these cytokines have been implicated in neuronal injury, a comprehensive model of pro-inflammatory CD40 ligand and amyloid-beta initiated Alzheimer's disease pathogenesis (mediated by multiple CNS cells) is proposed.

  13. 柑橘黄龙病发病机理、症状及防控措施%Citrus Yellow Dragon Disease Pathogenesis, Symptoms and Prevention Measures

    Institute of Scientific and Technical Information of China (English)

    邱志燏; 黄红兰; 舒畅; 邱俊洁

    2015-01-01

    The disease pathogenesis of Citrus Huanglong is that Huanglong pathogen transmits to roots through the vascular bundles, then damages the roots, and causes root rot. The plants cannot discharge metabolic wastes produced from plant circulation disorder from the root, causing lesions. Like a sieve catheter jam, root rot is the direct symptom of Huanglong bacteria harmful to citrus, while the secondary symptom is on citrus canopy. The secondary symptom is caused by a lack of food and water, so, the supplementation of sufficient nutrients and moisture can make the plant back to normal condition. Although the rotten roots cannot be cured, the root will grow, become normal and new roots, making the plant grow normally. Therefore, citrus Huanglong disease and its symptoms on the ground can be cured.%柑橘黄龙病由黄龙病菌通过维管束传输至根,为害根,造成根腐烂,进而导致根不能从土壤中吸收养分和水分,植物代谢废物不能从根系排出,产生植物汁液循环障碍,叶片和果实因缺乏养分和水分而产生病变。根腐烂是黄龙病菌危害柑橘的直接症状,叶片和果实表现为次生症状,次生症状是缺乏养分和水分所致。病发后采取每周喷施“果无缺”加施多元素叶面肥,试验表明,黄龙病黄化叶会转绿,黄龙病青果也会转变为正常果。研究还发现,腐烂的根虽然不能恢复正常,但根还会生长,进而形成正常的新的根系,使植株重新正常生长。

  14. Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants

    DEFF Research Database (Denmark)

    Spratley, Samantha J; Hill, Chris H; Viuff, Agnete H;

    2016-01-01

    Krabbe disease is a severe, fatal neurodegenerative disorder caused by defects in the lysosomal enzyme galactocerebrosidase (GALC). The correct targeting of GALC to the lysosome is essential for the degradation of glycosphingolipids including the primary lipid component of myelin. Over 100 differ...... to bind essential cofactors. The classification of disease pathogenesis presented here provides a molecular framework for appropriate targeting of future Krabbe disease therapies....

  15. [Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy].

    Science.gov (United States)

    Schuppan, Detlef

    2016-07-01

    Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.

  16. Etiology and pathogenesis of Parkinson disease.

    Science.gov (United States)

    Schapira, Anthony H V

    2009-08-01

    The etiology of Parkinson disease (PD) is multifactorial and is likely to involve different causes in different patients. Several different genes have been identified as causes of familial PD, including alpha-synuclein gene mutations and multiplications, and mutations of parkin, PINK1, DJ1, and LRRK2. The biochemical consequences of these mutations have served to reinforce the relevance of the pathways to pathogenesis previously characterized, for example, mitochondrial dysfunction, oxidative stress, and protein misfolding and aggregation. The recognition that glucocerebrosidase mutations represent a significant risk factor for PD has focused attention on lysosomal function and autophagy as relevant to PD. Several environmental factors have also been shown to influence the risk for PD, although odds ratios remain relatively modest. Specific toxins can cause dopaminergic cell death in man and animals, but they probably have limited relevance to the etiology of PD.

  17. [Etiology and pathogenesis of inflammatory bowel diseases].

    Science.gov (United States)

    Lukáš, Milan

    2014-01-01

    Zdenek Mařatka has been the first physician, who had brought a new information for the Czech medical community with topic of inflammatory bowel diseases, which had been systematic studied for him. He had prepared an original theory - two component hypothesis about origin of ulcerative colitis, which had been developed and innovated by him for long time. From the international point of view, Mařatka has had an extraordinary impact and significant contribution for recognition of ulcerative colitis and Crohn´s disease. Despite the fact that the true origin of ulcerative colitis and Crohn´s disease (UC) still remain elusive, basic as well as clinical research bring many new data on etiology and pathogenesis of this inflammatory condition. It seems clear that IBD originate from interaction of several intrinsic and extrinsic factors that contribute individually in a particular patient. Among internal factors the genes play an important role, because its influence on the mucosal immunity system and immunological response. Among the external factors importance are recognized the gut microbiota content, cigarette smoking and psychological stress.

  18. Pathogenesis of Nervous and Mental Diseases in Children.

    Science.gov (United States)

    Harms, Ernest, Ed.

    Major pathogenic sources of mental diseases in children and a classification of these diseases are considered. Contributions include the following: pathogenesis of mental diseases in childhood by Ernest Harms, organ inferiority and psychiatric disorders by Bernard Shulman and Howard Klapman, pathogenesis of neurological disorders by George Gold,…

  19. Research advances in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    WANG Hu

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.

  20. Pathogenesis of hyperinflation in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Gagnon, Philippe; Guenette, Jordan A; Langer, Daniel; Laviolette, Louis; Mainguy, Vincent; Maltais, François; Ribeiro, Fernanda; Saey, Didier

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during progression of the disease.

  1. An update on necrotizing enterocolitis: pathogenesis and preventive strategies

    Directory of Open Access Journals (Sweden)

    Jang Hoon Lee

    2011-09-01

    Full Text Available Necrotizing enterocolitis (NEC is one of the most critical morbidities in preterm infants. The incidence of NEC is 7% in very-low-birthweight infants, and its mortality is 15 to 30%. Infants who survive NEC have various complications, such as nosocomial infection, malnutrition, growth failure, bronchopulmonary dysplasia, retinopathy of prematurity, and neurodevelopmental delays. The most important etiology in the pathogenesis of NEC is structural and immunological intestinal immaturity. In preterm infants with immature gastrointestinal tracts, development of NEC may be associated with a variety of factors, such as colonization with pathogenic bacteria, secondary ischemia, genetic polymorphisms conferring NEC susceptibility, anemia with red blood cell transfusion, and sensitization to cow milk proteins. To date, a variety of preventive strategies has been accepted or attempted in clinical practice with regard to the pathogenesis of NEC. These strategies include the use of breast feeding, various feeding strategies, probiotics, prebiotics, glutamine and arginine, and lactoferrin. There is substantial evidence for the efficacy of breast feeding and the use of probiotics in infants with birth weights above 1,000 g, and these strategies are commonly used in clinical practice. Other preventive strategies, however, require further research to establish their effect on NEC.

  2. An update on necrotizing enterocolitis: pathogenesis and preventive strategies.

    Science.gov (United States)

    Lee, Jang Hoon

    2011-09-01

    Necrotizing enterocolitis (NEC) is one of the most critical morbidities in preterm infants. The incidence of NEC is 7% in very-low-birth-weight infants, and its mortality is 15 to 30%. Infants who survive NEC have various complications, such as nosocomial infection, malnutrition, growth failure, bronchopulmonary dysplasia, retinopathy of prematurity, and neurodevelopmental delays. The most important etiology in the pathogenesis of NEC is structural and immunological intestinal immaturity. In preterm infants with immature gastrointestinal tracts, development of NEC may be associated with a variety of factors, such as colonization with pathogenic bacteria, secondary ischemia, genetic polymorphisms conferring NEC susceptibility, anemia with red blood cell transfusion, and sensitization to cow milk proteins. To date, a variety of preventive strategies has been accepted or attempted in clinical practice with regard to the pathogenesis of NEC. These strategies include the use of breast feeding, various feeding strategies, probiotics, prebiotics, glutamine and arginine, and lactoferrin. There is substantial evidence for the efficacy of breast feeding and the use of probiotics in infants with birth weights above 1,000 g, and these strategies are commonly used in clinical practice. Other preventive strategies, however, require further research to establish their effect on NEC.

  3. The pathogenesis of foot-and-mouth disease in pigs

    Directory of Open Access Journals (Sweden)

    Carolina eStenfeldt

    2016-05-01

    Full Text Available The greatest proportion of foot-and-mouth disease (FMD clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies specific to pigs. However, accumulated evidence from FMD outbreaks and experimental investigations suggest that critical components of FMD pathogenesis, immunology, and vaccinology cannot be extrapolated from investigations performed in cattle to explain or predict outcomes of infection or vaccination in pigs. Furthermore, it has been shown that failure to account for these differences may have substantial consequences when FMD outbreaks occur in areas with dense pig populations. Recent experimental studies have confirmed some aspects of conventional wisdom by demonstrating that pigs are more susceptible to FMD virus (FMDV infection via exposure of the upper gastrointestinal tract (oropharynx than through inhalation of virus. The infection spreads rapidly within groups of pigs that are housed together, although efficiency of transmission may vary depending on virus strain and exposure intensity. Multiple investigations have demonstrated that physical separation of pigs is sufficient to prevent virus transmission under experimental conditions. Detailed pathogenesis studies have recently demonstrated that specialized epithelium within porcine oropharyngeal tonsils constitute the primary infection sites following simulated-natural virus exposure. Furthermore, epithelium of the tonsil of the soft palate supports substantial virus replication during the clinical phase of infection, thus providing large amounts of virus that can be shed into the environment. Due to massive amplification and shedding of virus, acutely infected pigs constitute a considerable source of contagion. FMDV infection results in modulation of several components of the host immune response. The infection is ultimately cleared in association with a strong humoral response and, in

  4. Mechanisms of Alzheimer’s Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors

    Science.gov (United States)

    Kocahan, Sayad; Doğan, Zumrut

    2017-01-01

    The characteristic features of Alzheimer’s disease (AD) are the appearance of extracellular amyloid-beta (Aβ) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aβ and NMDA receptors. Aβ-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression. PMID:28138104

  5. Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

    Science.gov (United States)

    García Martínez, F J; Menchén, L

    2016-09-01

    Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets.

  6. Pilonidal sinus disease - Etiological factors, pathogenesis and clinical features

    Directory of Open Access Journals (Sweden)

    Kazim Duman

    2016-12-01

    Full Text Available and lsquo;Pilonidal sinus' disease, which is most commonly seen in reproductive populations, such as young adults - mostly in males who are in their twenties - is actually a controversial disease in that there is no consensus on its many facets. It is sometimes seen as an infected abscess draining from an opening or a lesion extending to the perineum. It may also present as a draining fistula opening to skin. In terms of etiological factors, various theories (main theories being congenital and acquired have been established since it was first described, no universal understanding achieved. A long and significant post-operative care period with different lengths of recovery depending on the type of operation are quite prevalent with regards to recurrence and complication status. In order to prevent recurrence and improve the quality of life, etiological and predisposing factors as well as clinical features of sacrococcygeal pilonidal disease should be well known, a detailed differential diagnosis should be made, and a suitable and timely intervention should be performed. It was aimed here to explain the etiological factors, pathogenesis and clinical features of the disease that may present with various clinical symptoms. [Arch Clin Exp Surg 2016; 5(4.000: 228-232

  7. Host Antimicrobial Peptides in Bacterial Homeostasis and Pathogenesis of Disease

    Directory of Open Access Journals (Sweden)

    Derek R. Heimlich

    2014-11-01

    Full Text Available Innate immune responses function as a first line of host defense against the development of bacterial infection, and in some cases to preserve the sterility of privileged sites in the human host. Bacteria that enter these sites must counter host responses for colonization. From the host’s perspective, the innate immune system works expeditiously to minimize the bacterial threat before colonization and subsequent dysbiosis. The multifactorial nature of disease further challenges predictions of how each independent variable influences bacterial pathogenesis. From bacterial colonization to infection and through disease, the microenvironments of the host are in constant flux as bacterial and host factors contribute to changes at the host-pathogen interface, with the host attempting to eradicate bacteria and the bacteria fighting to maintain residency. A key component of this innate host response towards bacterial infection is the production of antimicrobial peptides (AMPs. As an early component of the host response, AMPs modulate bacterial load and prevent establishment of infection. Under quiescent conditions, some AMPs are constitutively expressed by the epithelium. Bacterial infection can subsequently induce production of other AMPs in an effort to maintain sterility, or to restrict colonization. As demonstrated in various studies, the absence of a single AMP can influence pathogenesis, highlighting the importance of AMP concentration in maintaining homeostasis. Yet, AMPs can increase bacterial virulence through the co-opting of the peptides or alteration of bacterial virulence gene expression. Further, bacterial factors used to subvert AMPs can modify host microenvironments and alter colonization of the residential flora that principally maintain homeostasis. Thus, the dynamic interplay between host defense peptides and bacterial factors produced to quell peptide activity play a critical role in the progression and outcome of disease.

  8. A Mitochondrial Perspective of Chronic Obstructive Pulmonary Disease Pathogenesis

    Science.gov (United States)

    Shadel, Gerald S.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.

  9. Pathogenesis of hyperinflation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Gagnon P

    2014-02-01

    Full Text Available Philippe Gagnon,1,2 Jordan A Guenette,3,4 Daniel Langer,5 Louis Laviolette,2 Vincent Mainguy,1 François Maltais,1,2 Fernanda Ribeiro,1,2 Didier Saey1,2 1Faculté de Médecine, Université Laval, 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, 3Centre for Heart Lung Innovation, University of British Columbia, St Paul's Hospital, 4Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada; 5Department of Kinesiology and Rehabilitation Sciences, KU Leuven, Leuven, Belgium Abstract: Chronic obstructive pulmonary disease (COPD is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious. Dynamic hyperinflation is highly prevalent in the advanced stages of COPD, and new evidence suggests that it also occurs in many patients with mild disease, independently of the presence of resting hyperinflation. Hyperinflation is clinically relevant for patients with COPD mainly because it contributes to dyspnea, exercise intolerance, skeletal muscle limitations, morbidity, and reduced physical activity levels associated with the disease. Various pharmacological and nonpharmacological interventions have been shown to reduce hyperinflation and delay the onset of ventilatory limitation in patients with COPD. The aim of this review is to address the more recent literature regarding the pathogenesis, assessment, and management of both static and dynamic lung hyperinflation in patients with COPD. We also address the influence of biological sex and obesity and new developments in our understanding of hyperinflation in patients with mild COPD and its evolution during

  10. Huntington's disease: clinical characteristics, pathogenesis and therapies.

    Science.gov (United States)

    Nakamura, Ken; Aminoff, Michael J

    2007-02-01

    Huntington's disease is a devastating disorder with no known cure. The disease results from an expanded sequence of CAG repeats in the huntingtin gene and leads to a movement disorder with associated cognitive and systemic deficits. Huntington's disease is diagnosed by genetic testing and disease progression can be followed with a variety of imaging modalities. The accumulation of aggregated huntingtin with associated striatal degeneration is evident at autopsy. The pathophysiology of Huntington's disease remains unknown, although protein aggregation, excitotoxicity, deficits in energy metabolism, transcriptional dysregulation and apoptosis may all be involved. Current pharmacologic therapy for Huntington's disease is limited and exclusively symptomatic. However, the disease is being heavily researched, and a wide range of disease-modifying therapies is currently under development. The efficacy of these therapies is being evaluated in transgenic models of Huntington's disease and in preliminary clinical trials.

  11. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  12. Peptic Ulcer Disease Different Pathogenesis of Duodenal and Gastric Ulcer

    Directory of Open Access Journals (Sweden)

    Hendra Koncoro

    2015-12-01

    Full Text Available Despite decrease frequency of Helicobacter pylori (H. pylori due to eradication therapy, peptic ulcer disease as a manifestation of this infection is still remain a health burden. Understanding the physiology of gastric acid secretion and its alteration by H. pylori induced inflammation will aid physician in differentiating peptic ulcer disease based on its location. Duodenal ulcer and gastric ulcer disease are two common condition that usually found in peptic ulcer. Recognition of symptoms and its pathogenesis may lead physician to understand the fate of each condition in the future. This article reviews concept of peptic ulcer pathogenesis according to ulcer etiology.

  13. Alzheimer's disease risk genes and mechanisms of disease pathogenesis.

    Science.gov (United States)

    Karch, Celeste M; Goate, Alison M

    2015-01-01

    We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome-technologic advances in methods to analyze millions of polymorphisms in thousands of subjects-have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2. We review the relationship between these AD risk genes and the cellular and neuropathologic features of AD. Understanding the mechanisms underlying the association of these genes with risk for disease will provide the most meaningful targets for therapeutic development to date. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. The pathogenesis of proventricular dilatation disease.

    Science.gov (United States)

    Tizard, Ian; Shivaprasad, H L; Guo, Jianhua; Hameed, Samer; Ball, Judith; Payne, Susan

    2016-12-01

    Bornaviruses cause neurologic diseases in several species of birds, especially parrots, waterfowl and finches. The characteristic lesions observed in these birds include encephalitis and gross dilatation of the anterior stomach - the proventriculus. The disease is thus known as proventricular dilatation disease (PDD). PDD is characterized by extreme proventricular dilatation, blockage of the passage of digesta and consequent death by starvation. There are few clinical resemblances between this and the bornaviral encephalitides observed in mammals. Nevertheless, there are common virus-induced pathogenic pathways shared across this disease spectrum that are explored in this review. Additionally, a review of the literature relating to gastroparesis in humans and the control of gastric mobility in mammals and birds points to several plausible mechanisms by which bornaviral infection may result in extreme proventricular dilatation.

  15. [Pathogenesis of parodontitis in rheumatic diseases].

    Science.gov (United States)

    Detert, J; Pischon, N; Burmester, G-R; Buttgereit, F

    2010-03-01

    Inflammatory periodontal disease (PD) is a common disease worldwide that has a primarily bacterial aetiology and is characterized by dysregulation of the host inflammatory response. The degree of inflammation varies among individuals with PD independently of the degree of bacterial infection, suggesting that alteration of the immune function may substantially contribute to its extent. Factors such as smoking, education, and body mass index (BMI) are discussed as potential risk factors for PD. Most PD patients respond to bacterial invaders by mobilizing their defensive cells and releasing cytokines such as interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and IL-6, which ultimately causes tissue destruction by stimulating the production of collagenolytic enzymes, such matrix metalloproteinases. Recently, there has been growing evidence suggesting an association between PD and the increased risk of systemic diseases, such ateriosclerosis, diabetes mellitus, stroke, and rheumatoid arthritis (RA). PD and rheumatologic diseases such as RA share many pathological aspects and immunological findings.

  16. Podocyte biology and pathogenesis of kidney disease.

    Science.gov (United States)

    Reiser, Jochen; Sever, Sanja

    2013-01-01

    Proteinuric chronic kidney disease (CKD), once a rare affliction believed to be mainly caused by genetic mutations, has become a global pandemic that severely diminishes the quality of life for millions. Despite the changing face of CKD, treatment options and resources remain woefully antiquated and have failed to arrest or reverse the effects of kidney-related diseases. Histological and genetic data strongly implicate one promising target: the podocyte. Podocytes are terminally differentiated cells of the kidney glomerulus that are essential for the integrity of the kidney filter. Their function is primarily based on their intricate structure, which includes foot processes. Loss of these actin-driven membrane extensions is tightly connected to the presence of protein in the urine, podocyte loss, development of CKD, and ultimately renal failure.

  17. The pathogenesis, detection and prevention of Vibrio parahaemolyticus

    Directory of Open Access Journals (Sweden)

    Rongzhi eWang

    2015-03-01

    Full Text Available Vibrio parahaemolyticus, a Gram-negative motile bacterium that inhabits marine and estuarine environments throughout the world, is a major food-borne pathogen that causes life-threatening diseases in humans after the consumption of raw or undercooked seafood. The global occurrence of V. parahaemaolyticus accentuates the importance of investigating its virulence factors and their effects on the human host. This review describes the virulence factors of V. parahaemolyticus reported to date, including hemolysin, urease, two type III secretion systems (T3SS and two type VI secretion systems (T6SS, which both cause both cytotoxicity in cultured cells and enterotoxicity in animal models. We describe various types of detection methods, based on virulence factors, that are used for quantitative detection of V. parahaemolyticus in seafood. We also discuss some useful preventive measures and therapeutic strategies for the diseases mediated by V. parahaemolyticus, which can reduce, to some extent, the damage to humans and aquatic animals attributable to V. parahaemolyticus. This review extends our understanding of the pathogenic mechanisms of V. parahaemolyticus mediated by virulence factors and the diseases it causes in its human host. It should provide new insights for the diagnosis, treatment, and prevention of V. parahaemolyticus infection.

  18. [Pathogenesis and clinical condition of hyperphosphatemic diseases].

    Science.gov (United States)

    Hamano, Naoto; Fukagawa, Masafumi

    2016-02-01

    Phosphorus is essential mineral to life, which has the multiple roles like postural maintenance or production of energy in the cells. Phosphate overload is harmful and compensatory mechanisms exist. Phosphate is abolished through kidneys and target organ of the compensatory mechanism is also kidneys. It is necessary to evaluate renal function and source of phosphate for estimating the cause of hyperphosphatemia. Acute hyperphosphatemia may cause severe acute kidney injury and avoidance of massive phosphate overload is needed. Chronic hyperphosphatemia have an impact on prognosis because the risk of cardiovascular event increases. Adequate restriction of phosphate intake and use of phosphate absorbent is needed for improvement of prognosis of patients with chronic kidney disease.

  19. Mitochondrial dysfunction in the limelight of Parkinson's disease pathogenesis.

    Science.gov (United States)

    Banerjee, Rebecca; Starkov, Anatoly A; Beal, M Flint; Thomas, Bobby

    2009-07-01

    Parkinson's disease (PD) is a progressive neurodegenerative movement disorder with unknown etiology. It is marked by widespread neurodegeneration in the brain with profound loss of A9 midbrain dopaminergic neurons in substantia nigra pars compacta. Several theories of biochemical abnormalities have been linked to pathogenesis of PD of which mitochondrial dysfunction due to an impairment of mitochondrial complex I and subsequent oxidative stress seems to take the center stage in experimental models of PD and in postmortem tissues of sporadic forms of illness. Recent identification of specific gene mutations and their influence on mitochondrial functions has further reinforced the relevance of mitochondrial abnormalities in disease pathogenesis. In both sporadic and familial forms of PD abnormal mitochondrial paradigms associated with disease include impaired functioning of the mitochondrial electron transport chain, aging associated damage to mitochondrial DNA, impaired calcium buffering, and anomalies in mitochondrial morphology and dynamics. Here we provide an overview of specific mitochondrial functions affected in sporadic and familial PD that play a role in disease pathogenesis. We propose to utilize these gained insights to further streamline and focus the research to better understand mitochondria's role in disease development and exploit potential mitochondrial targets for therapeutic interventions in PD pathogenesis.

  20. Pathogenesis of growth failure in renal diseases.

    Science.gov (United States)

    Ahmed, T M; Yi, Z W; Chan, J C

    1994-01-01

    This article reviews our current understanding of the mechanisms of growth failure in chronic renal disease. The neuro-endocrine control of growth hormone secretion and insulin-like growth factor gene expression subject to use of corticosteroids, uremia, and metabolic acidosis are presented. It has been shown in other non-growth hormone deficient conditions such as Turner's syndrome that the use of exogenous growth hormone increases linear growth but also accelerates closure of the growth plate with no significant difference in the final height of such children. An understanding of growth factors is especially important and timely because of the tendency these days to use growth hormone to overcome the growth impairment of children with chronic renal failure.

  1. RNA metabolism in the pathogenesis of Parkinson׳s disease.

    Science.gov (United States)

    Lu, Bingwei; Gehrke, Stephan; Wu, Zhihao

    2014-10-10

    Neurodegenerative diseases such as Parkinson׳s disease are progressive disorders of the nervous system that affect the function and maintenance of specific neuronal populations. While most disease cases are sporadic with no known cause, a small percentage of disease cases are caused by inherited genetic mutations. The identification of genes associated with the familial forms of the diseases and subsequent studies of proteins encoded by the disease genes in cellular or animal models have offered much-needed insights into the molecular and cellular mechanisms underlying disease pathogenesis. Recent studies of the familial Parkinson׳s disease genes have emphasized the importance of RNA metabolism, particularly mRNA translation, in the disease process. It is anticipated that continued studies on the role of RNA metabolism in Parkinson׳s disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease.

  2. The pathogenesis of Foot-and-Mouth Disease in pigs

    Science.gov (United States)

    The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental invest...

  3. Foot-and-mouth disease: Host range and pathogenesis

    DEFF Research Database (Denmark)

    Alexandersen, Søren; Mowat, N.

    2005-01-01

    In this chapter the host range of foot-and-mouth disease (FMD) under natural and experimental conditions is reviewed. The routes and sites of infection, incubation periods and clinical and pathological findings are described and highlighted in relation to progress in understanding the pathogenesis...

  4. Using 'omics' to define pathogenesis and biomarkers of Parkinson's disease.

    Science.gov (United States)

    Caudle, W Michael; Bammler, Theo K; Lin, Yvonne; Pan, Sheng; Zhang, Jing

    2010-06-01

    Although great effort has been put forth to uncover the complex molecular mechanisms exploited in the pathogenesis of Parkinson's disease, a satisfactory explanation remains to be discovered. The emergence of several -omics techniques, transcriptomics, proteomics and metabolomics, have been integral in confirming previously identified pathways that are associated with dopaminergic neurodegeneration and subsequently Parkinson's disease, including mitochondrial and proteasomal function and synaptic neurotransmission. Additionally, these unbiased techniques, particularly in the brain regions uniquely associated with the disease, have greatly enhanced our ability to identify novel pathways, such as axon-guidance, that are potentially involved in Parkinson's pathogenesis. A comprehensive appraisal of the results obtained by different -omics has also reconfirmed the increase in oxidative stress as a common pathway likely to be critical in Parkinson's development/progression. It is hoped that further integration of these techniques will yield a more comprehensive understanding of Parkinson's disease etiology and the biological pathways that mediate neurodegeneration.

  5. Correlation between mitochondrial dysfunction and the pathogenesis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xiao-yu LIU

    2014-02-01

    Full Text Available Parkinson's disease (PD is a progressive neurodegenerative disease. A growing number of studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of PD. Therefore, this review will mainly discuss the research progress on the correlation between PD and abnormal mitochondrial dynamics, mitochondrial autophapy as well as mitochondrial DNA mutations and mitochondrial complex Ⅰ inhibition.doi:10.3969/j.issn.1672-6731.2014.02.012

  6. Inflammatory bowel diseases: from pathogenesis to laboratory testing.

    Science.gov (United States)

    Basso, Daniela; Zambon, Carlo-Federico; Plebani, Mario

    2014-04-01

    Inflammatory bowel diseases (IBDs), which comprise the two major clinical subtypes, Crohn's disease and ulcerative colitis, incur high morbidity and potential mortality. The present study reviews data on the pathogenesis and diagnosis of IBDs. The pathogenesis depends on complex interactions between susceptibility genes, environmental factors, and innate and adaptive immunity, the understanding of which is crucial to discovering novel laboratory biomarkers. Traditional laboratory tests for the diagnosis, prognosis and assessment of disease activity of IBDs are reported on, and the biochemical properties, pre-analytical and analytical aspects and clinical utility of the fecal markers lactoferrin and calprotectin are described. DNA testing and established (ASCA and pANCA) and emerging (ACCA, ALCA, AMCA, OmpC) serum markers are described; a further aspect to be addressed is the clinical use of pharmacogenetics for the treatment of IBDs.

  7. Genetics, Disease Prevention and Treatment

    Science.gov (United States)

    ... the genetic terms used on this page Genetics, Disease Prevention and Treatment Overview How can learning about my family's health history help me prevent disease? How can I learn about my family's health ...

  8. Heart Disease and Stroke Prevention

    Science.gov (United States)

    ... Heart Health and Stroke Heart disease and stroke prevention Related information Learn more about healthy eating and ... top More information on Heart disease and stroke prevention Read more from womenshealth.gov A Lifetime of ...

  9. Understanding mechanisms of the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Metin; Basaranoglu; Serra; Kayacetin; Nevin; Yilmaz; Ertugrul; Kayacetin; Orhan; Tarcin; Abdullah; Sonsuz

    2010-01-01

    A central issue in the understanding of the pathogenesis of nonalcoholic fatty liver disease is the problem of the underlying mechanisms which are not fully understood.In the setting of excessive central adiposity,insulin resistance is the major underlying cause of fat accumulation in hepatocytes.Because of the difficulties with human trials,several animal models have been developed for this purpose mainly characterized as follows:genetically disturbed or murine fatty liver,methionine-choline deficient diet...

  10. Molecular Therapy and Prevention of Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    Hubert E. Blum

    2008-01-01

    Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.

  11. Legg-Calve-Perthes disease: etiology, pathogenesis, and biology.

    Science.gov (United States)

    Kim, Harry K W

    2011-09-01

    Legg-Calve-Perthes disease is a complex pediatric hip disorder with many uncertainties. Various theories on its etiology have been proposed but none have been validated conclusively. Through experimental studies, however, some insight into the pathogenesis of a femoral head deformity after ischemic necrosis has been gained. These studies reveal that mechanical and biological factors contribute to the development of the femoral head deformity. Better understanding of the pathobiology of Legg-Calve-Perthes disease will lead to the development of more effective treatments, which are able to specifically target the pathogenic processes.

  12. [Ulcer disease: challenging problems of etiology, pathogenesis, differential treatment].

    Science.gov (United States)

    Tsimmerman, Ia S

    2012-01-01

    This review summarizes the data of Russian and foreign authors as well as the results of original studies on etiology pathogenesis, and differential treatment of ulcer disease (UD). The author's original concepts of UD pathogenesis and relations between man and Helicobacter pylori are discussed. The pathogenetic role of disturbances in the system of gastroduodental self-regulatory function and psychosomatic mechanisms as well as immune deficiency and impaired antioxidatve protection is considered. Peculiarities and results of UD eradication therapy intended to eliminate H. pylori infection are described. The importance of the choice of the UD treatment strategy on an individual basis is emphasized as opposed to the use of universal standards and therapeutic modalities influencing only local pathogenic factors, such as acidopeptic ones and H. pylori infection.

  13. Contribution of pertussis toxin to the pathogenesis of pertussis disease.

    Science.gov (United States)

    Carbonetti, Nicholas H

    2015-11-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease.

  14. Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

    Science.gov (United States)

    Shahane, Anupama

    2013-07-01

    The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and

  15. Surgical site infections in dermatologic surgery: etiology, pathogenesis, and current preventative measures.

    Science.gov (United States)

    Saleh, Karim; Schmidtchen, Artur

    2015-05-01

    Surgical site infections (SSIs) after dermatologic surgery continue to represent undesirable complications that affect patients in several aspects. The etiology and pathogenesis of SSIs are not completely understood, and as a result, current preventative measures are debatable. To review and summarize the current available literature specific to SSIs in dermatologic surgery. The pathogenesis of SSIs, factors contributing to SSIs, current preventative guidelines, and evidence supporting their use are explored. A review of the medical literature. Most measures used to prevent SSIs in dermatologic surgery are based on studies of wounds in general surgery. Evidence specific to dermatologic surgery is scarce. More research related to the pathogenesis of SSIs is needed to establish effective preventative measures that are key to reducing incidences of SSIs.

  16. Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

    Science.gov (United States)

    Ramos-Leví, Ana Maria; Marazuela, Mónica

    2016-10-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Role of Kupffer cells in the pathogenesis of liver disease

    Institute of Scientific and Technical Information of China (English)

    George Kolios; Vassilis Valatas; Elias Kouroumalis

    2006-01-01

    Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

  18. Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2014-10-01

    There have been considerable advances in uncovering the complex genetic mechanisms that underlie nervous system disease pathogenesis, particularly with the advent of exome and whole genome sequencing techniques. The emerging field of epigenetics is also providing further insights into these mechanisms. Here, we discuss our understanding of the interplay that exists between genetic and epigenetic mechanisms in these disorders, highlighting the nascent field of epigenetic epidemiology-which focuses on analyzing relationships between the epigenome and environmental exposures, development and aging, other health-related phenotypes, and disease states-and next-generation research tools (i.e., those leveraging synthetic and chemical biology and optogenetics) for examining precisely how epigenetic modifications at specific genomic sites affect disease processes.

  19. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    György Nagy

    2015-01-01

    Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  20. Selected Aspects in the Pathogenesis of Autoimmune Diseases.

    Science.gov (United States)

    Nagy, György; Huszthy, Peter C; Fossum, Even; Konttinen, Yrjö; Nakken, Britt; Szodoray, Peter

    2015-01-01

    Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  1. Antibody-Mediated Rejection: Pathogenesis, Prevention, Treatment, and Outcomes

    Directory of Open Access Journals (Sweden)

    Olivia R. Blume

    2012-01-01

    Full Text Available Antibody-mediated rejection (AMR is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP is effective in removing alloantibodies (DSAs from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.

  2. The developmental etiology and pathogenesis of Hirschsprung disease.

    Science.gov (United States)

    Butler Tjaden, Naomi E; Trainor, Paul A

    2013-07-01

    The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract. Derived from a multipotent, migratory cell population called the neural crest, a complete enteric nervous system is necessary for proper gut function. Disorders that arise as a consequence of defective neural crest cell development are termed neurocristopathies. One such disorder is Hirschsprung disease (HSCR), also known as congenital megacolon or intestinal aganglionosis. HSCR occurs in 1/5000 live births and typically presents with the inability to pass meconium, along with abdominal distension and discomfort that usually requires surgical resection of the aganglionic bowel. This disorder is characterized by a congenital absence of neurons in a portion of the intestinal tract, usually the distal colon, because of a disruption of normal neural crest cell migration, proliferation, differentiation, survival, and/or apoptosis. The inheritance of HSCR disease is complex, often non-Mendelian, and characterized by variable penetrance. Extensive research has identified a number of key genes that regulate neural crest cell development in the pathogenesis of HSCR including RET, GDNF, GFRα1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH. However, mutations in these genes account for only ∼50% of the known cases of HSCR. Thus, other genetic mutations and combinations of genetic mutations and modifiers likely contribute to the etiology and pathogenesis of HSCR. The aims of this review are to summarize the HSCR phenotype, diagnosis, and treatment options; to discuss the major genetic causes and the mechanisms by which they disrupt normal enteric neural crest cell development; and to explore new pathways that may contribute to HSCR pathogenesis.

  3. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  4. Anemia and bone disease of chronic kidney disease: pathogenesis, diagnosis, and management.

    Science.gov (United States)

    Shemin, Douglas

    2014-12-02

    Anemia and metabolic bone disease accompany chronic kidney disease (CKD), and worsen as CKD progresses. It is likely that both processes contribute to the increased morbidity and mortality seen in CKD. This paper briefly reviews the pathogenesis and diagnosis of anemia and bone disease in CKD, and summarizes recent consensus guidelines for treatment.

  5. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    Science.gov (United States)

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  6. Etiology and pathogenesis of late-onset Alzheimer's disease.

    Science.gov (United States)

    Balin, Brian J; Hudson, Alan P

    2014-03-01

    Alzheimer's disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.

  7. Treating prolactinoma can prevent autoimmune diseases.

    Science.gov (United States)

    Watad, Abdulla; Versini, Mathilde; Jeandel, Pierre-Yves; Amital, Howard; Shoenfeld, Yehuda

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence.

  8. Sugary drinks in the pathogenesis of obesity and cardiovascular diseases.

    Science.gov (United States)

    Brown, C M; Dulloo, A G; Montani, J-P

    2008-12-01

    Soft drink overconsumption is now considered to be a major public health concern with implications for cardiovascular diseases. This follows a number of studies performed in animals suggesting that chronic consumption of refined sugars can contribute to metabolic and cardiovascular dysregulation. In particular, the monosaccharide fructose has been attracting increasing attention as the more harmful sugar component in terms of weight gain and metabolic disturbances. High-fructose corn syrup is gradually replacing sucrose as the main sweetener in soft drinks and has been blamed as a potential contributor to the current high prevalence of obesity. There is also considerable evidence that fructose, rather than glucose, is the more damaging sugar component in terms of cardiovascular risk. This review focuses on the potential role of sugar drinks, particularly the fructose component, in the pathogenesis of obesity and cardiovascular diseases.

  9. Neutrophils: the forgotten cell in JIA disease pathogenesis

    Directory of Open Access Journals (Sweden)

    Petty Howard R

    2007-06-01

    Full Text Available Abstract Juvenile idiopathic arthritis (JIA has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA.

  10. Cellular interactions in the pathogenesis of interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Gianluca Bagnato

    2015-03-01

    Full Text Available Interstitial lung disease (ILD encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells. New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis.

  11. Smoking and cardiovascular health: A review of the epidemiology, pathogenesis, prevention and control of tobacco

    Directory of Open Access Journals (Sweden)

    Prasad D

    2009-11-01

    Full Text Available The causal associations between cigarette smoking and human diseases are irrefutable. In this review, we focus on the epidemiological pattern of cigarette smoking on cardiovascular risk, the underlying mechanistic process of such a causal link, how to prevent premature cardiovascular morbidity and mortality particularly through smoking cessation, and the health benefits of such cessation measures. Finally, we conclude our review summarizing a few of the proven evidence-based tobacco control strategies and policies from across the globe. We did not conduct a systematic review but followed a similar structure. We abstracted the most relevant published literature on the electronic databases, namely, PubMed, Embase and the Cochrane Library applying specific search terms. We also searched gray literature and consulted experts in the field for cross-references. Smoking has been estimated to cause about 11% of all deaths due to cardiovascular disease. Smoking contributes to the pathogenesis of coronary artery disease and sudden death through a variety of mechanisms, including the promotion of atherosclerosis, the triggering of coronary thrombosis, coronary artery spasm, and cardiac arrhythmias, and through reduced capacity of the blood to deliver oxygen. Smoking cessation also confers substantial benefits on people with serious heart disease. Smoking cessation should be viewed as therapeutic rather than preventive intervention, similar to treating asymptomatic hypertension. Smoking cessation is highly cost-effective relative to other frequently used medical and surgical interventions. Tobacco related illnesses are important public health issues worldwide. It has been estimated that there are1.1 billion smokers worldwide and 250 million of them live in India.

  12. Dissecting Lyme borreliosis; Clinical aspects, pathogenesis and prevention

    NARCIS (Netherlands)

    J. Coumou

    2016-01-01

    Lyme borreliosis (LB) is the most prevalent vector-borne disease in Western Europe and Northeastern parts of the USA. The causative agents of LB are spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes ticks. Since the late 1970’s, researchers in the Un

  13. Heart Diseases--Prevention

    Science.gov (United States)

    ... you have a close family member who had heart disease at an early age. Fortunately, there are many things you can do reduce your chances of getting heart disease. You should Know your blood pressure and keep ...

  14. Novel players in coeliac disease pathogenesis: role of the gut microbiota

    Science.gov (United States)

    Verdu, Elena F.; Galipeau, Heather J.; Jabri, Bana

    2016-01-01

    Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause–effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host–microbial interactions can influence host responses to gluten. PMID:26055247

  15. Pathogenesis to Treatment: Preventing Preterm Birth Mediated by Infection

    Directory of Open Access Journals (Sweden)

    James A. McGregor

    1997-01-01

    Full Text Available Prevention of preterm birth and subsequent newborn immaturity is a primary goal of obstetrical care worldwide. Accumulated evidence shows that 1 as many as 25–50% of preterm births are caused by common genital tract infections and subsequent maternal/fetal inflammatory responses; 2 microbial and maternal host factors (phospholipases, proteases, etc. play roles in preterm labor and preterm premature rupture of membranes (pPROM; 3 integrated aspects of maternal and fetal host responses (inflammation, altered immune adaptations, endocrine and paracrine mechanisms play increasingly understood roles in premature activation of parturition; and 4 identification and systemic treatment of common genitourinary infections, most importantly bacterial vaginosis (BV, reduce the risks of preterm delivery and PROM.

  16. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

    Science.gov (United States)

    Singh, Siddharth; Dulai, Parambir S.; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J.

    2017-01-01

    Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research. PMID:27899815

  17. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes.

    Science.gov (United States)

    Singh, Siddharth; Dulai, Parambir S; Zarrinpar, Amir; Ramamoorthy, Sonia; Sandborn, William J

    2017-02-01

    Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15-40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

  18. [Transforming growth factor-beta controls pathogenesis of Crohn disease].

    Science.gov (United States)

    Friess, H; di Mola, F F; Egger, B; Scheuren, A; Kleeff, J; Zimmermann, A; Büchler, M W

    1998-01-01

    The pathogenetic mechanisms which contribute to the progression of Crohn's disease are still not known. Transforming growth factor-beta (TGF-beta) and its subtypes are multifunctional polypeptides which regulate immunological processes as well as the synthesis of the extracellular matrix and fibrogenesis. In the present study, Crohn's disease tissue samples of 18 patients undergoing intestinal resection were analyzed by Northern blot analysis, in situ hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%, 72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and immunostaining revealed that there was frequent coexpression of TGF-beta with its signaling receptors. Our data indicate that TGF-beta and their receptors seem to be involved in the pathogenesis of Crohn's disease. Their enhanced expression might contribute to the increase in extracellular matrix resulting in fibrosis and subsequently in intestinal obstruction.

  19. Current concepts of the pathogenesis of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    Although the cause of inflammatory bowel disease is not known, the pathogenesis involves an immune-mediated tissue damage that is the result of an interaction among genetic predisposing factors, exogenous triggers and endogenous modifying influences. Multiple genes are involved and operate at the level of the immune response and at the target organ. Exogenous triggers include the enteric microflora which might stimulate the mucosal immune system in genetically predisposed individuals. Endogenous modifying factors such as the psychoneuroendocrine system have regulatory effects on the immune system and the inflammatory response, and may influence the course of the disease. While autoimmune phenomena do occur, particularly in ulcerative colitis, there is no evidence that they are directly responsible for the tissue damage. It appears more likely, particularly in Crohn\\'s disease, that tissue injury may occur as an indirect or "bystander" effect of mucosal T-cell hyperactivation, perhaps in response to a normal enteric microbial antigen. Most of the immunologic and histologic features of Crohn\\'s disease can be explained by the effects of T-cell derived and other cytokines on the epithelium, the local immune system, the microvasculature, and the recruitment of auxiliary effector cells such as neutrophils.

  20. Role of HLA typing on Crohn's disease pathogenesis

    Science.gov (United States)

    Mahdi, Batool Mutar

    2015-01-01

    Crohn's disease (CD) is the main type of chronic inflammatory bowel disease of unknown etiology. Evidence from family and twin studies suggests that genetics plays a significant role in predisposing an individual to develop Crohn's disease. A susceptibility locus for Crohn's disease has been mapped 3 to chromosome 16: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators which is expressed in hematopoietic compartment cells and intestinal epithelial cells as well as in paneth cells, where NOD2 may play an important role in the pathogenesis of Crohn disease in the gastrointestinal system. This leads to alteration the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has two functions, first an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. Thus, NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in intestinal epithelial cells as well as in paneth cells. Further confirmation of a genetic predisposition comes from studies of the association between the human leukocyte antigen (HLA) system and CD. The immunogenetic predisposition may be considered an important requirement for the development of CD, as several alleles of human major histocompatibility complex had an association with CD. Although it is difficult to estimate the importance of this region in determining overall genetic susceptibility in a population, studies of HLA allele sharing within families suggest that this region contributes between 10% and 33% of the total genetic risk of Crohn's disease. PMID:26288728

  1. Clinical Relevance of Environmental Factors in the Pathogenesis of Autoimmune Thyroid Disease

    Directory of Open Access Journals (Sweden)

    Wilmar M. Wiersinga

    2016-06-01

    Full Text Available Genetic factors contribute for about 70% to 80% and environmental factors for about 20% to 30% to the pathogenesis of autoimmune thyroid disease (AITD. Relatives of AITD patients carry a risk to contract AITD themselves. The 5-year risk can be quantified by the so-called Thyroid Events Amsterdam-score, based on serum thyroid-stimulating hormone, thyroid peroxidase (TPO-antibodies and family history. Subjects at risk may ask what they can do to prevent development of AITD. This review summarizes what is known about modulation of exposure to environmental factors in terms of AITD prevention. To stop smoking decreases the risk on Graves disease but increases the risk on Hashimoto disease. Moderate alcohol intake provides some protection against both Graves and Hashimoto disease. Low selenium intake is associated with a higher prevalence of thyroid autoimmunity, but evidence that selenium supplementation may lower TPO antibodies and prevent subclinical hypothyroidism remains inconclusive. Low serum vitamin D levels are associated with a higher prevalence of TPO antibodies, but intervention studies with extra vitamin D have not been done yet. Stress may provoke Graves hyperthyroidism but not Hashimoto thyroiditis. Estrogen use have been linked to a lower prevalence of Graves disease. The postpartum period is associated with an increased risk of AITD. Taking together, preventive interventions to diminish the risk of AITD are few, not always feasible, and probably of limited efficacy.

  2. Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment.

    Science.gov (United States)

    de Bari, Ornella; Wang, Tony Y; Liu, Min; Paik, Chang-Nyol; Portincasa, Piero; Wang, David Q-H

    2014-01-01

    Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women.

  3. The pathogenesis, treatment and prevention of osteoporosis in men.

    Science.gov (United States)

    Mosekilde, Leif; Vestergaard, Peter; Rejnmark, Lars

    2013-01-01

    Testosterone stimulates longitudinal and appositional growth during childhood, whereas estrogen induces epiphysial closure. During adulthood, testosterone continues to stimulate periosteal growth, whereas estrogen is important for the maintenance of trabecular bone mass and structure. In males, testosterone is aromatized to estradiol. Both free and bioavailable plasma levels of testosterone and estradiol decrease with age in males, and fracture risk is associated with low estradiol levels. Testosterone may increase muscle mass and prevent fractures related to falls. Younger hypogonadal males should be treated with testosterone to attain peak bone mass and increase bone mineral density (BMD). Older hypogonadal males should be treated in cases of osteoporosis, reduced muscle strength and increased risk of falling. Secondary hyperparathyroidism caused by calcium and vitamin D insufficiency may reduce bone mass and strength and increase fracture risk and should be avoided. Since calcium supplementation has been associated with an increased risk of cardiovascular complications and renal stones, the dose should be tailored to the habitual daily calcium intake. Lifestyle-related risk factors (smoking, alcohol consumption, lack of physical activity and low body weight) should be addressed. The antifracture efficacy of antiresorptive and anabolic treatment for osteoporosis has not been documented in larger randomized controlled studies. However, changes in BMD and bone markers suggest similar effects in males and females of bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), nasal calcitonin, denosumab and teriparatide (parathyroid hormone [1-34]). The antiresorptive drugs should be used in males with BMD T-score less than -2.5 and one or more risk factors, or with hip and vertebral fractures. It seems appropriate to recommend a higher cut-off T-score (e.g. less than -1.0 standard deviation [SD]) in glucocorticoid-induced osteoporosis and in patients

  4. Huntington's disease: from molecular pathogenesis to clinical treatment.

    Science.gov (United States)

    Ross, Christopher A; Tabrizi, Sarah J

    2011-01-01

    Huntington's disease is a progressive, fatal, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long polyglutamine repeat in the huntingtin protein. Huntington's disease has served as a model for the study of other more common neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. These disorders all share features including: delayed onset; selective neuronal vulnerability, despite widespread expression of disease-related proteins during the whole lifetime; abnormal protein processing and aggregation; and cellular toxic effects involving both cell autonomous and cell-cell interaction mechanisms. Pathogenic pathways of Huntington's disease are beginning to be unravelled, offering targets for treatments. Additionally, predictive genetic testing and findings of neuroimaging studies show that, as in some other neurodegenerative disorders, neurodegeneration in affected individuals begins many years before onset of diagnosable signs and symptoms of Huntington's disease, and it is accompanied by subtle cognitive, motor, and psychiatric changes (so-called prodromal disease). Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset.

  5. Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention.

    Science.gov (United States)

    Lemon, Stanley M; Ott, Jördis J; Van Damme, Pierre; Shouval, Daniel

    2017-09-05

    Hepatitis A virus (HAV) infection is an ancient disease and likely to have afflicted mankind since humans first began to live in groups large enough to sustain transmission of the causative agent, HAV. In reviewing what was known as 'catarrhal jaundice' in 1912, Cockayne noted descriptions of epidemic jaundice extending back to antiquity1. The infectious nature of the disease was proven several decades later in deliberate human transmission studies2. Such experiments led to a clear distinction between hepatitis A ('infectious hepatitis') and hepatitis B ('homologous serum jaundice') and recognition of the lack of cross immunity between these two forms of transmissible hepatitis as early as 19453. However, the responsible virus was not identified until almost 30 years later, when small, round viral particles were discovered by immune electron microscopy in the feces of an experimentally-infected human subject by Feinstone et al. in 19734. This review provides an up-to-date in in-depth overview of HAV and the acute inflammatory hepatic infection it causes in humans, including recently recognized aspects of its molecular virology, evolution, natural history, pathogenesis, epidemiology and prevention. Copyright © 2017. Published by Elsevier B.V.

  6. Pathogenesis and Active Prevention of Testicular Germ Cell Neoplasia

    Directory of Open Access Journals (Sweden)

    Slowikowska-Hilczer J

    2007-01-01

    Full Text Available Most testicular neoplasms originate from fetal germ cells (germ cell tumors [GCT]. Intratubular germ cell neoplasia (ITGCN or testicular carcinoma in situ (CIS are terms used for the state when these cells are present in the seminiferous epithelium. The highest risk of neoplastic lesions occurs in testes with disturbed organogenesis (in our study, 65 %. Genetic, hormonal, and environmental factors are suspected to lead to disturbed testicular organogenesis (dysgenesis, which creates the milieu favorable for GCT development. An external environment can cause a block or delay in fetal germ and somatic cell differentiation. CIS cells in dysgenetic testes of children reveal a predominantly aneuploid DNA pattern (62.2–97.6 % of germ cells and they do not express an RBM protein (present in normal germ cells, this indicates that CIS cells are neoplastic from fetal life on. Most of the neoplastic germ cells die, however, some survive and proliferate, leading to a clonal expansion and giving rise to gonadoblastoma, CIS, and GCT. Neoplastic germ cells located inside underdeveloped testicular tubules have an intratesticular environment favorable for their survival – this was confirmed by the finding that the highest incidence of neoplastic lesions occurred in patients with partial (90.9 % and mixed gonadal dysgenesis (76.9 %. It was hypothesized that the transformation of CIS into overt GCT may be promoted by gonadotropin action. We found that in gonadal dysgenesis, serum concentrations of FSH and LH reveal highly significant, positive correlations with the number of CIS cells, even in childhood. At present, surgical biopsy of the testis is the only reliable method to detect CIS and hence to actively prevent the development of overt GCT. Accordingly, early bilateral gonadectomy is recommended in all types of disturbance of testicular organogenesis because of the high risk of various neoplastic lesions in dysgenetic testes (86 % of adult patients with

  7. Pathogenesis of Crohn’s disease: Bug or no bug

    Institute of Scientific and Technical Information of China (English)

    Marta; Maia; Bosca-Watts; Joan; Tosca; Rosario; Anton; Maria; Mora; Miguel; Minguez; Francisco; Mora

    2015-01-01

    The possibility of an infectious origin in inflammatory bowel disease(IBD)has been postulated since the first description of Crohn’s disease(CD).Many observations implicate bacteria as a trigger for the development of CD:lesions occur in regions with higher bacterial concentrations;aphthous ulcers occur in Peyer’s patches;inflammation resolves when the fecal stream is diverted and is reactivated following reinfusion ofbowel contents;severity of the disease is correlated with bacterial density in the mucosa;granulomas can contain bacteria;and susceptible mice raised in germfree conditions develop inflammation when bacteria are introduced in the 1990’s,several studies sought to establish a relationship with viral infections and the onset of IBD,finally concluding that no direct link had been demonstrated.In the past fifteen years,evidence relating IBD pathogenesis to Mycobacterium avium paratuberculosis,salmonella,campylobacter,etc.,has been found.The tendency now under discussion to regard microbiota as the primary catalyst has led to the latest studies on microbiota as pathogens,focusing on Escherichia coli,mainly in ileal CD.The present review discusses the literature available on these"bugs".

  8. The relevance of iron in the pathogenesis of Parkinson's disease.

    Science.gov (United States)

    Sian-Hülsmann, Jeswinder; Mandel, Silvia; Youdim, Moussa B H; Riederer, Peter

    2011-09-01

    Alterations of iron levels in the brain has been observed and documented in a number of neurodegenerative disorders including Parkinson's disease (PD). The elevated nigral iron levels observed in PD may reflect a dysfunction of brain iron homeostasis. Under normal physiological conditions excess iron can be sequestrated in ferritin and neuromelanin. Alternatively, the excess iron may represent a component of brain iron deposition associated with ageing. The aetiology of idiopathic PD largely remains an enigma. However, intensive investigations have provided a host of putative mechanisms that might contribute to the pathogenesis underlying the characteristic degeneration of the dopaminergic neurons in the substantia nigra (SN). The mechanisms proposed include oxidative (and nitrative) stress, inflammation, excitotoxicity, mitochondrial dysfunction, altered proteolysis and finally apoptotic induced cell death. Iron-mediated cellular destruction is mediated primarily via reactive oxygen or/and nitrogen species induced oxidative stress. Furthermore, these pathogenic mechanisms appear to be closely interlinked to the cascade of events leading to cellular death. There are conflicting reports about the stage during disease progression at which nigral iron change occurs in PD. Some have found that there are no changes in iron content SN in asymptomatic incidental Lewy body disease, suggesting it may represent a secondary event in the cascade of neuronal degeneration. In contrast, others have found an elevation of iron in SN in pre-clinical stages. These discrepancies may be attributed to the occurrence of different sub-groups of the disease. This concurs with the notion that PD represents a group of related diseases with a number of potential pathogenic pathways.

  9. Molecular pathogenesis of retinal and choroidal vascular diseases.

    Science.gov (United States)

    Campochiaro, Peter A

    2015-11-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch's membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch's membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for VEGF

  10. Animal models to investigate the pathogenesis of rheumatic heart disease

    Directory of Open Access Journals (Sweden)

    Catherine M Rush

    2014-11-01

    Full Text Available Rheumatic fever (RF and rheumatic heart disease (RHD are sequelae of group A streptococcal (GAS infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unravelled partly due to experimentation on animal models.RF/RHD is a uniquely human condition and modelling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model. In Lewis rats immunized with rM, the development of hallmark histological features akin to RF/RHD, both in the myocardial and in valvular tissue have been reported, with the generation of heart tissue cross reactive antibodies and T cells. However, studies of cardiac function are more challenging in such a model. Recently a Lewis rat model of Sydenham’s chorea (SC and related neuropsychiatric disorders has also been described. Rodent models are very useful for assessing disease mechanisms due to the availability of reagents to precisely determine sequential events following infection with GAS or post-challenge with specific proteins and or carbohydrate preparations from GAS. However, studies of cardiac function are more problematic in such models. In this review an historical overview of animal models previously used and those that are currently available will be discussed in terms of their usefulness in modelling different aspects of the disease process. Ultimately, cardiologists, microbiologists, immunologists and physiologists may have to resort to diverse models to investigate different aspects of RF/RHD.

  11. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    Science.gov (United States)

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  12. Prevention of diseases after menopause.

    Science.gov (United States)

    Lobo, R A; Davis, S R; De Villiers, T J; Gompel, A; Henderson, V W; Hodis, H N; Lumsden, M A; Mack, W J; Shapiro, S; Baber, R J

    2014-10-01

    Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

  13. Re-Emergence of Zika Virus: A Review on Pathogenesis, Clinical Manifestations, Diagnosis, Treatment, and Prevention.

    Science.gov (United States)

    Shuaib, Waqas; Stanazai, Hashim; Abazid, Ahmad G; Mattar, Ahmed A

    2016-08-01

    Zika virus (ZKV) is an arbovirus of the Flaviviridae family, which includes West Nile, dengue fever, yellow fever, and Japanese encephalitis virus. It is transmitted by the Aedes genus of mosquitoes. Before 2015, ZKV outbreaks occurred in areas of Africa, the Pacific Islands, and Southeast Asia. The current large outbreak, which began in Brazil, has also emerged throughout a large part of South/Central America, a number of islands in the Caribbean, including Puerto Rico, the Virgin Islands, and Mexico. A sudden rise in the numbers of infants reported born with microcephaly in Brazil, and the detection of the single-stranded positive RNA virus in the amniotic fluid of affected newborns, has captured medical, mainstream media, and global political attention, causing considerable concern in a post-Ebola global community considerably more focused on the threat of internationally transmissible diseases. The goal of this article is to provide an overview of ZKV for clinicians, with the emphasis on pathogenesis, clinical manifestations, diagnosis, and treatment/preventive measures.

  14. New Concepts of Pathogenesis in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Claudio Fiocchi

    1995-01-01

    Full Text Available The precise etiology and mechanisms of inflammatory bowel disease (IBD are still unclear. Nevertheless, several concepts are gaining acceptance and constitute the basis for a better understanding of its pathogenesis and for improved therapy. The association of Crohn’s disease (CD and ulcerative colitis (UC with ‘western’ lifestyle is well recognized, and is considered a reason for the increasing frequency of CD and UC in countries with previously low incidence. Proposed linkages of CD and UC with particular human leukocyte antigen haplotypes suggest a genetic predisposition, but no uniform or consistent patterns have emerged. Similarly, the study of susceptibility or disease markers has not offered reproducible results. The search for specific infectious agents is being pursued, and the measles virus is presently considered a possible culprit. A true explosion has occurred in the area of animal models, and a large number of chemically or genetically induced experimental colitides are at hand. Immunological factors continue to dominate the bulk of basic research in IBD. This area is vast and complex, and autoantibodies, immune, epithelial and mesenchymal cells, lipid mediators, cytokines, neuropeptides and oxygen metabolites are under investigation. Finally, other factors whose role in IBD is uncertain, including smoking and possible abnormalities of intestinal permeability or mucus composition, continue to receive attention. These extensive and varied efforts are yielding some profits, and new forms of therapy are being devised. Based mostly on studies of soluble mediators, a number of novel immunosuppressive and highly specific blocking agents are being developed and undergoing clinical trials.

  15. Inflammatory bowel disease: etiology, pathogenesis and current therapy.

    Science.gov (United States)

    Ko, Joshua K; Auyeung, Kathy K

    2014-01-01

    Ulcerative colitis (UC) and Crohn's disease (CD) constitute the two major groups of idiopathic disorders in inflammatory bowel disease (IBD). Environmental factors, genetic factors and immune responses have been considered as the major etiology of IBD. Despite the diversified pathogenesis of the disease, no guaranteed curative therapeutic regimen has been developed so far. This review summarizes the knowledge on the pathophysiology and current treatment approaches of IBD. Since IBD is caused by excessive and tissue- disruptive inflammatory reactions of the gut wall, down-regulation of the immune responses may allow the damaged mucosa to heal and reset the physiological functions of the gut back to normal. Current pharmacotherapy through modulation of neutrophil-derived factors, cytokines, adhesion molecules and reactive oxygen/nitrogen metabolites has been utterly described. Categories of treatment modalities include corticosteroids, aminosalicylates, immunomodulators, antibiotics, probiotics, and a series of unique novel agents. The use of anti-tumor necrosis factor monoclonal antibody (Infliximab), recombinant anti-inflammatory cytokines and related gene therapy has been covered. In addition, discussions on dietary supplementation and heparin treatment are also included. The anti-inflammatory and immunoregulatory potential of investigational agents such as nicotine and the filtered protective compounds from tobacco smoke, as well as active herbal medicinal compounds were tested in our previous experimental works, whereas promising findings have been presented here. With the discovery of novel target-oriented agents, more effective and relatively harmless approaches of IBD therapy could be established to achieve a curative outcome. Indeed, more experimental and clinical studies are needed to confirm the relevance of these therapies.

  16. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease.

    Science.gov (United States)

    Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-10-01

    It has been hypothesized that alterations in the composition of the gut microbiota might be associated with the onset of certain human pathologies, such as Alzheimer disease, a neurodegenerative syndrome associated with cerebral accumulation of amyloid-β fibrils. It has been shown that bacteria populating the gut microbiota can release significant amounts of amyloids and lipopolysaccharides, which might play a role in the modulation of signaling pathways and the production of proinflammatory cytokines related to the pathogenesis of Alzheimer disease. Additionally, nutrients have been shown to affect the composition of the gut microbiota as well as the formation and aggregation of cerebral amyloid-β. This suggests that modulating the gut microbiome and amyloidogenesis through specific nutritional interventions might prove to be an effective strategy to prevent or reduce the risk of Alzheimer disease. This review examines the possible role of the gut in the dissemination of amyloids, the role of the gut microbiota in the regulation of the gut-brain axis, the potential amyloidogenic properties of gut bacteria, and the possible impact of nutrients on modulation of microbiota composition and amyloid formation in relation to the pathogenesis of Alzheimer disease. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Office of Disease Prevention and Health Promotion

    Science.gov (United States)

    ... Patient Safety Healthy People healthfinder The Office of Disease Prevention and Health Promotion Our Work The Office of Disease Prevention and Health Promotion (ODPHP) leads efforts to improve ...

  18. Involvement of Fas/FasL system in the pathogenesis of autoimmune diseases and Wilson's disease.

    Science.gov (United States)

    Stassi, G; Di Felice, V; Todaro, M; Cappello, F; Zummo, G; Farina, F; Trucco, M; De Maria, R

    1999-01-01

    The interaction of Fas with FasL has been demonstrated to be implicated in the pathogenesis of several autoimmune and liver diseases. Recently, attention has been focused on the hypothesis that thyrocytes and beta cells undergo massive Fas/FasL-mediated apoptosis during autoimmune response. Similarly, hepatocyte cell death occurring following copper accumulation points towards the same mechanism.

  19. Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis.

    Science.gov (United States)

    Viola, Kirsten L; Klein, William L

    2015-02-01

    Protein aggregation is common to dozens of diseases including prionoses, diabetes, Parkinson's and Alzheimer's. Over the past 15 years, there has been a paradigm shift in understanding the structural basis for these proteinopathies. Precedent for this shift has come from investigation of soluble Aβ oligomers (AβOs), toxins now widely regarded as instigating neuron damage leading to Alzheimer's dementia. Toxic AβOs accumulate in AD brain and constitute long-lived alternatives to the disease-defining Aβ fibrils deposited in amyloid plaques. Key experiments using fibril-free AβO solutions demonstrated that while Aβ is essential for memory loss, the fibrillar Aβ in amyloid deposits is not the agent. The AD-like cellular pathologies induced by AβOs suggest their impact provides a unifying mechanism for AD pathogenesis, explaining why early stage disease is specific for memory and accounting for major facets of AD neuropathology. Alternative ideas for triggering mechanisms are being actively investigated. Some research favors insertion of AβOs into membrane, while other evidence supports ligand-like accumulation at particular synapses. Over a dozen candidate toxin receptors have been proposed. AβO binding triggers a redistribution of critical synaptic proteins and induces hyperactivity in metabotropic and ionotropic glutamate receptors. This leads to Ca(2+) overload and instigates major facets of AD neuropathology, including tau hyperphosphorylation, insulin resistance, oxidative stress, and synapse loss. Because different species of AβOs have been identified, a remaining question is which oligomer is the major pathogenic culprit. The possibility has been raised that more than one species plays a role. Despite some key unknowns, the clinical relevance of AβOs has been established, and new studies are beginning to point to co-morbidities such as diabetes and hypercholesterolemia as etiological factors. Because pathogenic AβOs appear early in the disease, they

  20. Microglial Activation in the Pathogenesis of Huntington's Disease.

    Science.gov (United States)

    Yang, Hui-Ming; Yang, Su; Huang, Shan-Shan; Tang, Bei-Sha; Guo, Ji-Feng

    2017-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by expanded CAG trinucleotide repeats (>36) in exon 1 of HTT gene that encodes huntingtin protein. Although HD is characterized by a predominant loss of neurons in the striatum and cortex, previous studies point to a critical role of aberrant accumulation of mutant huntingtin in microglia that contributes to the progressive neurodegeneration in HD, through both cell-autonomous and non-cell-autonomous mechanisms. Microglia are resident immune cells in the central nervous system (CNS), which function to surveil the microenvironment at a quiescent state. In response to various pro-inflammatory stimuli, microglia become activated and undergo two separate phases (M1 and M2 phenotype), which release pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), anti-inflammatory cytokines, and growth factors (TGF-β, CD206, and Arg1), respectively. Immunoregulation by microglial activation could be either neurotoxic or neuroprotective. In this review, we summarized current understanding about microglial activation in the pathogenesis and progression of HD, with a primary focus of M1 and M2 phenotype of activated microglia and their corresponding signaling pathways.

  1. Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Martin

    2011-01-01

    Full Text Available Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Parkinson's disease, supranuclear palsy, Huntington's disease, and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This paper focuses on the possible molecular mechanisms by which transglutaminase activity could be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases, and on the possible therapeutic effects of selective transglutaminase inhibitors for the cure of patients with diseases characterized by aberrant transglutaminase activity.

  2. A microarray screen for novel candidate genes in coeliac disease pathogenesis

    NARCIS (Netherlands)

    Diosdado, B; Wapenaar, MC; Franke, L; Duran, KJ; Goerres, MJ; Hadithi, M; Crusius, JBA; Meijer, JWR; Duggan, DJ; Mulder, CJJ; Holstege, FCP; Wijmenga, C

    Background and aims: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. Methods: cDNA microarrays representing 19

  3. [Understanding and treatment strategy of the pathogenesis of periodontal disease based on chronic inflammation].

    Science.gov (United States)

    Murakami, Tomohiko

    2016-05-01

    Prolonged inflammation continuously promotes the infiltration of macrophages in the organization and chronically induces the production of pro-inflammatory cytokines such as TNF and IL-1. In periodontal tissues, these inflammatory cytokines enhance the differentiation and activity of osteoclasts, which cause destruction of the alveolar bone. Therefore, inhibition of inflammatory cytokine production leads to the prevention or treatment of periodontal disease. IL-1 is a pro-inflammatory cytokine that strongly enhances the bone-resorbing activity of osteoclasts. Elucidation of mechanisms for the production of IL-1 is critical for understanding the pathogenesis of periodontal disease. This paper reviews recent findings of the molecular mechanisms regulating IL-1 production and focuses on inflammasome.

  4. Banting Lecture 2009: An Unfinished Journey: Molecular Pathogenesis to Prevention of Type 1A Diabetes

    Science.gov (United States)

    Eisenbarth, George S.

    2010-01-01

    The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Dr. Eisenbarth received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 69th Scientific Sessions, June 5–9, 2009, in New Orleans, Louisiana. He presented the Banting Lecture, An Unfinished Journey—Type 1 Diabetes—Molecular Pathogenesis to Prevention, on Sunday, June 7, 2009. PMID:20350969

  5. Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Sergio Rutella; Franco Locatelli

    2011-01-01

    The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens. For these reasons, the intestinal immune system is uniquely dedicated to protect against infections, while avoiding the development of destructive inflammatory responses to the microbiota. Several models have been proposed to explain how the immune system discriminates between, and appropriately responds to, commensal and pathogenic microorganisms. Dendritic cells (DCs) and regulatory T cells (Treg) are instrumental in maintaining immune homeostasis and tolerance in the gut. DCs are virtually omnipresent and are remarkably plastic, having the ability to adapt to the influences of the microenvironment. Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations. DCs in the draining mesenteric lymph nodes, in the intestinal lamina propria and in Peyer's patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance. In this respect, gut-resident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria. In contrast, migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses. Importantly, tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation, as shown both in pre-clinical models of colitis and in patients with inflammatory bowel disease (IBD). This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD. It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.

  6. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Agostinho, Paula; Cunha, Rodrigo A; Oliveira, Catarina

    2010-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the elderly. The increase of life-expectancy is transforming AD into a major health-care problem. AD is characterized by a progressive impairment of memory and other cognitive skills leading to dementia. The major pathogenic factor associated to AD seems to be amyloid-beta peptide (Aβ) oligomers that tend to accumulate extracellularly as amyloid deposits and are associated with reactive microglia and astrocytes as well as with degeneration of neuronal processes. The involvement of microglia and astrocytes in the onset and progress of neurodegenerative process in AD is becoming increasingly recognized, albeit it is commonly accepted that neuroinflammation and oxidative stress can have both detrimental and beneficial influences on the neural tissue. However, little is known about the interplay of microglia, astrocytes and neurons in response to Aβ, especially in the early phases of AD. This review discusses current knowledge about the involvement of neuroinflammation in AD pathogenesis, focusing on phenotypic and functional responses of microglia, astrocytes and neurons in this process. The abnormal production by glia cells of pro-inflammatory cytokines, chemokines and the complement system, as well as reactive oxygen and nitrogen species, can disrupt nerve terminals activity causing dysfunction and loss of synapses, which correlates with memory decline; these are phenomena preceding the neuronal death associated with late stages of AD. Thus, therapeutic strategies directed at controlling the activation of microglia and astrocytes and the excessive production of pro-inflammatory and pro-oxidant factors may be valuable to control neurodegeneration in dementia.

  7. Vaccine Preventable Disease on Campus.

    Science.gov (United States)

    Bart, Kenneth J.

    1984-01-01

    While morbidity and mortality from vaccine preventable diseases have declined, some college students remain susceptible to measles, rubella, diptheria, tetanus, or polio. Colleges and universities have the opportunity to ensure protection of students, faculty, and employees by establishing and enforcing immunization requirements. (Author/DF)

  8. Conduction Exercise Therapy in the Prevention and Treatment of Asthenopia Syndrome Based on Treatise on the Pathogenesis and Manifestations of All Diseases%基于《诸病源候论》导引法编创的"视疲劳防治五步功"阐释

    Institute of Scientific and Technical Information of China (English)

    吴晓云; 刘天君

    2012-01-01

    本研究在对导引法进行系统整理基础上,针对视疲劳的病因病机,以该篇中适合的导引条目为主,编创了一套"视疲劳防治五步功".除起式和收式外,该功法有5节正功:摩掌熨目、摩按眼周、亢引捏颈、仰趾益气、引气注目.本文从导引原文、功法操作、技术要领和功理阐释4个方面,对每一节功法进行详细说明.此为古法今用的尝试,体现了传统中医养生治未病的特色.%On the base of analyzing and studying on the Conduction Exercise in Treatise on the Pathogenesis and Manifestations of All Diseases and combining with pathogenesis of asthenopia syndrome, the authors created a set of Conduction Exercise method for preventing and treating asthenopia syndrome through selecting carefully the entries of Daoyin method mainly in Zhubing Yuanhou Lun. Besides the starting step and ending step, there are five sections. The names of these five sections are friction palms to heat the eyes, friction and pressing around the eyes, bend head back and pinch the neck, make toes dorsiflexion to nurture Qi, guiding the Qi to pour the eyes. Every section was specified from the original text, Daoyin method, exercise essentials and principle explanation. The Conduction Exercise method is a new attempt in using of ancient Daoyin method and extending modern TCM measures for health preserving and disease curing.

  9. MicroRNAs in inflammatory bowel disease--pathogenesis, diagnostics and therapeutics

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict;

    2012-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising ...... diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics....

  10. Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Fabian A. Cabezas-Opazo

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disease that affects millions of people worldwide. Currently, there is no effective treatment for AD, which indicates the necessity to understand the pathogenic mechanism of this disorder. Extracellular aggregates of amyloid precursor protein (APP, called Aβ peptide and neurofibrillary tangles (NFTs, formed by tau protein in the hyperphosphorylated form are considered the hallmarks of AD. Accumulative evidence suggests that tau pathology and Aβ affect neuronal cells compromising energy supply, antioxidant response, and synaptic activity. In this context, it has been showed that mitochondrial function could be affected by the presence of tau pathology and Aβ in AD. Mitochondria are essential for brain cells function and the improvement of mitochondrial activity contributes to preventing neurodegeneration. Several reports have suggested that mitochondria could be affected in terms of morphology, bioenergetics, and transport in AD. These defects affect mitochondrial health, which later will contribute to the pathogenesis of AD. In this review, we will discuss evidence that supports the importance of mitochondrial injury in the pathogenesis of AD and how studying these mechanisms could lead us to suggest new targets for diagnostic and therapeutic intervention against neurodegeneration.

  11. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Junjie Shao

    2015-05-01

    Full Text Available Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV to highly virulent hemorrhagic fever (HF causing viruses such as Lassa (LASV, Junin (JUNV, Machupo (MACV, Lujo (LUJV, Sabia (SABV, Guanarito (GTOV, and Chapare (CHPV, for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

  12. Topoisomerase I in Human Disease Pathogenesis and Treatments

    Directory of Open Access Journals (Sweden)

    Min Li

    2016-06-01

    Full Text Available Mammalian topoisomerase 1 (TOP1 is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA replication and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 catalytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in promoting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treatments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

  13. Topoisomerase I in Human Disease Pathogenesis and Treatments

    Institute of Scientific and Technical Information of China (English)

    Min Li; Yilun Liu

    2016-01-01

    Mammalian topoisomerase 1 (TOP1) is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA repli-cation and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 cat-alytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in pro-moting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treat-ments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

  14. Neuropathology in transplants in Parkinson's disease: implications for disease pathogenesis and the future of cell therapy.

    Science.gov (United States)

    Brundin, Patrik; Kordower, Jeffrey H

    2012-01-01

    Neural transplantation is over a century old, but the modern era encompasses only the last 30-40 years. For most of this time period, research has focused on reversing disability engendered by neurologic disease and brain damage. Only recently was it recognized that the underlying neurological disease itself might negatively impact the grafted neurons. We have found that a subset of neurons within embryonic neural grafts that survive more than 10 years in Parkinson patients display Lewy bodies, a classical feature of Parkinson's disease neuropathology. Additionally, the grafted cells placed in the Parkinson's disease brain eventually downregulate the expression of dopamine transporter and tyrosine hydroxylase in a manner similar to what is seen in the substantia nigra dopamine neurons that are degenerating due to the disease. We discuss these findings in terms of how they might improve our understanding of Parkinson's disease pathogenesis and the effects they may have on the future of neural cell replacement strategies.

  15. Do statins prevent Alzheimer's disease? A narrative review.

    Science.gov (United States)

    Daneschvar, Homayoun L; Aronson, Mark D; Smetana, Gerald W

    2015-11-01

    Alzheimer's disease is the most common cause of dementia and occurs commonly in patients 65 and older. There is an urgent need to find an effective management that could help prevent or at least slow down the progress of this major public health problem. Cholesterol related pathways might play a role in the pathogenesis of Alzheimer's disease. Treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) has been suggested to promote the prevention of Alzheimer's disease. In this review, we discuss potential pathogenetic pathways for the development of Alzheimer's disease and review the evidence regarding the value of statins as a strategy to prevent or delay progression of Alzheimer's disease. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Meningococcal disease: changes in epidemiology and prevention

    Directory of Open Access Journals (Sweden)

    Chang Q

    2012-09-01

    Full Text Available Qiuzhi Chang,1 Yih-Ling Tzeng,2 David S Stephens1–31Department of Epidemiology, Rollins School of Public Health, Emory University, 2Department of Medicine, Emory University School of Medicine, 3Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Atlanta, GAAbstract: The human bacterial pathogen Neisseria meningitidis remains a serious worldwide health threat, but progress is being made toward the control of meningococcal infections. This review summarizes current knowledge of the global epidemiology and the pathophysiology of meningococcal disease, as well as recent advances in prevention by new vaccines. Meningococcal disease patterns and incidence can vary dramatically, both geographically and over time in populations, influenced by differences in invasive meningococcal capsular serogroups and specific genotypes designated as ST clonal complexes. Serogroup A (ST-5, ST-7, B (ST-41/44, ST-32, ST-18, ST-269, ST-8, ST-35, C (ST-11, Y (ST-23, ST-167, W-135 (ST-11 and X (ST-181 meningococci currently cause almost all invasive disease. Serogroups B, C, and Y are responsible for the majority of cases in Europe, the Americas, and Oceania; serogroup A has been associated with the highest incidence (up to 1000 per 100,000 cases and large outbreaks of meningococcal disease in sub-Saharan Africa and previously Asia; and serogroups W-135 and X have emerged to cause major disease outbreaks in sub-Saharan Africa. Significant declines in meningococcal disease have occurred in the last decade in many developed countries. In part, the decline is related to the introduction of new meningococcal vaccines. Serogroup C polysaccharide-protein conjugate vaccines were introduced over a decade ago, first in the UK in a mass vaccination campaign, and are now widely used; multivalent meningococcal conjugate vaccines containing serogroups A, C, W-135, and/or Y were first used for adolescents in the US in 2005 and have now expanded

  17. Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Joshua S. Lichtman

    2016-02-01

    Full Text Available Improved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem.

  18. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-01-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

  19. Prevention of pelvic radiation disease

    Institute of Scientific and Technical Information of China (English)

    Lorenzo; Fuccio; Leonardo; Frazzoni; Alessandra; Guido

    2015-01-01

    Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal(GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessmentmethod, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.

  20. Proteomics in Veterinary Medicine: Applications and Trends in Disease Pathogenesis and Diagnostics

    National Research Council Canada - National Science Library

    Ceciliani, F; Eckersall, D; Burchmore, R; Lecchi, C

    2014-01-01

    ... of proteomics in the field of veterinary medicine. The aim of the present review is to provide an in-depth perspective about the application of proteomics to animal disease pathogenesis, as well as its utilization in veterinary diagnostics...

  1. Centers for Disease Control and Prevention

    Science.gov (United States)

    ... to site content En español Centers for Disease Control and Prevention CDC 24/7: Saving Lives. Protecting People.™ Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People ...

  2. How Can Heart Disease be Prevented?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Can Heart Disease Be Prevented? Taking action to control your risk factors can help prevent or delay coronary heart disease (CHD). Your risk for CHD increases with the ...

  3. Preventing Heart Disease - At Any Age

    Science.gov (United States)

    ... Food and Beverage Toolkit How to Help Prevent Heart Disease - At Any Age Updated:Apr 3,2017 You’ ... Here’s how: What You Can Do to Prevent Heart Disease All Age Groups No matter what your age, ...

  4. Legionella (Legionnaires' Disease and Pontiac Fever): Prevention

    Science.gov (United States)

    ... Program Unexplained Respiratory Disease Outbreaks (URDO) European Legionnaires’ Disease Surveillance Network (ELDSNet) Prevention Language: English Español (Spanish) Recommend on Facebook Tweet ...

  5. Clinical implications of shared genetics and pathogenesis in autoimmune diseases.

    Science.gov (United States)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-11-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the presence of autoreactive T cells. They are caused by a complex genetic predisposition that is attributable to multiple genetic variants, each with a moderate-to-low effect size. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. Here, we review the shared and specific genetic background of autoimmune diseases, summarize their treatment options and discuss how identifying the genetic and environmental factors that predispose patients to an autoimmune disease can help in the diagnosis and monitoring of patients, as well as the design of new treatments.

  6. Pathogenesis of Nonsteroidal Anti-Inflammatory Drug Gastropathy: Clues to Preventative Therapy

    Directory of Open Access Journals (Sweden)

    Salim MA Bastaki

    1999-01-01

    Full Text Available Gastric ulceration and bleeding are major impediments to the chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs. The development of effective therapies for prevention of these adverse effects requires better understanding of their pathogenesis. Several features of NSAIDs contribute to the development of damage in the stomach, including the topical irritant effects of these drugs on the epithelium, impairment of the barrier properties of the mucosa, suppression of gastric prostaglandin synthesis, reduction of gastric mucosal blood flow and interference with the repair of superficial injury. The presence of acid in the lumen of the stomach also contributes to the pathogenesis of NSAID-induced ulcers and bleeding in a number of ways. Acid impairs the restitution process, interferes with hemostasis and can inactivate several growth factors that are important in mucosal integrity and repair. Profound suppression of gastric acid secretion has been shown to be effective in preventing NSAID-induced ulceration. There is a strong possibility that new NSAIDs entering the market will have greatly reduced toxicity in the gastrointestinal tract.

  7. Prevention and treatment of chronic lung disease

    Directory of Open Access Journals (Sweden)

    Fabio Mosca

    2013-06-01

    Full Text Available The increased survival among very low birth weight (VLBW contributes to the overall increase in the incidence of chronic lung disease (CLD, also known as bronchopulmonary dysplasia (BPD, that remains a major complication of prematurity. The long-term health consequences of BPD include early and long term respiratory disease, susceptibility to respiratory infections, pulmonary hypertension, repeated hospitalizations, neurodevelopmental impairment and increased mortality. BPD pathogenesis is multifactorial and includes exposure to mechanical ventilation, oxygen toxicity, infection, and inflammation, but the real causes in single individuals have not been well clarified. In this review the current and potential future postnatal pharmacological (caffeine, diuretics, postnatal corticosteroids, bronchodilators, pulmonary vasodilators, anti-oxidants and non-pharmacological  strategies (ventilatory support, stem cells in the prevention and management of BPD will be presented. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  8. Linear IgA disease: clinical presentation, diagnosis, and pathogenesis.

    Science.gov (United States)

    Venning, Vanessa A

    2012-05-01

    Linear IgA disease is one of the rarer subepidermal blistering diseases. Linear IgA disease is a chronic, acquired, autoimmune blistering disease that is characterized by subepidermal blistering and linear deposition of IgA basement membrane antibodies. The disease affects both children and adults and, although there are some differences in their clinical presentations, there is considerable overlap with shared immunopathology and immunogenetics. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Macrophage models of Gaucher disease for evaluating disease pathogenesis and candidate drugs.

    Science.gov (United States)

    Aflaki, Elma; Stubblefield, Barbara K; Maniwang, Emerson; Lopez, Grisel; Moaven, Nima; Goldin, Ehud; Marugan, Juan; Patnaik, Samarjit; Dutra, Amalia; Southall, Noel; Zheng, Wei; Tayebi, Nahid; Sidransky, Ellen

    2014-06-11

    Gaucher disease is caused by an inherited deficiency of glucocerebrosidase that manifests with storage of glycolipids in lysosomes, particularly in macrophages. Available cell lines modeling Gaucher disease do not demonstrate lysosomal storage of glycolipids; therefore, we set out to develop two macrophage models of Gaucher disease that exhibit appropriate substrate accumulation. We used these cellular models both to investigate altered macrophage biology in Gaucher disease and to evaluate candidate drugs for its treatment. We generated and characterized monocyte-derived macrophages from 20 patients carrying different Gaucher disease mutations. In addition, we created induced pluripotent stem cell (iPSC)-derived macrophages from five fibroblast lines taken from patients with type 1 or type 2 Gaucher disease. Macrophages derived from patient monocytes or iPSCs showed reduced glucocerebrosidase activity and increased storage of glucocerebroside and glucosylsphingosine in lysosomes. These macrophages showed efficient phagocytosis of bacteria but reduced production of intracellular reactive oxygen species and impaired chemotaxis. The disease phenotype was reversed with a noninhibitory small-molecule chaperone drug that enhanced glucocerebrosidase activity in the macrophages, reduced glycolipid storage, and normalized chemotaxis and production of reactive oxygen species. Macrophages differentiated from patient monocytes or patient-derived iPSCs provide cellular models that can be used to investigate disease pathogenesis and facilitate drug development.

  10. Role of adipokines in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Pallavi M

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the hepatic manife-station of metabolic syndrome. The increased prevalence of obesity, diabetes, hypertension, hypertriglyceridaemia and hypercholesterolemia are considered to be the potential causative factors for NAFLD. NAFLD is emerging as a major clinical problem worldwide. Recently much attention has been focused in India as the prevalence of obesity and diabetes is rising. NAFLD is responsible for unexplained raise in transaminases, and an important cause of cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in India. NAFLD is a spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, potentially leading to fibrosis and cirrhosis. Studies have suggested that the adipokines are involved in the pathogenesis of NAFLD and its progression to NASH, through their metabolic and pro- or anti-inflammatory activity. Adipokines in particular tumor necrosis factor-α and interleukin-6 are believed to mediate the shift in pathology from steatosis to steatohepatitis. In addition, other adipokines such as adiponectin, leptin and resistin also play a crucial role in the development and progression of NAFLD through their metabolic and pro–or anti-inflammatory activity. This suggests that imbalance between pro-inflammatory and anti-inflammatory cytokines may have a role in the development of liver damage in NAFLD. Understanding the relationship between adipokines and NAFLD may play an important role in the early identification /diagnosis, treatment and also help in preventing disease progression.

  11. The base moments in etiological prevention of peri-odontal disease in children and adolescents

    OpenAIRE

    2011-01-01

    Anatomical and physiological features of the growing organism requires a different approach to prevention and treatment of periodontal disease. This article presents the highlights of the etiological prevention of periodontal diseases, taking into account the anatomical and physiological, and psycho-emotional features of childhood, are based on current data on the prevalence periodontal disease in children, recent research findings in the etiology and patho-genesis of periodontal disease

  12. The base moments in etiological prevention of peri-odontal disease in children and adolescents

    Directory of Open Access Journals (Sweden)

    Kharitonova T.L.

    2011-03-01

    Full Text Available Anatomical and physiological features of the growing organism requires a different approach to prevention and treatment of periodontal disease. This article presents the highlights of the etiological prevention of periodontal diseases, taking into account the anatomical and physiological, and psycho-emotional features of childhood, are based on current data on the prevalence periodontal disease in children, recent research findings in the etiology and patho-genesis of periodontal disease

  13. Dopaminergic neuronal imaging in genetic Parkinson's disease: insights into pathogenesis.

    Directory of Open Access Journals (Sweden)

    Alisdair McNeill

    Full Text Available OBJECTIVES: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease. METHODS: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated. RESULTS: Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin. The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations. CONCLUSIONS: The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss.

  14. Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease

    OpenAIRE

    2012-01-01

    A wealth of evidence indicates a fundamental role for inflammation in the pathogenesis of cardiovascular disease (CVD), contributing to the development and progression of atherosclerotic lesion formation, plaque rupture, and thrombosis. An increasing body of evidence supports a functional role for complement activation in the pathogenesis of CVD through pleiotropic effects on endothelial and haematopoietic cell function and haemostasis. Prospective and case control studies have reported stron...

  15. Influence of intestinal microbiota in celiac disease pathogenesis and risk

    OpenAIRE

    OLIVARES SEVILLA, MARTA

    2015-01-01

    [EN] Celiac disease (CD) is a chronic enteropathy triggered by cereal gluten proteins in genetically predisposed individuals. The etiology is strongly associated with the genes of the human leukocyte antigen (HLA) encoding the DQ2/DQ8 molecules. Most CD patients carry this genotype but this is also present in the 40% of the general population and only a small percentage develops the disease. Thus, the HLA-DQ genotype is necessary but not solely responsible for the disease development. Gluten ...

  16. Peptic Ulcer Disease Different Pathogenesis of Duodenal and Gastric Ulcer

    OpenAIRE

    Hendra Koncoro; I Dewa Nyoman Wibawa

    2015-01-01

    Despite decrease frequency of Helicobacter pylori (H. pylori) due to eradication therapy, peptic ulcer disease as a manifestation of this infection is still remain a health burden. Understanding the physiology of gastric acid secretion and its alteration by H. pylori induced inflammation will aid physician in differentiating peptic ulcer disease based on its location. Duodenal ulcer and gastric ulcer disease are two common condition that usually found in peptic ulcer. Recognition of symptoms ...

  17. Kawasaki Disease: Complications, Treatment and Prevention

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Kawasaki Disease: Complications, Treatment and Prevention Updated:May 8, ... possibility of heart and coronary artery involvement makes Kawasaki disease unpredictable, but these problems usually are not ...

  18. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    Science.gov (United States)

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  19. Osteoarthritis: pathogenesis and therapeutic interventions for a whole joint disease

    NARCIS (Netherlands)

    M. Siebelt (Michiel)

    2015-01-01

    markdownabstract__Abstract__ Osteoarthritis (OA) is an invalidating disease characterized by progressive cartilage degradation. OA is the most prevalent arthritic disease and leading cause of disability that effects approximately 34% of the population in the United states over age 65. Also in the

  20. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

    NARCIS (Netherlands)

    A. McNeill (Alisdair); R-M. Wu (Ruey-Meei); K.-Y. Tzen (Kai-Yuan); P.C. Aguiar (Patricia); J.M. Arbelo (Jose); P. Barone (Paolo); K.P. Bhatia (Kailash); O.G. Barsottini (Orlando); V. Bonifati (Vincenzo); S. Bostantjopoulou (Sevasti); R.A. Bressan (Rodrigo); G. Cossu (Giovanni); P. Cortelli (Pietro); A.C. Felicio (Andre); H.B. Ferraz (Henrique); J. Herrera (Joanna); H. Houlden (Henry); M. Hoexter (Marcelo); C. Isla (Concepcion); A.J. Lees (Andrew); O. Lorenzo-Betancor (Oswaldo); N.E. Mencacci (Niccolo); P. Pastor (Pau); S. Pappata (Sabina); M.T. Pellecchia (Maria Teresa); L. Silveria-Moriyama (Laura); A. Varrone (Andrea); T. Foltynie (Thomas); A.H.V. Schapira (Anthony)

    2013-01-01

    textabstractObjectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated fo

  1. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

    NARCIS (Netherlands)

    A. McNeill (Alisdair); R-M. Wu (Ruey-Meei); K.-Y. Tzen (Kai-Yuan); P.C. Aguiar (Patricia); J.M. Arbelo (Jose); P. Barone (Paolo); K.P. Bhatia (Kailash); O.G. Barsottini (Orlando); V. Bonifati (Vincenzo); S. Bostantjopoulou (Sevasti); R.A. Bressan (Rodrigo); G. Cossu (Giovanni); P. Cortelli (Pietro); A.C. Felicio (Andre); H.B. Ferraz (Henrique); J. Herrera (Joanna); H. Houlden (Henry); M. Hoexter (Marcelo); C. Isla (Concepcion); A.J. Lees (Andrew); O. Lorenzo-Betancor (Oswaldo); N.E. Mencacci (Niccolo); P. Pastor (Pau); S. Pappata (Sabina); M.T. Pellecchia (Maria Teresa); L. Silveria-Moriyama (Laura); A. Varrone (Andrea); T. Foltynie (Thomas); A.H.V. Schapira (Anthony)

    2013-01-01

    textabstractObjectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated

  2. Hidradenitis suppurativa : Pathogenesis, burden of disease and surgical strategies

    NARCIS (Netherlands)

    Janse, Ineke Christina

    2016-01-01

    The general aim of this thesis was to gain more knowledge about the cause, burden and surgical treatment of hidradenitis suppurativa (HS). HS is a chronic, debilitating inflammatory skin disease affecting the inguinal, axillary and gluteal regions. The disease usually develops after puberty, and the

  3. Hidradenitis suppurativa : Pathogenesis, burden of disease and surgical strategies

    NARCIS (Netherlands)

    Janse, Ineke Christina

    2016-01-01

    The general aim of this thesis was to gain more knowledge about the cause, burden and surgical treatment of hidradenitis suppurativa (HS). HS is a chronic, debilitating inflammatory skin disease affecting the inguinal, axillary and gluteal regions. The disease usually develops after puberty, and the

  4. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

    NARCIS (Netherlands)

    A. McNeill (Alisdair); R-M. Wu (Ruey-Meei); K.-Y. Tzen (Kai-Yuan); P.C. Aguiar (Patricia); J.M. Arbelo (Jose); P. Barone (Paolo); K.P. Bhatia (Kailash); O.G. Barsottini (Orlando); V. Bonifati (Vincenzo); S. Bostantjopoulou (Sevasti); R.A. Bressan (Rodrigo); G. Cossu (Giovanni); P. Cortelli (Pietro); A.C. Felicio (Andre); H.B. Ferraz (Henrique); J. Herrera (Joanna); H. Houlden (Henry); M. Hoexter (Marcelo); C. Isla (Concepcion); A.J. Lees (Andrew); O. Lorenzo-Betancor (Oswaldo); N.E. Mencacci (Niccolo); P. Pastor (Pau); S. Pappata (Sabina); M.T. Pellecchia (Maria Teresa); L. Silveria-Moriyama (Laura); A. Varrone (Andrea); T. Foltynie (Thomas); A.H.V. Schapira (Anthony)

    2013-01-01

    textabstractObjectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated fo

  5. Cytokines in Gaucher disease: Role in the pathogenesis of bone ...

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    2015-03-03

    Mar 3, 2015 ... The impact of therapy on bone manifestations of Gaucher disease . .... [3,15]. A recent study points to the fundamental role for. GBA (glucosidase, b, acid) ... phage-inflammatory protein-1 (MIP-1), pulmonary and activa- tion–regulated .... In contrast, autopsy reports of almost all patients with type 2 disease ...

  6. Prevention Of Chronic Renal Diseases

    Directory of Open Access Journals (Sweden)

    Fejzi Alushi

    2011-10-01

    Full Text Available It is easier to prevent a disease than to cure it. This postulate is a foundation stone of the contemporary medicine, furthermore its mission. The Chronic Kidney Diseases (CKD, amongst them the Chronic Pyelonephrites (CP and the mass kidney reduction  take an important  place in human pathologies in general, and in particular in renal ones. The Chronic Pyelonephrites  are chronic renal pathologies, which on one side are of various causes and on the other side are multi systemic. At the same time they tend, earlier or later, depending on their course, to bring the patient towards the Chronic Kidney Insufficiency  in stage of uremia, consequently in need of substitution therapies e.g. dialysis, peritoneum dialysis or transplant. It is worthy to emphasize that from the prevention and correct cure of CP make profit the patients, the family, the state and in the last analyses  the entire society, because in that way the budget expense destined for the fore going substitution cures, dialysis, peritoneum dialysis or transplant, is considerably  reduced. The same should be mentioned  in relation to the CP and the mass kidney reduction, speaking about our country, which are still at the first place as the very cause of Chronic Kidney  Insufficiencies (CRI, later on advancing toward uremia and terminal uremia along with its grave consequences. In general  the very foundation of the CP is on  the  infections of urinary roads, in particular on the complicated ones, among them it should be mentioned-congenital kidney anomalies, renal calculosis  so much present in our country, and pathologies of segment or vesical-ureteral reflux, and rarely the pathologies of prostate.

  7. The changing faces of IgG4-related disease: Clinical manifestations and pathogenesis.

    Science.gov (United States)

    Islam, Arshia Duza; Selmi, Carlo; Datta-Mitra, Ananya; Sonu, Rebecca; Chen, Mingyi; Gershwin, M Eric; Raychaudhuri, Siba P

    2015-10-01

    Since the earliest reports in 2001, immunoglobulin G4 (IgG4)-related disease has been defined as an autoimmune systemic disease characterized by the lymphoplasmacytic infiltration of affected tissues leading to fibrosis and obliterative phlebitis along with elevated serum IgG4 levels. Prior to this unifying hypothesis, a plethora of clinical manifestations were considered as separate entities despite the similar laboratory profile. The pathology can be observed in virtually all organs and may thus be a challenging diagnosis, especially when the adequate clinical suspicion is not present or when obtaining a tissue biopsy is not feasible. Nonetheless, the most frequently involved organs are the pancreas and exocrine glands but these may be spared. Immunosuppressants lead to a prompt clinical response in virtually all cases and prevent histological sequelae and, as a consequence, an early differential diagnosis from other conditions, particularly infections and cancer, as well as an early treatment should be pursued. We describe herein two cases in which atypical disease manifestations were observed, i.e., one with recurrent neck lymph node enlargement and proptosis, and one with jaundice. Our understanding of the pathogenesis of IgG4-related disease is largely incomplete but data support a significant role for Th2 cytokines with the contribution of innate immunity factors such as Toll-like receptors, macrophages and basophils. Further, macrophages activated by IL4 overexpress B cell activating factors and contribute to chronic inflammation and the development of fibrosis. We cannot rule out the possibility that the largely variable disease phenotypes reflect different pathogenetic mechanisms and the tissue microenvironment may then contribute to the organ involvement.

  8. Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology

    Science.gov (United States)

    In 2014, the GFRA (Global Foot-and-mouth disease Research Alliance) conducted a gap analysis of FMD (Foot-and-Mouth Disease) research. This work has been updated and reported in a series of papers, in this article we report findings in the fields of 1) pathogenesis and 2) molecular biology. The arti...

  9. Pathogenesis, diagnosis, and management of severe pelvic inflammatory disease and tuboovarian abscess.

    Science.gov (United States)

    Chappell, Catherine A; Wiesenfeld, Harold C

    2012-12-01

    Severe pelvic inflammatory disease and tuboovarian abscesses (TOAs) are common pelvic infections requiring inpatient admission. There are few large randomized trials guiding appropriate clinical management of TOA, including antibiotic selection and timing of surgical management and drainage. The pathogenesis, diagnosis, and management of severe pelvic inflammatory disease and TOA are summarized and reviewed from the most current literature.

  10. The epidemiology and the pathogenesis of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Karlinger, Kinga E-mail: karlking@radi.sote.hu; Gyoerke, Tamas; Makoe, Erno; Mester, Adam; Tarjan, Zsolt

    2000-09-01

    The etiology of inflammatory bowel disease (IBD) is still unknown. However, a satisfactory solution cannot be far away. IBD actually encompasses two diseases, i.e. Crohn's disease (CD) and ulcerous colitis (UC). These diseases resemble each other so closely that they cannot be distinguished even pathologically, but differ from each other sufficiently to regard them as independent entities. Epidemiological observations may be helpful in identifying the true causative factors of this evasive disease. Geographically, the prevalence of the disease has a slope from North to South and, to a lesser degree, from West to East. The Western-Eastern discrepancy can be attributed to a difference in Western life styles. The incidence of the disease has been increasing world-wide of late, but its spread has been slowing down in highly affected countries. Racial and ethnic relations in different populations and immigration studies offer interesting data which can reflect genetic, inherited, environmental and behavioural factors. The disease seems to have a characteristic racial-ethnic distribution: the Jewish population is highly susceptible everywhere, but its prevalence in that population nears that of the domestic society in which they live. In Hungary, the Roma (Gypsies) have a considerably lower prevalence than the average population. This can be attributed to a genetic or environmental influence. According to age, the onset of the disease occurs more often in the second or the third decade of life, but there also is another peak in the 60s. Regarding sexual distribution, there is a slight preponderance of colitis ulcerosa in men and of Crohn's disease in women. It may correspond to the stronger auto-immune affection in the process of Crohn's disease. Environmental factors and behavioural influences also are investigated. Diet, the role of the early ages, smoking habits and the influence of hormonal status and drugs are viewed as useful contributing factors in

  11. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

    Science.gov (United States)

    2011-01-01

    More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors. PMID:21304099

  12. Role of endoplasmic reticulum calcium signaling in the pathogenesis of Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Elena ePopugaeva

    2013-09-01

    Full Text Available Alzheimer disease (AD is a major threat of XXI century that is responsible for the majority of dementia in the elderly. Development of effective AD-preventing therapies are the top priority tasks for neuroscience research. Amyloid hypothesis of AD is a dominant idea in the field, but so far all amyloid-targeting therapies have failed in clinical trials. In addition to amyloid accumulation, there are consistent reports of abnormal calcium signaling in AD neurons. AD neurons exhibit enhanced intracellular calcium (Ca2+ liberation from the endoplasmic reticulum (ER and reduced store-operated Ca2+ entry (SOC. These changes occur primarily as a result of ER Ca2+ overload. We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease-modifying therapies. The current review summarizes recent data about changes in ER Ca2+ signaling in AD. Ca2+ channels that are discussed in the current review include: inositol trisphosphate receptors (InsP3R, ryanodine receptors (RyanR, presenilins as ER Ca2+ leak channels and neuronal SOC channels. We discuss how function of these channels is altered in AD and how important are resulting Ca2+ signaling changes for AD pathogenesis.

  13. Advances in the pathogenesis of inflammatory bowel diseases: Capri 2010.

    Science.gov (United States)

    Caprilli, Renzo; Latella, Giovanni; Frieri, Giuseppe

    2010-07-01

    The 5th International Meeting of Inflammatory Bowel Diseases was held in Capri (Italy) at Gran Hotel Quisisana from April 8 to 10, 2010. The meeting was restricted to 130 participants including invited speakers, authors of selected papers and key opinion leaders. The structure of the meeting consisted of eight sessions covering selected basic aspects of inflammatory bowel disease, and were designed to be very interactive and more focused on basic science than purely clinical aspects.

  14. Is Leishmania (Viannia braziliensis parasite load associated with disease pathogenesis?

    Directory of Open Access Journals (Sweden)

    Luiza de Oliveira Ramos Pereira

    2017-04-01

    Results and conclusion: The data revealed a tendency to higher tissue parasitism in the skin compared to mucous lesion sites and a reduction with disease progression. Parasite load was lower in poor compared to good responders to antimonials, and was also reduced in recurrent lesions compared to primary ones. However, parasite load became higher with sequential relapses, pointing to an immune system inability to control the infection. Therefore the parasite burden does not seem to be a good predictor of disease progression.

  15. The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson's Disease in Rats.

    Science.gov (United States)

    Mao, Zhijuan; Liu, Chanchan; Ji, Suqiong; Yang, Qingmei; Ye, Hongxiang; Han, Haiyan; Xue, Zheng

    2017-02-28

    The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.

  16. Recent insights into the molecular pathogenesis of Crohn's disease: a review of emerging therapeutic targets

    Directory of Open Access Journals (Sweden)

    Manuc TE

    2016-03-01

    Full Text Available Teodora-Ecaterina M Manuc,1 Mircea M Manuc,2 Mircea M Diculescu2 1Fundeni Clinical Institute, 2University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania Abstract: Chronic inflammatory bowel diseases (IBDs are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD

  17. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Huey-Kang Sytwu

    2013-05-01

    Full Text Available Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.

  18. Aetiology, classification and pathogenesis of pulp and periapical disease.

    Science.gov (United States)

    López-Marcos, Joaquín F

    2004-01-01

    At present, the majority of the treatments that are performed in the clinic are due to disease entities involving the dental pulp and periapex. Dental pulp is a richly vascularized and innervated tissue, enclosed by surrounding tissues that are incapable of expanding, such as dentin. It has terminal blood flow and small-gauge circulatory access the periapex. All of these characteristics severely constrain the defensive capacity of the pulp tissue when faced with the different aggressions it may be subjected to. Pulp tissue can also be affected by a retrograde infection, arising from the secondary canaliculi, from the periodontal ligament or from the apex during the course of periodontitis. Due to the fact that periapical disease is almost inevitably preceded by pulp disease, we shall begin by describing the causes of pulp disease and will then proceed to a discussion of the causes of periapical disease. The course of illness and classification of these pathological entities will depend on the aetiology involved. We will analyse pulp necrosis and pulp degeneration that are capable of triggering reversible apical periodontitis or irreversible apical periodontitis.

  19. Alternative RNA Splicing in the Pathogenesis of Liver Disease

    Directory of Open Access Journals (Sweden)

    Nicholas J. G. Webster

    2017-06-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is becoming increasingly prevalent due to the worldwide obesity epidemic and currently affects one-third of adults or about one billion people worldwide. NAFLD is predicted to affect over 50% of the world’s population by the end of the next decade. It is the most common form of liver disease and is associated with increased risk for progression to a more severe form non-alcoholic steatohepatitis, as well as insulin resistance, type 2 diabetes mellitus, cirrhosis, and eventually hepatocellular carcinoma. This review article will focus on the role of alternative splicing in normal liver physiology and dysregulation in liver disease.

  20. Crohn's disease: Evidence for involvement of unregulated transcytosis in disease etio-pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Jay Pravda

    2011-01-01

    Crohn's disease (CD) is a chronic inflammatory bowel disease. Research has identified genetic predisposition and environmental factors as key elements in the development of the disease. However, the precise mechanism that initiates immune activation remains undefined. One pathway for luminal antigenic molecules to enter the sterile lamina propria and activate an immune response is via transcytosis. Transcytosis, although tightly regulated by the cell, has the potential for transepithelial transport of bacteria and highly antigenic luminal molecules whose uncontrolled translocation into the lamina propria can be the source of immune activation. Viewed as a whole, the evidence suggests that unregulated intestinal epithelial transcytosis is involved in the inappropriate presentation of immunogenic luminal macromolecules to the intestinal lamina propria. Thus fulfilling the role of an early pre-morbid mechanism that can result in antigenic overload of the lamina propria and initiate an immune response culminating in chronic inflammation characteristic of this disease. It is the aim of this paper to present evidence implicating enterocyte transcytosis in the early etio-pathogenesis of CD.

  1. Does prevention for Alzheimer's disease exist?

    OpenAIRE

    Sonia Maria Dozzi Brucki

    2009-01-01

    Abstract The prevention of Alzheimer's disease is a growing public health concern amidst an ageing population. Meanwhile, there is no effective or curative treatment available where prevention could greatly reduce health costs. This review was based on reports of potential preventive factors, including modifiable lifestyle factors, as well as preventive pharmacological strategies. Although the present review was not systematic, the reports selected from PubMed using "Alzheimer's disease" and ...

  2. Pathogenesis, diagnosis and epizootiology of swine vesicular disease

    NARCIS (Netherlands)

    Dekker, Aaldert

    2000-01-01

    The work described in this thesis was initiated after the outbreaks of swine vesicular disease (SVD) in the Netherlands in 1992. The thesis starts with a general introduction on SVD and the virus causing SVD. Infection with SVD virus had been absent from the Netherlands for 17 years, and before 1992

  3. Astrogliosis: An integral player in the pathogenesis of Alzheimer's disease

    NARCIS (Netherlands)

    Osborn, L.M.; Kamphuis, W.; Wadman, W.J.; Hol, E.M.

    2016-01-01

    Alzheimer's disease is the main cause of dementia in the elderly and begins with a subtle decline in episodic memory followed by a more general decline in overall cognitive abilities. Though the exact trigger for this cascade of events remains unknown the presence of the misfolded amyloid-beta

  4. Involvement of morbilliviruses in the pathogenesis of demyelinating disease

    NARCIS (Netherlands)

    Sips, G. J.; Chesik, D.; Glazenburg, L.; Wilschut, J.; De Keyser, J.; Wilczak, N.

    2007-01-01

    Two members of the morbillivirus genus of the family Paramyxoviridae, canine distemper virus (CDV) and measles virus (MV), are well-known for their ability to cause a chronic demyelinating disease of the CNS in their natural hosts, dogs and humans, respectively. Both viruses have been studied for

  5. Astrogliosis : An integral player in the pathogenesis of Alzheimer's disease

    NARCIS (Netherlands)

    Osborn, Lana M; Kamphuis, W.; Wadman, Wytse J; Hol, Elly M

    2016-01-01

    Alzheimer's disease is the main cause of dementia in the elderly and begins with a subtle decline in episodic memory followed by a more general decline in overall cognitive abilities. Though the exact trigger for this cascade of events remains unknown the presence of the misfolded amyloid-beta

  6. Astrogliosis : An integral player in the pathogenesis of Alzheimer's disease

    NARCIS (Netherlands)

    Osborn, Lana M.; Kamphuis, Willem; Wadman, Wytse J.; Hol, Elly M.

    Alzheimer's disease is the main cause of dementia in the elderly and begins with a subtle decline in episodic memory followed by a more general decline in overall cognitive abilities. Though the exact trigger for this cascade of events remains unknown the presence of the misfolded amyloid-beta

  7. Parkinson's disease : The syndrome, the pathogenesis and pathophysiology

    NARCIS (Netherlands)

    Bartels, Anna L.; Leenders, Klaus L.

    Parkinson's disease (PD) is characterised by a slowly expanding degeneration of neurons particularly in the mesencephalon. The causes are unknown although risk factors in the genetic and toxic domain are being discovered. An important pathophysiological feature in PD is the loss of part of the

  8. Glucocerebrosidase mutations and the pathogenesis of Parkinson disease.

    Science.gov (United States)

    Beavan, Michelle S; Schapira, Anthony H V

    2013-12-01

    Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory.

  9. The puzzle of coeliac disease: pieces of the molecular pathogenesis

    NARCIS (Netherlands)

    Diosdado Calvo, María Begoña

    2006-01-01

    Coeliac disease (CD) is a chronic intolerance to a dietary protein called gluten. This protein is present in common cereals such as wheat, barley and rye, and it is needed to prepare the derivate products such as bread or pasta. CD only occurs in individuals that carry certain altered genes. The ide

  10. Pathogenesis and treatment of hypertension in polycystic kidney disease

    NARCIS (Netherlands)

    Neumann, J; Ligtenberg, G; Klein, IHHT; Blankestijn, PJ

    2002-01-01

    Purpose of review Hypertension is common in patients with autosomal dominant polycystic kidney disease. It may contribute to cardiovascular risk and to progression of renal failure. Recent findings Apart from fluid overload and renin activation, hypertensive patients with autosomal dominant polycyst

  11. Alcoholic liver disease: pathogenesis and new targets for therapy.

    Science.gov (United States)

    Altamirano, José; Bataller, Ramón

    2011-08-09

    Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. The spectrum of disease ranges from fatty liver to hepatic inflammation, necrosis, progressive fibrosis and hepatocellular carcinoma. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The most effective therapy for ALD is alcohol abstinence. However, for patients with severe forms of ALD (that is, alcoholic hepatitis) and for those who do not achieve abstinence from alcohol, targeted therapies are urgently needed. The development of new drugs for ALD is hampered by the scarcity of studies and the drawbacks of existing animal models, which do not reflect all the features of the human disease. However, translational research using liver samples from patients with ALD has identified new potential therapeutic targets, such as CXC chemokines, osteopontin and tumor necrosis factor receptor superfamily member 12A. The pathogenetic roles of these targets, however, remain to be confirmed in animal models. This Review summarizes the epidemiology, natural history, risk factors and current knowledge of the pathogenetic mechanisms of ALD. In addition, this article provides a detailed description of the findings of these translational studies and of the animal models used to study ALD.

  12. [New insights in pathogenesis and etiology of coronary artery disease].

    Science.gov (United States)

    Erbel, R; Görge, G

    2014-01-01

    In clinical practice the non-invasive diagnosis of "coronary heart disease" is based on the clinical findings, the detection of ischemia at rest or during exercise, and elevations of cardiac enzymes. However, due to the compensatory enlargement of the vessel diameter at the beginning of plaque growth, the so-called Glagov effect, early stages of plaque development are missed by the angiography. By means of coronary angiography, changes of the coronary arteries become visible only in patients with angiographically recognizable lumen narrowing compared to the reference vessel segment. Thus, early or diffuse stages of atherosclerosis cannot be detected by ECG, stress-tests or coronary angiography. This limitation explains discrepancies, like positive troponin-test and even transmural ischemia, without angiographic visible coronary lumen narrowing. Diagnostic procedures such as intravascular ultrasound, optical coherence tomography, measurements of vasomotion and computed tomography can, in contrast, detect earlier stages of coronary artery disease and thus contribute to clarification in these patients. In addition, plaque rupture and plaque-erosion lead to acute or recurrent microembolism to distal myocardium with subsequent myocardial necrosis. In patients with formerly unexplained cardiovascular events, intravascular ultrasound, optical coherence tomography, and measurements of vasomotion help to understand the underlying pathophysiology. In the report after cardiac catheterization, the term "ruled out coronary heart disease" should be replaced by "No signs of obstructive coronary heart disease" and additional testing should be performed as necessary.

  13. Pathogenesis, diagnosis and epizootiology of swine vesicular disease

    NARCIS (Netherlands)

    Dekker, Aaldert

    2000-01-01

    The work described in this thesis was initiated after the outbreaks of swine vesicular disease (SVD) in the Netherlands in 1992. The thesis starts with a general introduction on SVD and the virus causing SVD. Infection with SVD virus had been absent from the Netherlands for 17 years, and before 1992

  14. Pathogenesis of coeliac disease:implications for treatment

    Institute of Scientific and Technical Information of China (English)

    Jocelyn S Fraser; Paul J Ciclitira

    2001-01-01

    @@INTRODUCTION Coeliac disease(CD)is an enteropathy ,characterised by villous atrohy ,which occurs in genetically susceptible individuals .It affects mainly the proximal small intestine,and is caused by an intolerance to cereal storage proteins found in wheat ,barley and rye .

  15. Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis.

    Science.gov (United States)

    Kanthasamy, Anumantha G; Kitazawa, Masashi; Kanthasamy, Arthi; Anantharam, Vellareddy

    2005-08-01

    Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.

  16. GENE IMPRINTING: ENGRAVING THE PATHOGENESIS OF HERIDETARY DISEASES

    Directory of Open Access Journals (Sweden)

    Sandeep Satapathy

    2014-01-01

    Full Text Available Gene imprinting has conduited the scope of our understanding of phenotypic expression and its corelation with constituent genotype. It is an epigenetic process that involves DNA methylation and histone modulation to attain monoallelic gene expression without altering the genetic sequences. A distinctive model of non-mendelian genetics, imprinting extends the control over expression of traits and selection of the allele that would direct the same, in a manner decided by the parent of origin. The constitutive existence of this imprinting even after gametogenesis, throughout the somatic development extends a clue for its regulatory hold on several heridetary traits. Several heridetary diseases like Cancers, Russell-Silver syndrome, Beckwith-Wiedemann syndrome, Prader-Willi and Angelman Syndromes and Neurodegenration have shown to be a subsequent error in the genomic impriting process. So, understanding these epigenetic regulations can be a therapeutic strategy for disease modelling and especially targeting their patterns of heridetary inheritance.

  17. Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Ramón Cacabelos

    2017-03-01

    Full Text Available Parkinson’s disease (PD is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina, and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine, monoamine oxidase (MAO inhibitors (selegiline, rasagiline, and catechol-O-methyltransferase (COMT inhibitors (entacapone, tolcapone. The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in

  18. Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

    Science.gov (United States)

    Cacabelos, Ramón

    2017-01-01

    Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to

  19. 75 FR 30041 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-05-28

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and..., Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  20. Edema in renal diseases – current view on pathogenesis

    Directory of Open Access Journals (Sweden)

    Irina Bobkova

    2016-10-01

    Full Text Available Edema is a common complication of numerous renal disease. In the recent past several aspects of the pathophysiology of this condition have been elucidated. We herein present a case of nephrotic syndrome in a 30 year-old men. The discussion revolves around the following key questions on fluid accumulation in renal disease: 1. What is edema? What diseases can cause edema? 2. What are the mechanisms of edema in nephrotic syndrome?   2a. The “underfill” theory   2b. The “overfill” theory   2c. Tubulointerstitial inflammation   2d. Vascular permeability 3. What are the mechanisms of edema in nephritic syndrome? 4. How can the volume status be assessed in patients with nephrotic syndrome? 5. What are therapeutic strategies for edema management? 6. What are the factors affecting response to diuretics? 7. How can we overcome the diuretics resistance?   7a. Effective doses of loop diuretics   7b. Combined diuretic therapy   7c. Intravenous administration of diuretics   7d. Albumin infusions   7e. Alternative methods of edema management 8. Conclusion.

  1. The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review.

    Science.gov (United States)

    Manoharan, Shanmugam; Guillemin, Gilles J; Abiramasundari, Rajagopal Selladurai; Essa, Musthafa Mohamed; Akbar, Mohammed; Akbar, Mohammed D

    2016-01-01

    Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.

  2. The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review

    Science.gov (United States)

    Abiramasundari, Rajagopal Selladurai; Essa, Musthafa Mohamed; Akbar, Mohammed D.

    2016-01-01

    Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases. PMID:28116038

  3. The Etiology and Pathogenesis of Kienböck Disease.

    Science.gov (United States)

    Bain, Gregory Ian; MacLean, Simon Bruce Murdoch; Yeo, Chong Jin; Perilli, Egon; Lichtman, David M

    2016-11-01

    Kienböck disease is a condition that typically occurs in the "at-risk" patient, in the "at-risk" aspect of the proximal condyle of the "at-risk" lunate. In the active male, repetitive loading causes the stress fracture that commences in the single layer proximal subchondral bone plate. The lunate fracture commences at the point the lunate cantilevers over the edge of the distal radius, and then takes on the shape of the radius. We postulate that the stress fracture violates the parallel veins of the venous subarticular plexus-leading to localized venous hypertension and subsequent ischemia and edema of the fatty marrow. The increased osseous compartment pressure further potentiates the venous obstruction, producing avascular necrosis. If the fracture remains localized, it can heal or settle into a stable configuration, so that the wrist remains functional. Fractures of the subchondral bone plate produce irregularity of the lunate articular surfaces and secondary "kissing lesions" of the lunate facet and capitate, and subsequent degeneration. The lunate collapses when the fracture is comminuted, or there is disruption of the spanning trabeculae or a coronal fracture. The secondary effect of the lunate collapse is proximal migration of the capitate between the volar and dorsal fragments, producing collapse of the entire central column. The proximal carpal row is now unstable, and is similar to scapholunate instability, where the capitate migrates between the scaphoid and lunate. The scaphoid is forced into flexion by the trapezium, however, degeneration of the scaphoid and scaphoid facet only occurs in late disease or following failed surgery. In Kienböck disease, the secondary effects of the collapsing lunate are a "compromised" wrist, including: deformity and collapse of the central column, degeneration of the central column (perilunate) articulations, proximal row instability (i.e., between the central and radial columns), and degeneration of the radial column.

  4. Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    A.P. Bastos

    2011-07-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1 and polycystin-2 (PC2, respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

  5. Advance in the pathogenesis and treatment of Wilson disease

    Science.gov (United States)

    2012-01-01

    Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need. PMID:23210912

  6. Advance in the pathogenesis and treatment of Wilson disease

    Directory of Open Access Journals (Sweden)

    Dong Qin-Yun

    2012-11-01

    Full Text Available Abstract Wilson disease is an autosomal recessive disorder of copper metabolism. Diagnosis depends primarily on clinical features, biochemical parameters and the presence of the Kayser-Fleischer ring. Genetic analysis for mutations within ATP7B is a convincing diagnostic tool. The traditional treatment for WD includes chelation of excessive copper accumulation and reduction of copper intake. Medical therapy is effective but WD is not yet curable. Liver transplantation is especially helpful for patients who fail to respond to medical therapy or present with fulminant liver failure, although evaluation of its long-term effect are still in need.

  7. Reed-Sternberg cells in the pathogenesis of Hodgkin's disease.

    Science.gov (United States)

    Basić-Jukić, N; Basić-Koretić, M; Radman, I; Labar, B

    2001-01-01

    Hodgkin/Reed Stemberg (HRS) cells mediate the classical features of Hodgkin's disease. However, because of their rarity in tumor tissue, little is known about their origin and function. Recent advances in biotechnology, including the single cell manipulation, enabled the insight into the biology of HRS cell. It has been demonstrated that in the great majority of cases they are of germinal center B cell origin, with highly developed interactive network with adjacent cells via expression of cell adhesion molecules, tumor necrosis factor receptor superfamily, and elaboration of different cytokines.

  8. Pathogenesis and Associated Diseases of Kaposi's Sarcoma-associated Herpesvirus

    Institute of Scientific and Technical Information of China (English)

    Lin-ding WANG

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the primary etiological agent of Kaposi's sarcoma, primary effusion lymphoma and muticentric Castleman's disease. In common with the other herpesviruses, KSHV exhibits both latent and lytic life cycles, both of which are characterized by distinct gene expression profiles and programs. KSHV encodes proteins which play essential roles in the inhibition of host adaptive and innate immunity, the inhibition of apoptosis, and the regulation of the cell cycle. KSHV also encodes several proteins which have transforming and intrcellular signalling activity.

  9. Dominant protein interactions that influence the pathogenesis of conformational diseases.

    Science.gov (United States)

    Wright, Jordan; Wang, Xiaofan; Haataja, Leena; Kellogg, Aaron P; Lee, Jaemin; Liu, Ming; Arvan, Peter

    2013-07-01

    Misfolding of exportable proteins can trigger endocrinopathies. For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin. Both proinsulin and thyroglobulin normally form homodimers; the mutant versions of both proteins misfold in the ER, triggering ER stress, and, in both cases, heterozygosity creates potential for cross-dimerization between mutant and WT gene products. Here, we investigated these two ER-retained mutant secretory proteins and the selectivity of their interactions with their respective WT counterparts. In both cases and in animal models of these diseases, we found that conditions favoring an increased stoichiometry of mutant gene product dominantly inhibited export of the WT partner, while increased relative level of the WT gene product helped to rescue secretion of the mutant partner. Surprisingly, the bidirectional consequences of secretory blockade and rescue occur simultaneously in the same cells. Thus, in the context of heterozygosity, expression level and stability of WT subunits may be a critical factor influencing the effect of protein misfolding on clinical phenotype. These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies.

  10. Microparticles as players in the pathogenesis of cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Alexandru, N.; Georgescu, A.

    2015-07-01

    Cardiovascular diseases (CVD) are the largest cause of morbidity and mortality in the world and include all diseases and conditions of the heart and blood vessels. The main cause of most CVD is atherosclerosis, which is an abnormal build-up of fat and other substances which form plaque inside the arteries. Atherosclerosis is most serious when it leads to reduced or blocked blood supply to the heart (causing angina or heart attack) or to the brain (causing a stroke). The majority of CVD is caused by risk factors that can be controlled, treated or modified. Microparticles (MPs) are now recognized as potential biomarkers and key elements in the development of CVD. Although MP generation is a physiological phenomenon, their shedding from a variety of cell types into body fluid is intensified in response to cellular activation, high shear stress, as well as cellular apoptosis. In this review we outline distinct aspect of MP generation and their side as players n the CVD development.

  11. European Centre for Disease Prevention and Control.

    Science.gov (United States)

    Evans, Roger

    2014-11-04

    The European Centre for Disease Prevention and Control was set up in 2005 to strengthen Europe's defences against infectious diseases. The centre is an independent agency of the European Union and is based in Stockholm, Sweden.

  12. TOWARDS THE ELIMINATION OF PREVENTABLE DISEASES

    Directory of Open Access Journals (Sweden)

    O. V. Shamsheva

    2013-01-01

    Full Text Available The article presents incidence rates of major vaccine-preventable diseases in the world and the Russian Federation and cites mitigation measures that, in the end, must lead to the elimination of the diseases

  13. Pelvic inflammatory disease: current concepts in pathogenesis, diagnosis and treatment.

    Science.gov (United States)

    Mitchell, Caroline; Prabhu, Malavika

    2013-12-01

    Pelvic inflammatory disease (PID) is characterized by infection and inflammation of the upper genital tract in women and can cause significant reproductive health sequelae for women. Although a definitive diagnosis of PID is made by laparoscopic visualization of inflamed, purulent fallopian tubes, PID is generally a clinical diagnosis and thus represents a diagnostic challenge. Therefore, diagnosis and treatment algorithms advise a high index of suspicion for PID in any woman of reproductive age with pelvic or abdominal pain. Antibiotic therapy should be started early, and given for an adequate period of time to reduce the risk of complications. Coverage for anaerobic organisms should be considered in most cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases.

    Science.gov (United States)

    Casadevall, Arturo; Pirofski, Liise-Anne

    2012-05-17

    Only two decades ago antibodies to fungi were thought to have little or no role in protection against fungal diseases. However, subsequent research has provided convincing evidence that certain antibodies can modify the course of fungal infection to the benefit or detriment of the host. Hybridoma technology was the breakthrough that enabled the characterization of antibodies to fungi, illuminating some of the requirements for antibody efficacy. As discussed in this review, fungal-specific antibodies mediate protection through direct actions on fungal cells and through classical mechanisms such as phagocytosis and complement activation. Although mechanisms of antibody-mediated protection are often species-specific, numerous fungal antigens can be targeted to generate vaccines and therapeutic immunoglobulins. Furthermore, the study of antibody function against medically important fungi has provided fresh immunological insights into the complexity of humoral immunity that are likely to apply to other pathogens.

  15. Endothelial to Mesenchymal Transition (EndoMT in the Pathogenesis of Human Fibrotic Diseases

    Directory of Open Access Journals (Sweden)

    Sonsoles Piera-Velazquez

    2016-04-01

    Full Text Available Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG4-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Numerous studies have identified myofibroblasts as the cells responsible for the establishment and progression of the fibrotic process. Tissue myofibroblasts in fibrotic diseases originate from several sources including quiescent tissue fibroblasts, circulating CD34+ fibrocytes, and the phenotypic conversion of various cell types including epithelial and endothelial cells into activated myofibroblasts. However, the role of the phenotypic transition of endothelial cells into mesenchymal cells (Endothelial to Mesenchymal Transition or EndoMT in the pathogenesis of fibrotic disorders has not been fully elucidated. Here, we review the evidence supporting EndoMT’s contribution to human fibrotic disease pathogenesis.

  16. Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases

    Science.gov (United States)

    Piera-Velazquez, Sonsoles; Mendoza, Fabian A.; Jimenez, Sergio A.

    2016-01-01

    Fibrotic diseases encompass a wide spectrum of clinical entities including systemic fibrotic diseases such as systemic sclerosis, sclerodermatous graft versus host disease, nephrogenic systemic fibrosis, and IgG4-associated sclerosing disease, as well as numerous organ-specific disorders including radiation-induced fibrosis, and cardiac, pulmonary, liver, and kidney fibrosis. Although their causative mechanisms are quite diverse, these diseases share the common feature of an uncontrolled and progressive accumulation of fibrous tissue macromolecules in affected organs leading to their dysfunction and ultimate failure. The pathogenesis of fibrotic diseases is complex and despite extensive investigation has remained elusive. Numerous studies have identified myofibroblasts as the cells responsible for the establishment and progression of the fibrotic process. Tissue myofibroblasts in fibrotic diseases originate from several sources including quiescent tissue fibroblasts, circulating CD34+ fibrocytes, and the phenotypic conversion of various cell types including epithelial and endothelial cells into activated myofibroblasts. However, the role of the phenotypic transition of endothelial cells into mesenchymal cells (Endothelial to Mesenchymal Transition or EndoMT) in the pathogenesis of fibrotic disorders has not been fully elucidated. Here, we review the evidence supporting EndoMT’s contribution to human fibrotic disease pathogenesis. PMID:27077889

  17. Diagnosis by numbers: defining skin disease pathogenesis through collated gene signatures.

    Science.gov (United States)

    Salam, Amr; McGrath, John A

    2015-01-01

    Disease gene expression profiles can be utilized as biomarkers for diagnostic, prognostic, and targeted therapeutic purposes, although individual data sets may be of limited generic value. To develop broader clinical relevance from disease gene signatures, Inkeles et al. demonstrate how mining publically available microarray data from a range of skin disorders can elucidate disease pathways, generate a multi-disease classifier, and identify potential therapeutic targets. This integrative molecular classification and functional analysis offers a new approach to understanding disease pathogenesis, with significant implications for diagnostics and the development of personalized medicine.

  18. Tubular atrophy in the pathogenesis of chronic kidney disease progression.

    Science.gov (United States)

    Schelling, Jeffrey R

    2016-05-01

    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  19. Pathogenesis of intestinal strictures in Crohn's disease-an update.

    Science.gov (United States)

    Graham, M F

    1995-01-01

    : Stricture formation in Crohn's disease is a complication of an important wound healing process in the intestine. The smooth muscle cells of the intestinal musculares bear a responsibility for the repair of injured intestine, and effect this wound healing process by proliferating and laying down collagen at the site of injury. Injury in the submucosa, and chronicity of injury, are important factors in the development of stricture. The resultant accumulation of collagenous scar, thickening of the muscle layers, and contracture, all play a role in producing the critical architectural changes in the intestinal wall that impede the aboral movement of chyme. Important putative facets of intestinal smooth muscle cell biology that are involved in stricture formation include: the synthesis and secretion of procollagen; the peculiar response of these cells to cytokines, ascorbate, and corticosteroids; and changes in cell phenotype that result from chronic inflammation. Therapeutic modalities designed to ameliorate the stricturing process will need to modulate these biological activities in resident intestinal smooth muscle cells.

  20. Molecular and cellular pathogenesis of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Nichols, Kim E; Ma, Cindy S; Cannons, Jennifer L; Schwartzberg, Pamela L; Tangye, Stuart G

    2005-02-01

    X-linked lymphoproliferative disease (XLP) is an inherited immune defect caused by mutations in the Src homology 2 domain-containing gene 1A, which encodes the adapter protein, signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). SAP is expressed in T cells, natural killer (NK) cells, and NKT cells, where it binds to the cytoplasmic domain of the surface receptor SLAM (CD150) and the related receptors, 2B4 (CD244), CD84, Ly9 (CD229), NK-T-B-antigen, and CD2-like receptor-activating cytotoxic T cells. SAP also binds to the Src family tyrosine kinase Fyn and recruits it to SLAM, which leads to the generation of downstream phosphotyrosine signals. While the roles of the SLAM family receptors are only beginning to be understood, experiments suggest that these molecules regulate important aspects of lymphocyte function, such as proliferation, cytokine secretion, cytotoxicity, and antibody production. Thus, in XLP patients who lack functional SAP, the SLAM family receptors may not signal properly. This property likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia. Further studies of SAP and the SLAM family receptors will provide insights into XLP and elucidate the signaling events regulating lymphocyte ontogeny and function.

  1. Diminished reovirus capsid stability alters disease pathogenesis and littermate transmission.

    Directory of Open Access Journals (Sweden)

    Joshua D Doyle

    2015-03-01

    Full Text Available Reovirus is a nonenveloped mammalian virus that provides a useful model system for studies of viral infections in the young. Following internalization into host cells, the outermost capsid of reovirus virions is removed by endosomal cathepsin proteases. Determinants of capsid disassembly kinetics reside in the viral σ3 protein. However, the contribution of capsid stability to reovirus-induced disease is unknown. In this study, we found that mice inoculated intramuscularly with a serotype 3 reovirus containing σ3-Y354H, a mutation that reduces viral capsid stability, succumbed at a higher rate than those infected with wild-type virus. At early times after inoculation, σ3-Y354H virus reached higher titers than wild-type virus at several sites within the host. Animals inoculated perorally with a serotype 1 reassortant reovirus containing σ3-Y354H developed exaggerated myocarditis accompanied by elaboration of pro-inflammatory cytokines. Surprisingly, unchallenged littermates of mice infected with σ3-Y354H virus displayed higher titers in the intestine, heart, and brain than littermates of mice inoculated with wild-type virus. Together, these findings suggest that diminished capsid stability enhances reovirus replication, dissemination, lethality, and host-to-host spread, establishing a new virulence determinant for nonenveloped viruses.

  2. Value Thrombus Disease Foundational Disease Preventing and Controlling

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Regardless of artery thrombus, vein thrombus, disseminated intravascular coagulation (DIC) and so on are many because of the natural disease. In it pathogenesis has many sick factors the participation. Moreover manydisease and many syndrome oneself obviousty to become the foundation dsease which the thrombus gets sick.

  3. Review article: pathogenesis and pathophysiology of hepatorenal syndrome--is there scope for prevention?

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    2004-01-01

    The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research into the pathophy...... such as human albumin. In the future endothelins, adenosine antagonists, long-acting vasoconstrictors, and antileukotriene drugs may play a role in preventing and treating HRS.......The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research...... into the pathophysiology of ascites and HRS has stimulated new enthusiasm in their prevention and treatment. Patients with HRS have hyperdynamic circulatory dysfunction with reduced arterial blood pressure and reduced central blood volume, owing to preferential splanchnic arterial vasodilatation. Activation of potent...

  4. Secondary syphilis in cali, Colombia: new concepts in disease pathogenesis.

    Directory of Open Access Journals (Sweden)

    Adriana R Cruz

    Full Text Available Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp. Herein we describe a cohort of 57 patients (age 18-68 years with secondary syphilis (SS identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4, and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS. Most subjects enrolled were women (64.9%, predominantly Afro-Colombian (38.6% or mestizo (56.1%, and all were of low socio-economic status. Three (5.3% subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6% was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days. The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%, followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA target by real-time qualitative and quantitative PCR methods. Twelve (46% of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood and seven (64% were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66% skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a. None of the WB samples had sufficient DNA for typing. The clinical and microbiologic

  5. Design for Heart Disease Prevention Programs.

    Science.gov (United States)

    New York State Education Dept., Albany. Bureau of Continuing Education Curriculum Development.

    In this teaching and curriculum guide for community health education, a design is suggested for a course that could help prevent premature deaths due to heart disease. The course communicates facts regarding the causes of cardiovascular diseases, and outlines opportunities for attaining the degree of physical conditioning essential to prevention.…

  6. Preventive Effects of Catechins on Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Qiang Chen

    2016-12-01

    Full Text Available Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure.

  7. Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.

    OpenAIRE

    Levin, M; Holland, P C; Nokes, T J; Novelli, V; Mola, M; Levinsky, R J; Dillon, M J; Barratt, T M; Marshall, W C

    1985-01-01

    The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a facto...

  8. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review.

    OpenAIRE

    David Abelló; Elena Sancho; Jordi Camps; Jorge Joven

    2014-01-01

    Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON...

  9. Ebola (Ebola Virus Disease): Prevention

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is ... message, please visit this page: About CDC.gov . Ebola (Ebola Virus Disease) About Ebola Questions & Answers 2014- ...

  10. An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers.

    Science.gov (United States)

    Bright, Philip David; Mayosi, Bongani M; Martin, William John

    2016-10-01

    Acute rheumatic fever (ARF) and the related rheumatic heart disease (RHD) are autoimmune diseases thought to be triggered by group A streptococcal (GAS) pharyngitis. RHD is a leading cause of mortality in the developing world. The strong epidemiological association between GAS throat infection and ARF is highly suggestive of causation, but does not exclude other infections as contributory. There is good evidence of both humoral and cellular autoreactivity and GAS/self cross-reactivity in established RHD. RHD pathogenesis could feasibly be triggered and driven by humoral and/or cellular molecular cross-reactivity between GAS and host cardiac tissues (molecular mimicry). However, good evidence of humoral pathogenicity is lacking and the specific triggering event for RHD remains unknown. It is likely that the critical immunological events leading to ARF/RHD occur at the point of contact between GAS and the immune system in the throat, strongly implicating the mucosal immune system in RHD pathogenesis. Additionally, there is circumstantial evidence that continued live GAS may play a role in ARF/RHD pathogenesis. We suggest that future avenues for study should include the exclusion of GAS components directly contributing to RHD pathogenesis; large genome-wide association studies of patients with RHD looking for candidate genes involved in RHD pathogenesis; genome-wide association studies of GAS from patients with ARF taken at diagnosis to look for characteristics of rheumatogenic strains; and performing case/control studies of GAS pharyngitis/ARF/patients with RHD, and controls to identify microbiological, immunological and environmental differences to elucidate RHD pathogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. The role for dickkopf-homolog-1 in the pathogenesis of Crohn's disease-associated fistulae.

    Directory of Open Access Journals (Sweden)

    Sandra Michaela Frei

    Full Text Available BACKGROUND: One of the most challenging conditions in Crohn's disease (CD patients is the treatment of perianal fistulae. We have recently shown that epithelial-to-mesenchymal transition (EMT plays a crucial role during CD-fistulae development. Dickkopf-homolog 1 (DKK-1 is known to play a key role during EMT. Here, we investigated a role for DKK-1 in the pathogenesis of CD-associated fistulae. METHODS: Dkk-1 protein expression in CD-fistula specimens were investigated by immunohistochemistry. Colonic lamina propria fibroblasts (CLPF were obtained from either non-IBD control patients or patients with fistulizing CD. HT-29 intestinal epithelial cells (IEC were either grown as monolayers or spheroids. Cells were treated with either TNF-α, TGF-β or IL-13. Knock-down of DKK-1 or β-Catenin was induced in HT-29-IEC by siRNA technique. mRNA expression was determined by real-time-PCR. RESULTS: Dkk-1 protein was specifically expressed in transitional cells lining the fistula tracts. TGF-β induced DKK-1 mRNA expression in HT-29-IEC, but decreased it in fistula CLPF. On a functional level, DKK-1 knock-down prevented TGF-β-induced IL-13 mRNA expression in HT-29-IEC. Further, loss of β-Catenin was accompanied by reduced levels of DKK-1 and, again, IL-13 in IEC in response to TGF-β. In turn, treatment of HT-29-IEC as well as fistula CLPF with IL-13 resulted in decreased levels of DKK-1 mRNA. Treatment with TNF-α or the bacterial wall component, muramyl-dipeptide, decreased DKK-1 mRNA levels in HT-29-IEC, but enhanced it in fistula CLPF. DISCUSSION: We demonstrate that DKK-1 is strongly expressed in cells lining the CD-fistula tracts and regulates factors involved in EMT initiation. These data provide evidence for a role of DKK-1 in the pathogenesis of CD-associated perianal fistulae.

  12. Proteomics in veterinary medicine: applications and trends in disease pathogenesis and diagnostics.

    Science.gov (United States)

    Ceciliani, F; Eckersall, D; Burchmore, R; Lecchi, C

    2014-03-01

    Advancement in electrophoresis and mass spectrometry techniques along with the recent progresses in genomics, culminating in bovine and pig genome sequencing, widened the potential application of proteomics in the field of veterinary medicine. The aim of the present review is to provide an in-depth perspective about the application of proteomics to animal disease pathogenesis, as well as its utilization in veterinary diagnostics. After an overview on the various proteomic techniques that are currently applied to veterinary sciences, the article focuses on proteomic approaches to animal disease pathogenesis. Included as well are recent achievements in immunoproteomics (ie, the identifications through proteomic techniques of antigen involved in immune response) and histoproteomics (ie, the application of proteomics in tissue processed for immunohistochemistry). Finally, the article focuses on clinical proteomics (ie, the application of proteomics to the identification of new biomarkers of animal diseases).

  13. Does the microbiota play a role in the pathogenesis of autoimmune diseases?

    Science.gov (United States)

    McLean, Mairi H; Dieguez, Dario; Miller, Lindsey M; Young, Howard A

    2015-02-01

    The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the pathogenesis of autoimmune disease, with clear and increasing evidence that changes in the microbiota are associated with some of these diseases. Examples include type 1 diabetes, coeliac disease and rheumatoid arthritis, and these contribute significantly to global morbidity and mortality. Understanding the role of the microbiota in autoimmune diseases may offer novel insight into factors that initiate and drive disease progression, stratify patient risk for complications and ultimately deliver new therapeutic strategies. This review summarises the current status on the role of the microbiota in autoimmune diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. How to Prevent Heart Disease

    Science.gov (United States)

    ... of fat in the blood. High levels of triglycerides may also raise the risk of coronary artery disease, especially in women. Stay at a healthy weight. ... mostly because they are linked to other heart disease risk factors, ... triglyceride levels, high blood pressure, and diabetes. Controlling your ...

  15. Public knowledge of prevention of dental disease.

    Science.gov (United States)

    Gift, H C; Corbin, S B; Nowjack-Raymer, R E

    1994-01-01

    The authors present data describing the level and extent of the general public's knowledge of oral diseases and their prevention. They discuss data from the 1990 National Health Interview Survey's Health Promotion and Disease Prevention Supplement in the context of national oral health objectives. They focus on demographic and socioeconomic differences seen in the public's knowledge of the preventive purposes of fluorides and dental sealants for dental caries and of symptoms of gum disease. Reported low levels of knowledge regarding oral disease symptoms and their prevention show the continuing trend reported during the past decade. Racial and ethnic minorities and groups with low levels of formal education demonstrate the least knowledge of prevention of oral diseases. For example, 76 percent of those with more than 12 years of schooling know the preventive purpose of water fluoridation, compared with 61 percent of those with 12 years, and 36 percent of those with less than 12 years of school. Efforts to increase levels of knowledge about oral disease prevention are required to achieve national objectives for oral health.

  16. Prevention measures and exploratory pharmacological treatments of celiac disease.

    Science.gov (United States)

    Pinier, Maud; Fuhrmann, Gregor; Verdu, Elena F; Verdu, Elena; Leroux, Jean-Christophe

    2010-12-01

    Increasing prevalence, protean clinical manifestations, and lack of pharmacological therapy make celiac disease (CD) a complex and highly relevant illness in gastroenterology. This chronic inflammatory disorder of the small intestine is caused by the ingestion of gluten containing cereals in genetically susceptible individuals, leading to a variety of gastrointestinal (GI) and non-GI manifestations. Awareness among physicians is growing due to accessible and highly accurate diagnostic and screening methods. Recent evidence suggests a possible rising incidence of CD. Environmental factors such as early life gluten exposure, intestinal infections, short duration of breast-feeding, and changes in intestinal microbiota have been proposed to have a role in CD pathogenesis. Thus, prevention approaches to diminish the rising prevalence of CD are currently being evaluated. Still, the cornerstone treatment of CD remains a strict gluten-free diet. This nutritional regime is demanding, and non-adherence is common because of social isolation, financial issues, or restriction of food diversity. Allowing patients to occasionally consume small amounts of gluten would greatly improve their quality of life. Owing to recent advances in the understanding of the pathogenesis of CD, different targets have been identified and have motivated the development of several experimental therapeutic strategies. The main goal of this review is to discuss the mechanisms that can be exploited therapeutically to prevent or delay CD, disease associations and its complications. Current treatments for complications of CD, including refractory CD and malignancy, are beyond the scope of this review.

  17. [Neurosis and genetic theory of etiology and pathogenesis of ulcer disease].

    Science.gov (United States)

    Kolotilova, M L; Ivanov, L N

    2014-01-01

    Based on the analysis of literature data and our own research, we have developed the original concept of etiology and pathogenesis of peptic ulcer disease. An analysis of the literature shows that none of the theories of pathogenesis of peptic ulcer disease does not cover the full diversity of the involved functions and their shifts, which lead to the development of ulcers in the stomach and the duodenum. Our neurogenic-genetic theory of etiology and pathogenesis of gastric ulcer and duodenal ulcer very best explains the cause-and-effect relationships in the patient peptic ulcer, allowing options for predominance in one or the other case factors of neurosis or genetic factors. However, it is clear that the only other: combination of neurogenic factor with genetically modified reactivity of gastroduodenal system (the presence of the target organ) cause the chronicity of the sores. The theory of peptic ulcer disease related to psychosomatic pathologies allows us to develop effective schema therapy, including drugs with psychocorrective action. On the basis of our theory of the role of Helicobacter pylori infection is treated as a pathogenetic factor in the development of peptic ulcer disease.

  18. [The problems of etiology and pathogenesis of ulcer disease: rereading V. Kh. Vasilenko].

    Science.gov (United States)

    Tsimmerman, I S

    2011-01-01

    The author discusses the views of V. Kh. Vasilenko on etiology and pathogenesis of ulcer disease expounded in his last publications and compares them with modern concepts of the origin of this condition. The nature of ulcer disease as a systemic gastrointestinal pathology is considered with special emphasis on its difference from secondary (symptomatic) ulceration, pathogenetic significance of H. pylori infection, hereditary and environmental (non-infectious) factors. Much attention is given to the conditions facilitating the development of ulcer diseases at different combinations of internal and environmental factors including such poorly known ones as immune and sanogenetic mechanisms.

  19. Laminopathies: involvement of structural nuclear proteins in the pathogenesis of an increasing number of human diseases.

    Science.gov (United States)

    Maraldi, Nadir M; Squarzoni, Stefano; Sabatelli, Patrizia; Capanni, Cristina; Mattioli, Elisabetta; Ognibene, Andrea; Lattanzi, Giovanna

    2005-05-01

    Just at the beginning of the millennium the neologism laminopathies has been introduced in the scientific vocabulary. An exponential increase of interest on the subject started concomitantly, so that a formerly quite neglected group of rare human diseases is now widely investigated. This review will cover the history of the identification of the molecular basis for fourteen (since now) hereditary diseases arising from defects in genes that encode nuclear envelope and nuclear lamina-associated proteins and will also consider the hypotheses that can account for the role of structural nuclear proteins in the pathogenesis of diseases affecting a wide spectrum of tissues.

  20. Prevention of postoperative recurrence of Crohn's disease

    NARCIS (Netherlands)

    van Loo, E. S.; Dijkstra, G.; Ploeg, R. J.; Nieuwenhuijs, V. B.

    2012-01-01

    Background: Up to 75% of patients with Crohn's disease (CD) will have intestinal resection during their life. Most patients will, however, develop postoperative recurrence (endoscopic, clinical or surgical). Several medical and surgical strategies have been attempted to prevent postoperative recurre

  1. Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jie Zhang

    2015-11-01

    Full Text Available Overproduction of oxidants (reactive oxygen species and reactive nitrogen species in the human body is responsible for the pathogenesis of some diseases. The scavenging of these oxidants is thought to be an effective measure to depress the level of oxidative stress of organisms. It has been reported that intake of vegetables and fruits is inversely associated with the risk of many chronic diseases, and antioxidant phytochemicals in vegetables and fruits are considered to be responsible for these health benefits. Antioxidant phytochemicals can be found in many foods and medicinal plants, and play an important role in the prevention and treatment of chronic diseases caused by oxidative stress. They often possess strong antioxidant and free radical scavenging abilities, as well as anti-inflammatory action, which are also the basis of other bioactivities and health benefits, such as anticancer, anti-aging, and protective action for cardiovascular diseases, diabetes mellitus, obesity and neurodegenerative diseases. This review summarizes recent progress on the health benefits of antioxidant phytochemicals, and discusses their potential mechanisms in the prevention and treatment of chronic diseases.

  2. Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment.

    Science.gov (United States)

    Serpente, Maria; Bonsi, Rossana; Scarpini, Elio; Galimberti, Daniela

    2014-01-01

    Immune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches.

  3. MicroRNAs located in the Hox gene clusters are implicated in huntington's disease pathogenesis.

    Directory of Open Access Journals (Sweden)

    Andrew G Hoss

    2014-02-01

    Full Text Available Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD. MicroRNAs (miRNAs represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9 of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p up-regulated in HD at genome-wide significance (FDR q-value<0.05. Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were expressed at near zero levels in control brains. Expression was verified for all five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p were replicated in an independent sample (8HD/8C. Ectopic miR-10b-5p expression in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining suggesting increased expression may be a protective response. All of the miRNAs but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA sequencing in the same samples identified fifteen of 55 genes within the Hox cluster gene regions as differentially expressed in HD, and the Hox genes immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway analysis of mRNA targets of these miRNAs implicated functions for neuronal differentiation, neurite outgrowth, cell death and survival. In regression models among the HD brains, huntingtin CAG repeat size, onset age and age at death were independently found to be inversely related to miR-10b-5p levels. CAG repeat size and onset age were independently inversely related to miR-196a-5p, onset age was inversely related to miR-196b-5p and age at death was inversely related to miR-615-3p expression. These results suggest these Hox-related miRNAs may be involved in neuroprotective response in HD. Recently, miRNAs have shown promise as

  4. Preventive health measures in inflammatory bowel disease

    Science.gov (United States)

    Abegunde, Ayokunle T; Muhammad, Bashir H; Ali, Tauseef

    2016-01-01

    We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel disease OR Crohn’s disease OR ulcerative colitis) AND (health maintenance OR preventive health OR health promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify further relevant studies. Patients with IBD are at increased risk of developing adverse events related to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have suggested that IBD patients do not receive preventive services with the same thoroughness as patients with other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working knowledge of preventive health measures for IBD patients. A holistic approach and better communication between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services and streamline care. PMID:27678347

  5. A review of the role of oxidative stress in the pathogenesis of eye diseases

    Directory of Open Access Journals (Sweden)

    O. A. Oduntan

    2011-12-01

    Full Text Available Free radicals, referred to as oxidants are molecules in the body with unpaired electrons, hence are unstable and ready to bond with other molecules with unpaired electrons.  They include Reactive Oxygen Species (ROS such as superoxide anion radicals (·O¯, hydrogen peroxide (H202, and hydroxyl free radicals (·OH.  Endogenous sources of ROS include metabolic and other organic processes, while exogenous sources include ultraviolet radiation and environmental toxins such as smoke.  Antioxidants (oxidant scavengers such as ascorbate, alpha-tocopherol and glutathione as well as various enzymatic compounds such as superoxide dismutase (SOD, catalase and glutathione reductase are also present in the body and in manyfoods or food supplements.  An imbalance between oxidants and antioxidants in favour of oxidantsis termed oxidative stress and can lead to cell or tissue damage and aging. Oxidative stress has been implicated in the pathogenesis of many serious systemic diseases such as diabetes, cancer and neurological disorders.  Also, laboratory and epidemiological studies have implicated oxidative stress in the pathogenesis of the majority of common serious eye diseases such as cataract, primary open angle glaucoma and age-related macular degeneration. In this article, we reviewed the current information on the roles of oxidative stress in the pathogenesis of various eye diseases and the probable roles of antioxidants.  Eye care practitioners will find this article useful as it provides information on the pathogenesis of common eye diseases. (S Afr Optom 2011 70(4 182-190

  6. Strengthening the prevention of periodontal disease

    DEFF Research Database (Denmark)

    Petersen, Poul Erik; Ogawa, Hiroshi

    2005-01-01

    ; advanced disease with deep periodontal pockets (> or =6 mm) affects approximately 10% to 15% of adults worldwide. The available evidence shows that important risk factors for periodontal disease relate to poor oral hygiene, tobacco use, excessive alcohol consumption, stress, and diabetes mellitus......BACKGROUND: The aim of this paper is to provide an overview of the burden of periodontal disease in adult populations worldwide, to emphasize the essential risk factors common to periodontal disease and chronic diseases, to outline important new strategies for effective prevention of periodontal...... disease, and to inform about the role of the World Health Organization (WHO) in developing a national capacity for the prevention of disease. METHODS: Information about periodontal health status as measured by the Community Periodontal Index system is stored in the WHO Global Oral Health Data Bank...

  7. Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Lucy McMullen

    2015-12-01

    Full Text Available The relevance of alterations in gut microbiota in the pathogenesis of inflammatory bowel disease (IBD remains unclear. Currently there is conflicting evidence with regards to the roles of specific bacterial species. Escherichia coli (particularly the adherent invasive strain are more prevalent in those with IBD and are associated with higher risk of IBD. However, the organisms are also present in healthy individuals and colonisation does not correlate with the degree of inflammation in IBD. Campylobacter concisus is more prevalent in those with IBD and higher levels of C. concisus specific IgG antibodies are found in the serum of those with IBD compared to healthy controls. Further, C. concisus has immunogenic properties that stimulate an antibody response suggesting the bacteria might trigger or exacerbate disease. Conversely most mycobacteria are unlikely to be causative as they are not presentin microbial stool cultures early in disease. In various studies,Mycobacterium aviumparatuberculosishas been detected both more frequently and not at all in individuals with Crohn's disease. Similar conflict exists with respect to Yersinia enterocolitica,Bacteroidesvulgatus and Helicobacter hepaticus, which are also more prevalent in IBD. However, these organisms appear more likely to contribute to disease persistence than initial disease development. This review aims to summarise the current understanding of key bacterial species implicated in the pathogenesis of IBD.

  8. Does prevention for Alzheimer's disease exist?

    Directory of Open Access Journals (Sweden)

    Sonia Maria Dozzi Brucki

    Full Text Available Abstract The prevention of Alzheimer's disease is a growing public health concern amidst an ageing population. Meanwhile, there is no effective or curative treatment available where prevention could greatly reduce health costs. This review was based on reports of potential preventive factors, including modifiable lifestyle factors, as well as preventive pharmacological strategies. Although the present review was not systematic, the reports selected from PubMed using "Alzheimer's disease" and "prevention" as key-words, allow us to affirm that pursuing a healthy lifestyle; physical, cognitive, leisure activities; good social engagement; a high consumption of fish, low consumption of dietary fat and moderate consumption of wine, and control of vascular risk factors appear to be potential factors for delaying dementia.

  9. 78 FR 11889 - Centers for Disease Control and Prevention

    Science.gov (United States)

    2013-02-20

    ... HUMAN SERVICES Centers for Disease Control and Prevention Board of Scientific Counselors, National..., National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention... for Occupational Safety and Health, Centers for Disease Control and Prevention, Department of...

  10. Cardiac Hemodynamics in the Pathogenesis of Congenital Heart Disease and Aortic Valve Calcification

    Science.gov (United States)

    Nigam, Vishal

    2011-11-01

    An improved understanding of the roles of hemodynamic forces play in cardiac development and the pathogenesis of cardiac disease will have significant scientific and clinical impact. I will focus on the role of fluid dynamics in congenital heart disease and aortic valve calcification. Congenital heart defects are the most common form of birth defect. Aortic valve calcification/stenosis is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. Given the high incidence of these diseases and their associated morbidity and mortality, the potential translational impact of an improved understanding of cardiac hemodynamic forces is very large. Division of Pediatric Cardiology, Rady Children's Hospital, San Diego

  11. The role of synphilin-1 in the pathogenesis of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Rui ZHENG; Hai-Yan ZHOU; Sheng-Di CHEN

    2006-01-01

    Parkinson's disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, α-synuclein and parkin. Synphilin-1 is an α-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin- 1 is involved in the pathogenic process of PD.This review will provide an overall view of the role of synphilin- 1 in the pathogenesis of Parkinson's disease and the latest findings in this field.

  12. Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xu-Hua Xu; Yue Huang; Gang Wang; Sheng-Di Chen

    2012-01-01

    Although the pathogenesis of Alzheimer's disease (AD) is still not fully understood,it is acknowledged that intervention should be made at the early stage.Therefore,identifying biomarkers for the clinical diagnosis is critical.Metabolomics,a novel "omics",uses methods based on low-molecular-weight molecules,with high-throughput evaluation of a large number of metabolites that may lead to the identification of new disease-specific biomarkers and the elucidation of pathophysiological mechanisms.This review discusses metabolomics investigations of AD and potential future developments in this field.

  13. Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

    Directory of Open Access Journals (Sweden)

    R Anuradha

    Full Text Available Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+ or without (CP Ag- active infection; with clinically asymptomatic infections (INF; and in those without infection (endemic normal [EN]. Comparisons between the two actively infected groups (CP Ag+ compared to INF and those without active infection (CP Ag- compared to EN were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein, acute phase proteins (haptoglobin and serum amyloid protein-A, and inflammatory cytokines (IL-1β, IL-12, and TNF-α are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

  14. Metabolites of cerebellar neurons and hippocampal neurons play opposite roles in pathogenesis of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jing Du

    Full Text Available Metabolites of neural cells, is known to have a significant effect on the normal physiology and function of neurons in brain. However, whether they play a role in pathogenesis of neurodegenerative diseases is unknown. Here, we show that metabolites of neurons play essential role in the pathogenesis of Alzheimer's disease (AD. Firstly, in vivo and in vitro metabolites of cerebellar neurons both significantly induced the expression of Abeta-degrading enzymes in the hippocampus and cerebral cortex and promoted Abeta clearance. Moreover, metabolites of cerebellar neurons significantly reduced brain Abeta levels and reversed cognitive impairments and other AD-like phenotypes of APP/PS1 transgenic mice, in both early and late stages of AD pathology. On the other hand, metabolites of hippocampal neurons reduced the expression of Abeta-degrading enzymes in the cerebellum and caused cerebellar neurodegeneration in APP/PS1 transgenic mice. Thus, we report, for the first time, that metabolites of neurons not only are required for maintaining the normal physiology of neurons but also play essential role in the pathogenesis of AD and may be responsible for the regional-specificity of Abeta deposition and AD pathology.

  15. Prevention of allergic disease in childhood

    DEFF Research Database (Denmark)

    Halken, Susanne

    2004-01-01

    for this review was to evaluate possible preventive measures as regards prevention of development of allergic disease in childhood--primary prevention--and also some aspects of the effect of specific allergy treatment as regards secondary prevention in children with allergic asthma and allergic......) and/or hydrolyzed cow's milk-based formula the first 4-6 months as regards: (i) the allergy preventive effect of BM/extensively hydrolysed formula (eHF) compared with ordinary cow's milk-based formula, (ii) the effect of two different eHFs, a whey (Profylac) and a casein-based (Nutramigen) formula......, as regards development of cow's milk protein allergy (CMA), and (iii) a comparison of the preventive effect of eHF (Profylac/Nutramigen) with a partially hydrolyzed cow's milk-based formula (pHF) (NanHA) as regards development of CMA. None of the mothers had a restricted diet during pregnancy or lactation...

  16. Crohn’s Disease – The Pathogenesis of a Granulomatous Vasculitis: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Andrew J Wakefield

    1995-01-01

    Full Text Available Dissatisfied with traditional approaches to studying the pathogenesis of Crohn’s disease, the author and colleagues proposed and developed the hypothesis that Crohn’s disease is a granulomatous vasculitis mediated by a persistent viral infection of the mesenteric microvascular endothelium. Employing a range of techniques, the mesenteric vascular anatomy of intestine affected by Crohn’s disease was studied and the presence of a widespread multifocal vasculitis was demonstrated. Based upon certain behavioural characteristics of measles virus, including its tropism for intestinal endothelium and its ability to persist in human tissues, this agent was sought by in situ hybridization, electron microscopy and immunohistochemistry. The virus was detected in foci of granulomatous and lymphocytic inflammation. Recent epidemiological data from Sweden support the idea that early exposure to measles virus is a risk factor for the later development of Crohn’s disease. These data are consistent with the possibility of a persistent measles virus enteritis in the etiology and pathogenesis of Crohn’s disease and this hypothesis merits further study.

  17. The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment.

    Directory of Open Access Journals (Sweden)

    James T Rosenbaum

    Full Text Available Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray.An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED, 25 patients with nonspecific orbital inflammation (NSOI, 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA. Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets.Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED.This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.

  18. CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Lumine Matsumoto

    Full Text Available BACKGROUND: Alpha-synuclein (SNCA gene expression is an important factor in the pathogenesis of Parkinson's disease (PD. Gene multiplication can cause inherited PD, and promoter polymorphisms that increase SNCA expression are associated with sporadic PD. CpG methylation in the promoter region may also influence SNCA expression. METHODOLOGY/PRINCIPAL FINDINGS: By using cultured cells, we identified a region of the SNCA CpG island in which the methylation status altered along with increased SNCA expression. Postmortem brain analysis revealed regional non-specific methylation differences in this CpG region in the anterior cingulate and putamen among controls and PD; however, in the substantia nigra of PD, methylation was significantly decreased. CONCLUSIONS/SIGNIFICANCE: This CpG region may function as an intronic regulatory element for SNCA gene. Our findings suggest that a novel epigenetic regulatory mechanism controlling SNCA expression influences PD pathogenesis.

  19. Recent advances in pathogenesis and management of pruritus in cholestatic liver disease

    Directory of Open Access Journals (Sweden)

    WANG Man

    2014-11-01

    Full Text Available Pruritus is one of the common clinical manifestations of cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, and intrahepatic cholestasis of pregnancy. Potential incentives of itching include bile salts, histamine, progesterone metabolites, endogenous opioid substances, and lysophosphatidic acid, according to previous studies. However, the exact pathogenesis of cholestatic pruritus remains unclear, and the current treatment can only alleviate the symptoms in some of the patients. Novel methods for treating pruritus have been proposed and/or are being studied. The recent experimental and clinical studies on the pathogenesis and treatment of pruritus in cholestatic hepatitis are reviewed, in order to improve the understanding and management of cholestatic pruritus.

  20. Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

    Science.gov (United States)

    Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

    2017-01-01

    Alzheimer’s disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD. PMID:28966576

  1. Modifications and Trafficking of APP in the Pathogenesis of Alzheimer's Disease.

    Science.gov (United States)

    Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

    2017-01-01

    Alzheimer's disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD.

  2. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Xiao-xia DONG; Yan WANG; Zheng-hong QIN

    2009-01-01

    A pivotal role for excitotoxicity in neurodegenerative diseases is gaining increasingly more acceptance, but the underlying mechanisms through which it participates in neurodegeneration still need further investigation. Excessive activation of glutamate receptors by excitatory amino acids leads to a number of deleterious consequences, including impairment of calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Recent studies implicate excitotoxicity in a variety of neuropathological conditions, suggesting that neurodegenerative diseases with distinct genetic etiologies may share excitotoxicity as a common pathogenic pathway. Thus, understanding the pathways involved in excitotoxicity is of critical importance for the future clinical treatment of many neurodegenerafive diseases. This review discusses the current understanding of excitotoxic mechanisms and how they are involved in the pathogenesis of neurodegenerative diseases.

  3. Prevention of cardiovascular disease in women.

    Science.gov (United States)

    Bavry, Anthony A; Limacher, Marian C

    2014-11-01

    Cardiovascular disease is the leading cause of death among women. In fact, the cardiovascular disease mortality rate among women exceeds the rate in men. Unfortunately, many minority women are still unaware of the importance of this disease. All women, including those with no history of cardiovascular disease, should have an accurate estimate of the probability of a cardiovascular disease event (death, myocardial infarction, or stroke) usually within the next decade. Such an estimate will help determine if women are candidates for preventive measures and specific therapies such as aspirin. Data from the Framingham Heart Study were used to construct a risk score, which is now widely used; however, other risk scores are available. To prevent cardiovascular disease, women should refrain from smoking, maintain a healthy weight, eat a heart-healthy diet, be physically active, and have normal blood pressure and cholesterol levels. Aspirin can be considered for primary prevention, with expected benefit to prevent ischemic stroke; however, this needs to be balanced against potential bleeding risk. Hormone therapy is no longer recommended due to an increase in adverse events (most consistently seen as increased ischemic stroke risk). Folic acid is also no longer recommended due to lack of benefit.

  4. Microbial Sensing by the Intestinal Epithelium in the Pathogenesis of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Michael Scharl

    2010-01-01

    Full Text Available Recent years have raised evidence that the intestinal microbiota plays a crucial role in the pathogenesis of chronic inflammatory bowels diseases. This evidence comes from several observations. First, animals raised under germ-free conditions do not develop intestinal inflammation in several different model systems. Second, antibiotics are able to modulate the course of experimental colitis. Third, genetic polymorphisms in a variety of genes of the innate immune system have been associated with chronic intestinal inflammatory diseases. Dysfunction of these molecules results in an inappropriate response to bacterial and antigenic stimulation of the innate immune system in the gastrointestinal tract. Variants of pattern recognition receptors such as NOD2 or TLRs by which commensal and pathogenic bacteria can be detected have been shown to be involved in the pathogenesis of IBD. But not only pathways of microbial detection but also intracellular ways of bacterial processing such as autophagosome function are associated with the risk to develop Crohn's disease. Thus, the “environment concept” and the “genetic concept” of inflammatory bowel disease pathophysiology are converging via the intestinal microbiota and the recognition mechanisms for an invasion of members of the microbiota into the mucosa.

  5. Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Many advances have been made in the understanding of Crohn's disease (CD) pathogenesis during the last decade.CD is currently seen as a predominantly T-lymphocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines,chemokines and other mediators produced by a variety of cell types.Prevailing theories of CD pathogenesis suggest that patients' T-lymphocytes are inappropriately activated in the setting of an immune imbalance,which is itself caused by an unfortunate confluence of genetic and environmental factors.The T-cell response then leads to the chronic inflammation characteristic for the disease.Various environmental factors may play a role in the development of CD,but microbes are most consistently implied.This theory is based on epidemiological,clinicopathological,genetic and experimental evidence.Despite the abundance of arguments for the implication of bacteria in the aetiopathogenesis of CD,the precise role of bacteria in this disease still remains elusive.Three not necessarily mutually exclusive theories have been proposed:(1) an unidentified persistent pathogen;(2) an abnormally permeable mucosal barrier leading to excessive bacterial translocation;and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis").At present,one cannot exclude with certainty any of these three proposed hypotheses;they may all apply to CD to a certain extent.2008 WIG.All rights reserved.

  6. Intestinal Microbiota and the Innate Immune System – A Crosstalk in Crohn’s Disease Pathogenesis

    Science.gov (United States)

    Haag, Lea-Maxie; Siegmund, Britta

    2015-01-01

    Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder that can occur anywhere along the gastrointestinal tract. The precise etiology of CD is still unclear but it is widely accepted that a complex series of interactions between susceptibility genes, the immune system and environmental factors are implicated in the onset and perpetuation of the disease. Increasing evidence from experimental and clinical studies implies the intestinal microbiota in disease pathogenesis, thereby supporting the hypothesis that chronic intestinal inflammation arises from an abnormal immune response against the microorganisms of the intestinal flora in genetically susceptible individuals. Given that CD patients display changes in their gut microbiota composition, collectively termed “dysbiosis,” the question raises whether the altered microbiota composition is a cause of disease or rather a consequence of the inflammatory state of the intestinal environment. This review will focus on the crosstalk between the gut microbiota and the innate immune system during intestinal inflammation, thereby unraveling the role of the microbiota in CD pathogenesis. PMID:26441993

  7. Thioredoxin/Txnip: Redoxisome, As a Redox Switch for the Pathogenesis of Diseases

    Directory of Open Access Journals (Sweden)

    Eiji eYoshihara

    2014-01-01

    Full Text Available During the past few decades, it has been widely recognized that reducing-oxidizing (Redox responses occurring at the intra- and extra-cellular levels are one of most important biological phenomena and dysregulated redox responses are involved in the initiation and progression of multiple diseases. Thioredoxin 1 (Trx1 and Thioredoxin 2 (Trx2, mainly located in the cytoplasm and mitochondria, respectively, are ubiquitously expressed in variety of cells and control cellular reactive oxygen species (ROS by reducing the disulfides into thiol groups. Thioredoxin interacting protein (Txnip/TBP-2/VDUP1 directly binds to Trx1 & Trx2 (Trx and inhibit the reducing activity of Trx through their disulfide exchange. Recent studies have revealed that Trx1 and Txnip are involved in some critical redox-dependent signal pathways including NLRP3 inflammasome activation in a redox-dependent manner. Therefore, Trx/Txnip, a redox-sensitive signaling complex is a regulator of cellular redox status and has emerged as a key component in the link between redox-regulation and the pathogenesis of diseases. Here, we review the novel functional concept of the redox-related protein complex, named Redoxisome, consisting of Trx/Txnip, as a critical regulator for intra- and extra-cellular redox signaling, involved in the pathogenesis of various diseases such as cancer, autoimmune disease, and diabetes.

  8. The role of infectious mediators and gut microbiome in the pathogenesis of celiac disease.

    Science.gov (United States)

    Rostami Nejad, Mohammad; Ishaq, Sauid; Al Dulaimi, David; Zali, Mohammad Reza; Rostami, Kamran

    2015-04-01

    Celiac disease (CD) is an immune disorder that is associated with gluten sensitivity in people who are genetically predisposed. In celiac disease, food containing gluten mounts inflammatory response that results in villous atrophy in small bowel and increased permeability. This disorder is not only related to complications in the small bowel, but also has association with manifestations outside the GI tract. Small bowel mucosal immunity, exposed to infectious agents, is affected by CD; therefore, it is likely that patients with untreated celiac disease are more susceptible to infectious diseases. It is possible that sensitivity to gluten increases in patients infected with infectious diseases, and consequently infection may trigger CD in susceptible individuals. It is likely that, due to reduced immunity following the loss of intestinal villi, viral, bacterial, and parasitic infections develop faster in celiac disease patients and systemic complication occur more frequently. In addition, increased permeability, changing the microbiota following the chronic inflammation of the small intestine and abnormal immunological reactions are associated with celiac disease. PubMed, Medline, Google scholar, SID, and Magiran were searched for full text articles published between 1999 and 2014 in Persian and English. The associated keywords were used, and papers, which described particularly the impact of infectious agents on celiac disease, were selected. In this review, we have focused on the role of infectious agents and gut microbiota in the pathogenesis of celiac disease.

  9. Aspirin for Prevention of Cardiovascular Disease.

    Science.gov (United States)

    Mendy, Vincent L; Vargas, Rodolfo; Zhang, Lei

    2017-09-07

    We used data from the 2013 Mississippi Behavioral Risk Factor Surveillance System to examine aspirin use for the prevention of primary and secondary cardiovascular disease (CVD), based on the 2009 US Preventive Services Task Force (USPSTF) guidelines, among Mississippi men (aged 45-79 y) and women (aged 55-79 y) and to explore differences in aspirin use by sociodemographic characteristics. Among those without CVD, 39.1% of men and 45.9% of women reported taking aspirin, and among those with CVD, 85.9% of men and 85.1% of women reported taking aspirin. Data on preventive use of aspirin by sociodemographic characteristics yielded mixed results.

  10. Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

    Science.gov (United States)

    Osgood, Michael J.; Harrison, David G.; Sexton, Kevin W.; Hocking, Kyle M.; Voskresensky, Igor V.; Komalavilas, Padmini; Cheung-Flynn, Joyce; Guzman, Raul J.; Brophy, Colleen M.

    2014-01-01

    The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia. PMID:22445245

  11. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Oliveira C.P.M.S.

    2006-01-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  12. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

    Science.gov (United States)

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain

  13. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    C.P.M.S. Oliveira

    2006-02-01

    Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

  14. Escherichia coli-host macrophage interactions in the pathogenesis of inflammatory bowel disease.

    Science.gov (United States)

    Tawfik, Ahmed; Flanagan, Paul K; Campbell, Barry J

    2014-07-21

    Multiple studies have demonstrated alterations in the intestinal microbial community (termed the microbiome) in Crohn's disease (CD) and several lines of evidence suggest these changes may have a significant role in disease pathogenesis. In active and quiescent disease, both the faecal and mucosa-associated microbiome are discordant with matched controls with reduced biodiversity, changes in dominant organisms and increased temporal variation described. Mucosa-associated adherent, invasive Escherichia coli (E. coli) (AIEC), pro-inflammatory and resistant to killing by mucosal macrophages, appear to be particularly important. AIEC possess several virulence factors which may confer pathogenic potential in CD. Type-1 pili (FimH) allow adherence to intestinal cells via cell-surface carcinoembryonic antigen-related cell adhesion molecules and possession of long polar fimbrae promotes translocation across the intestinal mucosa via microfold (M)-cells of the follicle-associated epithelium. Resistance to stress genes (htrA, dsbA and hfq) and tolerance of an acidic pH may contribute to survival within the phagolysosomal environment. Here we review the current understanding of the role of mucosa-associated E. coli in Crohn's pathogenesis, the role of the innate immune system, factors which may contribute to prolonged bacterial survival and therapeutic strategies to target intracellular E. coli.

  15. Morquio disease: the role of cartilage canals in the pathogenesis of chondrogenic dwarfism.

    Science.gov (United States)

    Zustin, Jozef

    2010-12-01

    Chondrogenic dwarfism in Morquio disease (mucopolysaccharidosis IV) has been suggested to be strongly linked to the abnormal lysosomal storage of cartilaginous extracellular matrix waste products within chondrocytes and fibroblasts. The specific genetic defects of enzymes of the keratan sulfate and chondroitin-6-sulfate metabolism have been detected at the molecular level and importantly contributed to the current knowledge on the phenotype of this rare metabolic disorder. However, the pathogenesis of this epiphyseal centered progressive skeletal disease does not seem to be fully explained by the dysfunction of the chondrocyte cytoplasm that presents with vacuolar changes in adult patients. I propose that the accumulation of extracellular matrix degradation product-laden macrophages within epiphyseal cartilage canals during the early postnatal period causes dysregulation in the synchronized process of the neoformation and resorption of the maturing radial growing epiphyses. Similarly, the resorption of pannus tissue following the microtraumatisation of weight-bearing joints and epiphysis-type bones becomes impacted. If the hypothesis is valid, the early pathogenesis in Morquio disease could be because of the inadequate regression of cartilage canals and impaired resorption and restitution of pannus tissue.

  16. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  17. Functional impacts of the intestinal microbiome in the pathogenesis of inflammatory bowel disease.

    Science.gov (United States)

    Li, Jennifer; Butcher, James; Mack, David; Stintzi, Alain

    2015-01-01

    : The human intestinal microbiome plays a critical role in human health and disease, including the pathogenesis of inflammatory bowel disease (IBD). Numerous studies have identified altered bacterial diversity and abundance at varying taxonomic levels through biopsies and fecal samples of patients with IBD and diseased model animals. However, inconsistent observations regarding the microbial compositions of such patients have hindered the efforts in assessing the etiological role of specific bacterial species in the pathophysiology of IBD. These observations highlight the importance of minimizing the confounding factors associated with IBD and the need for a standardized methodology to analyze well-defined microbial sampling sources in early IBD diagnosis. Furthermore, establishing the linkage between microbiota compositions with their function within the host system can provide new insights on the pathogenesis of IBD. Such research has been greatly facilitated by technological advances that include functional metagenomics coupled with proteomic and metabolomic profiling. This review provides updates on the composition of the microbiome in IBD and emphasizes microbiota dysbiosis-involved mechanisms. We highlight functional roles of specific bacterial groups in the development and management of IBD. Functional analyses of the microbiome may be the key to understanding the role of microbiota in the development and chronicity of IBD and reveal new strategies for therapeutic intervention.

  18. The isolation, pathogenesis, diagnosis, transmission, and control of avian bornavirus and proventricular dilatation disease.

    Science.gov (United States)

    Hoppes, Sharman; Gray, Patricia L; Payne, Susan; Shivaprasad, H L; Tizard, Ian

    2010-09-01

    Proventricular dilatation disease (PDD) is a common infectious neurologic disease of birds comprising a dilatation of the proventriculus by ingested food as a result of defects in intestinal motility, which affects more than 50 species of psittacines, and is also known as Macaw wasting disease, neuropathic ganglioneuritis, or lymphoplasmacytic ganglioneuritis. Definitive diagnosis of PDD has been problematic due to the inconsistent distribution of lesions. Since its discovery, avian bornavirus (ABV) has been successfully cultured from the brains of psittacines diagnosed with PDD, providing a source of antigen for serologic assays and nucleic acid for molecular assays. This article provides evidence that ABV is the etiologic agent of PDD. Recent findings on the transmission, epidemiology, pathogenesis, diagnosis, and control of ABV infection and PDD are also reviewed. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Seven challenges in modeling vaccine preventable diseases

    Directory of Open Access Journals (Sweden)

    C.J.E. Metcalf

    2015-03-01

    Full Text Available Vaccination has been one of the most successful public health measures since the introduction of basic sanitation. Substantial mortality and morbidity reductions have been achieved via vaccination against many infections, and the list of diseases that are potentially controllable by vaccines is growing steadily. We introduce key challenges for modeling in shaping our understanding and guiding policy decisions related to vaccine preventable diseases.

  20. Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25-35).

    NARCIS (Netherlands)

    Kaminsky, Y.G.; Marlatt, M.W.; Smith, M.A.; Kosenko, E.A.

    2010-01-01

    Amyloid-beta peptide (Abeta) is a central player in the pathogenesis and diagnosis of Alzheimer disease. It aggregates to form the core of Alzheimer disease-associated plaques found in coordination with tau deposits in diseased individuals. Despite this clinical relevance, no single hypothesis

  1. 78 FR 25279 - Centers for Disease Control and Prevention

    Science.gov (United States)

    2013-04-30

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 12... and Prevention and the Agency for Toxic Substances and Disease Registry. Elaine L. Baker,...

  2. 75 FR 30040 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-05-28

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 1:30... Disease Control and Prevention. BILLING CODE 4163-18-P...

  3. 75 FR 39544 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-07-09

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC... Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  4. 76 FR 10371 - Disease, Disability, and Injury Prevention and Control

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    2011-02-24

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the... and Prevention and the Agency for Toxic Substances and Disease Registry. Dated: February 14,...

  5. 75 FR 7606 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-02-22

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the... for Disease Control and Prevention. BILLING CODE 4163-18-P...

  6. A possible role for humoral immunity in the pathogenesis of Parkinson's disease.

    Science.gov (United States)

    Orr, Carolyn F; Rowe, Dominic B; Mizuno, Yoshikuni; Mori, Hideo; Halliday, Glenda M

    2005-11-01

    The pathogenesis of idiopathic Parkinson's disease is unknown, but nigral degeneration and depigmentation are associated with microglial inflammation and anti-inflammatory medications appear to protect against the disease. The possibility that humoral immunity may play a role in initiating or regulating the inflammation has been suggested by experimental studies triggering dopamine cell death using a variety of transfer strategies and the observation of CD8+ T lymphocytes and complement in the nigra in Parkinson's disease. We analysed the association between degeneration and humoral immune markers in brain tissue of patients with idiopathic (n = 13) or genetic (n = 2 with alpha-synuclein and n = 1 with parkin mutations) Parkinson's disease and controls without neurological disease (n = 12) to determine the humoral immune involvement in Parkinson's disease. Formalin-fixed tissue samples from the substantia nigra and primary visual cortex for comparison were stained for alpha-synuclein, major histocompatibility complex II (HLA), immunoglobulin M (IgM), immunoglobulin G (IgG), IgG subclasses 1-4 and IgG receptors FcgammaR I-III. Antigen retrieval and both single immunoperoxidase and double immunofluorescence procedures were employed to determine the cell types involved and their pattern and semiquantitative densities. Significant dopamine neuron loss occurred in all patients with Parkinson's disease, negatively correlating with disease duration (r = -0.76, P = 0.002). Although all patients had increased inflammatory HLA immunopositive microglia, the degree of inflammation was similar throughout the disease (r = 0.08, P = 0.82). All patients with Parkinson's disease had IgG binding on dopamine neurons but not IgM binding. Lewy bodies were strongly immunolabelled with IgG. A mean 30 +/- 12% of dopamine nigral neurons were immunoreactive for IgG in Parkinson's disease with the proportion of IgG immunopositive neurons negatively correlating with the degree of cell loss in

  7. Pathogenesis of coronary artery disease: focus on genetic risk factors and identification of genetic variants

    Directory of Open Access Journals (Sweden)

    Sayols-Baixeras S

    2014-01-01

    Full Text Available Sergi Sayols-Baixeras, Carla Lluís-Ganella, Gavin Lucas, Roberto ElosuaCardiovascular Epidemiology and Genetics Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, SpainAbstract: Coronary artery disease (CAD is the leading cause of death and disability worldwide, and its prevalence is expected to increase in the coming years. CAD events are caused by the interplay of genetic and environmental factors, the effects of which are mainly mediated through cardiovascular risk factors. The techniques used to study the genetic basis of these diseases have evolved from linkage studies to candidate gene studies and genome-wide association studies. Linkage studies have been able to identify genetic variants associated with monogenic diseases, whereas genome-wide association studies have been more successful in determining genetic variants associated with complex diseases. Currently, genome-wide association studies have identified approximately 40 loci that explain 6% of the heritability of CAD. The application of this knowledge to clinical practice is challenging, but can be achieved using various strategies, such as genetic variants to identify new therapeutic targets, personal genetic information to improve disease risk prediction, and pharmacogenomics. The main aim of this narrative review is to provide a general overview of our current understanding of the genetics of coronary artery disease and its potential clinical utility.Keywords: coronary artery disease, pathogenesis, genetic risk factors, genetic variants

  8. Periodontal disease and subgingival microbiota as contributors for rheumatoid arthritis pathogenesis: modifiable risk factors?

    Science.gov (United States)

    Scher, Jose U; Bretz, Walter A; Abramson, Steven B

    2014-07-01

    Since the early 1900s, the role of periodontal disease in the pathogenesis of rheumatoid arthritis has been a matter of intense research. The last decade has witnessed many advances supporting a link between periodontitis, the presence of specific bacterial species (i.e. Porphyromonas gingivalis) and their effects in immune response. This review will examine available evidence on the individuals. Epidemiological studies have stressed the commonalities shared by periodontal disease and rheumatoid arthritis. Many groups have focused their attention toward understanding the periodontal microbiota and its alterations in states of health and disease. The presence of circulating antibodies against periodontopathic bacteria and associated inflammatory response has been found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. Most recently, the periodontal microbiota of smokers and patients with RA has been elucidated, revealing profound changes in the bacterial communities compared with those of healthy controls. This has led to several small clinical trials of progressive disease treatment as adjuvant for disease-modifying therapy in RA. Smoking and periodontal disease are emerging risk factors for the development of RA. Epidemiological, clinical, and basic research has further strengthened this association, pointing toward changes in the oral microbiota as possible contributors to systemic inflammation and arthritis.

  9. MicroRNAs in inflammatory bowel disease--pathogenesis, diagnostics and therapeutics.

    Science.gov (United States)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

    2012-09-14

    The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD. The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are evolutionary conserved in animals and plants, and regulate specific target mRNAs at the post-transcriptional level. MiRNAs are involved in several biological processes, including development, cell differentiation, proliferation and apoptosis. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome. Thus, miRNA deregulation often results in an impaired cellular function, and a disturbance of downstream gene regulation and signaling cascades, suggesting their implication in disease etiology. Despite the identification of more than 1900 mature human miRNAs, very little is known about their biological functions and functional targets. Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients. Thus, there is great promise that miRNAs will aid in the early diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics.

  10. MicroRNAs in inflammatory bowel disease-pathogenesis,diagnostics and therapeutics

    Institute of Scientific and Technical Information of China (English)

    Mehmet Coskun; Jacob Tveiten Bjerrum; Jakob Benedict Seidelin; Ole Haagen Nielsen

    2012-01-01

    The pathogenesis of inflammatory bowel disease (IBD)is complex and largely unknown.Until recently,research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD.However,in the last few years,new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs,called microRNAs (miRs or miRNAs) and IBD.The short (approximately 22 nucleotides),endogenous,single-stranded RNAs are evolutionary conserved in animals and plants,and regulate specific target mRNAs at the post-transcriptional level.MiRNAs are involved in several biological processes,including development,cell differentiation,proliferation and apoptosis.Furthermore,it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome.Thus,miRNA deregulation often results in an impaired cellular function,and a disturbance of downstream gene regulation and signaling cascades,suggesting their implication in disease etiology.Despite the identification of more than 1900 mature human miRNAs,very little is known about their biological functions and functional targets.Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients.Thus,there is great promise that miRNAs will aid in the early diagnosis of IBD,and in the development of personalized therapies.Here,we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis,diagnostics and therapeutics.

  11. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods

    Directory of Open Access Journals (Sweden)

    Mark A Moyad

    2015-01-01

    Full Text Available Cardiovascular disease (CVD has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin.

  12. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis.

    Science.gov (United States)

    Tuk, Bert

    2016-01-01

    Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

  13. The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Seoyoung Yoon

    2015-09-01

    Full Text Available Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer

  14. 75 FR 18848 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Prevention...

    Science.gov (United States)

    2010-04-13

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the..., PhD, Scientific Review Officer, National Center for Chronic Disease Prevention and Health...

  15. Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease.

    Science.gov (United States)

    Cătană, Cristina-Sorina; Berindan Neagoe, Ioana; Cozma, Vasile; Magdaş, Cristian; Tăbăran, Flaviu; Dumitraşcu, Dan Lucian

    2015-05-21

    Inflammatory bowel diseases (IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis. These idiopathic diseases have environmental, genetic, immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type (Th) 1 and Th2 immune responses, other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin, microRNAs, and serum proinflammatory cytokines. An efficient strategy for IBD therapy is represented by the combination of IL-17A and IL-17F in acute IL-17A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17F knockout, DSS-induced colitis have been observed. Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused review in order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.

  16. Immunogenetic Pathogenesis of Celiac Disease and Non-celiac Gluten Sensitivity.

    Science.gov (United States)

    Escudero-Hernández, Celia; Peña, Amado Salvador; Bernardo, David

    2016-07-01

    Celiac disease is the most common oral intolerance in Western countries. It results from an immune response towards gluten proteins from certain cereals in genetically predisposed individuals (HLA-DQ2 and/or HLA-DQ8). Its pathogenesis involves the adaptive (HLA molecules, transglutaminase 2, dendritic cells, and CD4(+) T-cells) and the innate immunity with an IL-15-mediated response elicited in the intraepithelial compartment. At present, the only treatment is a permanent strict gluten-free diet (GFD). Multidisciplinary studies have provided a deeper insight of the genetic and immunological factors and their interaction with the microbiota in the pathogenesis of the disease. Similarly, a better understanding of the composition of the toxic gluten peptides has improved the ways to detect them in food and drinks and how to monitor GFD compliance via non-invasive approaches. This review, therefore, addresses the major findings obtained in the last few years including the re-discovery of non-celiac gluten sensitivity.

  17. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Christina Rose Kyrtsos

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ deposition and the presence of neurofibrillary tangles (NFTs within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  18. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S

    2015-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.

  19. Alzheimer's disease prevention: A way forward.

    Science.gov (United States)

    Bermejo-Pareja, F; Llamas-Velasco, S; Villarejo-Galende, A

    2016-12-01

    This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  20. Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer's and Parkinson's diseases.

    Directory of Open Access Journals (Sweden)

    Igor F Tsigelny

    Full Text Available BACKGROUND: Misfolding and pathological aggregation of neuronal proteins has been proposed to play a critical role in the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD and Parkinson's disease (PD are frequent neurodegenerative diseases of the aging population. While progressive accumulation of amyloid beta protein (Abeta oligomers has been identified as one of the central toxic events in AD, accumulation of alpha-synuclein (alpha-syn resulting in the formation of oligomers and protofibrils has been linked to PD and Lewy body Disease (LBD. We have recently shown that Abeta promotes alpha-syn aggregation and toxic conversion in vivo, suggesting that abnormal interactions between misfolded proteins might contribute to disease pathogenesis. However the molecular characteristics and consequences of these interactions are not completely clear. METHODOLOGY/PRINCIPAL FINDINGS: In order to understand the molecular mechanisms involved in potential Abeta/alpha-syn interactions, immunoblot, molecular modeling, and in vitro studies with alpha-syn and Abeta were performed. We showed in vivo in the brains of patients with AD/PD and in transgenic mice, Abeta and alpha-synuclein co-immunoprecipitate and form complexes. Molecular modeling and simulations showed that Abeta binds alpha-syn monomers, homodimers, and trimers, forming hybrid ring-like pentamers. Interactions occurred between the N-terminus of Abeta and the N-terminus and C-terminus of alpha-syn. Interacting alpha-syn and Abeta dimers that dock on the membrane incorporated additional alpha-syn molecules, leading to the formation of more stable pentamers and hexamers that adopt a ring-like structure. Consistent with the simulations, under in vitro cell-free conditions, Abeta interacted with alpha-syn, forming hybrid pore-like oligomers. Moreover, cells expressing alpha-syn and treated with Abeta displayed increased current amplitudes and calcium influx consistent with the

  1. Pathogenesis of common glomerular diseases – role of the podocyte cytoskeleton

    Directory of Open Access Journals (Sweden)

    Kumagai T

    2012-10-01

    Full Text Available Takanori Kumagai, Flaviana Mouawad, Tomoko TakanoDepartment of Medicine, McGill University Health Centre, Montreal, Quebec, CanadaAbstract: Glomerulus is the filtration unit of the kidney where the first step of urine formation takes place. In the glomerulus, water and small molecules including waste products of the body are filtered into the urine, while large molecules essential for body function such as albumin are retained. When this barrier function of the kidney is impaired, protein leakage into the urine (proteinuria occurs. Proteinuria is not only a hallmark of many glomerular diseases but also a prognostic marker of kidney disease progression. Visceral glomerular epithelial cells (commonly called podocytes are known to have an important role in the maintenance of glomerular barrier function. In the last decade, remarkable progress has been made in podocyte biology, mainly led by the discoveries of important proteins that work together to maintain the intricate morphology and function of podocytes. Most of these so-called podocyte proteins modulate the actin cytoskeleton either directly or indirectly. The aim of the current review is to discuss the pathogenesis of common glomerular diseases with a particular focus on the role of the actin cytoskeleton in podocytes. The diseases covered include minimal change disease, focal segmental glomerulosclerosis (idiopathic and hereditary, membranous nephropathy, hypertensive glomerulosclerosis, and diabetic nephropathy.Keywords: glomerular disease, podocyte, cytoskeleton, proteinuria

  2. Lysosomal Ca(2+) homeostasis: role in pathogenesis of lysosomal storage diseases.

    Science.gov (United States)

    Lloyd-Evans, Emyr; Platt, Frances M

    2011-08-01

    Disrupted cellular Ca(2+) signaling is believed to play a role in a number of human diseases including lysosomal storage diseases (LSD). LSDs are a group of ∼50 diseases caused predominantly by mutations in lysosomal proteins that result in accumulation of macromolecules within the lysosome. We recently reported that Niemann-Pick type C (NPC) is the first human disease to be associated with defective lysosomal Ca(2+) uptake and defective NAADP-mediated lysosomal Ca(2+) release. These defects in NPC cells leads to the disruption in endocytosis and subsequent lipid storage that is a feature of this disease. In contrast, Chediak-Higashi Syndrome cells have been reported to have enhanced lysosomal Ca(2+) uptake whilst the TRPML1 protein defective in mucolipidosis type IV is believed to function as a Ca(2+) channel. In this review we provide a summary of the current knowledge on the role of lysosomal Ca(2+) signaling in the pathogenesis of this group of diseases.

  3. IgG4-Related Disease without Overexpression of IgG4: Pathogenesis Implications

    Directory of Open Access Journals (Sweden)

    Naoshi Nishina

    2012-01-01

    Full Text Available IgG4-related disease is a new disease group that affects multiple organs. It is characterized by high serum IgG4 and abundant infiltration of IgG4-bearing plasma cells in the affected organ. Here, we describe an intriguing case that suggested that IgG4-related disease might present without IgG4 overexpression or infiltration, at least during a relapse. A 47-year-old man had been diagnosed with systemic lupus erythematosus 15 years. He was admitted due to a pituitary mass, systemic lymphadenopathy, and multiple nodules in the lungs and kidneys. The serum IgG4 level was normal and histopathological examination of the pituitary mass showed abundant lymphocyte and plasma cell infiltration with very few IgG4-positive cells. When we examined specimens preserved from 15 years ago, we found high serum IgG4 levels and IgG4-bearing plasma cell infiltration. This resulted in a diagnosis of IgG4-related disease, and we considered the current episode to be a relapse without IgG4 overexpression. This case indicated that, to clarify the pathogenesis of IgG4-related disease, current cases should repeat specimen evaluations over the course of IgG4-related disease to define diagnostic markers.

  4. Periodontal Disease and Subgingival Microbiota as Contributors for RA Pathogenesis: Modifiable Risk Factors?

    Science.gov (United States)

    Scher, Jose U.; Bretz, Walter A.; Abramson, Steven B.

    2014-01-01

    Purpose of review Since the early 1900s, the role of periodontal disease in the pathogenesis of rheumatoid arthritis has been a matter of intense research. The last decade has witnessed many advances supporting a link between periodontitis, the presence of specific bacterial species (i.e., Porphyromonas ginigivalis) and their effects in immune response. This review will examine available evidence on the subject. Recent findings Epidemiological studies have stressed the commonalities shared by periodontal disease and rheumatoid arthritis. Many groups have focused their attention towards understanding the periodontal microbiota and its alterations in states of health and disease. The presence of circulating antibodies against periodontopathic bacteria and associated inflammatory response has been found in both RA patients and subjects at-risk for disease development. Most recently, the periodontal microbiota of smokers and patients with RA has been elucidated, revealing profound changes in the bacterial communities compared to that of healthy controls. This has led to several small clinical trials of PD treatment as adjuvant for disease-modifying therapy in RA. Summary Smoking and periodontal disease are emerging risk factors for the development of RA. Epidemiological, clinical and basic research has further strengthened this association, pointing towards changes in the oral microbiota as possible contributors to systemic inflammation and arthritis. PMID:24807405

  5. Transcriptional Activation of Mucin by Pseudomonas aeruginosa Lipopolysaccharide in the Pathogenesis of Cystic Fibrosis Lung Disease

    Science.gov (United States)

    Li, Jian-Dong; Dohrman, Austin F.; Gallup, Marianne; Miyata, Susumu; Gum, James R.; Kim, Young S.; Nadel, Jay A.; Prince, Alice; Basbaum, Carol B.

    1997-02-01

    An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a CI ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyrphostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

  6. Hashimoto′s encephalopathy and motor neuron disease: A common autoimmune pathogenesis?

    Directory of Open Access Journals (Sweden)

    Harzheim Michael

    2006-01-01

    Full Text Available Hashimoto′s encephalopathy is a rare complication of autoimmune thyroiditis not associated with thyroidal function decline. We report a 50-year-old man presenting with lower motor neuron symptoms evolving over 3 years and changes in behavior associated with attentive and cognitive impairment occurring in the last few months. Memory deficits, emotional instability, marked dysarthria, mild symmetric weakness of the lower extremities, and fasciculations were the most striking clinical features. EEG was diffusely slow, cranial MRI revealed multiple subcortical white matter lesions, CSF protein was slightly elevated, electromyographic recordings showed acute and chronic denervation, and extremely high TPO antibody titers were found in the serum. Hashimoto′s encephalopathy and lower motor neuron disease were diagnosed. As repeated high-dose intravenous methylprednisolone administration followed by oral tapering improved both central nervous system and lower motor neuron symptoms, the question was raised whether there was a common autoimmune pathogenesis of both clinically distinct diseases.

  7. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review.

    Science.gov (United States)

    Abelló, David; Sancho, Elena; Camps, Jordi; Joven, Jorge

    2014-11-14

    Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism's antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.

  8. Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches.

    Science.gov (United States)

    Sartor, R Balfour; Wu, Gary D

    2017-02-01

    Intestinal microbiota are involved in the pathogenesis of Crohn's disease, ulcerative colitis, and pouchitis. We review the mechanisms by which these gut bacteria, fungi, and viruses mediate mucosal homeostasis via their composite genes (metagenome) and metabolic products (metabolome). We explain how alterations to their profiles and functions under conditions of dysbiosis contribute to inflammation and effector immune responses that mediate inflammatory bowel diseases (IBD) in humans and enterocolitis in mice. It could be possible to engineer the intestinal environment by modifying the microbiota community structure or function to treat patients with IBD-either with individual agents, via dietary management, or as adjuncts to immunosuppressive drugs. We summarize the latest information on therapeutic use of fecal microbial transplantation and propose improved strategies to selectively normalize the dysbiotic microbiome in personalized approaches to treatment. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. POSSIBLE ROLE OF PROBIOTIC MICROORGANISMS OF BIFIDOBACTERIUM AND LACTOBACILLUS GENUS IN PATHOGENESIS OF AUTOIMMUNE THYROID DISEASES

    Directory of Open Access Journals (Sweden)

    E. P. Kiseleva

    2010-01-01

    Full Text Available It was revealed, that, in blood samples of the patients with autoimmune thyroid diseases, serum antibodies against cell-free fraction of Bifidobacterium bifidum 791 and Lactobacillus plantarum B-01 were detected, respectively, in 71 and 63% of cases, that being two-fold higher than appropriate frequencies in healthy blood donors. An evidence was obtained that presence of some components specifically reacting with autoantibodies against thyroid peroxidase and thyroglobulin on the surface of the microorganisms cells and competing for binding of these immunoglobulins with thyroid antigens. One may also suggest a presence of bacterial components, interacting with thyroid peroxidase. The data obtained let us suggest that probiotic microorganisms of Bifidobacterium and Lactobacillus genus could take part in pathogenesis of autoimmune thyroid diseases, by means of molecular mimicry mechanisms.

  10. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection.

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    Asuncion Mejias

    2013-11-01

    Full Text Available BACKGROUND: Respiratory syncytial virus (RSV is the leading cause of viral lower respiratory tract infection (LRTI and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV LRTI, and to identify biomarkers that can objectively assess RSV disease severity. METHODS AND FINDINGS: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135, HRV (n = 30, and influenza (n = 16 LRTI, and healthy age- and sex-matched controls (n = 39. A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US with high sensitivity (94% [95% CI 87%-98%] and specificity (98% [95% CI 88%-99%]. It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo. We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. CONCLUSIONS: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues

  11. Prevention strategies for Alzheimer’s disease

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    Gauthier Serge

    2012-06-01

    Full Text Available Abstract Symptomatic treatment during the dementia stage of Alzheimer’s disease(AD cannot delay or halt the progression of this disease. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated neurodegenerative condition, and its associated burden for individuals and society. Age, gender, family history, ApoE4, systolic blood pressure, body mass index, total cholesterol level and physical activity are all used as component of dementia risk score. There have been numerous challenges in conducting primary prevention trials in AD. Enrichment strategies for prevention studies include studying those subjects with more risk factors for AD, such as older age, those with a positive family history of late onset AD, and those who are ApoE4 positive. Each of these strategies is designed to increase the probability of developing AD thereby decreasing the sample size or the duration of follow up. Another strategy would be to target directly the pathophysiology of AD in its preclinical stages and use the biomarkers in prevention trial as surrogate markers. This will be done first in carriers of dominantly inherited early onset AD. As this research takes place networks of memory clinics must prepare to transfer new knowledge to persons interested in a preventive approach to AD.

  12. Immune-Mediated Inflammation May Contribute to the Pathogenesis of Cardiovascular Disease in Mucopolysaccharidosis Type I.

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    Omar Khalid

    Full Text Available Cardiovascular disease, a progressive manifestation of α-L-iduronidase deficiency or mucopolysaccharidosis type I, continues in patients both untreated and treated with hematopoietic stem cell transplantation or intravenous enzyme replacement. Few studies have examined the effects of α-L-iduronidase deficiency and subsequent glycosaminoglycan storage upon arterial gene expression to understand the pathogenesis of cardiovascular disease.Gene expression in carotid artery, ascending, and descending aortas from four non-tolerized, non-enzyme treated 19 month-old mucopolysaccharidosis type I dogs was compared with expression in corresponding vascular segments from three normal, age-matched dogs. Data were analyzed using R and whole genome network correlation analysis, a bias-free method of categorizing expression level and significance into discrete modules. Genes were further categorized based on module-trait relationships. Expression of clusterin, a protein implicated in other etiologies of cardiovascular disease, was assessed in canine and murine mucopolysaccharidosis type I aortas via Western blot and in situ immunohistochemistry.Gene families with more than two-fold, significant increased expression involved lysosomal function, proteasome function, and immune regulation. Significantly downregulated genes were related to cellular adhesion, cytoskeletal elements, and calcium regulation. Clusterin gene overexpression (9-fold and protein overexpression (1.3 to 1.62-fold was confirmed and located specifically in arterial plaques of mucopolysaccharidosis-affected dogs and mice.Overexpression of lysosomal and proteasomal-related genes are expected responses to cellular stress induced by lysosomal storage in mucopolysaccharidosis type I. Upregulation of immunity-related genes implicates the potential involvement of glycosaminoglycan-induced inflammation in the pathogenesis of mucopolysaccharidosis-related arterial disease, for which clusterin

  13. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

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    Chang RB

    2015-04-01

    Full Text Available Renbao Chang,1 Xudong Liu,1 Shihua Li,2 Xiao-Jiang Li1,2 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Abstract: Huntington’s disease (HD is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. Keywords: transgenic animal models, Huntington’s disease, pathogenesis, therapy

  14. Alzheimer's disease - the ways of prevention.

    Science.gov (United States)

    Kivipelto, M; Solomon, A

    2008-01-01

    Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.

  15. Antioxidants and coronary artery disease: from pathophysiology to preventive therapy.

    Science.gov (United States)

    Leopold, Jane A

    2015-03-01

    Oxidant stress in the cardiovascular system may occur when antioxidant capacity is insufficient to reduce reactive oxygen species and other free radicals. Oxidant stress has been linked to the pathogenesis of atherosclerosis and incident coronary artery disease. As a result of this connection, early observational studies focused on dietary antioxidants, such as β-carotene, α-tocopherol, and ascorbic acid, and demonstrated an inverse relationship between intake of these antioxidants and major adverse cardiovascular events. These findings supported a number of randomized trials on the use of selected antioxidants as primary or secondary prevention strategies to decrease cardiac risk; however, many of these studies reported disappointing results with little or no observed risk reduction in antioxidant-treated patients. Several plausible explanations for these findings have been suggested, including incorrect antioxidant choice or dose, synthetic versus dietary antioxidants as the intervention, and patient selection, all of which will be important to consider when designing future clinical trials. This review will focus on the contemporary evidence that is the basis for our current understanding of the role of antioxidants in cardiovascular disease prevention.

  16. Antioxidants and Coronary Artery Disease: From Pathophysiology to Preventive Therapy

    Science.gov (United States)

    Leopold, Jane A.

    2014-01-01

    Oxidant stress in the cardiovascular system may occur when antioxidant capacity is insufficient to reduce reactive oxygen species and other free radicals. Oxidant stress has been linked to the pathogenesis of atherosclerosis and incident coronary artery disease. As a result of this connection, early observational studies focused on dietary antioxidants, such as β-carotene, α-tocopherol, and ascorbic acid, and demonstrated an inverse relationship between intake of these antioxidants and major adverse cardiovascular events. These findings supported a number of randomized trials of selected antioxidants as primary and secondary prevention to decrease cardiac risk; however, many of these studies reported disappointing results with little or no observed risk reduction in antioxidant treated patients. Several plausible explanations for these findings have been suggested, including incorrect antioxidant choice or dose, synthetic versus dietary antioxidant as the intervention, and patient selection, all of which will be important to consider when designing future clinical trials. This review will focus on the contemporary evidence that is the basis for our current understanding of the role of antioxidants in cardiovascular disease prevention. PMID:25369999

  17. A Tale of Two Maladies? Pathogenesis of Depression with and without the Huntington's Disease Gene Mutation.

    Science.gov (United States)

    Du, Xin; Pang, Terence Y C; Hannan, Anthony J

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression), cognitive deficits (culminating in dementia), and motor abnormalities (including chorea). Having reached the twentieth anniversary of the discovery of the "genetic stutter" which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviors as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data, and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalize to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.

  18. Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

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    Alexei A Podtelezhnikov

    Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age, Alz (Alzheimer, Inflame (inflammation, and NdStress (neurodegenerative stress. BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.

  19. [The role of gender in the pathogenesis and development of autoimmune diseases].

    Science.gov (United States)

    Tomczyńska, Małgorzata; Salata, Ireneusz; Saluk, Joanna

    2016-09-29

    Autoimmune diseases occur with greater frequency in women than in men, suggesting that the mechanism of pathogenesis is conditioned by gender. So far not defined clearly factors responsible for the development and course of these diseases depending on sex. However, it was found there is a clear sexual dimorphism of the immune system, which may determine the process of autoimmunity. The causes of the increased incidence of women in autoimmune diseases are attributed to the action of the hormones estrogen, which can promote the process of autoimmunity and enhance the clinical symptoms of the disease. As shown sex hormones have immunomodulatory activities on dendritic cells, macrophages, neutrophils, B and T cells. In the both situation the response to strange antigens and mechanism of autoimmunity sex hormones have been shown to play contributory roles in process of cytokine production, the expression of cytokine receptors and response of effector cells. According to recent research, the development of autoimmune diseases is determined by genetic factors. Changes in the autosomal genes X and Y chromosomes play an important role in the progression of autoimmune processes, especially that the X chromosome has genes responsible for the regulation of the immune system.

  20. Cross Talk between NOTCH Signaling and Biomechanics in Human Aortic Valve Disease Pathogenesis

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    Richard C. Godby

    2014-12-01

    Full Text Available Aortic valve disease is a burgeoning public health problem associated with significant mortality. Loss of function mutations in NOTCH1 cause bicuspid aortic valve (BAV and calcific aortic valve disease. Because calcific nodules manifest on the fibrosa side of the cusp in low fluidic oscillatory shear stress (OSS, elucidating pathogenesis requires approaches that consider both molecular and mechanical factors. Therefore, we examined the relationship between NOTCH loss of function (LOF and biomechanical indices in healthy and diseased human aortic valve interstitial cells (AVICs. An orbital shaker system was used to apply cyclic OSS, which mimics the cardiac cycle and hemodynamics experienced by AVICs in vivo. NOTCH LOF blocked OSS-induced cell alignment in human umbilical vein endothelial cells (HUVECs, whereas AVICs did not align when subjected to OSS under any conditions. In healthy AVICs, OSS resulted in decreased elastin (ELN and α-SMA (ACTA2. NOTCH LOF was associated with similar changes, but in diseased AVICs, NOTCH LOF combined with OSS was associated with increased α-SMA expression. Interestingly, AVICs showed relatively higher expression of NOTCH2 compared to NOTCH1. Biomechanical interactions between endothelial and interstitial cells involve complex NOTCH signaling that contributes to matrix homeostasis in health and disorganization in disease.

  1. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis.

    Science.gov (United States)

    Robinson, Dionne P; Klein, Sabra L

    2012-08-01

    During pregnancy, it is evolutionarily advantageous for inflammatory immune responses that might lead to fetal rejection to be reduced and anti-inflammatory responses that promote transfer of maternal antibodies to the fetus to be increased. Hormones modulate the immunological shift that occurs during pregnancy. Estrogens, including estradiol and estriol, progesterone, and glucocorticoids increase over the course of pregnancy and affect transcriptional signaling of inflammatory immune responses at the maternal-fetal interface and systemically. During pregnancy, the reduced activity of natural killer cells, inflammatory macrophages, and helper T cell type 1 (Th1) cells and production of inflammatory cytokines, combined with the higher activity of regulatory T cells and production of anti-inflammatory cytokines, affects disease pathogenesis. The severity of diseases caused by inflammatory responses (e.g., multiple sclerosis) is reduced and the severity of diseases that are mitigated by inflammatory responses (e.g., influenza and malaria) is increased during pregnancy. For some infectious diseases, elevated inflammatory responses that are necessary to control and clear a pathogen have a negative consequence on the outcome of pregnancy. The bidirectional interactions between hormones and the immune system contribute to both the outcome of pregnancy and female susceptibility to disease.

  2. 75 FR 34750 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-06-18

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates: 8... Excellence in Youth Violence Prevention (U01), Funding Opportunity Announcement (FOA) CE10-004,...

  3. Backyard poultry: legislation, zoonoses and disease prevention.

    Science.gov (United States)

    Whitehead, M L; Roberts, V

    2014-10-01

    In law, backyard poultry are "food-producing animals" and "farmed animals" and are subject to regulations regarding welfare, prescribing, banned procedures, disposal of carcases, feeding bans, notifiable diseases and disease surveillance in addition to those applying to most other pets. Many owners and some veterinary surgeons are unclear about the requirements of these regulations. Backyard poultry are also associated with some different zoonotic disease risks to mammalian pets. Because a high proportion of poultry morbidity and mortality relates to infectious diseases, the health of backyard poultry is amenable to improvement through basic husbandry, biosecurity, hygiene and preventive medicine measures that can be incorporated into a simple "flock-health plan". This article reviews these topics.

  4. [New insight in pathogenesis of podocyte disfunction in minimal change disease].

    Science.gov (United States)

    Liu, Shanshan; Chen, Jianghua

    2016-03-01

    Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.

  5. Pathogenesis of Parkinson disease--the gut-brain axis and environmental factors.

    Science.gov (United States)

    Klingelhoefer, Lisa; Reichmann, Heinz

    2015-11-01

    Parkinson disease (PD) follows a defined clinical pattern, and a range of nonmotor symptoms precede the motor phase. The predominant early nonmotor manifestations are olfactory impairment and constipation. The pathology that accompanies these symptoms is consistent with the Braak staging system: α-synuclein in the dorsal motor nucleus of the vagus nerve, the olfactory bulb, the enteric nervous system (ENS) and the submandibular gland, each of which is a gateway to the environment. The neuropathological process that leads to PD seems to start in the ENS or the olfactory bulb and spreads via rostrocranial transmission to the substantia nigra and further into the CNS, raising the intriguing possibility that environmental substances can trigger pathogenesis. Evidence from epidemiological studies and animal models supports this hypothesis. For example, in mice, intragastric administration of the pesticide rotenone can almost completely reproduce the typical pathological and clinical features of PD. In this Review, we present clinical and pathological evidence to support the hypothesis that PD starts in the gut and spreads via trans-synaptic cell-to-cell transfer of pathology through the sympathetic and parasympathetic nervous systems to the substantia nigra and the CNS. We also consider how environmental factors might trigger pathogenesis, and the potential for therapeutically targeting the mechanisms of these initial stages.

  6. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Stojsavljević, Sanja; Gomerčić Palčić, Marija; Virović Jukić, Lucija; Smirčić Duvnjak, Lea; Duvnjak, Marko

    2014-12-28

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The "two-hit" hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

  7. Neuroinflammation - an early event in both the history and pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Eikelenboom, Piet; van Exel, Erik; Hoozemans, Jeroen J M; Veerhuis, Rob; Rozemuller, Annemieke J M; van Gool, Willem A

    2010-01-01

    About hundred years ago, Oskar Fischer proposed that the senile plaques are the consequence of the deposition of a foreign substance that could induce an inflammatory response leading to an abnormal neuritic response of the surrounding neurons. To show that the interest in inflammation in Alzheimer's disease (AD) is not only an early event in the history of AD but that inflammation is also an early event in the pathogenesis of AD. Evaluation of the neuropathological, epidemiological and genetic evidence for a role of inflammation early in the pathogenesis of AD. Neuropathological studies show presence of activated microglia and inflammation-related mediators in the cerebral neocortex of autopsied patients with a low Braak stage for AD pathology. Prospective population-based cohort studies indicate that higher serum levels of acute phase proteins predict dementia. On a genetic level, it was found that the production capacity of proinflammatory cytokines after stimulation with lipopolysaccharide (a process that is under strong genetic control) is higher in offspring with a parental history of late-onset AD. Neuropathological studies show that a neuroinflammatory response in the cerebral neocortex parallels the early stages of AD pathology and precedes the late stage, tau-related pathology. Epidemiological and genetic studies indicate that systemic markers of the innate immunity are risk factors for late-onset AD. Copyright 2010 S. Karger AG, Basel.

  8. The pervasiveness of interleukin-1 in Alzheimer pathogenesis: a role for specific polymorphisms in disease risk

    Science.gov (United States)

    Griffin, W.S.T.; Nicoll, J.A.R.; Grimaldi, L.M.E.; Sheng, J.G.; Mrak, R.E.

    2013-01-01

    Interleukin-1 (IL-1) has been implicated as a key molecule in Alzheimer pathogenesis based on findings of an IL-1 overexpression in Alzheimer brain that is directly related to plaque progression and tangle formation, and on findings that IL-1 induces excessive synthesis, translation, and processing of neuronal β-amyloid precursor protein (βAPP) as well as synthesis of most known plaque-associated proteins. In addition, IL-1 activates astrocytes, with the important consequence of over-expression of the neuritogenic cytokine S100β and overgrowth of dystrophic neurites in neuritic plaques. As further evidence of the importance of IL-1 in Alzheimer pathogenesis, two new genetic studies of inheritance of specific polymorphisms in IL-1 genes in Alzheimer and control patients show that homozygosity for a specific IL-1A gene polymorphism at least triples risk for development of Alzheimer’s disease. This increase is associated with earlier age of onset. Homozygosity for this polymorphism plus another in the IL-1B gene further increases risk. PMID:10959036

  9. Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease

    Science.gov (United States)

    Carter, Angela M.

    2012-01-01

    A wealth of evidence indicates a fundamental role for inflammation in the pathogenesis of cardiovascular disease (CVD), contributing to the development and progression of atherosclerotic lesion formation, plaque rupture, and thrombosis. An increasing body of evidence supports a functional role for complement activation in the pathogenesis of CVD through pleiotropic effects on endothelial and haematopoietic cell function and haemostasis. Prospective and case control studies have reported strong relationships between several complement components and cardiovascular outcomes, and in vitro studies and animal models support a functional effect. Complement activation, in particular, generation of C5a and C5b-9, influences many processes involved in the development and progression of atherosclerosis, including promotion of endothelial cell activation, leukocyte infiltration into the extracellular matrix, stimulation of cytokine release from vascular smooth muscle cells, and promotion of plaque rupture. Complement activation also influences thrombosis, involving components of the mannose-binding lectin pathway, and C5b-9 in particular, through activation of platelets, promotion of fibrin formation, and impairment of fibrinolysis. The participation of the complement system in inflammation and thrombosis is consistent with the physiological role of the complement system as a rapid effector system conferring protection following vessel injury. However, in the context of CVD, these same processes contribute to development of atherosclerosis, plaque rupture, and thrombosis. PMID:24278688

  10. Complement Activation: An Emerging Player in the Pathogenesis of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Angela M. Carter

    2012-01-01

    Full Text Available A wealth of evidence indicates a fundamental role for inflammation in the pathogenesis of cardiovascular disease (CVD, contributing to the development and progression of atherosclerotic lesion formation, plaque rupture, and thrombosis. An increasing body of evidence supports a functional role for complement activation in the pathogenesis of CVD through pleiotropic effects on endothelial and haematopoietic cell function and haemostasis. Prospective and case control studies have reported strong relationships between several complement components and cardiovascular outcomes, and in vitro studies and animal models support a functional effect. Complement activation, in particular, generation of C5a and C5b-9, influences many processes involved in the development and progression of atherosclerosis, including promotion of endothelial cell activation, leukocyte infiltration into the extracellular matrix, stimulation of cytokine release from vascular smooth muscle cells, and promotion of plaque rupture. Complement activation also influences thrombosis, involving components of the mannose-binding lectin pathway, and C5b-9 in particular, through activation of platelets, promotion of fibrin formation, and impairment of fibrinolysis. The participation of the complement system in inflammation and thrombosis is consistent with the physiological role of the complement system as a rapid effector system conferring protection following vessel injury. However, in the context of CVD, these same processes contribute to development of atherosclerosis, plaque rupture, and thrombosis.

  11. The danger model approach to the pathogenesis of the rheumatic diseases.

    Science.gov (United States)

    Pacheco-Tena, César; González-Chávez, Susana Aideé

    2015-01-01

    The danger model was proposed by Polly Matzinger as complement to the traditional self-non-self- (SNS-) model to explain the immunoreactivity. The danger model proposes a central role of the tissular cells' discomfort as an element to prime the immune response processes in opposition to the traditional SNS-model where foreignness is a prerequisite. However recent insights in the proteomics of diverse tissular cells have revealed that under stressful conditions they have a significant potential to initiate, coordinate, and perpetuate autoimmune processes, in many cases, ruling over the adaptive immune response cells; this ruling potential can also be confirmed by observations in several genetically manipulated animal models. Here, we review the pathogenesis of rheumatic diseases such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis including ankylosing spondylitis, psoriasis, and Crohn's disease and provide realistic approaches based on the logic of the danger model. We assume that tissular dysfunction is a prerequisite for chronic autoimmunity and propose two genetically conferred hypothetical roles for the tissular cells causing the disease: (A) the Impaired cell and (B) the paranoid cell. Both roles are not mutually exclusive. Some examples in human disease and in animal models are provided based on current evidence.

  12. Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases

    Science.gov (United States)

    Liu, Gang; Cooley, Marion A.; Jarnicki, Andrew G.; Hsu, Alan C-Y.; Nair, Prema M.; Haw, Tatt Jhong; Fricker, Michael; Gellatly, Shaan L.; Kim, Richard Y.; Inman, Mark D.; Tjin, Gavin; Wark, Peter A.B.; Walker, Marjorie M.; Horvat, Jay C.; Oliver, Brian G.; Argraves, W. Scott; Knight, Darryl A.; Burgess, Janette K.; Hansbro, Philip M.

    2016-01-01

    Airway and/or lung remodeling, involving exaggerated extracellular matrix (ECM) protein deposition, is a critical feature common to pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). Fibulin-1 (Fbln1), an important ECM protein involved in matrix organization, may be involved in the pathogenesis of these diseases. We found that Fbln1 was increased in COPD patients and in cigarette smoke–induced (CS-induced) experimental COPD in mice. Genetic or therapeutic inhibition of Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-α, IL-33, and CXCL1) in experimental COPD. Fbln1c–/– mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases. PMID:27398409

  13. The Danger Model Approach to the Pathogenesis of the Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    César Pacheco-Tena

    2015-01-01

    Full Text Available The danger model was proposed by Polly Matzinger as complement to the traditional self-non-self- (SNS- model to explain the immunoreactivity. The danger model proposes a central role of the tissular cells’ discomfort as an element to prime the immune response processes in opposition to the traditional SNS-model where foreignness is a prerequisite. However recent insights in the proteomics of diverse tissular cells have revealed that under stressful conditions they have a significant potential to initiate, coordinate, and perpetuate autoimmune processes, in many cases, ruling over the adaptive immune response cells; this ruling potential can also be confirmed by observations in several genetically manipulated animal models. Here, we review the pathogenesis of rheumatic diseases such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis including ankylosing spondylitis, psoriasis, and Crohn’s disease and provide realistic approaches based on the logic of the danger model. We assume that tissular dysfunction is a prerequisite for chronic autoimmunity and propose two genetically conferred hypothetical roles for the tissular cells causing the disease: (A the Impaired cell and (B the paranoid cell. Both roles are not mutually exclusive. Some examples in human disease and in animal models are provided based on current evidence.

  14. High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.

    Directory of Open Access Journals (Sweden)

    Lisa Gruber

    Full Text Available BACKGROUND: Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis. METHODS: TNF(ΔARE/WT mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors. RESULTS: HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT. Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria. CONCLUSIONS: HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease

  15. High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.

    Science.gov (United States)

    Gruber, Lisa; Kisling, Sigrid; Lichti, Pia; Martin, François-Pierre; May, Stephanie; Klingenspor, Martin; Lichtenegger, Martina; Rychlik, Michael; Haller, Dirk

    2013-01-01

    Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis. TNF(ΔARE/WT) mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors. HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT). Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria. HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease-relevant mouse model through mechanisms that involve increased

  16. 76 FR 9018 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2011-02-16

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and... meetings and other committee management activities, for both the Centers for Disease Control and...

  17. 75 FR 27797 - Disease, Disability, and Injury Prevention and Control

    Science.gov (United States)

    2010-05-18

    ...: 2010-11887] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease... Centers for Disease Control and Prevention (CDC), announces the aforementioned meeting: Times and Date: 11... Services Office, Centers for Disease Control and Prevention. [FR Doc. 2010-11887 Filed 5-17-10; 8:45...

  18. 75 FR 30409 - Centers for Disease Control and Prevention

    Science.gov (United States)

    2010-06-01

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Centers for Disease Control and Prevention. BILLING CODE 4163-18-P ...)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  19. Mycoplasma bovis pathogenesis, diagnostic methods and epidemiology of relevance for control and prevention

    DEFF Research Database (Denmark)

    Nielsen, Liza Rosenbaum

    routes are direct cattle-to-cattle contact, contaminated milk and milking equipment, and aerosols moving between animals over short distances (few meters), so any prevention method that can mitigate those routes will reduce the size and duration of outbreaks. Less common transmission routes include semen...... the herd becomes exposed to M. bovis - or new strains of M. bovis. Luckily this also has great benefits on the general health and production in cattle farms. The general prevention measures can to some extent be supported by diagnostic testing prior to movement of cattle, even though it is not possible...

  20. Osteoarthritis and age. Role of aging in the etiology and pathogenesis of the disease

    Directory of Open Access Journals (Sweden)

    L. V. Luchikhina

    2017-01-01

    Full Text Available The paper considers current views on the mechanisms for the development and progression of osteoarthritis (OA and gives the definition of the disease. It describes the processes underlying aging and OA at the molecular and cellular level, with emphasis on the role of chronic nonspecific inflammation. The possible mechanisms of chronic age-related inflammation (inflammaging, the mainstay of which is systemic aging of the immune system, are characterized. On the basis of the data available in the literature, it is concluded that aging and OA have common intracellular transcription cascades and pathophysiological mechanisms: chronic nonspecific inflammation and metabolic disorders are substantially implicated in the pathogenesis of these conditions. Metabolic and structural changes occurring in the cartilage and other tissues of the locomotor apparatus with aging are noted to serve as a favorable platform for the further development and progression of OA.

  1. Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.

    Directory of Open Access Journals (Sweden)

    Raquel María Fernández

    Full Text Available Hirschsprung disease (HSCR is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS and neuroblastoma (NB in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18 in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype.

  2. Lipid-Mediated Oxidative Stress and Inflammation in the Pathogenesis of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Tahira Farooqui

    2011-01-01

    Full Text Available Parkinson's disease (PD is a neurodegenerative movement disorder of unknown etiology. PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, depletion of dopamine in the striatum, abnormal mitochondrial and proteasomal functions, and accumulation of α-synuclein that may be closely associated with pathological and clinical abnormalities. Increasing evidence indicates that both oxidative stress and inflammation may play a fundamental role in the pathogenesis of PD. Oxidative stress is characterized by increase in reactive oxygen species (ROS and depletion of glutathione. Lipid mediators for oxidative stress include 4-hydroxynonenal, isoprostanes, isofurans, isoketals, neuroprostanes, and neurofurans. Neuroinflammation is characterized by activated microglial cells that generate proinflammatory cytokines, such as TNF-α and IL-1β. Proinflammatory lipid mediators include prostaglandins and platelet activating factor, together with cytokines may play a prominent role in mediating the progressive neurodegeneration in PD.

  3. Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics

    Directory of Open Access Journals (Sweden)

    Xuan Cheng

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

  4. Dietary polyphenols and the prevention of diseases.

    Science.gov (United States)

    Scalbert, Augustin; Manach, Claudine; Morand, Christine; Rémésy, Christian; Jiménez, Liliana

    2005-01-01

    Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as tea, coffee, or wine. Experimental studies on animals or cultured human cell lines support a role of polyphenols in the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes, or osteoporosis. However, it is very difficult to predict from these results the effects of polyphenol intake on disease prevention in humans. One of the reasons is that these studies have often been conducted at doses or concentrations far beyond those documented in humans. The few clinical studies on biomarkers of oxidative stress, cardiovascular disease risk factors, and tumor or bone resorption biomarkers have often led to contradictory results. Epidemiological studies have repeatedly shown an inverse association between the risk of myocardial infarction and the consumption of tea and wine or the intake level of some particular flavonoids, but no clear associations have been found between cancer risk and polyphenol consumption. More human studies are needed to provide clear evidence of their health protective effects and to better evaluate the risks possibly resulting from too high a polyphenol consumption.

  5. Advances in understanding gray matter pathology in multiple sclerosis: Are we ready to redefine disease pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zivadinov Robert

    2012-03-01

    Full Text Available Abstract The purpose of this special issue in BMC Neurology is to summarize advances in our understanding of the pathological, immunological, imaging and clinical concepts of gray matter (GM pathology in patients with multiple sclerosis (MS. Review articles by Lucchinetti and Popescu, Walker and colleagues, Hulst and colleagues and Horakova and colleagues summarize important recent advances in understanding GM damage and its implications to MS pathogenesis. They also raise a number of important new questions and outline comprehensive approaches to addressing those questions in years to come. In the last decade, the use of immunohistochemistry staining methods and more advanced imaging techniques to detect GM lesions, like double inversion recovery, contributed to a surge of studies related to cortical and subcortical GM pathology in MS. It is becoming more apparent from recent biopsy studies that subpial cortical lesions in early MS are highly inflammatory. The mechanisms responsible for triggering meningeal inflammation in MS patients are not yet elucidated, and they should be further investigated in relation to their role in initiating and perpetuating the disease process. Determining the role of antigens, environmental and genetic factors in the pathogenesis of GM involvement in MS is critical. The early involvement of cortical and subcortical GM damage in MS is very intriguing and needs to be further studied. As established in numerous cross-sectional and longitudinal studies, GM damage is a better predictor of physical disability and cognitive impairment than WM damage. Monitoring the evolution of GM damage is becoming an important marker in predicting future disease course and response to therapy in MS patients.

  6. THE EFFECT OF FCγ RECEPTOR ON THE PATHOGENESIS OF GRAVES' DISEASE

    Institute of Scientific and Technical Information of China (English)

    Pu dan(蒲丹); Guo Hui(郭辉); Luo Wentian(雒文田); Liu Qiuyue(刘秋月); Aosai Fumie

    2004-01-01

    Objective To explore the roles of Fcγ receptor in the pathogenesis of Graves' disease. Methods Fcγ receptor gene knockout mice(Fcγ R KO mice) which were rooted in C57BL/6 mice and wild type C57BL/6 mice were immunized by hTSH receptor expressing cells (DAP3.WT).1-2×107 DAP3.WT cells were peritoneally injected into mice every two weeks for a total of six times.Two weeks after final immunization, mice were killed for measurement of total thyroxine,TRAb and pathological examination.Results The thyroxine level of the immunized Fcγ receptor gene knockout mice was significantly lower than that of the immunized wild type control mice (2.2±0.31 vs.3.32±0.59g·dL-1,P<0.05), but there was no significant difference between immunized Fcγ R KO mice and non-immunized wild type control group.The TRAb levels of the immunized Fγ R KO mice significantly increased compared to those of the immunized wild type mice (21.75±8.21 vs.14.11±6.21, P<0.05). The lymphocyte cells infiltration and destruction of thyroid follicles were found in the thyroid gland of the immunized Fcγ R KO mice. Conclusion These results suggest that Fcγ receptor may be involved in the pathogenesis of Graves'disease.

  7. Crohn's disease: a role of gut microbiota and Nod2 gene polymorphisms in disease pathogenesis.

    Science.gov (United States)

    Hrnčířová, Lucia; Krejsek, Jan; Šplíchal, Igor; Hrnčíř, Tomáš

    2014-01-01

    Crohn's disease is a chronic immune-mediated intestinal inflammation targeted against a yet incompletely defined subset of commensal gut microbiota and occurs on the background of a genetic predisposition under the influence of environmental factors. Genome-wide association studies have identified about 70 genetic risk loci associated with Crohn's disease. The greatest risk for Crohn's disease represent polymorphisms affecting the CARD15 gene encoding nucleotide-binding oligomerization domain 2 (NOD2) which is an intracellular sensor for muramyl dipeptide, a peptidoglycan constituent of bacterial cell wall. The accumulated evidence suggests that gut microbiota represent an essential, perhaps a central factor in the induction and maintaining of Crohn's disease where dysregulation of normal co-evolved homeostatic relationships between intestinal microbiota and host mucosal immune system leads to intestinal inflammation. Taken together, these findings identify Crohn's disease as a syndrome of overlapping phenotypes that involves variable influences of genetic and environmental factors. A deeper understanding of different genetic abnormalities underlying Crohn's disease together with the identification of beneficial and harmful components of gut microbiota and their interactions are essential conditions for the categorization of Crohn's disease patients, which enable us to design more effective, preferably causative, individually tailored therapy.

  8. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  9. Bridging Lung Development with Chronic Obstructive Pulmonary Disease. Relevance of Developmental Pathways in Chronic Obstructive Pulmonary Disease Pathogenesis.

    Science.gov (United States)

    Boucherat, Olivier; Morissette, Mathieu C; Provencher, Steeve; Bonnet, Sébastien; Maltais, François

    2016-02-15

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation. This generic term encompasses emphysema and chronic bronchitis, two common conditions, each having distinct but also overlapping features. Recent epidemiological and experimental studies have challenged the traditional view that COPD is exclusively an adult disease occurring after years of inhalational insults to the lungs, pinpointing abnormalities or disruption of the pathways that control lung development as an important susceptibility factor for adult COPD. In addition, there is growing evidence that emphysema is not solely a destructive process because it is also characterized by a failure in cell and molecular maintenance programs necessary for proper lung development. This leads to the concept that tissue regeneration required stimulation of signaling pathways that normally operate during development. We undertook a review of the literature to outline the contribution of developmental insults and genes in the occurrence and pathogenesis of COPD, respectively.

  10. Challenge of liver disease in systemic lupus erythematosus: Clues for diagnosis and hints for pathogenesis

    Science.gov (United States)

    Bessone, Fernando; Poles, Natalia; Roma, Marcelo G

    2014-01-01

    Systemic lupus erythematosus (SLE) encompass a broad spectrum of liver diseases. We propose here to classify them as follows: (1) immunological comorbilities (overlap syndromes); (2) non-immunological comorbilities associated to SLE; and (3) a putative liver damage induced by SLE itself, referred to as “lupus hepatitis”. In the first group, liver injury can be ascribed to overlapping hepatopathies triggered by autoimmune mechanisms other than SLE occurring with higher incidence in the context of lupus (e.g., autoimmune hepatitis, primary biliary cirrhosis). The second group includes non-autoimmune liver diseases, such as esteatosis, hepatitis C, hypercoagulation state-related liver lesions, hyperplasic parenchymal and vascular lesions, porphyria cutanea tarda, and drug-induced hepatotoxicity. Finally, the data in the literature to support the existence of a hepatic disease produced by SLE itself, or the occurrence of a SLE-associated prone condition that increases susceptibility to acquire other liver diseases, is critically discussed. The pathological mechanisms underlying each of these liver disorders are also reviewed. Despite the high heterogeneity in the literature regarding the prevalence of SLE-associated liver diseases and, in most cases, lack of histopathological evidence or clinical studies large enough to support their existence, it is becoming increasingly apparent that liver is an important target of SLE. Consequently, biochemical liver tests should be routinely carried out in SLE patients to discard liver disorders, particularly in those patients chronically exposed to potentially hepatotoxic drugs. Diagnosing liver disease in SLE patients is always challenging, and the systematization of the current information carried out in this review is expected to be of help both to attain a better understanding of pathogenesis and to build an appropriate work-up for diagnosis. PMID:25018850

  11. Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases.

    Science.gov (United States)

    Zhou-Suckow, Zhe; Duerr, Julia; Hagner, Matthias; Agrawal, Raman; Mall, Marcus A

    2017-03-01

    Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na(+) channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD. In this review, we summarize recent progress in the understanding of causes of impaired MCC and in vivo consequences of airway mucus obstruction that can be inferred from studies in βENaC-overexpressing mice. These studies confirm that mucus hyperconcentration on airway surfaces plays a critical role in the pathophysiology of impaired MCC, mucus adhesion and airway plugging that cause airflow obstruction and provide a nidus for bacterial infection. In addition, these studies support the emerging concept that excess airway mucus per se, probably via several mechanisms including hypoxic epithelial necrosis, retention of inhaled irritants or allergens, and potential immunomodulatory effects, is a potent trigger of chronic airway inflammation and associated lung damage, even in the absence of bacterial infection. Finally, these studies suggest that improvement of mucus clearance may be a promising therapeutic strategy for a spectrum of muco-obstructive lung diseases.

  12. Liver-adipose tissue crosstalk: A key player in the pathogenesis of glucolipid metabolic disease.

    Science.gov (United States)

    Ye, De-Wei; Rong, Xiang-Lu; Xu, Ai-Min; Guo, Jiao

    2017-06-01

    Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 (FGF21) and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.

  13. Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Brent J. Ryan

    2014-01-01

    Full Text Available Tissue inflammation results in the production of numerous reactive oxygen, nitrogen and chlorine species, in addition to the products of lipid and sugar oxidation. Some of these products are capable of chemically modifying amino acids. This in turn results in changes to the structure and function of proteins. Increasing evidence demonstrates that such oxidative post-translational modifications result in the generation of neo-epitopes capable of eliciting both innate and adaptive immune responses. In this paper, we focus on how free radicals and related chemical species generated in inflammatory environments modulate the antigenicity of self-proteins, resulting in immune responses which involve the generation of autoantibodies against key autoantigens in autoimmune diseases. As examples, we will focus on Ro-60 and C1q in systemic lupus erythematosus, along with type-II collagen in rheumatoid arthritis. This review also covers some of the emerging literature which demonstrates that neo-epitopes generated by oxidation are conserved, as exemplified by the evolutionarily conserved pathogen-associated molecular patterns (PAMPs. We discuss how these observations relate to the pathogenesis of both human autoimmune diseases and inflammatory disease, such as atherosclerosis. The potential for these neo-epitopes and the immune responses against them to act as biomarkers or therapeutic targets is also discussed.

  14. The Contribution of Small Airway Obstruction to the Pathogenesis of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Hogg, James C; Paré, Peter D; Hackett, Tillie-Louise

    2017-04-01

    The hypothesis that the small conducting airways were the major site of obstruction to airflow in normal lungs was introduced by Rohrer in 1915 and prevailed until Weibel introduced a quantitative method of studying lung anatomy in 1963. Green repeated Rohrer's calculations using Weibels new data in 1965 and found that the smaller conducting airways offered very little resistance to airflow. This conflict was resolved by seminal experiments conducted by Macklem and Mead in 1967, which confirmed that a small proportion of the total lower airways resistance is attributable to small airways Hogg, Macklem, and Thurlbeck used this technique to show that small airways become the major site of obstruction in lungs affected by emphysema. These and other observations led Mead to write a seminal editorial in 1970 that postulated the small airways are a silent zone within normal lungs where disease can accumulate over many years without being noticed. This review provides a progress report since the 1970s on methods for detecting chronic obstructive pulmonary disease, the structural nature of small airways' disease, and the cellular and molecular mechanisms that are thought to underlie its pathogenesis.

  15. Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.

    Science.gov (United States)

    Wang, Aifeng; Wang, Yongping; Wang, Guobao; Zhou, Zhanmei; Xun, Zhang; Tan, Xiaohui

    2012-05-01

    Anti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic glomerulonephritis with immunoglobulin G (IgG) autoantibodies to the non-collagenous (NC1) domain of α3(IV) collagen presenting along the GBM. The patient clinically manifests with rapidly progressive glomerulonephritis (RPGN) with pulmonary hemorrhage (Goodpasture syndrome). In rare cases, other immunocomplexes of IgA or IgM are involved, but their specificities have not been determined. We report a rare case of a 31-year-old female who was diagnosed as having anti-GBM disease with extensive IgA deposits in the mesangium. This patient presented heavy hematuria, proteinuria with increasing creatinine, but no lung hemorrhage. Renal biopsy showed crescentic glomerulonephritis (type Ⅰ) with strong IgA (3+) as lump and branch shape. Therapies with pulse methylprednisolone, plasmapheresis and cyclophosphamide administration were less effective. This case is different from the present type Ⅰ crescentic glomerulonephritis and the specificity of IgA deposits may implicate the pathogenesis of anti-GBM disease.

  16. Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

    Science.gov (United States)

    Simone, Chiara; Ramirez, Agnese; Bucchia, Monica; Rinchetti, Paola; Rideout, Hardy; Papadimitriou, Dimitra; Re, Diane B; Corti, Stefania

    2016-03-01

    Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches.

  17. An update on the role of the inflammasomes in the pathogenesis of kidney diseases.

    Science.gov (United States)

    Darisipudi, Murthy N; Knauf, Felix

    2016-04-01

    Innate immune response pathways play a critical role as the first line of defense. Initiation of an immune response requires sensors that can detect noxious stimuli within the cellular microenvironment. Inflammasomes are signaling platforms that are assembled in response to both microbe-specific and nonmicrobial antigens. Upon activation, proinflammatory cytokines are released to engage immune defenses and to trigger an inflammatory cell death referred to as pyroptosis. The aim of this review is to provide an overview of the current knowledge of the role of the inflammasomes in the pathogenesis of kidney diseases. As crystal deposition in the kidney is a frequent cause of acute kidney injury and chronic kidney disease in children, recent insights into mechanisms of inflammasome activation by renal crystals are highlighted. This may be of particular interest to pediatric patients and nephrologists in need of new therapeutic approaches. Lastly, current data findings that inflammasomes are not only of major importance in host defense but are also a key regulator of the intestinal microbiota and the progression of systemic diseases are reviewed.

  18. Transgenic animal models for study of the pathogenesis of Huntington's disease and therapy.

    Science.gov (United States)

    Chang, Renbao; Liu, Xudong; Li, Shihua; Li, Xiao-Jiang

    2015-01-01

    Huntington's disease (HD) is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner.

  19. The complexities of the pathology-pathogenesis relationship in Alzheimer disease.

    Science.gov (United States)

    Castellani, Rudy J; Perry, George

    2014-04-15

    Current pathogenic theories for Alzheimer disease (AD) and aging favor the notion that lesions and their constituent proteins are the initiators of disease due to toxicity. Whether this is because structural pathology is traditionally viewed as deleterious, and whether this, in turn, is a fundamental misinterpretation of the relationship between pathology and pathogenesis across the spectrum of chronic diseases, remains to be determined. As more and more detailed information about the biochemical constituents of AD lesions becomes available, it may also be argued that just as much knowledge of cellular physiology as pathophysiology has been gained. Indeed, essentially all major proteins in AD lesions are derived from molecular cascades, which are in turn highly conserved across cells, tissues, and species. Moreover, the lesions themselves are observed in the cognitively intact, and sometimes in large numbers, while major consensus criteria indicate that an extent of pathology is normal with advanced age. As the medical science community continues to pursue lesion targeting for therapeutic purposes, the notion that AD pathology is indicative of an active host response or environmental adaptation, and therefore a poor target, is becoming clearer. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Proteomic and genomic studies of non-alcoholic fatty liver disease--clues in the pathogenesis.

    Science.gov (United States)

    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production.

  1. The 5-lipoxygenase pathway: oxidative and inflammatory contributions to the Alzheimer’s disease pathogenesis

    Directory of Open Access Journals (Sweden)

    Praticò eDomenico

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is the most common, and, arguably, one of the most-well studied, neurodegenerative conditions. Several decades of investigation have revealed that amyloid-β and tau proteins are critical pathological players in this condition. Genetic analyses have revealed specific mutations in the cellular machinery that produces amyloid-β, but these mutations are found in only a small fraction of patients with the early-onset variant of AD. In addition to development of amyloid-β and tau pathology, oxidative damage and inflammation are consistently found in the brains of these patients. The 5-lipoxygenase protein enzyme (5LO and its downstream leukotriene metabolites have long been known to be important modulators of oxidation and inflammation in other disease states. Recent in vivo evidence using murine knock-out models has implicated the 5LO pathway, which also requires the 5LO activating protein (FLAP, in the molecular pathology of AD, including the metabolism of amyloid-β and tau. In this manuscript, we will provide an overview of 5LO and FLAP, discussing their involvement in biochemical pathways relevant to AD pathogenesis. We will also discuss how the 5LO pathway contributes to the molecular and behavioral insults seen in AD and provide an assessment of how targeting these proteins could lead to therapeutics relevant not only for Alzheimer’s disease, but also other related neurodegenerative conditions.

  2. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Imene Soufli; Ryma Toumi; Hayet Rafa; Chafia Touil-Boukoffa

    2016-01-01

    Inflammatory bowel diseases(IBDs), including Crohn’s disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.

  3. Etiology and pathogenesis of Parkinson’s disease: role of mitochondrial pathology

    Directory of Open Access Journals (Sweden)

    Ottolini D

    2013-05-01

    Full Text Available Denis Ottolini, Tito Calì, Marisa BriniDepartment of Comparative Biomedicine and Food Science, University of Padova, Padova, ItalyAbstract: Neurons critically rely on mitochondrial activity: they are characterized by high energy demand and they are totally dependent on the process of oxidative phosphorylation to produce adenosine triphosphate. Thus, any impairment in mitochondrial function results in neuronal damage and degeneration. Some particular neuronal populations are more susceptible to mitochondrial damage, as it has been recently proposed for the ventral midbrain dopaminergic neurons, the degeneration of which represents a clinical sign of Parkinson’s disease. Different cellular pathways are involved in the pathogenesis of this neurodegenerative disease, but intriguingly both sporadic and familial forms share common features that essentially recapitulate mitochondrial dysfunction. Mitochondrial biogenesis, bioenergetics, mitochondria dynamics, and quality-control process are the main affected pathways. General consensus agrees on the possibility that deficiency in these processes may represent the cause rather than the consequence of neurodegeneration. In this review, we will discuss these aspects and the substantial achievements that have been reached in recent years in identifying specific defects in precise biological processes, eg, mitochondrial quality control. The development of cell and animal genetic models has been an important tool to dissect numerous molecular details; for this reason, we will mainly refer to experiments performed on them.Keywords: mitochondria, Parkinson’s disease, α-synuclein, PINK1/parkin, DJ-1, LRRK2

  4. Dissecting the role of Engrailed in adult dopaminergic neurons: Insights into Parkinson disease pathogenesis

    Science.gov (United States)

    Rekaik, Hocine; Blaudin de Thé, François-Xavier; Prochiantz, Alain; Fuchs, Julia; Joshi, Rajiv L.

    2016-01-01

    The homeoprotein Engrailed (Engrailed-1/Engrailed-2, collectively En1/2) is not only a survival factor for mesencephalic dopaminergic (mDA) neurons during development, but continues to exert neuroprotective and physiological functions in adult mDA neurons. Loss of one En1 allele in the mouse leads to progressive demise of mDA neurons in the ventral midbrain starting from 6 weeks of age. These mice also develop Parkinson disease-like motor and non-motor symptoms. The characterization of En1 heterozygous mice have revealed striking parallels to central mechanisms of Parkinson disease pathogenesis, mainly related to mitochondrial dysfunction and retrograde degeneration. Thanks to the ability of homeoproteins to transduce cells, En1/2 proteins have also been used to protect mDA neurons in various experimental models of Parkinson disease. This neuroprotection is partly linked to the ability of En1/2 to regulate the translation of certain nuclear-encoded mitochondrial mRNAs for complex I subunits. Other transcription factors that govern mDA neuron development (e.g. Foxa1/2, Lmx1a/b, Nurr1, Otx2, Pitx3) also continue to function for the survival and maintenance of mDA neurons in the adult and act through partially overlapping but also diverse mechanisms. PMID:26459030

  5. Dissecting the role of Engrailed in adult dopaminergic neurons--Insights into Parkinson disease pathogenesis.

    Science.gov (United States)

    Rekaik, Hocine; Blaudin de Thé, François-Xavier; Prochiantz, Alain; Fuchs, Julia; Joshi, Rajiv L

    2015-12-21

    The homeoprotein Engrailed (Engrailed-1/Engrailed-2, collectively En1/2) is not only a survival factor for mesencephalic dopaminergic (mDA) neurons during development, but continues to exert neuroprotective and physiological functions in adult mDA neurons. Loss of one En1 allele in the mouse leads to progressive demise of mDA neurons in the ventral midbrain starting from 6 weeks of age. These mice also develop Parkinson disease-like motor and non-motor symptoms. The characterization of En1 heterozygous mice have revealed striking parallels to central mechanisms of Parkinson disease pathogenesis, mainly related to mitochondrial dysfunction and retrograde degeneration. Thanks to the ability of homeoproteins to transduce cells, En1/2 proteins have also been used to protect mDA neurons in various experimental models of Parkinson disease. This neuroprotection is partly linked to the ability of En1/2 to regulate the translation of certain nuclear-encoded mitochondrial mRNAs for complex I subunits. Other transcription factors that govern mDA neuron development (e.g. Foxa1/2, Lmx1a/b, Nurr1, Otx2, Pitx3) also continue to function for the survival and maintenance of mDA neurons in the adult and act through partially overlapping but also diverse mechanisms.

  6. Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease

    Science.gov (United States)

    Benjamin, Mina M.; Khalil, Raouf A.

    2012-01-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM). MMPs could also regulate the activity of several non-ECM bioactive substrates, and consequently affect different cellular functions. Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and others. Pro-MMPs are cleaved into active MMPs, which in turn act on various substrates in the ECM and on the cell surface. MMPs play an important role in the regulation of numerous physiological processes including vascular remodeling and angiogenesis. MMPs may also be involved in vascular diseases such as hypertension, atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in the hemodynamic and vascular changes associated with pregnancy and preeclampsia. The role of MMPs is commonly assessed by measuring their gene expression, protein amount, and proteolyic activity using gel zymography. Because there are no specific activators of MMPs, MMP inhibitors are often used to investigate the role of MMPs in different physiologic processes and in the pathogenesis of specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline and marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic tools in cancer, autoimmune and cardiovascular disease. Although several MMP inhibitors have been synthesized and tested both experimentally and clinically, only on MMP inhibitor, i.e. doxycycline, is currently approved by the Food and Drug Administration. This is mainly due to the undesirable side effects of MMP inhibitors especially on the musculoskeletal system. While most experimental and clinical trials of MMP inhibitors have not demonstrated significant benefits, some trials still showed promising results. With the advent of new genetic and pharmacological tools, disease-specific MMP inhibitors

  7. Mitochondrial DNA disease: new options for prevention.

    Science.gov (United States)

    Craven, Lyndsey; Elson, Joanna L; Irving, Laura; Tuppen, Helen A; Lister, Lisa M; Greggains, Gareth D; Byerley, Samantha; Murdoch, Alison P; Herbert, Mary; Turnbull, Doug

    2011-10-15

    Very recently, two papers have presented intriguing data suggesting that prevention of transmission of human mitochondrial DNA (mtDNA) disease is possible. [Craven, L., Tuppen, H.A., Greggains, G.D., Harbottle, S.J., Murphy, J.L., Cree, L.M., Murdoch, A.P., Chinnery, P.F., Taylor, R.W., Lightowlers, R.N. et al. (2010) Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature, 465, 82-85. Tachibana, M., Sparman, M., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C., Kolotushkina, O. and Mitalipov, S. (2009) Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature, 461, 367-372.] These recent advances raise hopes for families with mtDNA disease; however, the successful translational of these techniques to clinical practice will require further research to test for safety and to maximize efficacy. Furthermore, in the UK, amendment to the current legislation will be required. Here, we discuss the clinical and scientific background, studies we believe are important to establish safety and efficacy of the techniques and some of the potential concerns about the use of these approaches.

  8. [Cardiovascular disease prevention and life style modifications].

    Science.gov (United States)

    Baudet, M; Daugareil, C; Ferrieres, J

    2012-04-01

    Cardiovascular diseases are mainly caused by atherosclerosis, the development of which is highly dependent on our Western lifestyle. Slowing this pathology depends on the reduction of risk factors such as hypercholesterolemia, high blood pressure, smoking, lack of physical activity, excess weight and diabetes. Drug treatment exists and is very effective, but too often they treat the immediate abnormality such as diabetes, high blood pressure and hypercholesterolemia and not the underlying causes: poor eating habits, lack of physical activity and excess weight. These have a negative impact on endothelial function, oxidative stress, and can trigger inflammation, arrythmias and thrombosis. Cardiovascular prevention must therefore target sedentary lifestyle, excess weight, and favor low-calorie, low-salt food and Mediterranean diet. The way this diet works begins to be understood and goes beyond simple cardiovascular prevention. Therapeutic education holds a growing and complementary role in the Public Health system which should call upon the strengths of all healthcare professionals.

  9. Modern views on the pathogenesis of hard dental tissues and periodontium lesions and means of their treatment in children with chronic diseases of the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Krupey V.Y.

    2014-09-01

    Full Text Available Changes in the mouth covity often reflect regularities of pathogenesis of a number of disease states, and primarily from the digestive tract. Therefore, the purpose of the study was to clarify pathogenesis of certain lesions of hard dental tissues and periodontal tissues in children with chronic diseases of the gastrointestinal tract and development of schemes for their treatment. The study observed 441 children aged from 7 to 15 years with dental caries and generalized chronic catarrhal gingivitis on the background of chronic gastritis and duodenitis, duodenal ulcer and malabsorption syndrome. All the children were divided into 2 groups - basic and comparison one. The study identified the most dan¬gerous and little-known way of pathogenesis, which passes through the general processes of reducing the production of various proteins (immune system and antiseptics, is a violation of the general and local resistance and, ultimately, mineral metabolism. Such disorders impair complete mineralization of tooth enamel, reduce optimal composition and properties of saliva stimulating glycolysis processes in oral cavity. Prevention of dental caries and generalized chronic catarrhal gingivitis in children with chronic pathology of the gastrointestinal tract is based on the use of developed therapeutic and prophylactic complex, which includes mucosal gel Kvertulin, probiotic Latsidofil and drug Calcium D.

  10. 77 FR 12845 - Centers for Disease Control and Prevention (CDC)

    Science.gov (United States)

    2012-03-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Disease, Disability, and Injury... Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (CDC/ATSDR... meetings and other committee management activities, for both the Centers for Disease Control and...

  11. Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma.

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C; Bardeesy, Nabeel; Baumert, Thomas F; Chung, Raymond T

    2014-11-01

    Hepatitis C virus (HCV) is one of the major aetiologic agents that causes hepatocellular carcinoma (HCC) by generating an inflammatory, fibrogenic, and carcinogenic tissue microenvironment in the liver. HCV-induced HCC is a rational target for cancer preventive intervention because of the clear-cut high-risk condition, cirrhosis, associated with high cancer incidence (1% to 7% per year). Studies have elucidated direct and indirect carcinogenic effects of HCV, which have in turn led to the identification of candidate HCC chemoprevention targets. Selective molecular targeted agents may enable personalized strategies for HCC chemoprevention. In addition, multiple experimental and epidemiological studies suggest the potential value of generic drugs or dietary supplements targeting inflammation, oxidant stress, or metabolic derangements as possible HCC chemopreventive agents. While the successful use of highly effective direct-acting antiviral agents will make important inroads into reducing long-term HCC risk, there will remain an important role for HCC chemoprevention even after viral cure, given the persistence of HCC risk in persons with advanced HCV fibrosis, as shown in recent studies. The successful development of cancer preventive therapies will be more challenging compared to cancer therapeutics because of the requirement for larger and longer clinical trials and the need for a safer toxicity profile given its use as a preventive agent. Molecular biomarkers to selectively identify high-risk population could help mitigate these challenges. Genome-wide, unbiased molecular characterization, high-throughput drug/gene screening, experimental model-based functional analysis, and systems-level in silico modelling are expected to complement each other to facilitate discovery of new HCC chemoprevention targets and therapies. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Host immune response and acute disease in a zebrafish model of francisella pathogenesis

    Science.gov (United States)

    Vojtech, L.N.; Sanders, G.E.; Conway, C.; Ostland, V.; Hansen, J.D.

    2009-01-01

    Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebraflsh were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebraflsh following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebraflsh mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-l?? (IL-1??), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebraflsh to heat-killed bacteria demonstrated that the significant induction of IL-?? was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebraflsh share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach. Copyright ?? 2009, American Society for Microbiology. All Rights Reserved.

  13. Review article: pathogenesis and pathophysiology of hepatorenal syndrome--is there scope for prevention?

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    2004-01-01

    The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research into the pathophy...

  14. Nutrition for the Prevention of Chronic Diseases.

    Science.gov (United States)

    Kimokoti, Ruth W; Millen, Barbara E

    2016-11-01

    Chronic non-communicable diseases (NCDs) are the leading causes of morbidity and mortality in the United States and globally, and are attributable largely to poor nutrition and suboptimal lifestyle behaviors. The 2015-2020 Dietary Guidelines for Americans promote healthy eating and lifestyle patterns across the lifespan to reduce risk of NCDs. Physicians are well positioned to provide lifestyle preventive interventions that are personalized to their patients' biological needs and cultural preferences through multidisciplinary team activities or referral to professional nutrition and physical activity experts. They can also advocate for environmental changes in healthcare and community settings that promote healthful lifestyle behaviors.

  15. Is periodontal disease during orthodontics preventable?

    Science.gov (United States)

    Vaughan, O B

    1990-01-01

    Periodontal disease during orthodontic therapy is preventable and is controllable and in continuous studies after orthodontic therapy has been completed, it has been shown that under the properly controlled regimen of treatment the destruction to the periodontal tissues of the teeth is not accentuated to a statistically significant degree as greater than that which occurs during the same interim without orthodontic therapy. This encourages us; however, the difficulties cited in the paper above challenges us and our finest professional skills in the proper care of the orthodontic patients with periodontal complications.

  16. 77 FR 46096 - Centers for Disease Control and Prevention

    Science.gov (United States)

    2012-08-02

    ... No: 2012-18852] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention... Disease Control and Prevention (CDC), announces the following meeting of the aforementioned committee... Science and Public Health Practice Executive Assistant, Centers for Disease Control and Prevention,...

  17. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut.

    Science.gov (United States)

    Michielan, Andrea; D'Incà, Renata

    2015-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability. These alterations may represent a primary dysfunction in Crohn's disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course. Functional tests, such as the sugar absorption tests or the novel imaging technique using confocal laser endomicroscopy, allow an in vivo assessment of gut barrier integrity. Antitumor necrosis factor-α (TNF-α) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.

  18. Pathogenesis of Graves` disease and therapeutic implications; Pathogenese des Morbus Basedow und therapeutische Implikationen

    Energy Technology Data Exchange (ETDEWEB)

    Seif, F.J. [Tuebingen Univ. (Germany). Medizinische Klinik und Poliklinik

    1997-12-01

    Graves` disease presents itself clinically mainly as hyperthyroidism and infiltrative ophthalmopathy and to a minimal extent also as dermopathy and acropachy. Autoimmune processes are the basic pathogenesis. Stimulating antibodies against the TSH receptor cause hyperthyroidism. Autoantibodies and autoreactive T lymphocytes against primarily thyroidal antigens cross-react with similar antigens of the eye muscles and orbital connective tissue, thus spreading the disease from the thyroid to the eyes. The therapeutic goal comprises not only the treatment of hyperthyroidism, but also the induction of a steady immuntolerance in order to minimize the irreversible damage to the eye. The therapeutic armamentarium is formed by antithyroid drugs, glucocorticoids, retrobulbar radition and thyroid ablation, either by nearly total thyroidectomy or by radioiodine. The different indications for both ablative procedures are discussed. (orig.) [Deutsch] Der Morbus Basedow manifestiert sich klinisch hauptsaechlich als Hyperthyreose und infiltrative Orbitopathie, waehrend Demopathie und Akropathie selten sind. Der Krankheit liegt ein Autoimmunprozess zugrunde, wobei stimuliernde Autoantikoerper gegen den TSH-Rezeptor die Hyperthyreose hervorrufen. Autoantikoerper und T-Lymphozyten gegen primaer thyreoidale Antigene verursachen durch Kreuzreaktion mit aehnlichen Antigenen an den Augenmuskeln und orbitalem Bindegewebe die Orbitopathie. Das therapeutsiche Ziel besteht nicht nur in der Behandlung der Hyperthyreose, sondern vor allem in der Induktion einer immuntoleranten Remission, um die irreversiblen Schaeden am Auge zu minimieren. Die Therapie umfasst Thyreostatika, Glukokortikoide und Orbitaspitzenbestrahlung sowie eine Schilddruesenablation entweder durch fast totale Schilddruesenresektion oder durch Radiojodtherapie. Die Differentialindikationen fuer die beiden ablativen Massnahmen werden eroertert. (orig.)

  19. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Salem, Mohammad; Pedersen, Jannie

    2013-01-01

    The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway constitute the fulcrum in many vital cellular processes, including cell growth, differentiation, proliferation, and regulatory immune functions. Various cytokines, growth factors, and protein tyrosine kinases com...... be of interest for clinicians involved in IBD therapy. Further, it is described how these signaling pathways have been exploited for the development of promising novel JAK inhibitors with anti-inflammatory effects verified in clinical trials....... communicate through the JAK/STAT pathway and regulate the transcription of numerous genes. In addition to their critical roles in a plethora of key cellular activities, the JAK/STAT signaling pathways also have been implicated in the pathogenesis of several diseases, including inflammatory bowel disease (IBD......), especially since a JAK inhibitor recently has been shown to be effective in the treatment of ulcerative colitis. The aim of this review is to highlight the recent findings on the regulatory mechanism of JAK/STAT signaling pathways and to reveal the evolving comprehension of their interface which might...

  20. Telomeres and Telomerase: Role in Marek’s Disease Virus Pathogenesis, Integration and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Ahmed Kheimar

    2017-07-01

    Full Text Available Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGGn that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract this shortening, vertebrates encode the telomerase complex that maintains telomere length in certain cell types via de novo addition of telomeric repeats. Several herpesviruses, including the highly oncogenic alphaherpesvirus Marek’s disease virus (MDV, harbor telomeric repeats (TMR identical to the host telomere sequences at the ends of their linear genomes. These TMR facilitate the integration of the MDV genome into host telomeres during latency, allowing the virus to persist in the host for life. Integration into host telomeres is critical for disease and tumor induction by MDV, but also enables efficient reactivation of the integrated virus genome. In addition to the TMR, MDV also encodes a telomerase RNA subunit (vTR that shares 88% sequence identity with the telomerase RNA in chicken (chTR. vTR is highly expressed during all stages of the virus lifecycle, enhances telomerase activity and plays an important role in MDV-induced tumor formation. This review will focus on the recent advances in understanding the role of viral TMR and vTR in MDV pathogenesis, integration and tumorigenesis.

  1. Telomeres and Telomerase: Role in Marek's Disease Virus Pathogenesis, Integration and Tumorigenesis.

    Science.gov (United States)

    Kheimar, Ahmed; Previdelli, Renato L; Wight, Darren J; Kaufer, Benedikt B

    2017-07-04

    Telomeres protect the ends of vertebrate chromosomes from deterioration and consist of tandem nucleotide repeats (TTAGGG)n that are associated with a number of proteins. Shortening of the telomeres occurs during genome replication, thereby limiting the replication potential of somatic cells. To counteract this shortening, vertebrates encode the telomerase complex that maintains telomere length in certain cell types via de novo addition of telomeric repeats. Several herpesviruses, including the highly oncogenic alphaherpesvirus Marek's disease virus (MDV), harbor telomeric repeats (TMR) identical to the host telomere sequences at the ends of their linear genomes. These TMR facilitate the integration of the MDV genome into host telomeres during latency, allowing the virus to persist in the host for life. Integration into host telomeres is critical for disease and tumor induction by MDV, but also enables efficient reactivation of the integrated virus genome. In addition to the TMR, MDV also encodes a telomerase RNA subunit (vTR) that shares 88% sequence identity with the telomerase RNA in chicken (chTR). vTR is highly expressed during all stages of the virus lifecycle, enhances telomerase activity and plays an important role in MDV-induced tumor formation. This review will focus on the recent advances in understanding the role of viral TMR and vTR in MDV pathogenesis, integration and tumorigenesis.

  2. Formation of parkin aggregates and enhanced PINK1 accumulation during the pathogenesis of Parkinson's disease.

    Science.gov (United States)

    Um, Ji Won; Park, Hyun Jung; Song, Jihwan; Jeon, Iksoo; Lee, Gwang; Lee, Phil Hyu; Chung, Kwang Chul

    2010-03-19

    Parkinson's disease (PD) is a devastating neurodegenerative disease characterized by a distinct set of motor symptoms. Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) or parkin have been linked to early-onset autosomal recessive forms of familial PD. We have recently shown that parkin (an E3 ubiquitin ligase) and PINK1 (a serine/threonine kinase) affect one other's stability, solubility, and tendency to form cytoprotective aggresomes (Um et al., 2009). Here we validated the functional relevance of this mutual interaction under pathologic PD conditions, by investigating the changes of expression and solubility of these factors in response to PD-linked toxins. Consistent with our previous cell culture data, exposure of human dopaminergic neuroblastoma SH-SY5Y cells to PD-linked toxins (1-methyl-4-phenylpyridinium ion, 6-hydroxydopamine, or MG132) reduced Nonidet P-40-soluble parkin levels and induced PINK1 accumulation. Consistent with our previous findings from parkin knockout mice, rat models of PD (6-hydroxydopamine-, rotenone-, or MG132-induced PD) were also associated with an increase in soluble and insoluble PINK1 levels as well as enhanced formation of parkin aggregates. These findings suggest that both PINK1 and parkin play important roles in regulating the formation of Lewy bodies during the pathogenesis of sporadic and familial PD.

  3. Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Kim Wilkinson

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is increasing in prevalence with the aging population. Deposition of amyloid-β (Aβ in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with Aβ appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear Aβ, but binding of microglia to Aβ also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS. Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for Aβ. Of particular interest are SCARA-1 (scavenger receptor A-1, CD36, and RAGE (receptor for advanced glycation end products. SCARA-1 appears to be involved in the clearance of Aβ, while CD36 and RAGE are involved in activation of microglia by Aβ. In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with Aβ and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD.

  4. Exploring the Role of Paraoxonases in the Pathogenesis of Coronary Artery Disease: A Systematic Review

    Directory of Open Access Journals (Sweden)

    David Abelló

    2014-11-01

    Full Text Available Paraoxonases (PON are three enzymes (PON1, PON2 and PON3 that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.

  5. Influenza vaccines for preventing cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Christine Clar

    Full Text Available ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL, Database of Abstracts of Reviews of Effects (DARE, Economic Evaluation Database (EED and Health Technology Assessment database (HTA, MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov. We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication.Selection criteria:Randomised controlled trials (RCTs of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events.Data collection and analysis:We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs, and we used random-effects models.MAIN RESULTS: We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251, in addition to the two included in the previous version of the review. Four of these trials (n = 10,347 focused on prevention of influenza in the general or elderly population

  6. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment.

    Science.gov (United States)

    Holt, Patrick G; Sly, Peter D

    2012-05-04

    Prospective birth cohort studies tracking asthma initiation and consolidation in community cohorts have identified viral infections occurring against a background of allergic sensitization to aeroallergens as a uniquely potent risk factor for the expression of acute severe asthma-like symptoms and for the ensuing development of asthma that can persist through childhood and into adulthood. A combination of recent experimental and human studies have suggested that underlying this bipartite process are a series of interactions between antiviral and atopic inflammatory pathways that are mediated by local activation of myeloid cell populations in the airway mucosa and the parallel programming and recruitment of their replacements from bone marrow. Targeting key components of these pathways at the appropriate stages of asthma provides new opportunities for the treatment of established asthma but, more crucially, for primary and secondary prevention of asthma during childhood.

  7. Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment.

    Science.gov (United States)

    Alzohairy, Mohammad A

    2016-01-01

    Neem (Azadirachta indica) is a member of the Meliaceae family and its role as health-promoting effect is attributed because it is rich source of antioxidant. It has been widely used in Chinese, Ayurvedic, and Unani medicines worldwide especially in Indian Subcontinent in the treatment and prevention of various diseases. Earlier finding confirmed that neem and its constituents play role in the scavenging of free radical generation and prevention of disease pathogenesis. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF. It is considered as safe medicinal plants and modulates the numerous biological processes without any adverse effect. In this review, I summarize the role of Azadirachta indica in the prevention and treatment of diseases via the regulation of various biological and physiological pathways.

  8. Vitamin D regulates the production of vascular endothelial growth factor: A triggering cause in the pathogenesis of rheumatic heart disease?

    Science.gov (United States)

    Sarkar, Subendu; Chopra, Seema; Rohit, Manoj Kumar; Banerjee, Dibyajyoti; Chakraborti, Anuradha

    2016-10-01

    Rheumatic heart disease (RHD) remains a major cause of cardiac related mortality and morbidity in the developing countries due to poor diagnosis and lack of proper therapeutics. The definite reason of heart valve injury during RHD is poorly understood. Valvular endothelial cells play an important role in pathogenesis of different cardiovascular diseases. Besides, the regulation of vitamin D (calciferol) and VEGF (vascular endothelial growth factor) results in the functional changes in endothelial cells. However, the crosstalk between vitamin D and VEGF in the pathogenesis of RHD is not yet unfurled. Evidences in the concerned fields are documented by searching through Google Scholar and Pubmed. Literature based survey has revealed that vascular endothelium, especially endothelial cells play important roles in valvular remodelling during cardiovascular diseases. Endothelial cell dysfunction leads to heart valve remodelling, which furthermore initiates the pathogenesis of valvular heart disease. Vitamin D has the potential to maintain the concentration of VEGF in the circulation and induce the function of endothelial cells. Hence, we hypothesize that vitamin D and VEGF homeostasis can alter the function of endothelial cells, which may subsequently trigger the valvular remodelling or even damage of heart valves during the progression of RHD pathogenesis. Our hypothesis shed light on the evidence based knowledge translation of plausible cellular phenomena due to vitamin D/VEGF homeostasis during valvular vandalism in RHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Pathogenesis of primary foot-and-mouth disease virus infection in the nasopharynx of vaccinated and non-vaccinated cattle

    Science.gov (United States)

    A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection in vaccinated and non-vaccinated cattle following simulated-natural virus exposure. FMDV genome and infectious virus were detected during the initial phase of infection from b...

  10. [110th volume of the Dutch Journal of Dentistry 1. Aspects of the pathogenesis, etiology and prevention of dental caries placed against the concepts of the 1950].

    Science.gov (United States)

    ten Cate, J M

    2003-03-01

    This paper discusses three articles on cariology from the 1950's in view of the current consensus of the pathogenesis, aetiology and prevention of dental caries. While 50 years ago the battle between researchers favouring the chemo parasitary versus those in support of the proteolytic theory of caries was at its peak, bacteria and acids formed in plaque have since been generally accepted as the cause of dental caries. Attention has shifted to the inhibiting role of fluoride in the initiation and progression of tooth decay, and the possible, additive action of antimicrobial therapy. As tooth decay is now a disease less common and progressing more slowly, there is scope for a more directed intervention and a preventive rather than a restorative therapeutic approach. In spite of the successes obtained a sizeable proportion of the population still suffers from dental caries and care should be taken not to diminish the attention for tooth decay both in the general dental practice and in dental research.

  11. A Mathematical Model of the Pathogenesis, Prevention, and Reversal of Type 2 Diabetes.

    Science.gov (United States)

    Ha, Joon; Satin, Leslie S; Sherman, Arthur S

    2016-02-01

    Type 2 diabetes (T2D) is generally thought to result from the combination of 2 metabolic defects, insulin resistance, which increases the level of insulin required to maintain glucose within the normal range, and failure of insulin-secreting pancreatic β-cells to compensate for the increased demand. We build on a mathematical model pioneered by Topp and colleagues to elucidate how compensation succeeds or fails. Their model added a layer of slow negative feedback to the classic insulin-glucose loop in the form of a slow, glucose-dependent birth and death law governing β-cell mass. We add to that model regulation of 2 aspects of β-cell function on intermediate time scales. The model quantifies the relative contributions of insulin action and insulin secretion defects to T2D and explains why prevention is easier than cure. The latter is a consequence of a threshold separating the normoglycemic and diabetic states (bistability), which also underlies the success of bariatric surgery and acute caloric restriction in rapidly reversing T2D. The threshold concept gives new insight into "Starling's Law of the Pancreas," whereby insulin secretion is higher for prediabetics and early diabetics than for normal individuals.

  12. Role of TGFβ signaling in the pathogenesis of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Rommy eVon Bernhardi

    2015-10-01

    Full Text Available Aging is the main risk factor for Alzheimer’s disease (AD; being associated with conspicuous changes on microglia activation. Aged microglia exhibit an increased expression of cytokines, exacerbated reactivity to various stimuli, oxidative stress, and reduced phagocytosis of Aβ. Whereas normal inflammation is protective, it becomes dysregulated in the presence of a persistent stimulus, or in the context of an inflammatory environment, as observed in aging. Thus, neuroinflammation can be a self-perpetuating deleterious response, becoming a source of additional injury to host cells in neurodegenerative diseases. In aged individuals, although TGFβ is upregulated, its canonical Smad3 signaling is greatly reduced and neuroinflammation persists. This age-related Smad3 impairment reduces protective activation while facilitating cytotoxic activation of microglia through several cellular mechanisms, potentiating microglia-mediated neurodegeneration. Here, we critically discuss the role of TGFβ-Smad signaling on the cytotoxic activation of microglia and its relevance in the pathogenesis of AD. Other protective functions, such as phagocytosis, although observed in aged animals, are not further induced by inflammatory stimuli and TGFβ1. Analysis in silico revealed that increased expression of receptor SR-A, involved in Aβ uptake and cell activation, by microglia exposed to TGFβ, through a Smad3-dependent mechanism could be mediated by transcriptional co-factors Smad2/3 over the MSR1 gene. We discuss that changes of TGFβ-mediated regulation could at least partially mediate age-associated microglia changes, and, together with other changes on inflammatory response, could result in the reduction of protective activation and the potentiation of cytotoxicity of microglia, resulting in the promotion of neurodegenerative diseases.

  13. Dental caries: Strategies to control this preventable disease

    Directory of Open Access Journals (Sweden)

    Andrew Rugg-Gunn

    2013-11-01

    Full Text Available Objective. To provide a brief commentary review of strategies to control dental caries. Dental decay is one of man’s most prevalent diseases. In many counties, severity increased in parallel with importation of sugar, reaching its zenith about 1950s and 1960s. Since then, severity has declined in many countries, due to the wide use of fluoride especially in toothpaste, but dental caries remains a disease of medical, social and economic importance. Within the EU in 2011, the cost of dental treatment was estimated to be €79 billion. The pathogenesis is well understood: bacteria in dental plaque (biofilm metabolise dietary sugars to acids which then dissolve dental enamel and dentine. Possible approaches to control caries development, therefore, involve: removal of plaque, reducing the acidogenic potential of plaque, reduction in sugar consumption, increasing the tooth’s resistance to acid attack, and coating the tooth surface to form a barrier between plaque and enamel. At the present time, only three approaches are of practical importance: sugar control, fluoride, and fissure sealing. The evidence that dietary sugars are the main cause of dental caries is extensive, and comes from six types of study. Without sugar, caries would be negligible. Fluoride acts in several ways to aid caries prevention. Ways of delivering fluoride can be classed as: ‘automatic’, ‘home care’ and ‘professional care’: the most important of these are discussed in detail in four articles in this issue of the Acta Medica Academica. Conclusion. Dental caries is preventable – individuals, communities and countries need strategies to achieve this.

  14. Dental caries: strategies to control this preventable disease.

    Science.gov (United States)

    Rugg-Gunn, Andrew

    2013-11-01

    To provide a brief commentary review of strategies to control dental caries. Dental decay is one of man's most prevalent diseases. In many counties, severity increased in parallel with importation of sugar, reaching its zenith about 1950s and 1960s. Since then, severity has declined in many countries, due to the wide use of fluoride especially in toothpaste, but dental caries remains a disease of medical, social and economic importance. Within the EU in 2011, the cost of dental treatment was estimated to be €79 billion. The pathogenesis is well understood: bacteria in dental plaque (biofilm) metabolise dietary sugars to acids which then dissolve dental enamel and dentine. Possible approaches to control caries development, therefore, involve: removal of plaque, reducing the acidogenic potential of plaque, reduction in sugar consumption, increasing the tooth's resistance to acid attack, and coating the tooth surface to form a barrier between plaque and enamel. At the present time, only three approaches are of practical importance: sugar control, fluoride, and fissure sealing. The evidence that dietary sugars are the main cause of dental caries is extensive, and comes from six types of study. Without sugar, caries would be negligible. Fluoride acts in several ways to aid caries prevention. Ways of delivering fluoride can be classed as: 'automatic', 'home care' and 'professional care': the most important of these are discussed in detail in four articles in this issue of the Acta Medica Academica. Dental caries is preventable - individuals, communities and countries need strategies to achieve this. Copyright © 2013 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  15. Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H

    1992-01-01

    disease activity. Histamine is suggested to be involved in the pathogenesis of psoriasis and the histamine-2 receptor antagonist ranitidine has been shown to be of value to reduce severe psoriatic disease. The finding that CsA and Mx efficiently reduce histamine formation and release raises...... the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed....... A consequence of this may be induction of interferon-gamma (IFN-g) production and release by cytotoxic T cells, subsequently leading to expression of MHC II molecules on non-immune tissues. As immunotherapy may be of value in some autoimmune diseases the use of histamine-2 receptor antagonists should...

  16. Mobile Health, a Key Factor Enhancing Disease Prevention Campaigns: Looking for Evidences in Kidney Disease Prevention

    Directory of Open Access Journals (Sweden)

    Nicole Roque Matias

    2017-01-01

    Full Text Available Background: Progressive chronic kidney disease (CKD failure and kidney diseases are increasing at an alarming rate all over the world. However, despite the remarkable advance in health technology, where it has become possible to successfully screen patients and predict kidney progression, a large portion of the world population is still unaware of their disease and risk exposure. Mobile Health (mHealth solutions associated with health campaigns and programs proved to be an effective mean to enhance awareness and behaviour change at individual and social level. Objective: The aim of this survey was to present the results of an environmental scan of what has been happening in the field of kidney disease prevention campaigns in recent years, with a focus on the use of mobile health as a tool to enhance the campaign's effects on targeting people and change their behaviour. Methodology: It was conducted a systematic and comprehensive review, combining experimental studies with theoretical perspectives, to look for evidence regarding the evaluation of kidney disease prevention campaigns. The databases consulted for the present survey were: MEDLINE, PubMed, Google Scholar, PsycINFO, SAGE Journals Online, and Web of Science among other sources, for an analysis period from January 2000 to June 2016. Results: Concerning the 14 analyzed examples with impact on kidney disease prevention campaign evaluation, two main campaigns were referred: The World Kidney Day (WKD campaign, and the Kidney Early Evaluation Program (KEEP. The indicators used in this analisys were in most cases comparable regarding the campaign messages, objectives and interventions tools, although em both cases the use of mHealth or other technologies is residually comparing to other diseases prevention campaigns or programs. Conclusions: This review pointed to the inexistence of behavioural change evidence as a target of the kidney disease prevention campaigns and their evaluation. General

  17. Vaccine-preventable diseases: the role of the European Centre for Disease Prevention and Control.

    Science.gov (United States)

    Kramarz, P; Lopalco, P L; Huitric, E; Pastore Celentano, L

    2014-05-01

    The role of the European Centre for Disease Prevention and Control (ECDC) is to strengthen the capacity of the European Union (EU) Member States to protect human health through the prevention and control of infectious diseases. The main objective of the programme on vaccine-preventable diseases and invasive bacterial infections (VPD) is to provide robust evidence and high-quality technical support to the EU Member States to help them in their efforts to prevent and control VPD. Since the establishment of ECDC, several existing VPD surveillance networks have been transferred to ECDC, namely EU-IBIS, DIPNET and EUVAC. In addition to surveillance of diseases, ECDC is collecting information and monitoring other parameters that are of crucial importance for a well-functioning immunization system, including vaccination coverage. The VPD programme also provides independent scientific opinions in the area of immunization and initiates and coordinates scientific studies in the area of vaccination to answer specific questions of public health importance, including risk perception and analysis of behaviour in different population groups. One of the overall ECDC priorities over recent years is the Centre's involvement in measles elimination. The 'Message' tool and the 'Measles Atlas' are examples of work aiming at supporting the efforts of Member States in the elimination phase.

  18. Function of Moxibustion Therapy in Disease Prevention and Healthcare

    Institute of Scientific and Technical Information of China (English)

    严洁; 常小荣; 王超; 沈菁; 吴焕淦

    2010-01-01

    @@ The moxibustion therapy for disease prevention and healthcare is also termed "healthcare moxibustion" or "treating subclinical conditions", i.e., prevention before onset of diseases. In Chinese medicine, the prevention of diseases has been emphasized and the idea and therapeutic principle of "preventing it before it occurs" have been stressed. As early as in the Huang Di Nei Jing (Yellow Emperor's Inner Classic), the ideological system on "treating subclinical conditions" had been established.

  19. Cardiovascular disease: primary prevention, disease modulation and regenerative therapy.

    LENUS (Irish Health Repository)

    Sultan, Sherif

    2012-10-01

    Cardiovascular primary prevention and regeneration programs are the contemporary frontiers in functional metabolic vascular medicine. This novel science perspective harnesses our inherent ability to modulate the interface between specialized gene receptors and bioavailable nutrients in what is labeled as the nutrient-gene interaction. By mimicking a natural process through the conveyance of highly absorbable receptor specific nutrients, it is feasible to accelerate cell repair and optimize mitochondrial function, thereby achieving cardiovascular cure. We performed a comprehensive review of PubMed, EMBASE and Cochrane Review databases for articles relating to cardiovascular regenerative medicine, nutrigenomics and primary prevention, with the aim of harmonizing their roles within contemporary clinical practice. We searched in particular for large-scale randomized controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular regenerative programs, such as nitric oxide and glucose metabolism. Scientific research on \\'cardiovascular-free\\' centenarians delineated that low sugar and low insulin are consistent findings. As we age, our insulin level increases. Those who can decelerate the rapidity of this process are prompting their cardiovascular rejuvenation. It is beginning to dawn on some clinicians that contemporary treatments are not only failing to impact on our most prevalent diseases, but they may be causing more damage than good. Primary prevention programs are crucial elements for a better outcome. Cardiovascular primary prevention and regeneration programs have enhanced clinical efficacy and quality of life and complement our conventional endovascular practice.

  20. Proteomic analysis of human substantia nigra identifies novel candidates involved in Parkinson's disease pathogenesis.

    Science.gov (United States)

    Licker, Virginie; Turck, Natacha; Kövari, Enikö; Burkhardt, Karim; Côte, Mélanie; Surini-Demiri, Maria; Lobrinus, Johannes A; Sanchez, Jean-Charles; Burkhard, Pierre R

    2014-03-01

    Parkinson's disease (PD) pathology spreads throughout the brain following a region-specific process predominantly affecting the substantia nigra (SN) pars compacta. SN exhibits a progressive loss of dopaminergic neurons responsible for the major cardinal motor symptoms, along with the occurrence of Lewy bodies in the surviving neurons. To gain new insights into the underlying pathogenic mechanisms in PD, we studied postmortem nigral tissues dissected from pathologically confirmed PD cases (n = 5) and neurologically intact controls (n = 8). Using a high-throughput shotgun proteomic strategy, we simultaneously identified 1795 proteins with concomitant quantitative data. To date, this represents the most extensive catalog of nigral proteins. Of them, 204 proteins displayed significant expression level changes in PD patients versus controls. These were involved in novel or known pathogenic processes including mitochondrial dysfunction, oxidative stress, or cytoskeleton impairment. We further characterized four candidates that might be relevant to PD pathogenesis. We confirmed the differential expression of ferritin-L and seipin by Western blot and demonstrated the neuronal localization of gamma glutamyl hydrolase and nebulette by immunohistochemistry. Our preliminary findings suggest a role for nebulette overexpression in PD neurodegeneration, through mechanisms that may involve cytoskeleton dynamics disruption. All MS data have been deposited in the ProteomeXchange with identifier PXD000427 (http://proteomecentral.proteomexchange.org/dataset/PXD000427).

  1. [Basic and clinical studies on pathogenesis of pulmonary Mycobacterium avium complex disease].

    Science.gov (United States)

    Suzuki, K

    1997-10-01

    I have studied pathogenesis of pulmonary Mycobacterium avium complex disease (PMAC), using mouse and human alveolar macrophage (PAM) model of the infection as well as clinical evaluations. The mouse model revealed no relation between natural resistance against the bacteria and the activation of macrophages which was evaluated on the basis of releasing capacities of prostaglandin E2 and superoxide anion. The PAM model suggested that TNF-alpha and GM-CSF could activate PAM to restrict the intracellular growth of the bacteria, probably not through the superoxide anion release, but through the myeloperoxidasae-halide system. It was also found that rifamycins in combination with clarithromycin could have a good bactericidal effect in the PAM-model of the infection. Clinical evaluations suggested that defect in local pulmonary defense, such as healed pulmonary tuberculous lesions, pneumoconiosis, and COPD was more important predisposing factor than defect in systemic defense in the development of PMAC. Most patients having PMAC without predisposing factors are elderly women, the reason of which is the most important question to be answered in the future studies.

  2. Gastro-oesophageal reflux disease and obesity: pathogenesis and response to treatment.

    Science.gov (United States)

    Mion, François; Dargent, Jérôme

    2014-08-01

    The link between obesity and GERD is clear on all measures of the disease: clinical symptoms, erosive oesophagitis, acid esophageal exposure, and complications. The pathogenesis of this link may be due to general factors such as visceral adiposity, oestrogen levels, or decrease of Helicobacter pylori infection with increased gastric acid secretion. Increased abdominal pressure leads to disruption of the esophago-gastric junction and hiatal hernia, and esophageal motility may be modified by obesity. Weight loss does improve GERD, but lifestyle modifications and diet are usually insufficient in the long-term for morbid obesity. GERD and hiatal hernia are key issues in bariatric surgery, and are widely discussed because of important implications. It is not currently certain which procedure should be favoured in case of GERD; yet gastric bypass offers the best guarantee of success. Hiatal hernia repair is also deemed necessary by some authors at the same time of the bariatric surgery. Minimally invasive techniques pose a new challenge to this issue, both technically and theoretically. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease.

    Science.gov (United States)

    Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

    2014-10-28

    The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

  4. Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

    Science.gov (United States)

    Wang, Zi-Kai; Yang, Yun-Sheng; Chen, Ye; Yuan, Jing; Sun, Gang; Peng, Li-Hua

    2014-01-01

    The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models. PMID:25356041

  5. Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available Alzheimer's disease (AD is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

  6. An update on restless legs syndrome (Willis-Ekbom disease): clinical features, pathogenesis and treatment.

    Science.gov (United States)

    Garcia-Borreguero, Diego; Williams, Anne-Marie

    2014-08-01

    In recent years, there have been a number of advances in the field of restless legs syndrome (RLS) or Willis-Ekbom disease (WED). Here, we review recent studies pertaining to the diagnosis and clinical features, pathogenesis, and treatment of RLS/WED. Recent studies have added a temporal dimension to RLS/WED epidemiology by examining both the incidence and persistence rates in different populations. Diagnostic criteria have been modified to increase sensitivity, and new guidelines take into account recently published studies of different drug classes. Recent epidemiological findings have shown that RLS/WED is a common neurological disorder that affects up to 5% of the adult population in Western countries. In moderate and severe cases, RLS/WED has a strong impact on sleep and quality of life and can involve an increased cardiovascular risk. Diagnosis is made clinically by confirming the presence of the five essential criteria. However, in difficult cases objective tests such as the multiple suggested immobilization test (m-SIT) can be used. The pathophysiology is partially known, with several risk polymorphisms (BTBD-9 (BTB (POZ) domain containing 9), MEIS-1 (Meis homeobox 1), protein tyrosine phosphatase, receptor type, D, and others) playing an important role, along with dopaminergic and iron dysfunctions. The disorder frequently requires long-term treatment with low-dose dopamine agonists or α2δ ligands. Dopamine agonists are usually effective but the main complication, RLS/WED augmentation, can arise.

  7. Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease

    Science.gov (United States)

    Roh, Jee Hoon; Jiang, Hong; Finn, Mary Beth; Stewart, Floy R.; Mahan, Thomas E.; Cirrito, John R.; Heda, Ashish; Snider, B. Joy; Li, Mingjie; Yanagisawa, Masashi; de Lecea, Luis

    2014-01-01

    Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain. PMID:25422493

  8. Prevention of cardiovascular diseases, diabetes mellitus and chronic kidney diseases in general practice.

    NARCIS (Netherlands)

    Nielen, M.; Assendelft, P.; Drenthen, T.; Hombergh, P. van den; Dis, I. van; Schellevis, F.

    2009-01-01

    Purpose: To study the attitudes and working methods of general practitioners (GPs) in primary prevention of cardiovascular diseases, diabetes mellitus and chronic kidney diseases. Methods: A questionnaire with questions about primary prevention of cardiovascular diseases, diabetes mellitus and

  9. Chronic Beryllium Disease Prevention Program Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  10. The dual role of short fatty acid chains in the pathogenesis of autoimmune disease models

    Science.gov (United States)

    Mizuno, Miho; Noto, Daisuke; Kaga, Naoko; Chiba, Asako; Miyake, Sachiko

    2017-01-01

    Autoimmune diseases are influenced by both genetic and environmental factors. The gut environment has attracted much attention as an essential component that modulates immune responses, and therefore immune-mediated disorders, such as autoimmune diseases. Growing evidence suggests that microbiota and their metabolites are critical factors for immune modulation. Recently, we reported that the microbiome in patients with multiple sclerosis, an autoimmune disease targeting the myelin sheath of the central nervous system, is characterized by a reduction of bacteria belonging to Clostridia clusters IV and XIVa, which are potent producers of short-chain fatty acids (SCFAs) by fermentation of indigestible carbohydrates. In the present study, we investigated the role of SCFAs in the regulation of inflammation. We demonstrated that oral administration of SCFAs ameliorated the disease severity of systemic autoimmune inflammatory conditions mediated by lymphocytes such as experimental autoimmune encephalitis and collagen-induced arthritis. Amelioration of disease was associated with a reduction of Th1 cells and an increase in regulatory T cells. In contrast, SCFAs contributed to the exaggeration of K/BxN serum transfer arthritis, representing the effector phase of inflammation in rheumatoid arthritis. An increased understanding of the effect of microbiota metabolites will lead to the effective treatment and prevention of systemic inflammatory disorders. PMID:28235016

  11. Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cuiyan, E-mail: xj.cy.69@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Lei, Ronghui, E-mail: leirh@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Tiainen, Mika, E-mail: mika.tiainen@uef.fi [School of Pharmacy, University of Eastern Finland, Kuopio (Finland); Wu, Shixun, E-mail: wushixun313@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Zhang, Qiang, E-mail: wdrr@163.com [Department of Kashin–Beck Disease, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai 811602 (China); Pei, Fuxing, E-mail: peifuxing@vip.163.com [Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Guo, Xiong, E-mail: guox@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China)

    2014-08-15

    Kashin–Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ({sup 1}H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC–PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD. - Highlights: • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes.

  12. The role of heparan sulphate in pathogenesis of Crimean-Congo hemorrhagic fever disease

    Directory of Open Access Journals (Sweden)

    Fatma Mutlu Kukul Guven

    2013-04-01

    Full Text Available Background & objectives: Crimean-Congo hemorrhagic fever (CCHF is a viral infection typically transmitted by tick bite. This study is to define the level of heparan sulphate (HS in serum/urine since HS may play a role in the pathogenesis of hemorrhagic events in the patients with CCHF. Methods: In this study, the patient group consisted of 79 cases with a positive diagnosis of CCHF according to PCR/ELISA outcome among the patients referred to Cumhuriyet University, School of Medicine in 2010. A total of 81 volunteers who had not any viral or metabolic disease were enrolled as the control group. The blood samples were centrifuged, and the serum and urine samples obtained were stored at – 80°C until they were studied. Then, these samples were simultaneously dissolved, and HS level was spectrophotometrically measured using glycosaminoglycans specific 1– 9, dimethyl-methylene blue (DMMB stain. Results: A statistically significant increase in the HSserum values was found both in the individuals under and above 16 yr old in the patient groups compared to the controls (p <0.05. Also there was a statistically significant increase in the urine levels of HS in the cases >16 yr old compared to the controls (p <0.05. Interpretations & conclusion: Increase of the serum/urine levels of HS was though to be due to vascular endothelium damage and to liver injury as well as vascular endothelium damage in the patients who died. Further, comprehensive studies are needed to demonstrate whether the serum/urine levels of HS are correlated to liver and vascular endothelium damage and prognosis of the disease.

  13. Lamb Model of Respiratory Syncytial Virus–Associated Lung Disease: Insights to Pathogenesis and Novel Treatments

    Science.gov (United States)

    Ackermann, Mark R.

    2014-01-01

    Preterm birth is a risk factor for respiratory syncytial virus (RSV) bronchiolitis and hospitalization. The pathogenesis underlying this is not fully understood, and in vivo studies are needed to better clarify essential cellular features and molecular mechanisms. Such studies include analysis of lung tissue from affected human infants and various animal models. The preterm and newborn lamb lung has developmental, structural, cellular, physiologic, and immunologic features similar to that of human infants. Also, the lamb lung is susceptible to various strains of RSV that infect infants and cause similar bronchiolar lesions. Studies in lambs suggest that viral replication in airways (especially bronchioles) is extensive by 4 days after infection, along with bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia, and innate and adaptive immune responses. RSV bronchiolitis greatly affects airflow and gaseous exchange. RSV disease severity is increased in preterm lambs compared with full-term lambs; similar to human infants. The lamb is conducive to experimental assessment of novel, mechanistic therapeutic interventions such as delivery of vascular endothelial growth factor and enhancement of airway epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar development and surfactant protein A expression. Because the formalin-inactivated RSV vaccination enhances some inflammatory responses to RSV infection in lambs, this model has the potential to assess mechanisms of formalin-inactivated RSV enhanced disease as well as newly developed vaccines. PMID:24936027

  14. Dysregulated Lysine Acetyltransferase 2B Promotes Inflammatory Bowel Disease Pathogenesis Through Transcriptional Repression of Interleukin-10.

    Science.gov (United States)

    Bai, Alfa H C; Wu, William K K; Xu, Liangliang; Wong, Sunny H; Go, Minnie Y; Chan, Anthony W H; Harbord, Marcus; Zhang, Shenghong; Chen, Minhu; Wu, Justin C Y; Chan, Michael W Y; Chan, Matthew T V; Chan, Francis K L; Sung, Joseph J Y; Yu, Jun; Cheng, Alfred S L; Ng, Siew C

    2016-06-01

    Accumulating evidence supports epigenetic modifications in mediating intestinal immunity in inflammatory bowel disease [IBD] pathogenesis. This study aimed to identify key dysregulated epigenetic modulators and the molecular downstream pathways in IBD. Expression of 116 well-defined epigenetic modulators was profiled and validated in 96 intestinal tissues from patients with Crohn's disease [CD], ulcerative colitis [UC], and healthy controls using quantitative reverse transcriptase polymerase chain reaction [QRT-PCR], western blot, and immunohistochemistry. Dysregulation of histone modifications and IBD-related cytokines were examined by chromatin immunoprecipitation, luciferase activity, and gene expression analyses in normal colonic epithelial cell line, NCM460, upon small-molecule inhibition or RNA interference, followed by validation in primary colonic tissues. Targeted expression profiling uncovered seven differentially expressed epigenetic modulators, of which the down-regulation of lysine acetyltransferase 2B [KAT2B] mRNA and protein was the most significant and was consequently validated in inflamed CD and UC compared with healthy colonic tissues. KAT2B protein localised abundantly in nuclei of normal colonic epithelium but diminished in paired inflamed CD and UC tissues. Pharmacological inhibition of KAT2B by anacardic acid in NCM460 cells reduced the levels of histone H4 lysine 5 acetylation [H4K5ac] and interleukin-10 [IL-10] in a dose-dependent manner. Knockdown of KAT2B reduced the IL-10 promoter occupancy of KAT2B and H4K5ac, resulting in transcriptional silencing. IL-10 level was also diminished in inflamed IBD tissues. Our findings demonstrated a novel epigenetic mechanism of IL-10 dysregulation in IBD. Down-regulation of KAT2B may disrupt the innate and adaptive inflammatory responses due to the suppression of this crucial anti-inflammatory cytokine. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University

  15. Pathogenesis and management issues for non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Marko Duvnjak; Ivan Leroti(c); Neven Bar(s)i(c); Vedran Toma(s)i(c); Lucija Virovi(c) Juki(c); Vedran Velagi(c)

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists.Fatty liver has been documented in up to 10 to 15percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual.

  16. [Prevention of dementia (including Alzheimer's disease)].

    Science.gov (United States)

    Kornhuber, H H

    2004-05-01

    Prevention of dementia: Life expectancy still increases linearly, and the elderly part of the European population grows rapidly in relation to the young. Dementia, however, grows even more rapidly, because it increases exponentially after age 65; it will become a great burden if nothing is done. The discussion so far is concentrated on treatment, whereas prevention is neglected. The therapy of dementia, however, has limited effect. Contrary to a widespread opinion prevention is possible. Genetic factors alone dominate the fate of cognition only in about 3 % of the cases. Besides age, lifestyle and the vascular risk factors exercise a great influence. High blood pressure carries a fourfold risk, diabetes more than doubles the risk both of the vascular and of the Alzheimer type; combined even more. Especially cerebral microangiopathy is strongly associated with Alzheimer's dementia, it triggers the vicious circle which leads to amyloid deposition. The importance of the circulation is underestimated, because most of the microvascular cerebral lesions are not perceived by the patient. All the risk factors for Alzheimer's disease after age 65 are also vascular risk factors especially for microangiopathy: Apo-E4, oestrogen deficiency, insulin resistance, diabetes, arterial hypertension, high cholesterol, old age and increased plasma homocystin which is often caused by alcohol consumption even in moderate doses. A healthy life style with daily outdoor activity and a Mediterranean diet not only reduces the risk of dementia, but also of coronary death and cancer. Cognitively stimulating activity protects even more than physical activity against dementia; the basis for this is acquired in youth by education. Therapy with statins is advisable if atherosclerosis cannot be reasonably counteracted by physical activity and diet.

  17. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  18. [Prevention of Alzheimer's Disease and Nutrients].

    Science.gov (United States)

    Otsuka, Mieko

    2016-07-01

    The dietary recommendations for the prevention and management of Alzheimer's disease (AD), are the Mediterranean diet and the Japanese-style diet, both of which contain well-balanced nutrients from fish and vegetables. These diets are rich in vitamin E, carotenes, antioxidant flavonoids, vitamin B12, folate, and n-3PUFA. According to recent review supplementation of folate and vitamin E may protect against elderly people's cognitive decline when the serum folate is <12 nmol/L or the vitamin E intake is <6.1 mg/day. Another nutritional topic with regard to dementia and diet is the association of type-2 diabetes and hyperinsulinemia with AD. Expression array data of the brain tissue of AD patients in the Hisayama study strongly suggests a disturbance in insulin signaling in the AD brain. The dysfunction of insulin signaling could directly lead to disrupted glucose utilization in the AD brain. Instead of improperly utilized glucose, the medium chain triglyceride ketone bodies can be an alternative energy resource for the AD brain. In conclusion, the dietary recommendations for the prevention and management of AD are a high consumption of fish, vegetables, and low glycemic index fruits; a moderate amount of meat and dairy products; and a lower amount of carbohydrates and refined sugar.

  19. The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease: A Mini Review

    Directory of Open Access Journals (Sweden)

    Shanmugam Manoharan

    2016-01-01

    Full Text Available Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer’s disease (AD, impairments in the movement, Parkinson’s disease (PD, and the inability to walk, talk, and think, Huntington’s disease (HD. Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.

  20. The role of DJ-1 in the pathogenesis of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Zhi-Quan WANG; Hai-Yan ZHOU; Sheng-Di CHEN

    2006-01-01

    Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder characterized clinically by bradykinesia, rigidity, tremor, gait dysfunction, and postural instability. Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease. Here, we focus on PARK7, a gene relates to an autosomal recessive form of early-onset Parkinsonism and encodes a protein named DJ- 1. Though the exact role of DJ-1 needs to be elucidated, it is generally thought to be functioned as a molecular chaperone and an oxidative sensor (or antioxidative factor). We will review the protective role of DJ-1 to prevent dopaminergic neurons in the substantia nigra pars compacta (SNpc) from degeneration and how its dysfunction would lead to neurodegeneration.

  1. Pathogenesis of diabetic vascular disease: evidence for the role of reduced heparan sulfate proteoglycan

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran

    1997-01-01

    properties of the vessel wall, and the growth regulation of intimal smooth muscle cells. Recent studies have shown that heparin increases the biosynthesis of heparan sulfate in endothelial cell cultures and prevents the characteristic glomerular basement membrane thickening when given to diabetic rats...... in susceptible patients is unknown, but increasing evidence has suggested that loss of the proteoglycan heparan sulfate in the vasculature may explain the widespread nature of the disease. Heparan sulfate is important for the glomerular endothelial cell and basement membrane charge densities, the anticoagulant......Insulin-dependent diabetic patients with increased urinary albumin excretion are characterized by elevated blood pressure and declining kidney function. In addition, such patients have a high risk of atherosclerotic vascular disease, proliferative retinopathy, and cardiomyopathy, suggesting...

  2. Craniofacial birth defects: The role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention.

    Science.gov (United States)

    Trainor, Paul A

    2010-12-01

    Of all the babies born with birth defects, approximately one-third display anomalies of the head and face [Gorlin et al., 1990] including cleft lip, cleft palate, small or absent facial and skull bones and improperly formed nose, eyes, ears, and teeth. Craniofacial disorders are a primary cause of infant mortality and have serious lifetime functional, esthetic, and social consequences that are devastating to both children and parents alike. Comprehensive surgery, dental care, psychological counseling, and rehabilitation can help ameliorate-specific problems but at great cost over many years which dramatically affects national health care budgets. For example, the Center for Disease Control and Prevention estimates that the lifetime cost of treating the children born each year with cleft lip and/or cleft palate alone to be US$697 million. Treating craniofacial malformations, of which in excess of 700 distinct syndromes have been described, through comprehensive, well-coordinated and integrated strategies can provide satisfactory management of individual conditions, however, the results are often variable and rarely fully corrective. Therefore, better techniques for tissue repair and regeneration need to be developed and therapeutic avenues of prevention need to be explored in order to eliminate the devastating consequences of head and facial birth defects. To do this requires a thorough understanding of the normal events that control craniofacial development during embryogenesis. This review therefore focuses on recent advances in our understanding of the basic etiology and pathogenesis of a rare craniofacial disorder known as Treacher Collins syndrome and emerging prospects for prevention that may have broad application to congenital craniofacial birth defects.

  3. ICT Research Directions in Disease Prevention

    DEFF Research Database (Denmark)

    Dahl, Mads Ronald; Boye, Niels; Hietala, Henri

    2011-01-01

    Despite long-term awareness that many chronic diseases are the product of unhealthy lifestyles our health promotion responses have not been very effective. One only needs to look at the statistics of OECD Health Data and CDC in USA to note that most countries are “in deep trouble”. Some call health...... the prevention of non-communicable (lifestyle related) diseases. What we have outlined in this report is a Health Outreach activity that is needed to support individuals in managing their lifestyles and where ICT can help individuals to navigate their health journeys. The White Paper is primarily aimed...... at providing a baseline for the planning of R&D activities that could be supported in the 8th Framework Program of the European Commission. In a nutshell, we would like to create a move towards a considered approach to “Engineer AwarenessTM”1 to move the field away from the medical push of “compliant patients...

  4. Necrotizing enterocolitis. New thoughts about pathogenesis and potential treatments.

    Science.gov (United States)

    MacKendrick, W; Caplan, M

    1993-10-01

    Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

  5. How Can Coronary Heart Disease Be Prevented or Delayed?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Can Coronary Heart Disease Be Prevented or Delayed? You can prevent ... the National Institutes of Health (NIH). Celebrating American Heart Month: NIH Advancing Heart Research 02/07/2014 ...

  6. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    William D. Phillips

    2016-06-01

    Full Text Available Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (IgG1 and IgG3 antibodies to the acetylcholine receptor (AChR. They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK, or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4, are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

  7. Advances in the pathogenesis of Alzheimer’s disease: a re-evaluation of amyloid cascade hypothesis

    Directory of Open Access Journals (Sweden)

    Dong Suzhen

    2012-09-01

    Full Text Available Abstract Alzheimer’s disease (AD is a common neurodegenerative disease characterized clinically by progressive deterioration of memory, and pathologically by histopathological changes including extracellular deposits of amyloid-beta (A-beta peptides forming senile plaques (SP and the intracellular neurofibrillary tangles (NFT of hyperphosphorylated tau in the brain. This review focused on the new developments of amyloid cascade hypothesis with details on the production, metabolism and clearance of A-beta, and the key roles of some important A-beta-related genes in the pathological processes of AD. The most recent research advances in genetics, neuropathology and pathogenesis of the disease were also discussed.

  8. Hot topics in the prevention of respiratory syncytial virus disease.

    Science.gov (United States)

    Habibi, Maximillian S; Patel, Sanjay; Openshaw, Peter

    2011-03-01

    The 7th International Respiratory Syncytial Virus Symposium took place in Hotel Blijdorp, Rotterdam, The Netherlands. The series has been running since 1996; this meeting took place after a 3-year gap, and was attended by approximately 200 clinicians, scientists and industry representatives from all over the world. The conference covered all aspects of respiratory syncytial virus disease, including virology, cell biology, pathogenesis, clinical presentation, diagnosis, immunology, vaccines, antivirals and other therapeutic approaches. Reviews by invited keynote speakers were accompanied by oral and poster presentations, with ample opportunity for discussion of unpublished work. This article summarizes a small selection of hot topics from the meeting, focused on pathogenesis, therapeutics and vaccine development.

  9. Tick-Associated Diseases: Symptoms, Treatment and Prevention

    Science.gov (United States)

    Anderson, Alice; Chaney, Elizabeth

    2009-01-01

    According to the Centers for Disease Control and Prevention (CDC), there are eleven tick-associated diseases prevalent in the United States. Most commonly diagnosed are Lyme disease, anaplasmosis (ehrlichiosis) and babeisois, with Lyme disease being the most common vector-borne disease in the country. In southeastern states, studies have shown the…

  10. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Directory of Open Access Journals (Sweden)

    Radha Ananthakrishnan

    2013-10-01

    Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

  11. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Science.gov (United States)

    Daffu, Gurdip; del Pozo, Carmen Hurtado; O’Shea, Karen M.; Ananthakrishnan, Radha; Ramasamy, Ravichandran; Schmidt, Ann Marie

    2013-01-01

    Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease. PMID:24084731

  12. Prion protein modulates cellular iron uptake: a novel function with implications for prion disease pathogenesis.

    Directory of Open Access Journals (Sweden)

    Ajay Singh

    Full Text Available Converging evidence leaves little doubt that a change in the conformation of prion protein (PrP(C from a mainly alpha-helical to a beta-sheet rich PrP-scrapie (PrP(Sc form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrP(Sc, nor the normal function of PrP(C is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron in prion disease pathogenesis. In this report, we provide evidence that PrP(C mediates cellular iron uptake and transport, and mutant PrP forms alter cellular iron levels differentially. Using human neuroblastoma cells as models, we demonstrate that over-expression of PrP(C increases intra-cellular iron relative to non-transfected controls as indicated by an increase in total cellular iron, the cellular labile iron pool (LIP, and iron content of ferritin. As a result, the levels of iron uptake proteins transferrin (Tf and transferrin receptor (TfR are decreased, and expression of iron storage protein ferritin is increased. The positive effect of PrP(C on ferritin iron content is enhanced by stimulating PrP(C endocytosis, and reversed by cross-linking PrP(C on the plasma membrane. Expression of mutant PrP forms lacking the octapeptide-repeats, the membrane anchor, or carrying the pathogenic mutation PrP(102L decreases ferritin iron content significantly relative to PrP(C expressing cells, but the effect on cellular LIP and levels of Tf, TfR, and ferritin is complex, varying with the mutation. Neither PrP(C nor the mutant PrP forms influence the rate or amount of iron released into the medium, suggesting a functional role for PrP(C in cellular iron uptake and transport to ferritin, and dysfunction of PrP(C as a significant contributing factor of brain iron imbalance in prion disorders.

  13. Pathogenesis of metastatic disease: implications for current therapy and for the development of new therapeutic strategies.

    Science.gov (United States)

    Poste, G

    1986-01-01

    Different tumor cell subpopulations coexisting within the same tumor exhibit varied susceptibilities to antineoplastic agents. Tumor cell heterogeneity is now recognized as the principal cause of treatment failure in cancer, and is a formidable obstacle to effective therapy and to the development of drug delivery systems for selective targeting of antineoplastic agents to tumor cells. Recent insights into the genesis of tumor cell heterogeneity during progressive tumor growth reveal new complexities that raise challenging questions about the adequacy of certain approaches to the current therapy of metastatic disease and impose challenging criteria for the development of improved therapeutic strategies. Many of the experimental approaches used in the search for new antineoplastic agents and targeted drug delivery systems ignore the pathogenesis of metastasis and the problem of tumor cell heterogeneity. The adoption of more relevant assay systems is an urgent priority. These include the greater use of metastatic tumor models and the increased use of human tumor cells to replace rodent cell systems which have been of limited predictive value in identifying effective anticancer agents. In contrast to current strategies for the development of new antineoplastic drugs which seek to identify agents with activity against a broad range of histologically diverse tumors, greater success may be achieved by seeking agents active only against specific cell lineages. Many established human tumor cell lines may not be suitable for this purpose because of extensive phenotypic change produced by prolonged passage ex vivo. Development of histiotype-specific human tumor cell screens will require an extensive research effort to identify target cells that display demonstrable phenotypic relatedness to tumor cells in neoplastic lesions. Major advances in the therapy of metastatic disease are considered unlikely in the next few years, and progress will stem from improved use of existing

  14. Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Kamran Qureshi; Gary A Abrams

    2007-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality.It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR,metabolic syndrome and NAFLD.

  15. Pathogenesis of Renal Disease in Systemic Lupus Erythematosus—The Role of Autoantibodies and Lymphocytes Subset Abnormalities

    Directory of Open Access Journals (Sweden)

    Desmond Y. H. Yap

    2015-04-01

    Full Text Available Lupus nephritis (LN is a common and severe organ manifestation of systemic lupus erythematosus (SLE, and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment.

  16. Adipokines and Osteoarthritis: Novel Molecules Involved in the Pathogenesis and Progression of Disease

    Directory of Open Access Journals (Sweden)

    Javier Conde

    2011-01-01

    Full Text Available Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases.

  17. [Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic's disease].

    Science.gov (United States)

    Csécsei, Péter; Trauninger, Anita; Komoly, Sámuel; Illés, Zsolt

    2009-11-15

    The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

  18. [Disease Prevention and Control Plan Swan Lake National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Disease Prevention and Control Plan for Swan Lake National Wildlife Refuge provides background information on disease surveillance; an inventory of Refuge...

  19. Dietary regulation of histone acetylases and deacetylases for the prevention of metabolic diseases.

    Science.gov (United States)

    Pham, Tho X; Lee, Jiyoung

    2012-11-28

    Age-related diseases such as type 2 diabetes, cardiovascular disease, and cancer involve epigenetic modifications, where accumulation of minute changes in the epigenome over time leads to disease manifestation. Epigenetic changes are influenced by life style and diets. This represents an avenue whereby dietary components could accelerate or prevent age-related diseases through their effects on epigenetic modifications. Histone acetylation is an epigenetic modification that is regulated through the opposing action of histone acetylases (HATs) and deacetylases (HDACs). These two families of enzymes play critical roles in metabolic processes and their dysregulation is associated with pathogenesis of several diseases. Dietary components, such as butyrate, sulforaphane, and curcumin, have been shown to affect HAT and HDAC activity, and their health benefits are attributed, at least in part, to epigenetic modifications. Given the decades that it takes to accumulate epigenetic changes, it is unlikely that pharmaceuticals could undo epigenetic changes without side effects. Therefore, long term consumption of dietary components that can alter the epigenome could be an attractive means of disease prevention. The goal of this review is to highlight the roles of diets and food components in epigenetic modifications through the regulation of HATs and HDACs for disease prevention.

  20. Dietary Regulation of Histone Acetylases and Deacetylases for the Prevention of Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Jiyoung Lee

    2012-11-01

    Full Text Available Age-related diseases such as type 2 diabetes, cardiovascular disease, and cancer involve epigenetic modifications, where accumulation of minute changes in the epigenome over time leads to disease manifestation. Epigenetic changes are influenced by life style and diets. This represents an avenue whereby dietary components could accelerate or prevent age-related diseases through their effects on epigenetic modifications. Histone acetylation is an epigenetic modification that is regulated through the opposing action of histone acetylases (HATs and deacetylases (HDACs. These two families of enzymes play critical roles in metabolic processes and their dysregulation is associated with pathogenesis of several diseases. Dietary components, such as butyrate, sulforaphane, and curcumin, have been shown to affect HAT and HDAC activity, and their health benefits are attributed, at least in part, to epigenetic modifications. Given the decades that it takes to accumulate epigenetic changes, it is unlikely that pharmaceuticals could undo epigenetic changes without side effects. Therefore, long term consumption of dietary components that can alter the epigenome could be an attractive means of disease prevention. The goal of this review is to highlight the roles of diets and food components in epigenetic modifications through the regulation of HATs and HDACs for disease prevention.

  1. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-06-09

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.

  2. Peroxisome proliferator activated receptor-γ in pathogenesis of experimental fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Cai-Yan Zhao; Ling-Ling Jiang; Li Li; Zhuo-Jun Deng; Bao-Li Liang; Jian-Mei Li

    2004-01-01

    AIM: To study the expression of peroxisome proliferator activated receptor-γ (PPARγ) in the liver of rats with fatty liver disease (FLD) and to explore the role of PPARγ in the pathogenesis of FLD to provide the basis for using PPARγligand to treat patients with FLD.METHODS: Forty Wistar rats were divided into 4 groups of ten rats each randomly: normal group (group A), alcohol group (group B), fat-rich diet group (group C), alcohol and fat-rich diet group (group D). The rats were sacrificed at the end of the 16th week from the feeding day. Alanine aminotransferase (ALT), tumor necrosis factor-alfa (TNFα)in serum and malondialdehyde (MDA) in liver homogenate were determined; livers were collected for observing pathologic changes by HE, Sudan Ⅳ, Masson stain under microscope. The morphologic results were analyzed by picture quantitative analysis technique. The changes of ultrastructure were also examined under electron microscope.The expression of PPARγ in liver was detected by immunohistochemistry and RT-PCR. The correlations between the expression of PPARγ and biochemical indexes, and liver histology were analyzed.RESULTS: The steatosis, inflammation, necrosis and fibrosis were present in livers of different experimental groups,especially in livers of alcohol and fat-rich diet group. The content of immunodetectable PPARγ was decreasedremarkably in the livers of model rats (group B-D); the level in alcohol and fat-rich diet group (3.43±1.48) was significantly lower than that in normal group (18.34±3.73), alcohol group (8.82±2.52) and fat-rich diet group (11.73±2.51) (all P<0.01).The level of PPARγ mRNA was also lower in the livers of model rats (group B-D) than in'livers of controls. The expression of PPARγ in rat liver correlated negatively with the degree of its inflammation, necrosis and fibrosis, as well as the level of serum TNFα and the content of MDA in liver homogenates, but not with steatosis or serum ALT.CONCLUSION: Decreased expression

  3. Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly.

    Science.gov (United States)

    Fatti, L M; Scacchi, M; Pincelli, A I; Lavezzi, E; Cavagnini, F

    2001-09-01

    Respiratory disorders are common and important complications in acromegaly. Patients suffering from acromegaly display a 1.6-3.3 fold increase in mortality rate, which is due to respiratory disorders in 25% of cases. In these patients, mortality for lung disease is 2-3 fold higher than in the general population. Every portion of the respiratory system may be involved. Deformities of facial bones, edema and hypertrophy of the mucosae and pharyngeal and laryngeal cartilages, enlargement of the tongue and inspiratory collapse of the hypopharinx, all may contribute to respiratory alterations. Nasal polyps, "hormonal rhinitis", changes of the voice and snoring are common occurrences. Though rarely, a laryngocele may ensue. Pneumomegaly is frequently observed and, as suggested by functional studies, might be due to an increased number rather than volume of the alveoli. An obstructive respiratory syndrome caused by mucosal thickening of the upper airways and bronchi is observed in 25% of female and 70% of male patients. The sleep apnea syndrome (SAS) affects 60-70% of acromegalic patients. SAS may be of obstructive, central or mixed type. Obstructive SAS is the prevailing form in acromegaly. It is due to intermittent obstruction of upper airways with preserved activity of the respiratory center, as testified by the remarkable thoracic and abdominal respiratory efforts. The pathogenesis of the central type of SAS is more complex. Narrowing of the upper airways may induce reflex inhibition of the respiratory center. Moreover, increased GH levels and, possibly, defects in the somatostatinergic pathways, may increase the ventilatory response of the respiratory center to carbon dioxide, thereby leading to respiratory arrest. In the mixed type of SAS, the phenomena underlying the other two forms coexist. Oxygen desaturation concomitant with the apneic episodes accounts for the frequent nocturnal wakening and diurnal drowsiness. Among the clinical correlates of SAS, arterial

  4. Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases.

    Science.gov (United States)

    Chen, Beidi; Sun, Luxi; Zhang, Xuan

    2017-09-01

    The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance. Epigenetic modifications triggered by environmental factors is an important mechanism that leads to altered gene expression. Researches addressing the role of DNA methylation, histone modification and non-coding RNA in AIDs have been increasing in recent years. Furthermore, studies showed that human microbiota and their metabolites can regulate immune cells and cytokines via epigenomic modifications. For example, short-chain fatty acids (SCFAs) produced by gut microbiota promote the differentiation of naïve T cell into Treg by suppressing histone deacetylases (HDACs). Therefore, we propose that dysbiosis and resulting metabolites may cause aberrant immune responses via epigenetic modifications, and lead to AIDs. With the development of high-throughput sequencing, metagenome analysis has been applied to investigate the dysbiosis in AIDs patients. We have tested the fecal, dental and salivary samples from treatment-naïve rheumatoid arthritis (RA) individuals by metagenomic shotgun sequencing and a metagenome-wide association study. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially restored after treatment. We also found functional changes of microbiota and molecular mimicry of human antigens in RA individuals. By integrating the analysis of multi-omics of microbiome and

  5. Centers for Disease Control and Prevention

    Science.gov (United States)

    ... Conditions ADHD Cancer Diabetes Heart Disease Flu (Influenza) Sexually Transmitted Diseases (STDs) Data & Statistics More Healthy Living Adolescent & School Health Food Safety Healthy Weight Overweight & Obesity ...

  6. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Eric R Kallwitz; Alan McLachlan; Scott J Cotler

    2008-01-01

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisorne proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.

  7. Iatrogenic disease in the elderly: risk factors, consequences, and prevention

    Directory of Open Access Journals (Sweden)

    Sompol Permpongkosol

    2011-03-01

    Full Text Available Sompol PermpongkosolDivision of Urology, Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAbstract: The epidemiology of iatrogenic disease in the elderly has not been extensively reported. Risk factors of iatrogenic disease in the elderly are drug-induced iatrogenic disease, multiple chronic diseases, multiple physicians, hospitalization, and medical or surgical procedures. Iatrogenic disease can have a great psychomotor impact and important social consequences. To identify patients at high risk is the first step in prevention as most of the iatrogenic diseases are preventable. Interventions that can prevent iatrogenic complications include specific interventions, the use of a geriatric interdisciplinary team, pharmacist consultation and acute care for the elderly units.Keywords: iatrogenic disease, elderly, risk factors, prevention

  8. The role of zinc in the pathogenesis and treatment of central nervous system (CNS) diseases. Implications of zinc homeostasis for proper CNS function.

    Science.gov (United States)

    Tyszka-Czochara, Małgorzata; Grzywacz, Agata; Gdula-Argasińska, Joanna; Librowski, Tadeusz; Wiliński, Bogdan; Opoka, Włodzimierz

    2014-01-01

    Zinc, the essential trace element, is known to play multiple biological functions in human organism. This metal is a component of many structural as well as regulatory and catalytic proteins. The precise regulation of zinc homeostasis is essential for central nervous system and for the whole organism. Zinc plays a significant role in the brain development and in the proper brain function at every stage of life. This article is a review of knowledge about the role of zinc in central nervous system (CNS) function. The influence of this biometal on etiopathogenesis, prevention and treatment of selected brain diseases and disorders was discussed. Zinc imbalance can result not only from insufficient dietary intake, but also from impaired activity of zinc transport proteins and zinc dependent regulation of metabolic pathways. It is known that some neurodegenerative processes are connected with zinc dyshomeostasis and it may influence the state of Alzheimer's disease, depression and ageing-connected loss of cognitive function. The exact role of zinc and zinc-binding proteins in CNS pathogenesis processes is being under intensive investigation. The appropriate zinc supplementation in brain diseases may help in the prevention as well as in the proper treatment of several brain dysfunctions.

  9. Health Promotion/Disease Prevention: New Directions for Geriatric Education.

    Science.gov (United States)

    Levkoff, Sue; And Others

    1996-01-01

    Describes 10 modules for primary care practitioners on health promotion/disease prevention for the elderly on these topics: Alzheimer's disease in minorities, dehydration, diabetes, elder abuse, geriatric nutrition, oncology, oral health in long-term care, incontinence, injury prevention, and physical activity. These areas are significant for…

  10. Action of mechanism of traditional Chinese medicine in prevention and treatment of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    HOU Yixin

    2016-04-01

    Full Text Available In recent years, extensive studies have been conducted on the pathogenesis of nonalcoholic fatty liver disease (NAFLD, and the action of mechanism of traditional Chinese medicine (TCM in NAFLD has become a new research topic. TCM has achieved good clinical efficacy in the treatment of NAFLD, with the advantages of specific, flexible, multilevel, and multi-target treatment. This article introduces the role of TCM in improving insulin, regulating lipid metabolism, preventing lipid peroxidation, regulating cytokines, regulating and maintaining the dynamic balance of factors involved in lipid metabolism, and maintaining the balance of intestinal microflora, and analyzes the major problems in TCM research.

  11. The blockade of renin-angiotensin-aldosterone system in hemodialysis patients to control hypertension and prevent cardiovascular disease: optimal pharmacotherapy.

    Science.gov (United States)

    Morishita, Yoshiyuki; Kusano, Eiji

    2011-10-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Hypertension (HT) is a major risk factor for CVD. The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of HT in HD patients. Previous studies suggested that the blockade of RAAS may be effective to control blood pressure (BP) and to prevent CVD in HD patients. A certain level of preventive effects against CVD by RAAS blockade in HD patients has been reported independently from a BP lowering effect. This review focuses on the effect of blocking RAAS in HD patients for the control of HT and the prevention of CVD.

  12. Heart Disease Prevention: Does Oral Health Matter?

    Science.gov (United States)

    ... Forum. 2013;16:e232. Chapple ILC, et al. Diabetes and periodontal diseases: Consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of Clinical Periodontology. 2013; ...

  13. RISC in PD: The Impact of MicroRNAs in Parkinson’s Disease Cellular and Molecular Pathogenesis

    Directory of Open Access Journals (Sweden)

    Sabrina Mahalia Heman-Ackah

    2013-11-01

    Full Text Available Parkinson’s disease (PD is a debilitating neurodegenerative disease characterized primarily by the selective death of dopaminergic (DA neurons in the substantia nigra pars compacta of the midbrain. Although several genetic forms of PD have been identified, the precise molecular mechanisms underlying DA neuron loss in PD remain elusive. In recent years, microRNAs (miRNAs have been recognized as potent post-transcriptional regulators of gene expression with fundamental roles in numerous biological processes. Although their role in PD pathogenesis is still a very active area of investigation, several seminal studies have contributed significantly to our understanding of the roles these small non-coding RNAs play in the disease process. Among these are studies which have demonstrated specific miRNAs that target and down-regulate the expression of PD-related genes as well as those demonstrating a reciprocal relationship in which PD-related genes act to regulate miRNA processing machinery. Concurrently, a wealth of knowledge has become available regarding the molecular mechanisms that unify the underlying etiology of genetic and sporadic PD pathogenesis, including dysregulated protein quality control by the ubiquitin-proteasome system and autophagy pathway, activation of programmed cell death, mitochondrial damage and aberrant DA neurodevelopment and maintenance. Following a discussion of the interactions between PD-related genes and miRNAs, this review highlights those studies which have elucidated the roles of these pathways in PD pathogenesis. We highlight the potential of miRNAs to serve a critical regulatory role in the implicated disease pathways, given their capacity to modulate the expression of entire families of related genes. Although few studies have directly linked miRNA regulation of these pathways to PD, a strong foundation for investigation has been laid and this area holds promise to reveal novel therapeutic targets for PD.

  14. Feline atopic dermatitis. A model for Langerhans cell participation in disease pathogenesis.

    OpenAIRE

    Roosje, P. J.; Whitaker-Menezes, D.; Goldschmidt, M. H.; Moore, P F; Willemse, T.; Murphy, G. F.

    1997-01-01

    Atopic dermatitis is a disorder characterized by cutaneous exanthemata as a consequence of exaggerated eczematous reactions to topical and systemic allergens. Langerhans cells, expressing CD1a and HLA-DR, and dermal dendritic cells, expressing HLA-DR, are known to be potent antigen-presenting cells and are thought to play an important role in the pathogenesis of atopic dermatitis. The immunophenotype of lesional skin in atopic dermatitis in humans involves increased numbers of CD1a+/MHC class...

  15. Occupational skin diseases and prevention among sanitation ...

    African Journals Online (AJOL)

    Methods: 273 sanitation workers and 113 administrative staff from 11 streets of Wuhan were .... type (formal or informal, off-the books) and resident .... Knowledge of protection n (%) .... prevented through engineering, medical and legislative.

  16. Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease.

    Science.gov (United States)

    Sharp, Robert C; Abdulrahim, Muna; Naser, Ebraheem S; Naser, Saleh A

    2015-01-01

    Genome wide association studies have identified several genes that might be associated with increase susceptibility to Type 1 Diabetes (T1D) and Crohn's disease. Both Crohn's disease and T1D have a profound impact on the lives of patients and it is pivotal to investigate the genetic role in patients acquiring these diseases. Understanding the effect of single nucleotide polymorphisms (SNP's) in key genes in patients suffering from T1D and Crohn's disease is crucial to finding an effective treatment and generating novel therapeutic drugs. This review article is focused on the impact of SNP's in PTPN2 (protein tyrosine phosphatase, non-receptor type 2) and PTPN22 (protein tyrosine phosphatase non-receptor type 22) on the development of Crohn's disease and T1D. The PTPN2 gene mutation in T1D patients play a direct role in the destruction of beta cells while in Crohn's disease patients, it modulates the innate immune responses. The PTPN22 gene mutations also play a role in both diseases by modulating intracellular signaling. Examining the mechanism through which these genes increase the susceptibility to both diseases and gaining a better understanding of their structure and function is of vital importance to understand the etiology and pathogenesis of Type 1 Diabetes and Crohn's disease.

  17. Host stress response is important for the pathogenesis of the deadly amphibian disease, Chytridiomycosis, in Litoria caerulea.

    Directory of Open Access Journals (Sweden)

    John D Peterson

    Full Text Available Chytridiomycosis, a disease caused by Batrachochytrium dendrobatidis, has contributed to worldwide amphibian population declines; however, the pathogenesis of this disease is still somewhat unclear. Previous studies suggest that infection disrupts cutaneous sodium transport, which leads to hyponatremia and cardiac failure. However, infection is also correlated with unexplained effects on appetite, skin shedding, and white blood cell profiles. Glucocorticoid hormones may be the biochemical connection between these disparate effects, because they regulate ion homeostasis and can also influence appetite, skin shedding, and white blood cells. During a laboratory outbreak of B. dendrobatidis in Australian Green Tree Frogs, Litoria caerulea, we compared frogs showing clinical signs of chytridiomycosis to infected frogs showing no signs of disease and determined that diseased frogs had elevated baseline corticosterone, decreased plasma sodium and potassium, and altered WBC profiles. Diseased frogs also showed evidence of poorer body condition and elevated metabolic rates compared with frogs showing no signs of disease. Prior to displaying signs of disease, we also observed changes in appetite, body mass, and the presence of shed skin associated with infected but not yet diseased frogs. Collectively, these results suggest that elevated baseline corticosterone is associated with chytridiomycosis and correlates with some of the deleterious effects observed during disease development.

  18. [Immunotherapeutic approach for the prevention and treatment of chronic diseases].

    Science.gov (United States)

    Bagnato, Barbara; Marino, Maria Giulia; Franco, Elisabetta

    2013-01-01

    Alzheimer disease, diabetes and cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Different immunotherapeutic approaches for prevention and treatment of these diseases are currently object of several researches. In this paper, recent trials describing active and passive immunotherapy for the management of these pathologies are discussed. The recent immunotherapeutic and preventive approaches for the treatment of Alzheimer's disease are based on the use of β-amyloid peptides and to tau-based immunization strategies but new possibility are explored. Immunotherapeutic vaccine against angiotensin II showed promising results for the management of hypertension. Heath shock proteins and β2-glycoprotein I have been tested to reduce atherosclerosis. Insulin agonists were used for preventing type 1 diabetes in mouse; IL-1β was effective in experimental type 2 diabetes. Research in the field of immunological approach to treatment and prevention of chronic diseases is promising even if the present results have been obtained mainly in animal models.

  19. Gliadin is a Good Substrate of Several Transglutaminases: Possible Implication in the Pathogenesis of Coeliac Disease

    DEFF Research Database (Denmark)

    Skovbjerg, Hanne; Norén, Ove; Anthonsen, Dorit

    2002-01-01

    Coeliac disease, enzymatic assay, Europium, gliadin, human, microbial, microtitre plate, patogenesis, transglutaminase, vegetable......Coeliac disease, enzymatic assay, Europium, gliadin, human, microbial, microtitre plate, patogenesis, transglutaminase, vegetable...

  20. Prevention and management of limb contractures in neuromuscular diseases.

    Science.gov (United States)

    Skalsky, Andrew J; McDonald, Craig M

    2012-08-01

    Limb contractures are a common impairment in neuromuscular diseases. They contribute to increased disability from decreased motor performance, mobility limitations, reduced functional range of motion, loss of function for activities of daily living, and increased pain. The pathogenesis of contractures is multifactorial. Myopathic conditions are associated with more severe limb contractures compared with neuropathic disorders. Although the evidence supporting the efficacy of multiple interventions to improve range of motion in neuromuscular diseases in a sustained manner is lacking, there are generally accepted principles with regard to splinting, bracing, stretching, and surgery that help minimize the impact or disability from contractures.

  1. IMMUNOBIOLOGY OF DIPHTHERIA. RECENT APPROACHES FOR THE PREVENTION, DIAGNOSIS, AND TREATMENT OF DISEASE

    Directory of Open Access Journals (Sweden)

    D. V. Kolybo

    2013-08-01

    Full Text Available Diphtheria is a highly contagious life-threatening disease caused by the toxi genic strains of Corynebacterium diphtheria, which are transformed by a bacteriophage carrying the toxin gene. Diphtheria causative agent and its major virulence factor diphtheria toxin are well studied, but outbreaks of disease still occur worldwide. Rapid development of new methods in immunology and molecular biology is currently leading to improvement of prophylaxis, diagnosis and treatment of diphtheria. This review highlights the microbiological, epidemiological and immunological aspects of diphtheria infection, role of diphtheria toxin and others virulence factors in diphtheria pathogenesis and role of humoral anti-toxic immunity in the protection against disease. Perspectives in development of new diagnostic tests, anti-diphtheria vaccines, immunobiological preparations and antidotes for prevention of diphtheria infection, and other anti-diphteria means was also discussed.

  2. The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Svenja eHartmann

    2015-11-01

    Full Text Available Rho-associated kinases ROCK1 and ROCK2 are serine/threonine kinases that are downstream targets of the small GTPases RhoA, RhoB, and RhoC. ROCKs are involved in diverse cellular activities including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, remodeling of the extracellular matrix and smooth muscle cell contraction. The role of ROCK1 and ROCK2 has long been considered to be similar; however, it is now clear that they do not always have the same functions. Moreover, depending on their subcellular localization, activation, and other environmental factors, ROCK signaling can have different effects on cellular function. With respect to the heart, findings in isoform-specific knockout mice argue for a role of ROCK1 and ROCK2 in the pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively. Increased ROCK activity could play a pivotal role in processes leading to cardiovascular diseases such as hypertension, pulmonary hypertension, angina pectoris, vasospastic angina, heart failure, and stroke, and thus ROCK activity is a potential new biomarker for heart disease. Pharmacological ROCK inhibition reduces the enhanced ROCK activity in patients, accompanied with a measurable improvement in medical condition. In this review, we focus on recent findings regarding ROCK signaling in the pathogenesis of cardiovascular disease, with a special focus on differences between ROCK1 and ROCK2 function.

  3. The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease.

    Science.gov (United States)

    Hartmann, Svenja; Ridley, Anne J; Lutz, Susanne

    2015-01-01

    Rho-associated kinases ROCK1 and ROCK2 are serine/threonine kinases that are downstream targets of the small GTPases RhoA, RhoB, and RhoC. ROCKs are involved in diverse cellular activities including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, remodeling of the extracellular matrix and smooth muscle cell contraction. The role of ROCK1 and ROCK2 has long been considered to be similar; however, it is now clear that they do not always have the same functions. Moreover, depending on their subcellular localization, activation, and other environmental factors, ROCK signaling can have different effects on cellular function. With respect to the heart, findings in isoform-specific knockout mice argue for a role of ROCK1 and ROCK2 in the pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively. Increased ROCK activity could play a pivotal role in processes leading to cardiovascular diseases such as hypertension, pulmonary hypertension, angina pectoris, vasospastic angina, heart failure, and stroke, and thus ROCK activity is a potential new biomarker for heart disease. Pharmacological ROCK inhibition reduces the enhanced ROCK activity in patients, accompanied with a measurable improvement in medical condition. In this review, we focus on recent findings regarding ROCK signaling in the pathogenesis of cardiovascular disease, with a special focus on differences between ROCK1 and ROCK2 function.

  4. Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hammer, J H

    1992-01-01

    The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize autoantig......The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize...... the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed...

  5. Prevention of oral diseases and oral health promotion.

    Science.gov (United States)

    Gift, H C

    1991-06-01

    Research and activities, as promoted in 1989 and 1990, in oral disease prevention and health promotion are summarized. Significant syntheses of research findings have occurred, as a result of planning and workship activities, which will direct oral health promotion in the 1990s. Original research on established and new preventive therapies for dental caries, periodontal diseases, oral mucosal alterations, soft-tissue lesions, precancers and cancers, and trauma are reported, opportunities to prevent oral diseases or maintain oral health through changes in individual behaviors, professional orientation, and social and environmental changes are addressed.

  6. Reducing cholesterol to prevent coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Matthew J. Sorrentino

    2005-01-01

    @@ Coronary heart disease (CHD) remains the number one killer of men and women in the United States of America despite major advances in interventional technologies for the treatment of coronary artery disease. CHD is rapidly becoming a major cause of morbidity and mortality in developing nations as well and is now recognized as the leading cause of death worldwide.

  7. Physician Performance Assessment: Prevention of Cardiovascular Disease

    Science.gov (United States)

    Lipner, Rebecca S.; Weng, Weifeng; Caverzagie, Kelly J.; Hess, Brian J.

    2013-01-01

    Given the rising burden of healthcare costs, both patients and healthcare purchasers are interested in discerning which physicians deliver quality care. We proposed a methodology to assess physician clinical performance in preventive cardiology care, and determined a benchmark for minimally acceptable performance. We used data on eight…

  8. Role of the Innate Immune System in the Pathogenesis of Inflammatory Bowel Disease

    NARCIS (Netherlands)

    van Lierop, Pieter P. E.; Samsom, Janneke N.; Escher, Johanna C.; Nieuwenhuis, Edward E. S.

    2009-01-01

    Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it

  9. A survey of veterinarian involvement in zoonotic disease prevention practices.

    Science.gov (United States)

    Lipton, Beth A; Hopkins, Sharon G; Koehler, Jane E; DiGiacomo, Ronald F

    2008-10-15

    To determine the extent to which practicing veterinarians in King County, Washington, engaged in commonly recommended practices for the prevention of zoonotic diseases. Cross-sectional survey. Sample Population-Licensed veterinarians practicing clinical medicine in King County, Washington. A survey was sent between September and November 2006 to 454 licensed veterinarians practicing clinical medicine in King County. 370 valid responses were received. A high proportion (280/362 [77%]) of respondents agreed that it was very important for veterinarians to educate clients on zoonotic disease prevention, but only 43% (158/367) reported that they had initiated discussions about zoonotic diseases with clients on a daily basis, and only 57% (203/356) indicated that they had client educational materials on zoonotic diseases available in their practices. Thirty-one percent (112/360) of respondents indicated that there were no written infection-control guidelines for staff members in the practice, and 28% (105/371) reported having been infected with a zoonotic disease in practice. Results illustrated that veterinarians recognize their important role in zoonotic disease prevention and suggested that veterinarians would welcome stronger partnerships with public health agencies and other health professionals in this endeavor. Methods to increase veterinarians' involvement in zoonotic disease prevention include discussing zoonotic diseases more frequently with clients, physicians, and public health agencies; encouraging higher risk individuals to discuss zoonotic diseases; having educational materials on zoonotic diseases available for clients; improving infection-control practices; and ensuring that continuing education courses on zoonotic diseases are regularly available.

  10. U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease.

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka

    2015-01-01

    Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self-RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD.

  11. Disease prevention in the trout hatchery

    Science.gov (United States)

    Fish, F.F.

    1939-01-01

    With the comparatively recent evolution of fish hatching into true fish culture the problems offered by fish disease have likewise evolved from more or less of a petty annoyance into a first class headache.

  12. treatment and prevention of pneumococcal disease

    African Journals Online (AJOL)

    the absence of anti-pneumolysin antibody. Moreover, this toxin also .... monoclonal antibody. While the .... In addition to playing a significant role in the disease process, the toxin is .... Construction and immunological characterization of a novel ...

  13. Division for Heart Disease and Stroke Prevention: Data Trends & Maps

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDC Division for Heart Disease and Stroke Prevention's Data Trends & Maps online tool allows searching for and view of health indicators related to Heart...

  14. Incidence of behavior's habits in the cardiovascular disease prevention

    National Research Council Canada - National Science Library

    Carpi-Ballester, Amparo; Zurriaga-Llorens, Rosario; Gonzalez-Navarro, Pilar; Marzo-Campos, Juan C; Buunk, Abraham P

    2007-01-01

    .... Theory of Planed Behavior is a prevailing model in the study of health. Using this theoretical framework, the objective of this descriptive study is to test the impact of behavioral habits on preventive behaviours of cardiovascular disease...

  15. Hormone Therapy Not Advised for Preventing Disease After Menopause

    Science.gov (United States)

    ... Hormone Therapy Not Advised for Preventing Disease After Menopause Benefits of treatment don't outweigh the risks, ... attack, stroke and blood clots. Women typically enter menopause around the age of 50. Following menopause, women's ...

  16. The re-emergency and persistence of vaccine preventable diseases

    Directory of Open Access Journals (Sweden)

    RODRIGO C.N. BORBA

    2015-08-01

    Full Text Available The introduction of vaccination worldwide dramatically reduced the incidence of pathogenic bacterial and viral diseases. Despite the highly successful vaccination strategies, the number of cases among vaccine preventable diseases has increased in the last decade and several of those diseases are still endemic in different countries. Here we discuss some epidemiological aspects and possible arguments that may explain why ancient diseases such as, measles, polio, pertussis, diphtheria and tuberculosis are still with us.

  17. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bert Tuk

    2016-08-01

    Full Text Available Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

  18. Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics.

    Science.gov (United States)

    Davies, Katherine M; Mercer, Julian F B; Chen, Nicholas; Double, Kay L

    2016-04-01

    Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease. © 2016 Authors; published by Portland Press Limited.

  19. Development and Coherence of Beliefs Regarding Disease Causality and Prevention

    Science.gov (United States)

    Sigelman, Carol K.

    2014-01-01

    Guided by a naïve theories perspective on the development of thinking about disease, this study of 188 children aged 6 to 18 examined knowledge of HIV/AIDS causality and prevention using parallel measures derived from open-ended and structured interviews. Knowledge of both risk factors and prevention rules, as well as conceptual understanding of…

  20. Development and Coherence of Beliefs Regarding Disease Causality and Prevention

    Science.gov (United States)

    Sigelman, Carol K.

    2014-01-01

    Guided by a naïve theories perspective on the development of thinking about disease, this study of 188 children aged 6 to 18 examined knowledge of HIV/AIDS causality and prevention using parallel measures derived from open-ended and structured interviews. Knowledge of both risk factors and prevention rules, as well as conceptual understanding of…

  1. [Prevention of asthma and allergic diseases in children].

    Science.gov (United States)

    Rancé, F; de Blic, J; Scheinmann, P

    2003-03-01

    Allergic diseases have become a major public health problem in industrialized countries, justifying the development of prevention programs. A review of the literature on allergens and atopic symptoms, age of primary sensitization and other factors associated with allergic diseases development is presented and is followed by a discussion on prevention measures. The most recent physiopathological and immunological data indicate that persistent asthma and allergic diseases in adults may be associated with events in early childhood. The parallel increase in autoimmune and allergic diseases has been correlated with regulatory mechanism defects, contradicting the previous theory that involved a predominantly Th1 or Th2 pathway. The primary prevention of asthma and allergic diseases thus appear to be somewhat utopian. Indeed based on recent results, the risk of developing allergies appears to be related to modern "clean" lyfestyles. Secondary prevention is probably necessary, possibly through specific immunotherapy. Tertiary prevention must also be considered. Passive smoking must be prevented as it can alter the development of the respiratory system and promote allergen sensitization. Randomized, controlled, prospective studies are needed to evaluate the efficacy of the preventive measures.

  2. Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease.

    Science.gov (United States)

    Percy, Maire E; Kruck, Theo P A; Pogue, Aileen I; Lukiw, Walter J

    2011-11-01

    In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD.

  3. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Price

    2015-06-01

    Full Text Available Dendritic cells (DCs are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are 4 main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in autoimmune pathogenesis and regulation, as well as the genetic and environmental signals that influence their function. Specific topics to be addressed include: impact of susceptibility loci on DC subsets, alterations in DC subset development, the role of infection- and host-derived innate inflammatory signals, and the role of the intestinal microbiota on DC phenotype. The effects of these various signals on disease progression and the relative effects of DC subset composition and maturation level of DCs will be examined. These areas will be explored using examples from several autoimmune diseases but will focus mainly on type 1 diabetes.

  4. Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer’s Disease Pathogenesis

    Science.gov (United States)

    Kyrtsos, Christina Rose; Baras, John S.

    2015-01-01

    Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain. PMID:26448331

  5. Neuropsychiatric manifestations of Fahr′s disease pathogenesis and potential for treatment

    Directory of Open Access Journals (Sweden)

    Raheel Mushtaq

    2013-01-01

    Full Text Available Fahr′s disease (FD is a rare neuropsychiatric disease consisting of bilateral basal ganglia calcification with neurological, cognitive, and psychiatric manifestations. We report here a sporadic case of FDs with its neuropsychology.

  6. Neuropsychiatric manifestations of Fahr′s disease pathogenesis and potential for treatment

    OpenAIRE

    Raheel Mushtaq; Sheikh Shoib; M. S. V. K Raju; Nilesh Naphade; Tabindah Shah; Alka Pawar

    2013-01-01

    Fahr's disease (FD) is a rare neuropsychiatric disease consisting of bilateral basal ganglia calcification with neurological, cognitive, and psychiatric manifestations. We report here a sporadic case of FDs with its neuropsychology.

  7. Differentiating clinical care from disease prevention: a prerequisite for practicing quaternary prevention

    Directory of Open Access Journals (Sweden)

    Charles Dalcanale Tesser

    Full Text Available Abstract: This article contends that the distinction between clinical care (illness and prevention of future disease is essential to the practice of quaternary prevention. The authors argue that the ongoing entanglement of clinical care and prevention transforms healthy into "sick" people through changes in disease classification criteria and/or cut-off points for defining high-risk states. This diverts health care resources away from those in need of care and increases the risk of iatrogenic harm in healthy people. The distinction in focus is based on: (a management of uncertainty (more flexible when caring for ill persons; (b guarantee of benefit (required only in prevention; (c harm tolerance (nil or minimal in prevention. This implies attitudinal differences in the decision-making process: greater skepticism, scientism and resistance towards preventive action. These should be based on high-quality scientific evidence of end-outcomes that displays a net positive harm/benefit ratio.

  8. Pathogenesis of new sub-genotypes of Newcastle disease virus strains from Israel and Pakistan

    Science.gov (United States)

    Newcastle disease (ND) is a devastating disease of poultry worldwide caused by virulent strains of Newcastle disease virus (NDV). New genotypes and sub-genotypes of NDV frequently emerge. In the past few years, NDV strains belonging to sub-genotype VIIi and XIIIb emerged in the Middle East and Asi...

  9. Common Mechanism of Pathogenesis in Gastrointestinal Diseases Implied by Consistent Efficacy of Single Chinese Medicine Formula: A PRISMA-Compliant Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Ling, Wei; Li, Yang; Jiang, Wei; Sui, Yi; Zhao, Hai-Lu

    2015-07-01

    Gastrointestinal (GI) disorders often manifest similar symptoms with overlapping clinical diagnosis and unmet medical needs. Traditional Chinese medicine (TCM) has history-proven benefits for GI diseases; albeit language barrier prevents Western readers from accessing the original reports in Chinese. The TCM formula Si-Ni-San (SNS) consists of 4 herbs targeting on homeostatic disturbances characterized by "reflux" and "irritable" problems. Here we used SNS as a therapeutic tool to explore the common mechanisms of pathogenesis in non-neoplastic GI diseases.Data sources from PUBMED, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials. Comparisons were SNS as intervention and Western conventional medicine as control, which treat patients with upper GI disorders (gastroesophageal reflux disease, peptic ulcer, chronic gastritis, duodenogastric reflux), lower GI diseases (irritable bowel syndrome, ulcerative colitis), and functional dyspepsia. Participants and studies in accordance with the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement were eligible. We used the Jadad scale to assess methodological qualities, the fixed or random-effect model to evaluate therapeutic efficacy, and the funnel plots to explore publication bias. Outcome was clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology.We included 83 studies involving 7762 participants: 1708 versus 1397 of the upper GI disorders in 34 studies, 901 versus 768 of the lower GI diseases in 19 studies, 1641 versus 1348 of functional dyspepsia in 30 studies, and 328 versus 287 of relapse rate in 8 studies. Six studies had a Jadad score >2 points and the rest were data showed significant efficacy of SNS for the upper GI disorders (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 3.09-4.92), lower GI diseases (OR = 4.91, 95% CI = 3.71-6.51), and functional dyspepsia (N = 2989; OR

  10. Coronary angiography and pathogenesis of coronary artery disease in young male survivors of myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Szamosi, A.; Hamsten, A.; Walldius, G.; Faire, U. de

    Coronary angiography was performed 3 to 6 months after myocardial infarction in 107 males below the age of 45 (mean age 39.7+-3.9, range 23-44 years). The coronary angiograms were allocated to various groups according to the presence or absence of obvious atheromatous changes. Metabolic evaluation included determination of cholesterol and triglyceride concentrations in the major serum lipoproteins. Marked elevation of low density lipoprotein (LDL) cholesterol concentration was found in patients with angiographic evidence of atheromatosis, in contrast to patients with normal coronary angiograms or with single occlusion and no other abnormalities. Thus, there was a correlation between angiographic appearance of the coronary arteries and disturbances of LDL metabolism. It is proposed that coronary angiography may distinguish between atheromatous and nonatheromatous pathogenesis of myocardial infarction at young age.

  11. Orphan diseases of the nose and paranasal sinuses: Pathogenesis – clinic – therapy

    Directory of Open Access Journals (Sweden)

    Laudien, Martin

    2015-12-01

    Full Text Available Rare rhinological diseases are a diagnostic challenge. Sometimes it takes months or even years from the primary manifestation of the disease until the definitive diagnosis is establibshed. During these times the disease proceeds in an uncontrolled or insufficiently treated way. (Irreversible damage results and sometimes life-threatening situations occur. The unexpected course of a (misdiagnosed disease should lead to further diagnostic reflections and steps in order to detect also rare diseases as early as possible.The present paper discusses granulomatous diseases of the nose and paranasal sinuses caused by mycobacteria, treponema, Klebsiella, fungi, and protozoa as well as vasculitis, sarcoidosis, rosacea, cocaine-induced midline destruction, nasal extranodal NK/T cell lymphoma, and cholesterol granuloma. Furthermore, diseases with disorders of the mucociliary clearance such as primary ciliary dyskinesia and cystic fibrosis are presented, taking into consideration the current literature.

  12. Travel related diseases and optimizing preventive strategies

    NARCIS (Netherlands)

    Wieten, R.W.

    2016-01-01

    With the figure of 1 billion annual travellers continuously increasing, travel is becoming more and more common. The binding element of this thesis is the aim to contribute to the improvement of pre-travel healthcare. The diseases studied either carry a high mortality (rabies, malaria, yellow fever)

  13. The molecular pathogenesis of Cushing's disease%库欣病的分子发病机制

    Institute of Scientific and Technical Information of China (English)

    魏薇; 王卫庆

    2014-01-01

    Cushing's disease is a condition of an excess of the steroid hormone cortisol in the blood caused by a pituitary corticotropic adenoma secreting adrenocorticotropic hormone.Cushing's disease in familial endocrine syndromes with pituitary adenomas is related to the gene mutation of MEN-1 and GNAS1.And the abnormal expression of the PTTG and p27 genes,hormone related receptors and ligands are involved in the pathogenesis of sporadic Cushing's disease,which cause the proliferation of the corticotroph cells and excessive ACTH secretion.Further understanding of the molecular pathogenesis of Cushing's disease is helpful in early diagnosis and targeted therapy.%库欣病是垂体促肾上腺皮质激素(ACTH)腺瘤分泌过多ACTH,刺激肾上腺过度合成和分泌糖皮质激素所致.家族性内分泌综合征伴垂体ACTH腺瘤与多发性内分泌腺瘤病(MEN)-1及GNAS1基因突变相关.散发性库欣病的发病机制涉及PTTG、p27基因和激素相关受体、配体的异常表达,造成垂体ACTH细胞的过度增殖和激素分泌.进一步了解库欣病的分子发病机制对早期诊断和靶向治疗有重要意义.

  14. 77 FR 4048 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-01-26

    ... Dengue Epidemiology, Outcomes, and Prevention in Sentinel Surveillance and Research Sites in Puerto Rico... to ``Evaluation of Dengue Epidemiology, Outcomes and Prevention in Sentinel Surveillance and Research... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention...

  15. SIRT7 Represses Myc Activity to Suppress ER Stress and Prevent Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jiyung Shin

    2013-11-01

    Full Text Available Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

  16. SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease.

    Science.gov (United States)

    Shin, Jiyung; He, Ming; Liu, Yufei; Paredes, Silvana; Villanova, Lidia; Brown, Katharine; Qiu, Xiaolei; Nabavi, Noushin; Mohrin, Mary; Wojnoonski, Kathleen; Li, Patrick; Cheng, Hwei-Ling; Murphy, Andrew J; Valenzuela, David M; Luo, Hanzhi; Kapahi, Pankaj; Krauss, Ronald; Mostoslavsky, Raul; Yancopoulos, George D; Alt, Frederick W; Chua, Katrin F; Chen, Danica

    2013-11-14

    Nonalcoholic fatty liver disease is the most common chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.

  17. Prevention of Cardiovascular Diseases in Deprived Neighbourhoods

    OpenAIRE

    El Fakiri, Fatima

    2008-01-01

    textabstractWorldwide, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality even though mortality rates in the industrialised countries have declined over the past decades. Recent WHO reports show that an estimated 17 million people die every year of CVD, particularly from myocardial infarction and strokes [1]. In Western countries, such as the Netherlands, discrepancies in cardiovascular morbidity and mortality according to ethnicity and socio-economic status sti...

  18. Leveraging human-centered design in chronic disease prevention.

    Science.gov (United States)

    Matheson, Gordon O; Pacione, Chris; Shultz, Rebecca K; Klügl, Martin

    2015-04-01

    Bridging the knowing-doing gap in the prevention of chronic disease requires deep appreciation and understanding of the complexities inherent in behavioral change. Strategies that have relied exclusively on the implementation of evidence-based data have not yielded the desired progress. The tools of human-centered design, used in conjunction with evidence-based data, hold much promise in providing an optimal approach for advancing disease prevention efforts. Directing the focus toward wide-scale education and application of human-centered design techniques among healthcare professionals will rapidly multiply their effective ability to bring the kind of substantial results in disease prevention that have eluded the healthcare industry for decades. This, in turn, would increase the likelihood of prevention by design.

  19. A tale of two maladies? Pathogenesis of depression with and without the Huntington’s disease gene mutation

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2013-07-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression, cognitive deficits (culminating in dementia and motor abnormalities (including chorea. Having reached the 20th anniversary of the discovery of the ‘genetic stutter’ which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviours as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalise to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.

  20. Schisandrin B as a Hormetic Agent for Preventing Age-Related Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Philip Y. Lam

    2012-01-01

    Full Text Available Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of neurodegenerative diseases, with the latter preceding the appearance of clinical symptoms. The energy failure resulting from mitochondrial dysfunction further impedes brain function, which demands large amounts of energy. Schisandrin B (Sch B, an active ingredient isolated from Fructus Schisandrae, has been shown to afford generalized tissue protection against oxidative damage in various organs, including the brain, of experimental animals. Recent experimental findings have further demonstrated that Sch B can protect neuronal cells against oxidative challenge, presumably by functioning as a hormetic agent to sustain cellular redox homeostasis and mitoenergetic capacity in neuronal cells. The combined actions of Sch B offer a promising prospect for preventing or possibly delaying the onset of neurodegenerative diseases, as well as enhancing brain health.